William Borkowsky, M.D.

Correlation of HIV-Specific Immunity, Viral Control, and Diversification following Planned Multiple Exposures to Autologous HIV in a Pediatric Population
Borkowsky, William; McFarland, Elizabeth J; Yogev, Ram; Li, Yonghua; Harding, Paul
2011 Oct;18(10):1628-1631, Clinical & vaccine immunology
Repeated controlled exposure to autologous virus was previously shown to result in increased CD8 T lymphocyte response to HIV antigens and accompanying reduction in viremia. We attempted to see if this immunity contributed to virologic control by correlating the immune response with quasispecies envelope diversification, an indicator of immune selection. The greatest diversification was seen in those with the greatest reduction in viremia but was unrelated to the frequency of Env-specific gamma interferon-producing cells. There was a trend toward correlation between the response to multiple HIV antigens and diversification
— id: 138109, year: 2011, vol: 18, page: 1628, stat: Journal Article,

Body fat distribution in perinatally HIV-infected and HIV-exposed but uninfected children in the era of highly active antiretroviral therapy: outcomes from the Pediatric HIV/AIDS Cohort Study
Jacobson DL; Patel K; Siberry GK; Van Dyke RB; Dimeglio LA; Geffner ME; Chen JS; McFarland EJ; Borkowsky W; Silio M; Fielding RA; Siminski S; Miller TL
2011 Dec;94(6):1485-1495, American journal of clinical nutrition
BACKGROUND: Associations between abnormal body fat distribution and clinical variables are poorly understood in pediatric HIV disease. OBJECTIVE: Our objective was to compare total body fat and its distribution in perinatally HIV-infected and HIV-exposed but uninfected (HEU) children and to evaluate associations with clinical variables. DESIGN: In a cross-sectional analysis, children aged 7-16 y in the Pediatric HIV/AIDS Cohort Study underwent regionalized measurements of body fat via anthropometric methods and dual-energy X-ray absorptiometry. Multiple linear regression was used to evaluate body fat by HIV, with adjustment for age, Tanner stage, race, sex, and correlates of body fat in HIV-infected children. Percentage total body fat was compared with NHANES data. RESULTS: Males accounted for 47% of the 369 HIV-infected and 51% of the 176 HEU children. Compared with HEU children, HIV-infected children were older, were more frequently non-Hispanic black, more frequently had Tanner stage >/=3, and had lower mean height (-0.32 compared with 0.29), weight (0.13 compared with 0.70), and BMI (0.33 compared with 0.63) z scores. On average, HIV-infected children had a 5% lower percentage total body fat (TotF), a 2.8% lower percentage extremity fat (EF), a 1.4% higher percentage trunk fat (TF), and a 10% higher trunk-to-extremity fat ratio (TEFR) than did the HEU children and a lower TotF compared with NHANES data. Stavudine use was associated with lower EF and higher TF and TEFR. Non-nucleotide reverse transcriptase inhibitor use was associated with higher TotF and EF and lower TEFR. CONCLUSION: Although BMI and total body fat were significantly lower in the HIV-infected children than in the HEU children, body fat distribution in the HIV-infected children followed a pattern associated with cardiovascular disease risk and possibly related to specific antiretroviral drugs
— id: 147202, year: 2011, vol: 94, page: 1485, stat: Journal Article,

Susceptibility of Human Th17 Cells to Human Immunodeficiency Virus and Their Perturbation during Infection
El Hed, Aimee; Khaitan, Alka; Kozhaya, Lina; Manel, Nicolas; Daskalakis, Demetre; Borkowsky, William; Valentine, Fred; Littman, Dan R; Unutmaz, Derya
2010 Mar 15;201(6):843-854, Journal of infectious diseases
Background. Identification of the Th17 T cell subset as important mediators of host defense and pathology prompted us to determine their susceptibility to human immunodeficiency virus (HIV) infection. Methods and results. We found that a sizeable portion of Th17 cells express HIV coreceptor CCR5 and produce very low levels of CCR5 ligands macrophage inflammatory protein (MIP)-1alpha and MIP-1beta. Accordingly, CCR5(+) Th17 cells were efficiently infected with CCR5-tropic HIV and were depleted during viral replication in vitro. Remarkably, HIV-infected individuals receiving treatment had significantly reduced Th17 cell counts, compared with HIV-uninfected subjects, regardless of viral load or CD4 cell count, whereas treatment-naive subjects had normal levels. However, there was a preferential reduction in CCR5(+) T cells that were also CCR6 positive, which is expressed on all Th17 cells, compared with CCR6(-)CCR5(+) cells, in both treated and untreated HIV-infected subjects. This observation suggests preferential targeting of CCR6(+)CCR5(+) Th17 cells by CCR5-tropic viruses in vivo. Th17 cell levels also inversely correlated with activated CD4(+) T cells in HIV-infected individuals who are receiving treatment. Conclusions. Our findings suggest a complex perturbation of Th17 subsets during the course of HIV disease potentially through both direct viral infection and virus indirect mechanisms, such as immune activation
— id: 107380, year: 2010, vol: 201, page: 843, stat: Journal Article,

Immunogenicity and Immunologic Memory after Hepatitis B Virus Booster Vaccination in HIV-Infected Children Receiving Highly Active Antiretroviral Therapy
Abzug, Mark J; Warshaw, Meredith; Rosenblatt, Howard M; Levin, Myron J; Nachman, Sharon A; Pelton, Stephen I; Borkowsky, William; Fenton, Terence
2009 Sep 15;200(6):935-946, Journal of infectious diseases
Background. Hepatitis B virus (HBV) is an important cause of comorbidity in human immunodeficiency virus (HIV)-infected individuals. The immunogenicity of HBV vaccination in children receiving highly active antiretroviral therapy (HAART) was investigated. Methods. HIV-infected children receiving HAART who had low to moderate HIV loads and who had previously received 3 doses of HBV vaccine were given an HBV vaccine booster. Concentrations of antibody to hepatitis B surface antigen (anti-HBs) were determined before vaccination and at weeks 8, 48, and 96. A subset of subjects was administered a subsequent dose, and anti-HBs was measured before and 1 and 4 weeks later. Results. At entry, 24% of 204 subjects were seropositive. Vaccine response occurred in 46% on the basis of seropositivity 8 weeks after vaccination and in 37% on the basis of a 4-fold rise in antibody concentration. Of 69 subjects given another vaccination 4-5 years later, immunologic memory was exhibited by 45% on the basis of seropositivity 1 week after vaccination and by 29% on the basis of a 4-fold rise in antibody concentration at 1 week. Predictors of response and memory included higher nadir and current CD4 cell percentage, higher CD19 cell percentage, and undetectable HIV load. Conclusions. HIV-infected children frequently lack protective levels of anti-HBs after previous HBV vaccination, and a significant proportion of them do not respond to booster vaccination or demonstrate memory despite receiving HAART, leaving this population insufficiently protected from infection with HBV. Trial registration. ClinicalTrials.gov identifier: NCT00013871
— id: 101641, year: 2009, vol: 200, page: 935, stat: Journal Article,

Implementation of HIV testing at 2 New York City bathhouses: from pilot to clinical service
Daskalakis, Demetre; Silvera, Richard; Bernstein, Kyle; Stein, Dylan; Hagerty, Robert; Hutt, Richard; Maillard, Alith; Borkowsky, William; Aberg, Judith; Valentine, Fred; Marmor, Michael
2009 Jun 1;48(11):1609-1616, Clinical infectious diseases
BACKGROUND: Commercial sex venues (e.g., bathhouses) that cater to men who have sex with men (MSM) continue to function in most urban areas. These venues present a challenge to developing strategies to prevent the spread of the human immunodeficiency virus (HIV), but they also provide opportunities for interventions to reduce the risk and rate of disease transmission. Several cities in the United States have developed programs that offer HIV testing in these venues. Similar programs have not existed before in New York City. METHODS: A pilot HIV testing program was implemented at 2 New York City bathhouses. Testing included rapid HIV testing, the use of the serologic testing algorithm for recent HIV seroconversion, and pooled plasma HIV viral load to detect and date incident and acute HIV infections. In addition to HIV tests, behavioral and demographic data were collected from 493 presumed HIV-negative participants. RESULTS: The pilot program recruited MSM who were at high risk for HIV infection. Of the 493 men tested, 20 (4%) were found to be positive for HIV, and 8 (40%) of these 20 men demonstrated evidence of acute or recent HIV infection. The program tested men often not tested in more traditional medical settings. Significant disparities were demonstrated in the testing habits of MSM who reported having sex with women and had not disclosed same-sex activities to their caregivers. CONCLUSIONS: Bathhouse-based testing for HIV infection can be implemented in New York City and would include a population of MSM who are at high risk for HIV infection. Because of the high rate of recent HIV infection, expanded testing in these venues may be a good strategy to reduce the forward transmission of HIV in this highly sexually active population
— id: 98009, year: 2009, vol: 48, page: 1609, stat: Journal Article,

HIV protease inhibitors inhibit the development of preerythrocytic-stage plasmodium parasites
Hobbs, Charlotte V; Voza, Tatiana; Coppi, Alida; Kirmse, Brian; Marsh, Kennan; Borkowsky, William; Sinnis, Photini
2009 Jan 1;199(1):134-141, Journal of infectious diseases
Recent studies have demonstrated that human immunodeficiency virus (HIV) protease inhibitors (PIs) exert inhibitory effects on erythrocytic stages of the human-malaria parasite Plasmodium falciparum in vitro and on erythrocytic stages of the rodent-malaria parasite Plasmodium chabaudi in vivo. Although it remains unclear how HIV PIs inhibit the parasite, the effect seen on parasite development in the erythrocytic stages is potent. The effect on preerythrocytic stages has not yet been investigated. Using the rodent parasite Plasmodium berghei, we screened a panel of HIV PIs in vitro for effects on the preerythrocytic stages. Our data indicated that the HIV PIs lopinavir and saquinavir affect preerythrocytic-stage parasite development in vitro. We then evaluated the effect of HIV PIs on preerythrocytic stages in vivo using the rodent parasite Plasmodium yoelii. We found that lopinavir/ritonavir had a dose-dependent effect on liver-stage parasite development. Given that sub-Saharan Africa is where the HIV/AIDS pandemic intersects with malaria, these results merit analysis in clinical settings
— id: 93220, year: 2009, vol: 199, page: 134, stat: Journal Article,

Erythema Induratum of Bazin in a Child: Evidence for a Cell-Mediated Hyper-response to Mycobacterium tuberculosis
Lighter, Jennifer; Tse, Doris B; Li, Yonghua; Borkowsky, William
2009 Apr;28(4):326-328, Pediatric infectious disease journal
Tuberculids are chronic nodular skin eruptions believed to be a systemic reaction to Mycobacterium tuberculosis. We report on a 6-year-old boy with tender subcutaneous lesions on his legs. A tuberculin skin test resulted in 2.5 cm of induration and an interferon-gamma releasing assay was also markedly positive. A diagnosis of erythema induratum of Bazin was confirmed on skin biopsy. The patient was successfully treated with multi-drug antituberculosis therapy
— id: 95181, year: 2009, vol: 28, page: 326, stat: Journal Article,

Role of molecular mimickry of hepatitis C-virus (HCV) protein with platelet GPIIIa in hepatitis C-related immunologic thrombocytopenia
Zhang, Wei; Nardi, Michael A; Borkowsky, William; Li, Zongdong; Karpatkin, Simon
2009 Apr 23;113(17):4086-4093, Blood
HIV-1-ITP patients have a unique Ab against platelet GPIIIa49-66 capable of inducing oxidative platelet fragmentation in the absence of complement. HIV-1-seropositive drug abusers are more prone to develop immune thrombocytopenia (HIV-1-ITP) than non-drug abusers and have a higher coinfection with Hepatitis C virus than non-drug abusers (90% vs 30%). Molecular mimickry with a Hepatitis C protein was sought by screening a phage peptide library with anti-GPIIIa49-66 antibody as bait for peptides sharing homology sequences with HCV protein. Several phage peptide clones had 70% homology with HCV protein. Sera from dually infected thrombocytopenic patients with HCV and HIV-ITP reacted strongly with 4 non-conserved peptides from HCV core-envelope 1. Reactivity correlated inversely with platelet count, r(2)=0.7, p<0.01. Ab raised against peptide PHC09 in GPIIIa(-/-) mice induced severe thrombocytopenia in wild-type mice. Affinity-purified IgG against PHC09 induced oxidative platelet fragmentation in vitro. Drug abusers dually infected with HCV and HIV-1 had a greater incidence and severity of thrombocytopenia as well as greater incidence and titer of anti-GPIIIa49-66/PHC09 Ab. NZB/W F1 mice injected with recombinant core envelope 1 developed Ab vs PHC09 and significantly decreased their platelet count, p<0.001. Thus, HCV core envelope 1 can induce thrombocytopenia by molecular mimicry with GPIIIa49-66
— id: 95182, year: 2009, vol: 113, page: 4086, stat: Journal Article,

Structured treatment interruptions (STIs) in HIV-1 infected pediatric populations increases interferon gamma production and reduces viremia
Borkowsky, William; Yogev, Ram; Muresan, Petronella; McFarland, Elizabeth; Frenkel, Lisa; Fenton, Terry; Capparelli, Edmond; Moye, Jack; Harding, Paul; Ellis, Nina; Heckman, Barbara; Kraimer, Joyce
2008 Jun 6;26(24):3086-3089, Vaccine
We assessed the effect of progressively longer antiretroviral structured treatment interruptions (STIs) starting with 3 days, increasing by 2 days in length each cycle on HIV-specific immune responses. As well, we correlated these responses with control of HIV viremia. Eight individuals became viremic and reached cycle 13 with an STI of >/=27 days. HIV-specific gamma-interferon production to inactivated HIV and vaccinia vectors expressing gag, env, nef, and pol increased (>10-fold) in six of eight subjects. Median plasma RNA levels peaked @ cycle 7 and declined to levels <10(4)cp/ml after cycle 10. In a subset of five who reached cycle 17, HIV-specific IFN-gamma frequencies increased from cycle 8 to cycle 17 with evidence of improved virologic control over comparable periods off antiretroviral therapy. This allowed us to conclude that exposure to autologous virus increased HIV-specific immune responses and decreased HIV RNA were seen in those who have had >13 interruptions, with STI intervals that exceeded 27 days
— id: 78746, year: 2008, vol: 26, page: 3086, stat: Journal Article,

Planned multiple exposures to autologous virus in HIV type 1-infected pediatric populations increases HIV-specific immunity and reduces HIV viremia
Borkowsky, William; Yogev, Ram; Muresan, Petronella; McFarland, Elizabeth; Frenkel, Lisa; Fenton, Terry; Capparelli, Edmund; Moye, Jack; Harding, Paul; Ellis, Nina; Heckman, Barbara; Kraimer, Joyce
2008 Mar;24(3):401-411, AIDS research & human retroviruses
We tested to determine if planned multiple exposures to autologous HIV in pediatric patients with HIV-1 infection will induce cellular immunity that controls viremia. A prospective multicenter study of aviremic pediatric patients on highly active antiretroviral therapy who underwent progressively longer antiretroviral treatment interruptions in cycles starting with 3 days, increasing by 2 days in length each consecutive cycle, was conducted. Eight individuals became viremic and reached Cycle 13 or greater with an 'off-therapy' interval of >or=27 days. HIV-specific interferon-gamma (IFN-gamma) production to inactivated HIV and vaccinia vectors expressing gag, env, nef, and pol increased (>10-fold) from baseline in six of eight subjects. The HIV-specific lymphoproliferative response as measured by the median stimulation index (SI) increased in the treatment group from 1 at baseline to 16, 12, 4, and 3 at Cycles 7, 10, 13, and 17, respectively. Median plasma RNA levels peaked at Cycle 7 (4.45 log) and declined to levels <10(4) cp/ml after Cycle 10 (4.1, 3.5, and 3.4 at Cycles 10, 13, and 17). In a subset of five patients who reached Cycle 17, HIV-specific IFN-gamma frequencies were 4- to 30-fold higher and median RNA levels were 0.32-2.10 (median 1.3) log lower than at comparable days off treatment at Cycle 8 (17 days off therapy). A second group of children, not undergoing drug interruption, did not develop significant increases in either HIV-specific IFN-gamma production or SI. Increased HIV-specific immune responses and decreased HIV RNA were seen in those children who have had >10 cycles of antiretroviral discontinuations of increasing durations acting as autologous virus vaccinations. Other studies may have failed due to an insufficient number of exposures to HIV; most of the studies had fewer than six drug interruptions
— id: 78747, year: 2008, vol: 24, page: 401, stat: Journal Article,

Hyper interleukin-10 in an HIV-positive child with t-cell lymphoma and candidal sepsis
Lighter, Jennifer; Tse, Doris B; Kaul, Aditya; Borkowsky, William
2008 Sep-Oct;7(5):228-231, Journal of the International Association of Physicians in AIDS Care : JIAPAC
We describe a case in which a human immunodeficiency virus (HIV)-positive child presented in severe metabolic acidosis secondary to his candidal sepsis and T-cell lymphoma, a rare finding in pediatric AIDS. Significantly elevated levels of Interleukin-10 (IL-10) were found in the patient's serum, which may have played a role in acute demise
— id: 92164, year: 2008, vol: 7, page: 228, stat: Journal Article,

Impaired immunity to recall antigens and neoantigens in severely immunocompromised children and adolescents during the first year of effective highly active antiretroviral therapy
Rigaud, Mona; Borkowsky, William; Muresan, Petronella; Weinberg, Adriana; Larussa, Phillip; Fenton, Terry; Read, Jennifer S; Jean-Philippe, Patrick; Fergusson, Elaine; Zimmer, Bonnie; Smith, Dorothy; Kraimer, Joyce
2008 Oct 15;198(8):1123-1130, Journal of infectious diseases
BACKGROUND: We studied whether severely immunocompromised, human immunodeficiency virus (HIV)-infected children who were beginning highly active antiretroviral therapy (HAART) or changing HAART regimens could spontaneously respond to a recall antigen (tetanus toxoid [TT] vaccine) or respond to a recall antigen and neoantigen (hepatitis A virus [HAV] vaccine) after 3 vaccinations. METHODS: A total of 46 children who had CD4 cell percentages <15% and who demonstrated a >0.75-log reduction in plasma HIV RNA levels within 4 weeks of starting HAART were randomized to receive vaccinations with either TT or HAV vaccines during the first 6 months of HAART. Study subjects then received the alternate vaccine during the next 6 months of HAART. RESULTS: Despite the early decline in viremia and the later increase in the percentage of CD4 T cells, spontaneous recovery of cell-mediated immunity (CMI) was not seen for TT. Serologic responses to TT required 3 vaccinations and were comparable in both groups. Serologic responses to HAV were infrequent and of low titer, although the group that received HAV vaccine after receiving TT vaccine performed somewhat better. CMI to HAV was virtually absent. CONCLUSIONS: Severely immunocompromised children who are receiving HAART develop CMI and antibody to a recall antigen independent of the timing of vaccination, but they require a primary series of vaccinations. Antibodies to a neoantigen, HAV, developed when vaccination was delayed after initiation of HAART. CMI to a neoantigen was difficult to establish. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00004735/PACTG P1006
— id: 93360, year: 2008, vol: 198, page: 1123, stat: Journal Article,

Pharmacokinetics of high-dose lopinavir-ritonavir with and without saquinavir or nonnucleoside reverse transcriptase inhibitors in human immunodeficiency virus-infected pediatric and adolescent patients previously treated with protease inhibitors
Robbins, Brian L; Capparelli, Edmund V; Chadwick, Ellen G; Yogev, Ram; Serchuck, Leslie; Worrell, Carol; Smith, Mary Elizabeth; Alvero, Carmelita; Fenton, Terence; Heckman, Barbara; Pelton, Stephen I; Aldrovandi, Grace; Borkowsky, William; Rodman, John; Havens, Peter L
2008 Sep;52(9):3276-3283, Antimicrobial agents & chemotherapy
Human immunodeficiency virus (HIV)-infected children and adolescents who are failing antiretrovirals may have a better virologic response when drug exposures are increased, using higher protease inhibitor doses or ritonavir boosting. We studied the pharmacokinetics and safety of high-dose lopinavir-ritonavir (LPV/r) in treatment-experienced patients, using an LPV/r dose of 400/100 mg/m(2) orally every 12 h (p.o. q12h) (without nonnucleoside reverse transcriptase inhibitor [NNRTI]), or 480/120 mg/m(2) p.o. q12h (with NNRTI). We calculated the LPV inhibitory quotient (IQ), and when the IQ was <15, saquinavir (SQV) 750 mg/m(2) p.o. q12h was added to the regimen. We studied 26 HIV-infected patients. The median age was 15 years (range, 7 to 17), with 11.5 prior antiretroviral medications, 197 CD4 cells/ml, viral load of 75,577 copies/ml, and a 133-fold change in LPV resistance. By treatment week 2, 14 patients had a viral-load decrease of >0.75 log(10), with a median maximal decrease in viral load of -1.57 log(10) copies/ml at week 8. At week 2, 19 subjects showed a median LPV area under the concentration-time curve (AUC) of 157.2 (range, 62.8 to 305.5) microg x h/ml and median LPV trough concentration (C(trough)) of 10.8 (range, 4.1 to 25.3) microg/ml. In 16 subjects with SQV added, the SQV median AUC was 33.7 (range, 4.4 to 76.5) microg x h/ml and the median SQV C(trough) was 2.1 (range, 0.2 to 4.1) microg/ml. At week 24, 18 of 26 (69%) subjects remained in the study. Between weeks 24 and 48, one subject withdrew for nonadherence and nine withdrew for persistently high virus load. In antiretroviral-experienced children and adolescents with HIV, high doses of LPV/r with or without SQV offer safe options for salvage therapy, but the modest virologic response and the challenge of adherence to a regimen with a high pill burden may limit the usefulness of this approach
— id: 95183, year: 2008, vol: 52, page: 3276, stat: Journal Article,

Continuous improvement in the immune system of HIV-infected children on prolonged antiretroviral therapy
Weinberg A.; Dickover R.; Britto P.; Hu C.; Patterson-Bartlett J.; Kraimer J.; Gutzman H.; Shearer W.T.; Rathore M.; McKinney R.; Knapp K.; Utech J.; Jones S.; McCauley J.; Haak M.; Viani R.; Darcey A.; Mathison C.; Choi Y.I.I.; Hurwitz J.; Simonetti J.; Frere M.; Champion S.; Weiner L.B.; Contello K.A.; Holz W.; Famiglietti M.; Scott G.B.; Mitchell C.D.; Taybo L.; Willumsen S.; Mirza A.; Alvarez A.; Mahmoudi S.; Thoma K.; Abzug M.; Barr E.; Paul S.; Burchett S.; Kneut C.; Calles N.; Jackson C.; Paul M.E.; Wara D.W.; Trevithick D.; Deygoo N.; Borkowsky W.; Chandwani S.; Akleh S.; Jimenez E.; Acevedo M.; Burgos I.M.; Fabregas L.; Febo Rodriguez I.L.; Santos Otero R.E.; Cruz M.; Lugo L.; Luzuriaga K.
2008 ;22(17):2267-2277, AIDS
Background: The goal of HAART is to promote reconstitution of CD4 + T cells and other immune responses. We evaluated the extent and the kinetics of immune reconstitution in HIV-infected children over 144 weeks of successful HAART. Methods: Thirty-seven children receiving their first HAART regimen had plasma HIV RNA; T cells and subpopulations; T-cell rearrangement excision circles (TREC) DNA; Candida, HIVCD4 and HIVCD8 enzyme-linked immunospot measured at regular intervals. Results: Plasma HIV RNA became undetectable in 81% of patients at 24 weeks and remained undetectable in 77% at 144 weeks. In contrast, CD4+% continuously increased. Distribution of T-cell subpopulations changed rapidly during the first 48 weeks of HAART and more slowly thereafter. At 144 weeks, total, naive and activated CD4+% and naive CD8+% of HIV-infected children were not significantly different from those of healthy age-matched controls, whereas total and activated CD8+% remained elevated. CD4+ and CD8+ TREC content increased only during the first 48 weeks of HAART. They positively correlated with each other and with total CD4+%, naive CD4+% and naive CD8+%. Candida and HIVCD4 enzyme-linked immunospot increased over time reaching peak values at 48 weeks and 144 weeks, respectively. HIVCD8 enzyme-linked immunospot decreased in magnitude over 144 weeks of HAART but retained its breadth. Baseline CD4+% positively correlated with CD4+% and with functional immune reconstitution at week 144, whereas baseline TREC correlated with TREC at week 144. Conclusion: HIV-infected children acquired normal distribution of CD4+ T cells and other subpopulations and recovered CD4-mediated HIV immunity after 144 weeks of HAART. copyright 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins
— id: 91335, year: 2008, vol: 22, page: 2267, stat: Journal Article,

Role of Molecular Mimickry of Hepatitis C Virus (HCV) Protein with Platelet GPIIIa in Hepatitis C-Related Immunologic Thrombocytopenia
Zhang, W; Nardi, MA; Borkowsky, W; Karpatkin, S
2008 NOV 16 ;112(11):153-153, Blood
— id: 93283, year: 2008, vol: 112, page: 153, stat: Journal Article,

Pertussis booster vaccination in HIV-infected children receiving highly active antiretroviral therapy
Abzug, Mark J; Song, Lin-Ye; Fenton, Terence; Nachman, Sharon A; Levin, Myron J; Rosenblatt, Howard M; Pelton, Stephen I; Borkowsky, William; Edwards, Kathryn M; Peters, Jody
2007 Nov;120(5):e1190-e1202, Pediatrics
OBJECTIVE: Our goal was to evaluate the immunogenicity and safety of pertussis booster vaccination in children infected with HIV on highly active antiretroviral therapy (HAART). PATIENTS AND METHODS: HIV-infected children on stable HAART for > or = 3 months with plasma HIV-RNA concentrations of < 30,000 to 60,000 copies per mL who previously received > or = 4 doses of diphtheria-tetanus-pertussis (DTP)-containing vaccine were eligible. Diphtheria-tetanus-acellular pertussis (DTaP) vaccine was administered to subjects 2 to < 7 years old who had 4 previous DTP-containing vaccines, subjects 2 to < 7 years old who had > or = 5 previous DTP-containing vaccines and negative tetanus antibody, and subjects > or = 7 to < or = 13 years old who had negative tetanus antibody. Pertussis toxin and filamentous hemagglutinin antibodies were measured before and 8, 24, and 72 weeks after DTaP vaccine. RESULTS: Ninety-two subjects received DTaP vaccine and met criteria for analysis. Antibody concentrations were low at entry: pertussis toxin geometric mean concentration at 4.8 enzyme-linked immunosorbent assay units (EU) per mL and filamentous hemagglutinin geometric mean concentration at 4.1 EU/mL. Pertussis toxin and filamentous hemagglutinin geometric mean concentrations rose to 22.3 and 77.0 EU/mL, respectively, 8 weeks after the study DTaP vaccine. Antibody concentrations fell by 24 weeks after vaccination but remained higher than before vaccination. Predictors of response 8 weeks after DTaP vaccine included the concentration of homologous antibody, lower HIV-RNA level, and higher CD4 percentage at entry. One vaccinated subject experienced erythema and induration of > or = 25 mm. CONCLUSIONS: A DTaP vaccine booster was well tolerated by children on HAART and induced increases in antibodies. Antibody concentrations after vaccination were lower than those reported in populations uninfected by HIV. Although comparison among studies must be made with caution, these data suggest that children infected with HIV may be deficient in immunologic memory from previous DTP-containing vaccination and/or that immune reconstitution with HAART may be incomplete for pertussis antigens
— id: 78748, year: 2007, vol: 120, page: e1190, stat: Journal Article,

Distribution and evolution of T-cell receptor Vbeta repertoire on peripheral blood lymphocytes of newborn infants of human immunodeficiency virus (HIV)-infected mothers: differential display on CD4 and CD8 T cells and effect of HIV infection
Borkowsky, William; Chen, Song-He; Belitskaya-Levy, Ilana
2007 Sep;14(9):1215-1222, Clinical & vaccine immunology
Neonatal human peripheral blood mononuclear cells from 12 human immunodeficiency virus (HIV)-infected and 84 uninfected children were assessed for their distribution of T-cell receptors (TCRs) by flow cytometry employing monoclonal antibodies to 14 Vbeta types. Vbeta 2, 5c, and 13 were the most commonly found on CD4 cells (in that order). There was a bimodal distribution of Vbeta 2, being most common in 48% of individuals but in limiting frequency (<2% of CD4) in 21%. Vbeta 2, 3, 8b, and 13 were most commonly expressed on CD8 cells at similar frequencies. There was little difference in the pattern displayed among the infected compared to that of the uninfected. The variation of the distribution over time was studied in 12 infants (7 infected). Only a single HIV-infected child had a significant difference in the interquartile range; none of the HIV-negative patients showed a significant difference. In conclusion, newborns demonstrate different distributions of TCR Vbeta types on CD4 and CD8 cells. HIV infection produces no change in neonatal TCR and little change over the course of 2 years compared to that seen in the uninfected
— id: 75411, year: 2007, vol: 14, page: 1215, stat: Journal Article,

Severe varicella caused by varicella-vaccine strain in a child with significant T-cell dysfunction
Jean-Philippe, Patrick; Freedman, Abigail; Chang, Mary Wu; Steinberg, Sharon P; Gershon, Anne A; LaRussa, Philip S; Borkowsky, William
2007 Nov;120(5):e1345-e1349, Pediatrics
In March 1995, the US Food and Drug Administration approved a live attenuated varicella vaccine for use in healthy children 12 months to 12 years old. We report here an 18-month-old girl with cell-mediated immunodeficiency who developed a severe vaccine-associated rash and clinical evidence of vaccine-associated pneumonia 1 month after inadvertent receipt of varicella vaccine
— id: 75402, year: 2007, vol: 120, page: e1345, stat: Journal Article,

Natural history of HIV infected pediatric long-term or slow progressor population after the first decade of life
Ofori-Mante, Juliana A; Kaul, Aditya; Rigaud, Mona; Fidelia, Andre; Rochford, Gemma; Krasinski, Keith; Chandwani, Sulachni; Borkowsky, William
2007 Mar;26(3):217-220, Pediatric infectious disease journal
BACKGROUND: Perinatally infected long-term nonprogressors/slow progressors represent a select group of individuals. There is very limited information on this group of children beyond the first decade of life. A group of HIV-infected long-term nonprogressor/slow progressor children was studied. METHODS: We enrolled 20 HIV-infected adolescents who were receiving no or minimal therapy (defined as single or dual nucleoside therapy) before the age of 10 years and who had maintained CD4 counts above 25% for the first decade of life. We analyzed immunologic and virologic characteristics. Thymic receptor excision circles (TREC) were measured on stored frozen peripheral blood mononuclear cells. CD4 count, viral load and other pertinent information including race and age were obtained from individual medical records. RESULTS: Nine of the 20 patients recruited were noted to have developed falling CD4 counts at or around puberty, whereas the other 11 remained stable. There was no difference in TREC values or HIV RNA values before or after puberty between the 2 groups of patients. Those who remained stable, in terms of maintaining CD4 T cells as a group had falling viral loads with age. Those whose CD4 values declined after puberty had viral loads that did not decrease with age. CONCLUSION: A select group of patients who never received HAART during their first decade of life will continue to maintain good CD4 associated with declining HIV RNA values. Thymic output is not predictive of those that don't maintain CD4 T cells
— id: 72125, year: 2007, vol: 26, page: 217, stat: Journal Article,

Immunological memory after exposure to variola virus, monkeypox virus, and vaccinia virus
Sivapalasingam, Sumathi; Kennedy, Jeffrey S; Borkowsky, William; Valentine, Fred; Zhan, Ming-Xia; Pazoles, Pamela; Paolino, Anna; Ennis, Francis A; Steigbigel, Neal H
2007 Apr 15;195(8):1151-1159, Journal of infectious diseases
We compared cellular and humoral immunity to vaccinia virus (VV) in individuals exposed to 3 different orthopoxviruses: 154 individuals previously vaccinated with VV, 7 individuals with a history of monkeypox virus infection, and 8 individuals with a history of variola virus infection. Among individuals vaccinated >20 years prior, 9 (14%) of 66 individuals demonstrated VV-specific interferon (IFN)- gamma enzyme-linked immunospot (ELISPOT) assay responses; 21 (50%) of 42 had lymphoproliferative (LP) responses, and 29 (97%) of 30 had VV-specific neutralizing antibodies. One year after monkeypox virus infection, 6 of 7 individuals had IFN- gamma ELISPOT responses, all had VV-specific LP responses, and 3 of 7 had VV-specific neutralizing antibodies. Of 8 individuals with a history of variola virus infection, 1 had a VV-specific IFN- gamma ELISPOT response, 4 had LP responses against whole VV, 7 had LP responses against heat-denatured vaccinia antigen, and 7 had VV-specific neutralizing antibodies. Survivors of variola virus infection demonstrated VV-specific CD4 memory cell responses and neutralizing antibodies >40 years after infection
— id: 71299, year: 2007, vol: 195, page: 1151, stat: Journal Article,

Immunogenicity, safety, and predictors of response after a pneumococcal conjugate and pneumococcal polysaccharide vaccine series in human immunodeficiency virus-infected children receiving highly active antiretroviral therapy
Abzug, Mark J; Pelton, Stephen I; Song, Lin-Ye; Fenton, Terence; Levin, Myron J; Nachman, Sharon A; Borkowsky, William; Rosenblatt, Howard M; Marcinak, John F; Dieudonne, Arry; Abrams, Elaine J; Pathak, Indu
2006 Oct;25(10):920-929, Pediatric infectious disease journal
BACKGROUND: The immunogenicity and safety of 2 doses of pneumococcal conjugate vaccine (PCV) and 1 dose of pneumococcal polysaccharide vaccine (PPV) were evaluated in human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy (HAART). METHODS: Children 2 to <19 years, receiving stable HAART for > or =3-6 months, with HIV RNA PCR <30,000-60,000 copies/mL, received 2 doses of PCV and 1 dose of PPV at sequential 8-week intervals. Antibodies to pneumococcal serotypes (STs) 1 (PPV only) and 6B, 14, 19F, and 23F (PCV and PPV) were measured by ELISA. RESULTS: Two hundred sixty-three subjects were enrolled, of whom 225 met criteria for inclusion in the primary dataset. Antibody concentrations were low at entry, despite previous PPV in 75%. After vaccination, 76%-96% had concentrations > or =0.5 microg/mL and 62-88% > or =1.0 microg/mL to the 5 STs (geometric mean concentrations [GMCs] = 1.44-4.25 microg/mL). Incremental gains in antibody concentration occurred with each vaccine dose. Predictors of response included higher antibody concentration at entry, higher immune stratum (based on nadir CD4% before HAART and CD4% at screening), lower entry viral RNA, longer duration of the entry HAART regimen, and age <7 years. Response was more consistently related to screening CD4% than nadir CD4%. Seven percent had vaccine-related grade 3 events, most of which were local reactions. CONCLUSIONS: Two PCVs and 1 PPV were immunogenic and safe in HIV-infected children 2 to <19 years who were receiving HAART. Responses were suggestive of functional immune reconstitution. Immunologic status based on nadir and, especially, current CD4% and control of HIV viremia were independent determinants of response
— id: 78749, year: 2006, vol: 25, page: 920, stat: Journal Article,

Diagnostic assays: serology
Borkowsky W
Congenital and perinatal infections: a concise guide to diagnosis Totowa NJ : Humana Press, 2006,
— id: 3771, year: 2006, vol: , page: 3, stat: Chapter,

CCR5 expression and duration of high risk sexual activity among HIV-seronegative men who have sex with men
Thomas, Susan M; Tse, Doris B; Ketner, D Scott; Rochford, Gemma; Meyer, Daniel A; Zade, David D; Halkitis, Perry N; Nadas, Arthur; Borkowsky, William; Marmor, Michael
2006 Sep 11;20(14):1879-1883, AIDS
OBJECTIVES:: To test the hypothesis that in comparison with those with shorter risk duration, individuals with longer HIV risk duration would have reduced susceptibility to HIV-1 infection as measured by CCR5 expression, and to evaluate whether variation in CCR5 expression could be explained by known genetic polymorphisms. DESIGN AND METHODS:: A cross-sectional study of HIV-1 exposed but uninfected men who have sex with men. The risk duration was estimated from self-reported years since first receptive anal intercourse. CCR5 expression on peripheral blood CD4+ monocytes and T cells was determined by flow cytometry. The CCR5-Delta32 mutation and polymorphisms in the CCR5 promoter and CCR2 as well as the copy number of CCL3L1 were analyzed by polymerase chain reaction. Plasma levels of MIP-1alpha (CCL3), MIP-1beta (CCL4) and RANTES (CCL5) were also measured. As risk duration varied with age, analyses were restricted to 67 individuals aged 30-49 years. RESULTS:: Multiple linear regression analyses, adjusted for age and race, showed a significant negative association between HIV risk duration and CCR5 expression on monocytes (P = 0.01), and in a separate model, a similar negative association with CCR5 expression on T cells (P = 0.03). Low CCR5 expression was attributable mainly to CCR5-Delta32 heterozygosity and the CCR5-59029G allele. CONCLUSIONS:: We confirmed a role for reduced CCR5 expression in HIV-1 resistance. CCR5-Delta32 heterozygosity and the CCR5-59029G allele were significant predictors of low CCR5 expression. Individuals with high CCR5 expression who resisted infection despite long HIV risk duration form an interesting group within which to search for additional mechanisms of resistance to HIV infection
— id: 68188, year: 2006, vol: 20, page: 1879, stat: Journal Article,

Ritonavir-based highly active antiretroviral therapy in human immunodeficiency virus type 1-infected infants younger than 24 months of age
Chadwick, Ellen Gould; Rodman, John H; Britto, Paula; Powell, Christine; Palumbo, Paul; Luzuriaga, Katherine; Hughes, Michael; Abrams, Elaine J; Flynn, Patricia M; Borkowsky, William; Yogev, Ram
2005 Sep;24(9):793-800, Pediatric infectious disease journal
BACKGROUND: Few data are available regarding clinical outcomes or dosing requirements for the protease inhibitor ritonavir in human immunodeficiency virus (HIV)-infected children younger than under 24 months of age. METHODS: This prospective, multicenter phase I/II open label treatment trial used ritonavir, zidovudine and lamivudine to treat protease inhibitor-naive, HIV-infected infants between the ages of 4 weeks and 24 months. Two sequential dosing cohorts were treated with 350 or 450 mg/m(2) ritonavir every 12 hours; this report includes results of pharmacokinetics, safety, tolerability and efficacy through 104 weeks of follow-up of all subjects. RESULTS: Fifty HIV-infected children were treated. By week 16, 36 had achieved HIV-1 RNA <400 copies/mL (72% intent-to-treat, 84% as-treated analysis); by week 104, 18 maintained durable viral suppression (36% intent-to-treat, 46% as-treated). Poor medication adherence by caregiver report contributed to virologic failure. Few subjects experienced treatment-limiting toxicity: emesis or ritonavir refusal in 6 (12%); and severe but reversible anemia or elevated serum hepatic transaminases in 1 (4%) each. Apparent oral clearance was higher and the median predose concentrations were substantially lower than those found in adults. Median z scores for weight and height for age/gender were below normal at baseline but improved by week 104. CONCLUSIONS: A combination regimen of ritonavir, zidovudine and lamivudine was generally safe and produced sustained viral suppression in more than one-third of infants who initiated therapy before 2 years of age. Improved palatability of liquid preparations of protease inhibitors, supporting infrastructure and behavioral approaches to improve medication adherence with antiretrovirals will likely be necessary to further improve efficacy
— id: 78750, year: 2005, vol: 24, page: 793, stat: Journal Article,

Correlation between HIV-Specific CD8 cell production of interferon- gamma and plasma levels of HIV RNA in perinatally infected pediatric populations
Borkowsky, William; Zhan, Ming-Xia; Chen, Song-He; Ilmet, Tiina; Kaul, Aditya; Chandwani, Sulachni; Rigaud, Mona; Essajee, Shaffiq; Gruber, Caroline; Freedman, Abigail; Krasinski, Keith
2004 Sep 15;190(4):722-726, Journal of infectious diseases
BACKGROUND: CD8 cell responses to human immunodeficiency virus (HIV) have been correlated with virus control in adults, and this study outcome has been controversial. Attempts to establish the same correlation in small numbers of children have also been made, with similar controversy resulting. METHODS: A total of 110 perinatally infected children were studied. Nine of the children (mean age, 1.9 years vs. 11.8 years for the remaining 101 children) received treatment with antiretrovirals within the first 3 months of life. CD4 cell and HIV RNA levels were measured. Production of interferon- gamma after exposure to recombinant vaccinia vectors was measured by enzyme-linked immunospot (ELISPOT) assay. RESULTS: Responses to Pol and Gag antigens exceeded those to Nef and Env antigens, with responses significantly approximated by a quadratic function for which peak responses occurred at plasma HIV RNA levels of 103-104 HIV RNA copies/mL. Children who are treated early in life with highly active antiretroviral therapy have fewer total responses of ELISPOT-forming cells to HIV antigens than do children who are treated later in life
— id: 46157, year: 2004, vol: 190, page: 722, stat: Journal Article,

Mycobacterium tuberculosis-induced CXCR4 and chemokine expression leads to preferential X4 HIV-1 replication in human macrophages
Hoshino, Yoshihiko; Tse, Doris B; Rochford, Gemma; Prabhakar, Savita; Hoshino, Satomi; Chitkara, Nishay; Kuwabara, Kenichi; Ching, Elbert; Raju, Bindu; Gold, Jeffrey A; Borkowsky, William; Rom, William N; Pine, Richard; Weiden, Michael
2004 May 15;172(10):6251-6258, Journal of immunology
Opportunistic infections such as pulmonary tuberculosis (TB) increase local HIV-1 replication and mutation. As AIDS progresses, alteration of the HIV-1 gp120 V3 sequence is associated with a shift in viral coreceptor use from CCR5 (CD195) to CXCR4 (CD184). To better understand the effect of HIV/TB coinfection, we screened transcripts from bronchoalveolar lavage cells with high density cDNA arrays and found that CXCR4 mRNA is increased in patients with TB. Surprisingly, CXCR4 was predominately expressed on alveolar macrophages (AM). Mycobacterium tuberculosis infection of macrophages in vitro increased CXCR4 surface expression, whereas amelioration of disease reduced CXCR4 expression in vivo. Bronchoalveolar lavage fluid from TB patients had elevated levels of CCL4 (macrophage inflammatory protein-1beta), CCL5 (RANTES), and CX3CL1 (fractalkine), but not CXCL12 (stromal-derived factor-1alpha). We found that M. tuberculosis infection of macrophages in vitro increased viral entry and RT of CXCR4, using HIV-1, but not of CCR5, using HIV-1. Lastly, HIV-1 derived from the lung contains CD14, suggesting that they were produced in AM. Our results demonstrate that TB produces a permissive environment for replication of CXCR4-using virus by increasing CXCR4 expression in AM and for suppression of CCR5-using HIV-1 by increasing CC chemokine expression. These changes explain in part why TB accelerates the course of AIDS. CXCR4 inhibitors are a rational therapeutic approach in HIV/TB coinfection
— id: 42732, year: 2004, vol: 172, page: 6251, stat: Journal Article,

Perinatal Transmission and Viral Evolution of Hepatitis C Virus Quasispecies in Infants Coinfected With HIV
Pollack, Henry; Hou, Zhiying; Hughes, Austin L; Borkowsky, William
2004 Aug 1;36(4):890-899, Journal of acquired immune deficiency syndromes. JAIDS
OBJECTIVES:: Three HIV/hepatitis C virus (HCV)-coinfected children and the mothers of 2 were studied to examine the nature of perinatal HCV infection in HIV-coinfected infants and to assess the evolution of viral quasispecies thereafter. Sequences of the hypervariable region in the N terminus of the E2/NS1 region (HVR-1) of the children and their mothers were compared. HCV quasispecies changes in the infants were tracked over several years. METHODS:: Sequence similarity comparisons and phylogenetic trees were derived from cDNA of plasma isolates. Quantitation of plasma HCV and HIV was performed in the children, as well as CD4 T-cell percentage and liver transaminases. RESULTS:: Phylogenetic analysis of the mother-child pairs suggested that transmission of multiple dominant and nondominant variants identified in the mother were seen. HCV diversification in the children was seen as early as 2 months of life. The child with the best immune status and HIV control demonstrated the most diversification throughout. CONCLUSION:: Multiples HCV variants transmitted from mother to child and their early changes in the child may be related to maternal antibody. Variation after the 1st year of life may reflect immunologic pressure from the child. There was no trend suggesting that the presence or absence of selective immunologic pressure affected HCV load or liver transaminase values
— id: 55985, year: 2004, vol: 36, page: 890, stat: Journal Article,

Tuberculosis in children
Rigaud M; Borkowsky W
Tuberculosis Philadelphia : Lippincott Williams & Wilkins, 2004,
— id: 3960, year: 2004, vol: , page: 609, stat: Chapter,

Long-term effects of protease-inhibitor-based combination therapy on CD4 T-cell recovery in HIV-1-infected children and adolescents
Soh, Chang-Heok; Oleske, James M; Brady, Michael T; Spector, Stephen A; Borkowsky, William; Burchett, Sandra K; Foca, Marc D; Handelsman, Edward; Jimenez, Eleanor; Dankner, Wayne M; Hughes, Michael D
2003 Dec 20;362(9401):2045-2051, Lancet
BACKGROUND: There is limited evidence about longer-term effects of combination antiretroviral therapy that includes protease inhibitors (PIs) on the immunological status of HIV-1-infected children. Better understanding might help to resolve questions on when to initiate treatment. METHODS: The change in percentage of CD4-positive T lymphocytes (CD4%) was investigated in 1012 previously treated HIV-1-infected children (aged 0-17 years) who were enrolled in research clinics in the USA before 1996 and followed up to 2000. 702 started PI-based combination therapy. Data analyses ignored subsequent treatment changes. FINDINGS: Among the 1012 children, the median CD4% increased from 22% to 28% between 1996, when PIs were first prescribed, and 2000. For the 702 who started PI-based therapy, the mean CD4% increase after 3 years was largest among participants with the greatest immunosuppression (15.7%, 10.6%, 5.1%, and 2.0% for participants with CD4% before therapy of <5%, 5-14%, 15-24%, and >25%; p<0.0001). After adjustment for pre-PI CD4%, the mean increase was largest among the youngest participants (9.2%, 8.0%, and 4.3% for ages <5 years, 5-9 years, and >10 years; p=0.001). However, only a minority of significantly immunocompromised participants (33%, 26%, and 49% of those with pre-PI CD4% of <5%, 5-14%, or 15-24%) achieved CD4% values above 25%, whereas 84% of those with pre-PI values above 25% maintained such values. INTERPRETATION: Although PI-based therapy was associated with substantial improvements in CD4%, initiation before severe immunosuppression and at younger ages may be more effective for recovery or maintenance of normal CD4%. Randomised investigation of when to start combination therapy in children, particularly infants, is needed
— id: 42230, year: 2003, vol: 362, page: 2045, stat: Journal Article,

Diagnosis and treatment of cutaneous anthrax: In reply
Borkowsky, William; Chang, Mary Wu
2002 ;288(1):2083-2085 July 3,, JAMA
— id: 98808, year: 2002, vol: 288, page: 2083, stat: Journal Article,

Recombinant glycoprotein vaccines for human immunodeficiency virus-infected children and their effects on viral quasispecies
Essajee, Shaffiq M; Yogev, Ram; Pollack, Henry; Greenhouse, Bryan; Krasinski, Keith; Borkowsky, William
2002 Jan;9(1):79-82, Clinical & diagnostic laboratory immunology
In individuals infected with human immunodeficiency virus type 1 (HIV-1), specific immunity is associated with a more diverse viral repertoire and slower disease progression. Attempts to enhance antiviral immunity with therapeutic vaccination have shown that recombinant glycoprotein (RGP) vaccines are safe, well tolerated, and immunogenic, but the effect of RGP vaccines on the viral repertoire is unknown. We evaluated diversification of the viral envelope in 12 HIV-infected children who received placebo or RGP vaccines. At baseline, 11 of 12 patients had multiple viral variants. On follow-up 6 months later, children who had a strong vaccine-associated lymphoproliferative immune response showed less viral diversification than those in whom the immune response was weak or absent. These results suggest that the immune response elicited by RGP vaccines does not exert a significant selection pressure on the viral quasispecies and therefore may not be helpful in changing the course of the disease
— id: 39732, year: 2002, vol: 9, page: 79, stat: Journal Article,

Cutaneous anthrax associated with microangiopathic hemolytic anemia and coagulopathy in a 7-month-old infant
Freedman, Abigail; Afonja, Olubunmi; Chang, Mary Wu; Mostashari, Farzad; Blaser, Martin; Perez-Perez, Guillermo; Lazarus, Herb; Schacht, Robert; Guttenberg, Jane; Traister, Michael; Borkowsky, William
2002 Feb 20;287(7):869-874, JAMA
A 7-month-old infant with cutaneous anthrax developed severe systemic illness despite early treatment with antibiotics. The infant displayed severe microangiopathic hemolytic anemia with renal involvement, coagulopathy, and hyponatremia. These findings are unusual with cutaneous anthrax, but have been described in illness resulting from spider toxin and may delay correct diagnosis. The systemic manifestations of the disease persisted for nearly a month despite corticosteroid therapy, but resolved
— id: 26017, year: 2002, vol: 287, page: 869, stat: Journal Article,

Immunoreconstitution in children receiving highly active antiretroviral therapy depends on the CD4 cell percentage at baseline
Nikolic-Djokic, Divna; Essajee, Shaffiq; Rigaud, Mona; Kaul, Aditya; Chandwani, Sulachni; Hoover, William; Lawrence, Robert; Pollack, Henry; Sitnitskaya, Yekaterina; Hagmann, Stefan; Jean-Philippe, Patrick; Chen, Song He; Radding, Jayme; Krasinski, Keith; Borkowsky, William
2002 Feb 1;185(3):290-298, Journal of infectious diseases
The effect of highly active antiretroviral therapy (HAART) in 85 children infected with human immunodeficiency virus type 1 (HIV-1) was compared retrospectively among Centers for Disease Control and Prevention (CDC) immunologic groups 1-3. The duration of HAART did not vary significantly among the immunologic groups (median, 39.07 months). The CD4 cell percentage increased in 39.1%, 58.3%, and 90% of patients in CDC groups 1-3, respectively (P <.001). HAART resulted in the suppression of HIV-1 below detectable levels in 34.8%, 25%, and 32% of patients in the 3 CDC groups, respectively, and in a frequent switch from syncytium-inducing to nonsyncytium-inducing virus. Thymic excision circles increased in a subset of patients with increases in CD4 cell percentage independently of HIV RNA level. The results support the option of delaying HAART in early asymptomatic HIV-1 disease in children and the use of other markers of disease progression, in addition to virus load
— id: 42231, year: 2002, vol: 185, page: 290, stat: Journal Article,

Safety of 2 recombinant human immunodeficiency virus type 1 (HIV-1) envelope vaccines in neonates born to HIV-1-infected women
Cunningham CK; Wara DW; Kang M; Fenton T; Hawkins E; McNamara J; Mofenson L; Duliege AM; Francis D; McFarland EJ; Borkowsky W
2001 Mar 1;32(5):801-807, Clinical infectious diseases
To determine the safety of 2 candidate vaccines against human immunodeficiency virus type 1 (HIV-1), a randomized, placebo-controlled, multicenter trial compared low, medium, and high doses of the vaccines or an adjuvant among infants born to HIV-infected women. No local or systemic reactions of grade 2 or greater were reported 48 h after the subjects underwent immunization. Grade 3 or 4 chemistry toxicities occurred in 5 (3%) and grade 3 or 4 hematologic toxicities in 17 (11%) of 154 vaccinated subjects (not significantly different from 29 adjuvant recipients). CD4(+) cell percentages of < or = 20% occurred at least once in 9 vaccinated subjects and 1 control subject. Sustained CD4(+) cell percentages of < or = 20% occurred in 4 HIV-infected children. Fourteen infants (8%) were confirmed to be HIV-infected; median CD4(+) cell counts among these children were 2074, 1674, 1584, and 821 cells/mm(3) at birth and weeks 24, 52, and 104, respectively. Thus, both vaccines were safe and well tolerated in neonates, and there was no evidence of accelerated immunologic decline in HIV-infected infants
— id: 42234, year: 2001, vol: 32, page: 801, stat: Journal Article,

Human immunodeficiency virus type 1 (HIV-1) gp120-specific antibodies in neonates receiving an HIV-1 recombinant gp120 vaccine
McFarland EJ; Borkowsky W; Fenton T; Wara D; McNamara J; Samson P; Kang M; Mofenson L; Cunningham C; Duliege AM; Sinangil F; Spector SA; Jimenez E; Bryson Y; Burchett S; Frenkel LM; Yogev R; Gigliotti F; Luzuriaga K; Livingston RA
2001 Nov 15;184(10):1331-1335, Journal of infectious diseases
Infants born to human immunodeficiency virus type 1 (HIV-1)-infected mothers were immunized at birth and at ages 4, 12, and 20 weeks with low-, medium-, or high-dose recombinant gp120 vaccine with MF59 adjuvant (HIV-1(SF-2); n=52) or with MF59 alone as a placebo (n=9). An accelerated schedule (birth and ages 2, 8, and 20 weeks) was used for an additional 10 infants receiving the defined optimal dose and for 3 infants receiving placebo. At 24 weeks, anti-gp120 ELISA titers were greater for vaccine-immunized than for placebo-immunized infants on both schedules, and 87% of vaccinees had a vaccine-induced antibody response. At 12 weeks, antibody titers of infants on the accelerated vaccine schedule exceeded those of infants receiving placebo (4949 vs. 551; P=.01), and 63% of the vaccinees met the response criteria. Thus, an accelerated schedule of gp120 vaccinations generated an antibody response to HIV-1 envelope distinct from transplacental maternal antibody by age 12 weeks. These results provide support for further studies of vaccine strategies to prevent mother-to-infant HIV-1 transmission
— id: 42233, year: 2001, vol: 184, page: 1331, stat: Journal Article,

Prevalence of the t215y mutation in human immunodeficiency virus type 1-infected pregnant women in a new york cohort, 1995-1999
Sitnitskaya Y; Rochford G; Rigaud M; Essajee S; Pollack H; Krasinski K; Borkowsky aW
2001 Jul 1;33(1):E3-E7, Clinical infectious diseases
From 1997 through 1999, the prevalence of the zidovudine resistance mutation T215Y was 9.7% among pregnant women, and the human immunodeficiency virus type 1 (HIV-1) load in those with resistant virus was higher than that measured in women with wild-type HIV-1. All mutations were noted in women with zidovudine experience, which suggests that monotherapy may not be adequate prophylaxis for vertical transmission of HIV-1 infection in the current era
— id: 20631, year: 2001, vol: 33, page: E3, stat: Journal Article,

Immunotherapy for pregnant women and newborns
Borkowsky W
2000 Nov;918:313-317, Annals of the New York Academy of Sciences
— id: 32561, year: 2000, vol: 918, page: 313, stat: Journal Article,

Immunologic response to combination nucleoside analogue plus protease inhibitor therapy in stable antiretroviral therapy-experienced human immunodeficiency virus-infected children
Borkowsky W; Stanley K; Douglas SD; Lee S; Wiznia A; Pelton S; Yogev R; McIntosh K; Nachman S
2000 Jul;182(1):96-103, Journal of infectious diseases
The response of 40 immunologic parameters was studied for 147 clinically stable, protease inhibitor-naive, human immunodeficiency virus (HIV)-infected children aged 2-17 years when antiretroviral therapy was changed to either a dual nucleoside analogue regimen or a protease inhibitor-containing regimen. Immunologic response to therapy, as measured by lymphocyte subsets, 3-color flow cytometric measures, and lymphoproliferative assays, were investigated for changes in weeks 44 and 48. The most significant changes after baseline that were associated with the administration of a protease inhibitor-containing regimen were seen for percentages of CD8(+)/CD38(+)/HLA-DR(+), CD8(+)/CD95(+)/CD28(-), and CD8. The percentages of CD8(+)/CD38(+)/HLA-DR(+) and CD8(+)/CD95(+)/CD28(-) decreased from baseline medians of 33% and 46% to medians of 18% and 30% at week 44 (P<.0001 for both). Median CD4 cell count increased 168 cells/microL (from 694 cells/microL to 862 cells/microL; P=.02) by week 48 in this clinically stable population. Changes in lymphoproliferative responses to HIV antigens and recall antigens did not increase over time and between groups
— id: 11618, year: 2000, vol: 182, page: 96, stat: Journal Article,

Lymphoproliferative responses to recombinant HIV-1 envelope antigens in neonates and infants receiving gp120 vaccines. AIDS Clinical Trial Group 230 Collaborators
Borkowsky W; Wara D; Fenton T; McNamara J; Kang M; Mofenson L; McFarland E; Cunningham C; Duliege AM; Francis D; Bryson Y; Burchett S; Spector SA; Frenkel LM; Starr S; Van Dyke R; Jimenez E
2000 Mar;181(3):890-896, Journal of infectious diseases
Children of mothers infected with human immunodeficiency virus type 1 (HIV-1) were immunized at birth and at 1, 3, and 5 months with 1 of 3 doses of recombinant gp120 vaccines prepared from SF-2 or MN strains of HIV-1. A total of 126 children were not infected; 21 received adjuvant only. Vaccine recipients developed lymphoproliferative responses on >/=2 occasions, responding more often to homologous HIV-1 antigens than did adjuvant recipients (56% vs. 14%; P<.001). Responses were appreciated after 2 immunizations and were maintained for >84 weeks after the last immunization. An accelerated immunization schedule (birth, 2 weeks, 2 months, and 5 months) with the lowest dose of the SF-2 vaccine produced responses in all 11 vaccinees by 4 weeks. Responses to heterologous envelope antigens were also detected. Immune responses to vaccination are achievable at an age when some infection (perinatal or breast milk exposure related) may be prevented
— id: 11800, year: 2000, vol: 181, page: 890, stat: Journal Article,

Early Changes in Quasispecies Repertoire in HIV-Infected Infants: Correlation with Disease Progression
Essajee SM; Pollack H; Rochford G; Oransky I; Krasinski K; Borkowsky W
2000 Dec;16(18):1949-1957, AIDS research & human retroviruses
The evolution of HIV-1 quasispecies in patients during the first year of life was investigated in 10 vertically infected infants, using heteroduplex analysis of the V3-V5 region of env. Four subjects, who showed little viral evolution during the period of the study, had rapid progression of disease and early loss of CD4(+) cells. The remaining six subjects, who were slow progressors, evolved new viral variants within 6 months, and in one case by 1 month of age. Of the four patients who were PCR positive at birth, one was infected with multiple HIV-1 variants. These results show that in HIV-infected children, multiple variants may initiate infection and early quasispecies diversification is associated with a favorable clinical outcome
— id: 14545, year: 2000, vol: 16, page: 1949, stat: Journal Article,

Oral ganciclovir in children: pharmacokinetics, safety, tolerance, and antiviral effects [In Process Citation]
Frenkel LM; Capparelli EV; Dankner WM; Xu J; Smith IL; Ballow A; Culnane M; Read JS; Thompson M; Mohan KM; Shaver A; Robinson CA; Stempien MJ; Burchett SK; Melvin AJ; Borkowsky W; Petru A; Kovacs A; Yogev R; Goldsmith J; McFarland EJ; Spector SA
2000 Dec;182(6):1616-1624, Journal of infectious diseases
The pharmacokinetics, safety, tolerance, and antiviral effects of ganciclovir (Gcv) administered orally were evaluated in 36 children infected with cytomegalovirus (CMV) who were severely immunocompromised by infection with human immunodeficiency virus type 1. In this dose-escalation study, 30 mg/kg of Gcv administered every 8 h produced serum levels similar to the dose (1 g/8 h) effective for maintenance treatment of CMV retinitis in adults. In older children, serum Gcv concentrations were similar after the administration of capsules and suspension. All doses (10-50 mg/kg/8 h) studied were safe and, except for the volume of suspension or number of pills, were well tolerated. Oral Gcv was associated with a decrease in the detection of CMV by culture or polymerase chain reaction. CMV disease occurred in 3 children during the study: one developed Gcv resistance, another had harbored resistant virus at study entry, and a third had wild-type CMV
— id: 14546, year: 2000, vol: 182, page: 1616, stat: Journal Article,

Group-specific antibody levels surrounding invasive pneumococcal illness in children infected with human immunodeficiency virus
King JC Jr; Borkowsky W; Mahidhara N; Madore D; Shapiro ED; Rutstein RM; Tan TQ; Farley JJ; Dankner WM; Nachman S; Simoes E; Flynn PM; Clemens J; Hamilton RG
2000 May;181(5):1817-1821, Journal of infectious diseases
Pneumococcal antibody levels surrounding systemic pneumococcal illness (SPI) were measured in children infected with human immunodeficiency virus (HIV). Archived serum samples were collected from 28 HIV-infected children who had 34 cases of SPI, caused by pneumococcal groups 4, 6, 9, 14, 19, and 23. Serum samples collected within 23 weeks before and 13 weeks after the SPI were assayed by ELISA for antipneumococcal polysaccharide (PnPs) IgG antibody to 6 representative pneumococcal serotypes. There was a wide range (0. 16-30.80 microg/mL) of pre-SPI anti-PnPs antibody levels to the presumed infecting serotypes, with a geometric mean level of 0.83 microg/mL (n=34). Seventy-six percent of the antibody values were <2.0 microg/mL, and 95% were <5.0 microg/mL. Homologous seroresponses (>/=4-fold rise in anti-PnPs antibody) were detected in only 4 (27%) of 15 paired serum samples. Heterologous, noninfecting group seroresponses were detected frequently (72%) in the paired serum samples from these 4 homologous group seroresponders
— id: 14548, year: 2000, vol: 181, page: 1817, stat: Journal Article,

Nucleoside analogs plus ritonavir in stable antiretroviral therapy-experienced HIV-infected children: a randomized controlled trial. Pediatric AIDS Clinical Trials Group 338 Study Team
Nachman SA; Stanley K; Yogev R; Pelton S; Wiznia A; Lee S; Mofenson L; Fiscus S; Rathore M; Jimenez E; Borkowsky W; Pitt J; Smith ME; Wells B; McIntosh K
2000 Jan 26;283(4):492-498, JAMA
CONTEXT: Although protease inhibitors are used routinely in adults with human immunodeficiency virus (HIV) infection, the role of these drugs in the treatment of clinically stable HIV-infected children is not clear. OBJECTIVE: To evaluate the safety, tolerance, and virologic response produced by a change in antiretroviral therapy in HIV-infected children who were clinically and immunologically stable while receiving previous therapy. DESIGN: The Pediatric AIDS Clinical Trials Group 338, a multicenter, phase 2, randomized, open-label controlled trial conducted from February 6 to April 30, 1997 (patient entry period); patients were followed up for 48 weeks. SETTING: Pediatric HIV research clinics in the United States and Puerto Rico. PATIENTS: Two hundred ninety-seven antiretroviral-experienced, protease inhibitor-naive, clinically stable HIV-infected children aged 2 to 17 years. INTERVENTIONS: Children were randomized to receive zidovudine, 160 mg/m2 3 times per day, plus lamivudine, 4 mg/kg 2 times per day (n = 100); the same regimen plus ritonavir, 350 mg/m2 2 times per day (n = 100); or ritonavir, 350 mg/m2 2 times per day, and stavudine, 4 mg/kg 2 times per day (n = 97). MAIN OUTCOME MEASURE: Plasma HIV-1 RNA levels at study weeks 12 and 48, compared among the 3 treatment groups. RESULTS: At study week 12, 12% of patients in the zidovudine-lamivudine group had undetectable plasma HIV RNA levels (<400 copies/mL) compared with 52% and 54% of patients in the 2- and 3-drug ritonavir-containing groups, respectively (P<.001). Through study week 48, 70% of children continued receiving their ritonavir-containing regimen. At study week 48, 42% of children receiving ritonavir plus 2 nucleosides compared with 27% of those receiving ritonavir and a single nucleoside had undetectable HIV RNA levels (P = .04); however, similar proportions in each group continuing initial therapy had HIV RNA levels of less than 10000 copies/mL (58% vs 48%, respectively; P = .19). CONCLUSIONS: In our study, change in antiretroviral therapy to a ritonavir-containing regimen was associated with superior virologic response at study week 12 compared with change to a dual nucleoside analog regimen. More children receiving ritonavir in combination with 2 compared with 1 nucleoside analog had undetectable HIV RNA levels at study week 48
— id: 8572, year: 2000, vol: 283, page: 492, stat: Journal Article,

The impact of early initiation of highly active antiretroviral therapy on the human immunodeficiency virus type 1-specific CD8 T cell response in children
Spiegel HM; Chandwani R; Sheehy ME; Dobroszycki J; Fennelly G; Wiznia A; Radding J; Rigaud M; Pollack H; Borkowsky W; Rosenberg M; Nixon DF
2000 Jul;182(1):88-95, Journal of infectious diseases
This cross-sectional study investigated the effect of early highly active antiretroviral therapy (HAART) on human immunodeficiency virus (HIV) type 1-specific CD8 T cell responses in children. HIV-1-specific CD8 T cell responses were quantified using an enzyme-linked immunospot assay to measure interferon-gamma-secreting cells. HIV-1-infected children were classified by time of HAART initiation prior to age 1 year or after age 2 years as early (n=24) or late (n=28) treated. The magnitude and breadth of the HIV-1-specific CD8 T cell response was significantly lower in children receiving early compared with late HAART treatment (P=.0007 and.0001, respectively). However, total CD8 T cell responses in the early HAART treatment group did not differ significantly from those of age-matched non-HAART-treated controls (n=30). Thus, the reduced magnitude and breadth of the HIV-1-specific CD8 T cell response in early HAART-treated children is due to their younger age
— id: 14547, year: 2000, vol: 182, page: 88, stat: Journal Article,

Human immunodeficiency virus type 1- and cytomegalovirus-specific cytotoxic T lymphocytes can persist at high frequency for prolonged periods in the absence of circulating peripheral CD4(+) T cells
Spiegel HM; Ogg GS; DeFalcon E; Sheehy ME; Monard S; Haslett PA; Gillespie G; Donahoe SM; Pollack H; Borkowsky W; McMichael AJ; Nixon DF
2000 Jan;74(2):1018-1022, Journal of virology
CD4(+) T cells are thought to be critical in the maintenance of virus-specific CD8(+) cytotoxic T-cell (CTL) responses. In human immunodeficiency virus type 1 (HIV-1) infection, a selective decline in HIV-1-specific CTL as the CD4(+) T-cell count decreases has been reported. Using HLA-peptide tetrameric complexes, we show the presence at high frequency of HIV-1- and cytomegalovirus-specific CD8(+) T cells when the peripheral CD4(+) T-cell count was low or zero in three HIV-1-infected patients. No direct virus-specific CD8(+)-mediated effector activity was seen in these subjects, suggesting antigen unresponsiveness, although tetramer-sorted cells could be expanded in vitro in the presence of interleukin-2 into responsive effector cells. Thus, virus-specific CD8(+) T cells can be maintained in the peripheral circulation at high frequency in the absence of circulating peripheral CD4(+) T cells, but these cells may lack direct effector activity. Strategies designed to overcome this antigen unresponsiveness may be of value in therapies for the treatment of AIDS
— id: 14549, year: 2000, vol: 74, page: 1018, stat: Journal Article,

Immunologic and virologic responses to HAART in severely immunocompromised HIV-1-infected children
Essajee SM; Kim M; Gonzalez C; Rigaud M; Kaul A; Chandwani S; Hoover W; Lawrence R; Spiegel H; Pollack H; Krasinski K; Borkowsky W
1999 Dec 24;13(18):2523-2532, AIDS
OBJECTIVE: To determine the long-term immunologic and virologic effects of highly active antiretroviral therapy (HAART) in children with AIDS. DESIGN: A prospective observational study. SETTING: Two pediatric HIV clinics. PARTICIPANTS: Twenty-five protease-inhibitor naive HIV-infected children (aged 2-18 years) with advanced disease (CD4 < or =6%). INTERVENTION: HAART (one protease inhibitor and one or more nucleoside analogs). Diphtheria and tetanus immunization in six patients after 18 months of therapy. MAIN OUTCOME MEASURES: Changes in percentage of CD4 cells and plasma HIV-1 RNA levels; post-treatment assays of lymphoproliferative responses to recall antigens; CD4 cell memory phenotype. RESULTS: Median duration of follow-up was 18.8 months (range, 7.5-28 months). At baseline the CD4 cell percentage was 2% (range, 0-6%), this increased significantly to 16% (range, 3-48%) above baseline at 12 months (P = 0.002). The mean maximum CD4 cell increase was 20.7% (range 4-48%) which corresponds to 657x10(6) cells/l (range, 30-2240x10(6) cells/l) above baseline. By contrast, the median viral load was not significantly lower at 12 months than at baseline (P = 0.34), and only 25% of the patients had sustained undetectable viral load. Of the reconstituted CD4 cells 70% were naive, and none of the subjects had lymphoproliferative responses to tetanus and diphtheria although 40% did develop responses to Candida, an environmental antigen. A single immunization with diphtheria and tetanus toxoid produced lymphoproliferative responses to tetanus in three out of six patients. CONCLUSIONS: HAART was associated with sustained increases in CD4 cell counts, despite a high incidence of 'virologic failure'. CD4 counts and the proportion of naive cells were higher than have been reported in adults, which may be a reflection of greater thymic activity in children. Memory cell clones for antigens encountered in the past which are not prevalent before therapy could not be expanded without additional antigenic exposure
— id: 8585, year: 1999, vol: 13, page: 2523, stat: Journal Article,

A polymorphism in the regulatory region of the CC-chemokine receptor 5 gene influences perinatal transmission of human immunodeficiency virus type 1 to African-American infants
Kostrikis LG; Neumann AU; Thomson B; Korber BT; McHardy P; Karanicolas R; Deutsch L; Huang Y; Lew JF; McIntosh K; Pollack H; Borkowsky W; Spiegel HM; Palumbo P; Oleske J; Bardeguez A; Luzuriaga K; Sullivan J; Wolinsky SM; Koup RA; Ho DD; Moore JP
1999 Dec;73(12):10264-10271, Journal of virology
There are natural mutations in the coding and noncoding regions of the human immunodeficiency virus type 1 (HIV-1) CC-chemokine coreceptor 5 (CCR5) and in the related CCR2 protein (the CCR2-64I mutation). Individuals homozygous for the CCR5-Delta32 allele, which prevents CCR5 expression, strongly resist HIV-1 infection. Several genetic polymorphisms have been identified within the CCR5 5' regulatory region, some of which influence the rate of disease progression in adult AIDS study cohorts. We genotyped 1,442 infants (1,235 uninfected and 207 HIV-1 infected) for five CCR5 and CCR2 polymorphisms: CCR5-59353-T/C, CCR5-59356-C/T CCR5-59402-A/G, CCR5-Delta32, and CCR2-64I. The clinical significance of each genotype was assessed by measuring whether it influenced the rate of perinatal HIV-1 transmission among 667 AZT-untreated mother-infant pairs (554 uninfected and 113 HIV-1 infected). We found that the mutant CCR5-59356-T allele is relatively common in African-Americans (20.6% allele frequency among 552 infants) and rare in Caucasians and Hispanics (3.4 and 5.6% of 174 and 458 infants, respectively; P < 0.001). There were 38 infants homozygous for CCR5-59356-T, of whom 35 were African-Americans. Among the African-American infants in the AZT-untreated group, there was a highly significant increase in HIV-1 transmission to infants with two mutant CCR5-59356-T alleles (47.6% of 21), compared to those with no or one mutant allele (13.4 to 14.1% of 187 and 71, respectively; P < 0.001). The increased relative risk was 5.9 (95% confidence interval, 2.3 to 15.3; P < 0.001). The frequency of the CCR5-59356-T mutation varies between population groups in the United States, a low frequency occurring in Caucasians and a higher frequency occurring in African-Americans. Homozygosity for CCR5-59356-T is strongly associated with an increased rate of perinatal HIV-1 transmission
— id: 14550, year: 1999, vol: 73, page: 10264, stat: Journal Article,

Dynamics of human immunodeficiency virus type 1 replication in vertically infected infants
Luzuriaga K; Wu H; McManus M; Britto P; Borkowsky W; Burchett S; Smith B; Mofenson L; Sullivan JL
1999 Jan;73(1):362-367, Journal of virology
Plasma human immunodeficiency virus type 1 (HIV-1) turnover and kinetics were studied in children aged 15 days to 2 years following the initiation of a triple antiretroviral drug regimen consisting of zidovudine, lamivudine, and nevirapine. HIV-1 turnover was at least as rapid as that previously described in adults; turnover rates were more rapid in infants and children aged 3 months to 2 years than in infants less than 3 months of age. These data confirm the central role of HIV-1 replication in the pathogenesis of vertical HIV-1 infection and reinforce the importance of early, potent combination therapies for the long-term control of HIV-1 replication
— id: 14554, year: 1999, vol: 73, page: 362, stat: Journal Article,

Changes in frequency of HIV-1-specific cytotoxic T cell precursors and circulating effectors after combination antiretroviral therapy in children
Spiegel HM; DeFalcon E; Ogg GS; Larsson M; Beadle TJ; Tao P; McMichael AJ; Bhardwaj N; O'Callaghan C; Cox WI; Krasinski K; Pollack H; Borkowsky W; Nixon DF
1999 Aug;180(2):359-368, Journal of infectious diseases
Combination antiretroviral therapy has had a major role in reducing human immunodeficiency virus type 1 (HIV-1) plasma viral loads in HIV-1-infected adults but a variable effect in infants, in whom complete viral suppression appears to be less readily achieved. In adults, after the reduction in plasma viremia, there is a decrease in the numbers of circulating cytotoxic T cell (CTL) effectors and precursors in the majority of patients. This longitudinal study assessed the effect of combination drug therapy on the frequency of HIV-1-specific CTL responses in 8 HIV-1-infected children. Following treatment, the frequency of HIV-1-specific CTL responses initially increased, especially in children with incomplete viral suppression but with increasing CD4+ cell counts. In children with complete viral suppression, the frequency of HIV-1-specific CTL responses decreased, suggesting that viral replication is required to maintain CTL responses in the systemic circulation
— id: 14552, year: 1999, vol: 180, page: 359, stat: Journal Article,

Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy
Zhang L; Lewin SR; Markowitz M; Lin HH; Skulsky E; Karanicolas R; He Y; Jin X; Tuttleton S; Vesanen M; Spiegel H; Kost R; van Lunzen J; Stellbrink HJ; Wolinsky S; Borkowsky W; Palumbo P; Kostrikis LG; Ho DD
1999 Sep 6;190(5):725-732, Journal of experimental medicine
The role of the thymus in HIV-1 pathogenesis remains unclear. We developed an assay to quantify the number of recent thymic emigrants in blood based on the detection of a major excisional DNA byproduct (termed alpha1 circle) of T cell receptor rearrangement. By studying 532 normal individuals, we found that alpha1 circle numbers in blood remain high for the first 10-15 yr of life, a sharp drop is seen in the late teen years, and a gradual decline occurs thereafter. Compared with age-matched uninfected control individuals, alpha1 circle numbers in HIV-1-infected adults were significantly reduced; however, there were many individuals with normal alpha1 circle numbers. In 74 individuals receiving highly active antiretroviral therapy, we found no appreciable effect on alpha1 circle numbers in those whose baseline values were already within the normal range, but significant increases were observed in those with a preexisting impairment. The increases in alpha1 circle numbers were, however, numerically insufficient to account for the rise in levels of naive T lymphocytes. Overall, it is difficult to invoke thymic regenerative failure as a generalized mechanism for CD4 lymphocyte depletion in HIV-1 infection, as alpha1 circle numbers are normal in a substantial subset of HIV-1-infected individuals
— id: 14551, year: 1999, vol: 190, page: 725, stat: Journal Article,

Lymphoproliferative responses (LP) to receive HIV-1 envelope antigens in neonates & infants receiving gp120 vaccines
Borkowsky W; Wara D; McNamara J; Kang M; Fenton T; McFarland E; Cunningham C; Mofenson L; Duliege A; Francis D
1998 Feb 1-5;5:129-129, Conference on Retroviruses & Opportunistic Infections
Children born to HIV-infected mothers were immunized at birth and at 1, 3, & 5 months of age with recombinant gp120 vaccines prepared from either SF-2 [Chiron/Biocine (CB)] or MN [Vaxgen (VG)] drains of HIV-1. Doses of immunogen included 5, 15, & 50 micrograms (CB) or 30, 100, & 300 micrograms (VG). Of the 125 immunized children who proved to be HIV uninfected, 21 received adjuvant only; MF59 for CB & alum for VG. PBMC from the children (collected at birth, 1 month after each vaccination, and weeks 52, 76, and 104) were stimulated in vitro with rec GP120 autologous antigen (AA), and respective rec control antigen; A stimulation index (SI) greater than 3 was considered a (+) LP response and 2 or more (+) LPs defined a responder. (Table: see text) Many responses persisted for as long as the duration of the followup to date (104 weeks) without additional boosters given after 20 weeks. An SI greater than 3 was seen as early as 8 weeks of age (after 2 immunizations) in 14 CB and in 10 VG responders. Since perinatal HIV infection is usually evident prior to 8 weeks of age, an 'accelerated' immunization schedule (birth, 2 weeks, 2 months, 5 months) was adopted using only the 'optimal' vaccine doses (CB5* and VG100*). Currently, 11 of 11 CB5* vaccinees and 2 of 12 VG100* vaccinees with 2 or more postimmunization LP assays are responders
— id: 6009, year: 1998, vol: 5, page: 129, stat: Journal Article,

Safety and immunogenicity of HIV recombinant envelope vaccines in HIV-infected infants and children. National Institutes of Health-sponsored Pediatric AIDS Clinical Trials Group (ACTG-218)
Lambert JS; McNamara J; Katz SL; Fenton T; Kang M; VanCott TC; Livingston R; Hawkins E; Moye J Jr; Borkowsky W; Johnson D; Yogev R; Duliege AM; Francis D; Gershon A; Wara D; Martin N; Levin M; McSherry G; Smith G
1998 Dec 15;19(5):451-461, Journal of acquired immune deficiency syndromes & human retrovirology
Study objectives were to evaluate the safety and immunogenicity of three HIV recombinant glycoproteins in HIV-infected infants and children between 1 month and 18 years of age with asymptomatic (P-1) infection. Using Chiron rgp 120 (SF-2) 15 or 50 microg; MicroGeneSys rgp 160 (IIIB) 40 or 320 microg; Genentech rgp120 (MN) 75 or 300 microg; or adjuvant control (Alum or MF-59), children were randomized to a double-blind, placebo-controlled, dose-escalating study of vaccine administered intramuscularly at entry and 1, 2, 3, 4, and 6 months later. No adverse events were attributed to study vaccines. Between 30% and 56% of volunteers exhibited a lymphoproliferative response as defined in terms of stimulation index (SI) to vaccine antigens; 65% of vaccinees but none of placebo recipients exhibited moderate or strong responses after enzyme immunoassay to HIV specific antigens. CD4 cell counts and quantitative HIV culture did not differ significantly among vaccine and control groups, nor were differences found among groups in HIV disease progression. The rgp160 and gp120 subunit vaccines were safe and immunogenic in this population
— id: 14553, year: 1998, vol: 19, page: 451, stat: Journal Article,

Expression patterns of the HIV type 1 coreceptors CCR5 and CXCR4 on CD4+ T cells and monocytes from cord and adult blood
Mo H; Monard S; Pollack H; Ip J; Rochford G; Wu L; Hoxie J; Borkowsky W; Ho DD; Moore JP
1998 May 1;14(7):607-617, AIDS research & human retroviruses
We have measured the surface expression of the HIV-1 coreceptors CCR5 and CXCR4 on CD4+ T cells and monocytes from cord and adult blood. The expression of CCR5 was largely restricted to the memory (CD45RAlow) subset, whereas CXCR4 was expressed on both memory and naive (CD45RAhigh) T cells. The paucity of memory CD4+ T cells in cord blood means that CCR5-positive cells are relatively uncommon, so the overall extent of CCR5 expression was reduced in cord blood, compared with adult blood. IL-2 activation of CD4+ T cells from both cord and adult bloods caused a substantial increase in CCR5 expression, but moderately decreased CXCR4 expression. PHA stimulation increased CCR5 expression slightly, but only on naive cells. Monocytes expressed both CCR5 and CXCR4 at levels that differed little between cord and adult blood
— id: 14555, year: 1998, vol: 14, page: 607, stat: Journal Article,

Increased transmission of vertical hepatitis C virus (HCV) infection to human immunodeficiency virus (HIV)-infected infants of HIV- and HCV-coinfected women
Papaevangelou V; Pollack H; Rochford G; Kokka R; Hou Z; Chernoff D; Hanna B; Krasinski K; Borkowsky W
1998 Oct;178(4):1047-1052, Journal of infectious diseases
The transmission of perinatal hepatitis C virus (HCV) infection was studied retrospectively in 62 infants born to 54 HCV- and human immunodeficiency virus (HIV)-coinfected women enrolled in a prospective natural history study of HIV transmission. Infant HCV infection was assessed by nested RNA polymerase chain reaction. The overall rate of vertical HCV transmission was 16.4% (9/62). Most HCV-infected children did not develop antibodies to HCV. The rate of HCV infection was higher among HIV-infected infants (40%) than among HIV-uninfected infants (7.5%; odds ratio, 8.2; P = .009). This difference in transmission was not related to differences in maternal HCV load, as measured by branched DNA assay, or mode of delivery. Why HIV-infected infants of HCV- and HIV-coinfected women have significantly higher rates of perinatal HCV transmission remains to be elucidated. The rate of HCV transmission in HIV-uninfected infants of HCV- and HIV-coinfected women is similar to that reported for infants born to HIV-seronegative mothers
— id: 7730, year: 1998, vol: 178, page: 1047, stat: Journal Article,

Failure of Neutralizing gp120 Monoclonal Antibodies to Prevent HIV Infection of Choriocarcinoma-Derived Trophoblasts
Bourinbaiar AS; Borkowsky W; Krasinski KM; Fruhstorfer EC
1997 Jul-Aug;4(4):162-168, Journal of biomedical science
Although placental trophoblasts, the only fetal cells in direct contact with infectious maternal blood, can be infected with HIV, the precise cause for the low transmission rate of virus across the placental barrier is unknown. One of the most common conjectures is that maternal anti-HIV antibodies (Abs) contribute to the protection of the fetus. This hypothesis has been tested in vitro by infecting the CD4-negative placental trophoblast line, BeWo, with HIV-1(IIIB) in the presence of serial dilutions of neutralizing monoclonal Abs against the V3 loop (No. 694) or CD4-binding conformational domain (No. 588). The results, based on measurement of p24 production from virus-exposed cells, reveal that the titers of Abs, adequate in preventing the infection of control MT-4 T lymphocytes, were less effective in protecting trophoblasts. Furthermore, PCR analysis of HIV DNA formed after a single round of infection has shown no significant decrease in the number of viral copies in Ab-protected BeWo cells. An anti-HIV serum from a pregnant woman did also have no effect. Although our in vitro observations do not necessarily apply to the in vivo situation, the results suggest that the humoral immune response sustained by neutralizing Abs may be able to protect T lymphocytes, but not placental trophoblasts. The findings are consistent with recent clinical studies demonstrating a lack of correlation between the presence of neutralizing anti-HIV Abs in pregnant women and HIV transmission in utero.
— id: 42232, year: 1997, vol: 4, page: 162, stat: Journal Article,

Two newly identified mutations (Thr233Ile and Leu152Met) in partially adenosine deaminase-deficient (ADA-) individuals that result in differing biochemical and metabolic phenotypes
Hirschhorn R; Borkowsky W; Jiang CK; Yang DR; Jenkins T
1997 Jul;100(1):22-29, Human genetics
Deficiency of adenosine deaminase (ADA-) results in autosomal recessive immunodeficiency disease of varying severity. Partial ADA- [ADA deficiency in erythrocytes (RBCs) but substantial ADA in non-RBCs] has also been identified, primarily by population screening of healthy adults in Africa and newborns in New York State. Normal immune function and/or minimal elevations of toxic metabolites in childhood suggested that partial ADA deficiency was benign and therefore that six mutations identified in partially ADA-deficient newborns and expressing 8-80% of normal ADA in non-RBCs were not pathogenic. However, the lowest activity mutation (Arg211Cys) has now been reported in patients with adult-onset immunodeficiency. We have now molecularly and biochemically studied two additional individuals whom we found to represent opposite ends of the spectrum of partial ADA deficiency as to biochemical abnormalities and age of ascertainment. Homozygosity for a newly identified Leu152Met mutation expressing considerably less activity than the pathogenic Arg211Cys mutation was found in a currently healthy 10-year-old Afghanistani child (ascertained at birth). He had the highest accumulation of the metabolite dATP among 13 partially ADA-deficient patients studied, but considerably lower than in those with immunodeficiency. Homozygosity for a newly identified Thr233Ile mutation expressing somewhat greater ADA activity than Arg211Cys was found in a healthy young adult Kung individual, associated with very low metabolite concentrations. Biochemical findings and a family history suggestive of immunodeficiency in prior offspring support the idea that the Leu152Met mutation could result in disease in homozygous individuals challenged by severe environmental insult or in heterozygosity with a null mutation. The pathogenicity of the Thr233Ile mutation, as well as a previously described Ala215Thr mutation with relatively lower activity is less likely but will only be determined by long-term observation of individuals carrying these mutations. Although, in contrast to other partial mutations, neither of these two mutations are at CpG hot spots, the frequency of CpG mutations remains high for partial mutations but is also similarly high in ADA- immunodeficient patients (5/8 vs 12/21)
— id: 7164, year: 1997, vol: 100, page: 22, stat: Journal Article,

Impaired early growth of infants perinatally infected with human immunodeficiency virus: correlation with viral load
Pollack H; Glasberg H; Lee E; Nirenberg A; David R; Krasinski K; Borkowsky W; Oberfield S
1997 Jun;130(6):915-922, Journal of pediatrics
OBJECTIVE: To evaluate the effect of viral load on the early growth of infants infected with human immunodeficiency virus (HIV). METHODS: Plasma concentrations of p24-antigen and HIV ribonucleic acid were measured retrospectively and correlated with growth parameters for the first 18 months of life in a cohort of 47 term infants born to HIV-infected mothers prospectively enrolled in a study of perinatal HIV transmission. Comparisons of the mean weight and length of the 18 HIV-infected and 29 uninfected infants for each interval and across intervals were made. Viral load was correlated with standard deviation scores. Infants were stratified by high and low viral load during the first 6 months of life. RESULTS: At birth, no difference in weight and length was observed between HIV-infected and uninfected infants. Between birth and 6 months of age, the infected infants grew less rapidly than the uninfected infants, a finding temporally associated with an exponential increase in HIV viremia. The linear growth of infected infants remained consistently less than that of the uninfected infants after 6 months of life, although the differences were no longer statistically significant and tended to decrease with age in parallel with declines in viral load. The median plasma concentration of HIV ribonucleic acid was significantly higher at 3, 6, 12, and 18 months in infected infants in whom growth failure developed. Infants who had a high viral load in the first 6 months of life were significantly more likely to have severe growth failure. Though the mean SD for weight of the infected infants was always less than that of the uninfected infants, the differences were small and not significant. CONCLUSIONS: Our results confirm the observation that stunting is an early frequent finding in perinatal HIV infection. The deleterious effect of HIV on linear growth appears to be correlated with the level of postnatal HIV viremia, although the exact mechanism of this association remains to be elucidated
— id: 7235, year: 1997, vol: 130, page: 915, stat: Journal Article,

CD8+ T-cell-mediated suppression of HIV replication in the first year of life: association with lower viral load and favorable early survival
Pollack H; Zhan MX; Safrit JT; Chen SH; Rochford G; Tao PZ; Koup R; Krasinski K; Borkowsky W
1997 Jan;11(1):F9-13, AIDS
OBJECTIVE AND DESIGN: To study the role and development of non-cytotoxic CD8+ T-cell-mediated suppression of HIV replication in early perinatal HIV infection in a prospective study of vertically infected infants. CD8 T-cell-mediated HIV suppression was measured several times during the first year of life and correlated with viral load, cytotoxic T-cell (CTL) activity, in vitro antibody production (IVAP) and clinical outcome. METHODS: CD8+ T-cell-mediated HIV suppression was measured by comparing the amount of p24 antigen produced by endogenously infected lymphocytes with cultures of the same number of autologous CD4+ T cells from which CD8+ cells were removed immunomagnetically. CD8 viral suppressive activity (VSA) was defined as a > or = 50% reduction in p24 antigen in the cultures containing CD8+ cells. RESULTS: CD8+ T-cell-mediated HIV VSA was detected in 11/16 infants in the first year of life, including six/nine infants studied before 6 months and as early as 3 weeks of age. Infants who demonstrated CD8 VSA had a lower early peak and 6-month 'setpoint' plasma HIV RNA concentration than infants who lacked CD8 VSA [1.51 versus 4.94 and 0.094 versus 0.639 x 10(6) copies/ml, respectively, and higher CD4 percentage at 1 year of age. Survival of infants lacking CD8 VSA (four/six were rapid progressors) was shorter than for infants who demonstrated CD8 VSA (none out of 10 were rapid progressors). CD8 VSA was present before CTL and before or at the same time as IVAP in two of two and 11 of 14 infants studied, respectively. CONCLUSIONS: CD8+ T-cell-mediated VSA can be demonstrated in a large proportion of HIV-infected infants early in the course of infection. This non-cytolytic HIV-suppressive immune response appears to play an important protective role in the early control of perinatal HIV infection at a time when other immune responses are either absent or deficient
— id: 12412, year: 1997, vol: 11, page: F9, stat: Journal Article,

Dialyzable lymphoid extract (DLE) from mice resistant to STZ-induced diabetogenesis can interrupt the progress of diabetes in STZ-treated CD-1 mice
Borkowsky W; Pilson R; Lawrence HS
1996 ;9(1-3):149-157, Biotherapy
DLE was prepared from the minority of euglycemic CD-1 mice, previously injected with STZ, and was administered to hyperglycemic CD-1 male mice 1, 2 and 3 weeks after completion of multidose STZ. Mice treated with DLE derived from 2 x 10(7) (IX) or 10(8) lymphocyte equivalents (lymph.equ) were significantly less hyperglycemic than the saline treated controls (P < 0.001). The effects of DLE remained evident for more than 10 weeks after the final DLE treatment. Mice treated with DLE prepared from diabetic mice (hg DLE) developed a somewhat more rapid onset of hyperglycemia than the STZ treated control animals, although this effect did not achieve statistical significance (P = 0.1). This DLE was absorbed on a rat insulinoma cell line (RIN), which contains interspecies cross-reacting islet antigens, and compared to the unabsorbed DLE. Mice treated with hg DLE preabsorbed on RIN cells, showed a slower onset of hyperglycemia. DLE prepared from euglycemia mice and the RIN-absorbed fraction were equally capable of preventing hyperglycemia (P < 0.05). In order to determine whether the DLE effects were genetically restricted, DLE was prepared from BALB/c mice, normally resistant to the diabetogenic effects of multidose STZ, both before and after STZ treatment. STZ primed CD-1 mice treated with 3 weekly doses of 2 x 10(7) lymph. equ. of untreated BALB/c derived DLE, STZ treated BALB/c derived DLE, and STZ treated CD-1 DLE were all less hyperglycemic than the control mice, who received saline (P < 0.001). However, mice treated with CD-1 DLE were less hyperglycemic than the mice given BALB/c derived DLE (P < 0.05). These effects were relatively long-lived. Mice that were given the > 3,500 Dalton fraction of CD-1 DLE were significantly less hyperglycemic than either the control mice or those treated with the < 3,500 Dalton fraction of CD-1 DLE (P < 0.05). Effects remained evident for more than 3 months after the last dose of DLE. Pancreatic tissue from the mice treated with the > 3,500 Dalton fraction of CD-1 derived DLE revealed slightly more islets of a slightly greater size with less surrounding inflammation than either control mice or mice treated with the < 3,500 Dalton fraction of DLE
— id: 8019, year: 1996, vol: 9, page: 149, stat: Journal Article,

Randomized study of the tolerance and efficacy of high- versus low-dose zidovudine in human immunodeficiency virus-infected children with mild to moderate symptoms (AIDS Clinical Trials Group 128). Pediatric AIDS Clinical Trials Group
Brady MT; McGrath N; Brouwers P; Gelber R; Fowler MG; Yogev R; Hutton N; Bryson YJ; Mitchell CD; Fikrig S; Borkowsky W; Jimenez E; McSherry G; Rubinstein A; Wilfert CM; McIntosh K; Elkins MM; Weintrub PS
1996 May;173(5):1097-1106, Journal of infectious diseases
The current dosage of zidovudine for children is 180 mg/m2 every 6 h. To investigate whether a lower dosage was equally effective, human immunodeficiency virus (HIV)-infected children (3 months to 12 years) with mild to moderate symptoms were randomly assigned to receive either high-dose (180 mg/m2/dose) or low-dose (90 mg/m2/dose) zidovudine (double-blind). Treatments were compared with respect to neuropsychologic function, survival, clinical and laboratory evidence of disease progression, and safety and tolerance. Four hundred twenty-six HIV-infected children were enrolled; median time for receipt of study drug was 35 months. Zidovudine in either dose was well tolerated, with no difference in efficacy or tolerance by treatment group using any clinical or laboratory parameter. In children with mild to moderate disease, a reduction of zidovudine to 90 mg/m2/dose will result in substantial cost savings and should be the recommended dose
— id: 14556, year: 1996, vol: 173, page: 1097, stat: Journal Article,

Cytomegalovirus infection in human immunodeficiency virus type 1-infected children
Chandwani S; Kaul A; Bebenroth D; Kim M; John DD; Fidelia A; Hassel A; Borkowsky W; Krasinski K
1996 Apr;15(4):310-314, Pediatric infectious disease journal
BACKGROUND: Cytomegalovirus (CMV) is a frequent opportunistic infection in human immunodeficiency virus type 1 (HIV-1)-infected children. The interactions of CMV and HIV-1 in coinfected children are not well-characterized. OBJECTIVE: To evaluate the prevalence of asymptomatic CMV infection and symptomatic CMV disease and to assess the influence of CMV on clinical and laboratory markers of HIV disease progression in CMV-coinfected children. METHODS: Serial urine CMV cultures were performed on 500 children (131 HIV-1-infected (HIV+), 129 seroreverters born to HIV-infected mothers, and 240 HIV-uninfected (HIV-)). The clinical, immunologic and virologic data of 131 HIV+ children were analyzed. RESULTS: CMV was recovered in 40 of 131 HIV+ (31%), 22 of 129 seroreverters (17%) and 30 of 240 HIV- (13%) children. Of the 40 HIV+ children with CMV coinfection, 7 developed symptomatic CMV disease (17.5%) including chorioretinitis (3), colitis (2) and pneumonitis (2). The HIV+ children with symptomatic CMV disease had significantly lower mean CD4+ T lymphocyte proportions (17% vs. 26%; age-adjusted P = 0.013) and greater HIV p24 antigen concentrations (329 pg/ml vs. 57 pg/ml; age-adjusted P = 0.13) than HIV+ children with asymptomatic CMV infection. In a subset of children coinfected with CMV before 6 months of age (n = 11), 5 (45%) developed symptomatic CMV disease, and 4 of these 5 children died within 10 months of diagnosis of CMV disease. At the time of the first positive CMV culture in these children, mean CD4+ T lymphocyte proportions did not differ according to the presence or absence of CMV-related symptoms (symptomatic CMV+, 21% vs. asymptomatic CMV = 38%; P = 0.14). In HIV+ children with symptomatic CMV disease, p24 antigen concentrations were greater than in those with asymptomatic CMV infection (461 vs. 190 pg/ml, P = 0.06). CONCLUSIONS: Symptomatic CMV disease occurred in young CMV-coinfected children with low CD4+ lymphocytes and elevated HIV p24 antigen concentrations. Whether progressive immunodeficiency allows the emergence of CMV disease or CMV infection causes more rapidly progressive HIV-1 disease or whether there is a more complex relationship remains to be determined
— id: 12620, year: 1996, vol: 15, page: 310, stat: Journal Article,

Transfer factor--current status and future prospects
Lawrence HS; Borkowsky W
1996 ;9(1-3):1-5, Biotherapy
We have detected new clues to the composition and function of 'Transfer Factor' using the direct Leucocyte Migration Inhibition (LMI) test as an in vitro assay of Dialysates of Leucocyte Extracts (DLE). This approach has revealed two opposing antigen-specific activities to be present in the same > 3500 < 12,000 DA dialysis fraction - one activity is possessed of Inducer/Helper function (Inducer Factor). The opposing activity is possessed of Suppressor function (Suppressor Factor). When non-immune leucocyte populations are cultured with Inducer Factor they acquire the capacity to respond to specific antigen and inhibition of migration occurs. This conversion to reactivity is antigen-specific and dose-dependent. When immune leucocyte populations are cultured with Suppressor Factor their response to specific antigen is blocked and Inhibition of Migration is prevented
— id: 7079, year: 1996, vol: 9, page: 1, stat: Journal Article,

The amount of early p24 antigenemia and not the time of first detection of virus predicts the clinical outcome of infants vertically infected with human immunodeficiency virus
Papaevangelou V; Pollack H; Riguad M; Arlievsky N; Lu ML; Rochford G; Krasinski K; Borkowsky W
1996 Mar;173(3):574-578, Journal of infectious diseases
Twenty-three children vertically infected with human immunodeficiency virus type 1 (HIV-1) were studied for viremia during the first days of life. Nine had HIV-1 infection within the first week (early); 14 had HIV-1 first detected by day 11-90 (late). The groups had similar incidence and time of onset of symptomatic HIV-1 infection and survival. CD4 T cell percentages, rates of CD4 T cell attrition, quantitative cell-associated viremia, and p24 antigen concentrations were comparable. Children with peak antigen concentrations >100 pg/mL during the first 6 months (5 early, 6 late) fared worse than those with lower p24 levels. Thus, HIV-1-infected infants with detectable virus in the first few days of life do not have a worse prognosis than infants whose virus is detectable only later. Elevated p24 antigenemia during the first 6 months of life correlates strongly with poor clinical outcome and is independent of the time virus was first detected
— id: 6944, year: 1996, vol: 173, page: 574, stat: Journal Article,

Vaccination recommendations for HIV-1-infected children
Papaevangelou, V; Borkowsky, W
1996 JAN ;5(1):5-12, Clinical immunotherapeutics
Recommendations for the vaccination of HIV-1-infected children have been made by the Advisory Committee on Immunization Practices and the World Health Organization, and are reviewed in this article. The data on immunogenicity and safety of individual vaccines are also reviewed. In evaluating the risk of immunisation, it appears that HIV-1-infected children have a very low incidence of vaccine-induced illness after administration of live vaccines such as bacille Calmette-Guerin (BCG) or measles-mumps-rubella (MMR). Rates of the common adverse reactions are similar in HIV-1-infected and noninfected children. The immunogenicity and efficacy of the vaccines appears to be lower in HIV-infected children, However, a high proportion of asymptomatic HIV-infected children are able to mount protective levels of antibodies following vaccination, The ability to respond to vaccines correlates with the stage of HIV infection. Children with severe immunodeficiency have the lowest response rates and the most rapid decline of protective antibodies. Vaccination of HIV-infected children early in life before the onset of severe immunodeficiency, as well as the administration of additional booster vaccines, might increase the efficacy of vaccinations in HIV-infected children. Recommendations for vaccinating HIV-1-infected children are based on the general principles of active and passive immunisation, as well as on the data acquired on vaccine safety and efficacy through the immunisation of HIV-1-infected children. These recommendations attempt to balance the risks and benefits of immunisation of these children in order to achieve optimal levels of protection against infectious diseases. The Advisory Committee on Immunization Practices (ACIP) has published its recommendations for persons with altered immunocompetence.([1]) These recommendations, however, are for use in the US and for areas with similar epidemiology. The World Health Organization has made different recommendations for developing countries with a high prevalence of wild poliovirus infection and tuberculosis in respect of the use of the oral polio vaccine (OPV) and bacille Calmette-Guerin rin (BCG).([2]) In this article the current recommendations for vaccination of HIV-1-infected children will be reviewed. Furthermore, the immunogenicity and safety of individual vaccines will be discussed
— id: 53104, year: 1996, vol: 5, page: 5, stat: Journal Article,

Neurodevelopment, growth, and viral load in HIV-infected infants
Pollack H; Kuchuk A; Cowan L; Hacimamutoglu S; Glasberg H; David R; Krasinski K; Borkowsky W; Oberfield S
1996 Sep;10(3):298-312, Brain, behavior & immunity
The relation of HIV-1 infection to infant growth and neurodevelopment was studied prospectively in a cohort of 65 infants born to women at risk for HIV infection. No differences were observed at birth between infected infants (INF) and uninfected infants (SR) of HIV-infected women, and infants of uninfected women (SN) with similar socioeconomic background and exposure to drugs. However, postnatal linear growth and cognitive-motor development of INF infants were impaired when compared to SR and SN infants. Declines in linear growth were observed within the first 6 months of life, whereas delays in neurodevelopment were first appreciated at 12 months. In INF infants, decreased linear growth was positively correlated with developmental delay. Moreover, growth and development were both correlated with HIV viral load. INF infants with high plasma HIV RNA copies (> 5 x 10(5)/ ml) at 6 months of life were more likely to exhibit severe growth and developmental delay than infants with a lower viral burden. The implications of these findings with respect to the mechanism of action of HIV-related growth and neurodevelopmental impairments are discussed
— id: 12544, year: 1996, vol: 10, page: 298, stat: Journal Article,

Shortened survival in infants vertically infected with human immunodeficiency virus with elevated p24 antigenemia
Arlievsky NZ; Pollack H; Rigaud M; Kaul A; Krasinski K; Borkowsky W
1995 Oct;127(4):538-543, Journal of pediatrics
OBJECTIVE: To determine whether the amount of p24 antigenemia in the first 6 months of life is a predictor of survival in children infected vertically with human immunodeficiency virus type 1. METHODS: A retrospective study of vertically infected infants and children who were followed prospectively from early infancy and who had quantitation of plasma p24 antigen concentration in the first 6 months of life. Infants were first stratified by duration of survival as infants who died before 2 years of age (short-term survivors) and infants who survived to 2 years of age (intermediate-term survivors). The median p24 antigen concentration and the proportion of infants in each group with high concentrations of antigen were compared. Analyses with and excluding all p24 determinations made after the use of antiretroviral agents were compared Kaplan-Meier product limit analysis was used to compare survival in infants with low and high antigenemia during the first 6 months of life. RESULTS: The median p24 antigen concentration in 15 short-term survivors was 228 pg/ml, compared with 14 pg/ml in 26 intermediate-term survivors (p < 0.05). The proportion of children with > 100 pg/ml of p24 was higher in short-term than in intermediate-term survivors (p = 0.01). Survival to 2 years of age in infants in whom all p24 antigen values during the first 6 months of life were 100 pg/ml or less was 91%, in comparison with 39% in infants with values greater than 100 pg/ml (p = 0.0017). CONCLUSIONS: Elevated p24 antigenemia in the first 6 months of life is associated with shorter survival and may be a useful predictor of outcome
— id: 6802, year: 1995, vol: 127, page: 538, stat: Journal Article,

Protective effect of interferon-alpha against cell-mediated human immunodeficiency virus transmission resulting from coculture of infected lymphocytes with fetal trophoblasts
Bourinbaiar AS; Krasinski K; Borkowsky W; Lee-Huang S
1995 Jun;15(6):503-508, Journal of interferon & cytokine research
The hypothesis that the low transmission rate of HIV in utero may be due, in part, to the protective effect of IFN-producing placental trophoblasts was explored in vitro. The model consisted of H9 lymphocytes, as surrogates of maternal HIV-infected T cells, incubated for 3 h with JEG-3 trophoblasts in the presence of 10-fold dilutions of leukocyte-derived IFN-alpha (from 1000 to 0.1 IU/ml). The dose effect was monitored either directly, by measuring the levels of proviral DNA by PCR after a single round of infection, or indirectly, by coculturing infected JEG-3 with cord blood-derived MT-4 lymphocytes and determining the levels of p24 production by ELISA. Both assays revealed a dose-dependent blocking effect of IFN-alpha on cell-mediated HIV transmission. The complete inhibition of HIV infection was observed in the presence of 100 IU IFN-alpha. The efficacy of such a low dose could not be attributed to insufficient viral load because up to 10(8) infectious particles could be transmitted during cell-cell contact. An adhesion assay ruled out the possibility that IFN-alpha acts through prevention of lymphocyte-trophoblast contact. The results suggest that physiologic levels of IFN-alpha, present in the placental environment, may contribute to the protection of the fetus against HIV infection
— id: 6582, year: 1995, vol: 15, page: 503, stat: Journal Article,

The sensitivity of HIV-1 DNA polymerase chain reaction in the neonatal period and the relative contributions of intra-uterine and intra-partum transmission [see comments]
Dunn DT; Brandt CD; Krivine A; Cassol SA; Roques P; Borkowsky W; De Rossi A; Denamur E; Ehrnst A; Loveday C
1995 Sep;9(9):F7-11, AIDS
OBJECTIVE: To derive reliable estimates of the sensitivity of HIV-1 DNA polymerase chain reaction (PCR) in the neonatal period and to quantify the relative contributions of intra-uterine and intra-partum transmission. METHODS: After reviewing studies on the early diagnosis of HIV-1 infection, investigators were asked to provide published and unpublished PCR test results on prospectively followed, non-breastfed, vertically infected children. Age-specific estimates of the sensitivity of PCR were derived using distribution-free methods for interval-censored data. RESULTS: Data on 271 infected children were combined for analysis. PCR detected HIV-1 DNA in an estimated 38% [90% confidence interval (CI), 29-46] of HIV-infected children tested on the day of, or day after, birth. Sensitivity was observed to rise rapidly in the second week of life, reaching 93% (90% CI, 76-97) by 14 days of age. CONCLUSION: The sensitivity of PCR in the neonatal period is higher than previously reported. This affects the clinical interpretation of an early negative test result and encourages the use of PCR as an endpoint for trials to evaluate interventions to reduce vertical transmission in non-breastfed populations. Approximately one-third of vertically acquired HIV-1 infection could be attributable to intra-uterine transmission
— id: 14558, year: 1995, vol: 9, page: F7, stat: Journal Article,

Production of a human anti-CD4 monoclonal antibody with antiidiotype to anti-HIV type 1 glycoprotein 120
Karpatkin S; Nardi MA; Liu LX; Kouri YH; Borkowsky W
1995 Apr;11(4):509-515, AIDS research & human retroviruses
Human anti-CD4 IgG antibodies from 3 HIV-1-infected patients were affinity purified and shown to inhibit HIV-1 binding and infection of HBP-T cells. Lymphocytes from patient A, whose anti-CD4 inhibited HIV-1 binding by 68% and infection by 72%, were cultured and transformed with EBV. A human monoclonal antiidiotype antibody against anti-HIV-1 gp120 (2B) was produced, which inhibited infection of HBP-T cells by 68% at 1 microgram/ml. Mice were immunized with 2B to determine whether this anti-CD4 could be an internal image antiidiotype against anti-HIV-1 gp 120 (Ab1). Two mice produced antisera reactive with rgp120 on ELISA, whereas immunization with normal IgG produced minimal reactivity compared to unreactive normal mouse sera. However, immunoblot competition studies in which affinity-purified anti-HIV-1 gp120 (Ab1) bound to the gp120 band on nitrocellulose strips in the presence of 2B demonstrated enhancement of signal (i.e., binding of Ab2 to Ab1), rather than inhibition of Ab1 binding. Thus 2B is not an internal image of the paratope of anti-HIV-1 gp120 but yet it is capable of inducing an antibody against rgp120. This indicates that the anti-CD4 (Ab2) does bind to the binding site of Ab1, but not as a complete internal image. These data indicate the production of a human monoclonal antiidiotype antibody that inhibits binding of HIV-1 to CD4 and induces the production of antibody against HIV-1 gp120, without being an internal image antiidiotype (Ab2 beta)
— id: 6656, year: 1995, vol: 11, page: 509, stat: Journal Article,

Comparison of PCR and standard cytological staining for detection of Pneumocystis carinii from respiratory specimens from patients with or at high risk for infection by human immunodeficiency virus [published erratum appears in J Clin Microbiol 1996 Jan;34(1):236]
Leibovitz E; Pollack H; Moore T; Papellas J; Gallo L; Krasinski K; Borkowsky W
1995 Nov;33(11):3004-3007, Journal of clinical microbiology
The detection of Pneumocystis carinii DNA by PCR was compared with routine cytologic staining techniques (CYT). A total of 284 clinical respiratory specimens, including 137 bronchoalveolar lavage (BAL), 63 bronchoalveolar washing, 63 sputum, and 21 induced sputum samples, obtained from patients with or at high risk for human immunodeficiency virus infection were evaluated. Eighty specimens were positive by PCR, and 69 were positive by CYT. PCR was able to detect P. carinii in more bronchoalveolar washing specimens (15 versus 11) and in comparable BAL specimens (53 versus 54) compared with CYT. PCR was particularly more sensitive than CYT in detecting P. carinii in expectorated sputum (12 versus 4 samples). Of the 19 patients whose respiratory specimens were positive for P. carinii by PCR but negative by CYT, 5 had P. carinii pneumonia (PCP) confirmed by subsequent BAL and transbronchial or mediastinal lymph node biopsy and 9 had a clinical course highly suggestive of acute PCP. Eleven (58%) of the 19 patients with discordant PCR and CYT results had received prior anti-PCP prophylaxis. In this clinical setting in particular and in the evaluation of sputum specimens, the ability of PCR to detect a low parasitic load suggests that this technique may become an important additional tool, along with current cytological methods, for the detection of P. carinii
— id: 7195, year: 1995, vol: 33, page: 3004, stat: Journal Article,

Polymerase chain reaction is more sensitive than standard cytologic stains in detecting Pneumocystis carinii in bronchoalveolar lavages from human immunodeficiency virus type 1-infected infants and children with pneumonia
Leibovitz E; Pollack H; Rigaud M; Kaul A; Persaud D; Gallo L; Papellas J; Krasinski K; Borkowsky W
1995 Aug;14(8):714-716, Pediatric infectious disease journal
— id: 7910, year: 1995, vol: 14, page: 714, stat: Journal Article,

Acute renal failure in a human immunodeficiency virus-infected child secondary to bilateral fungus ball formation
Papaevangelou V; Lawrence R; Kaul A; Lefluer R; Ambrosino M; Krasinski K; Borkowsky W
1995 May;14(5):401-403, Pediatric infectious disease journal
— id: 6856, year: 1995, vol: 14, page: 401, stat: Journal Article,

CORRELATION BETWEEN THE MAGNITUDE OF VIRAL LOAD IN EARLY INFANCY AND SURVIVAL AMONG PERINATALLY HIV-INFECTED CHILDREN
POLLACK, H; ARLIEVSKY, N; RIGAUD, M; KAUL, A; KRASINSKI, K; BORKOWSKY, W
1995 APR 2 ;54(3):242-242, Journal of cellular biochemistry
— id: 87326, year: 1995, vol: 54, page: 242, stat: Journal Article,

Major histocompatibility complex class II DR alleles DRB1*1501 and those encoding HLA-DR13 are preferentially associated with a diminution in maternally transmitted human immunodeficiency virus 1 infection in different ethnic groups: determination by an automated sequence-based typing method
Winchester R; Chen Y; Rose S; Selby J; Borkowsky W
1995 Dec 19;92(26):12374-12378, Proceedings of the National Academy of Sciences of the United States of America
Transmission of human immunodeficiency virus 1 (HIV-1) from an infected women to her offspring during gestation and delivery was found to be influenced by the infant's major histocompatibility complex class II DRB1 alleles. Forty-six HIV-infected infants and 63 seroreverting infants, born with passively acquired anti-HIV antibodies but not becoming detectably infected, were typed by an automated nucleotide-sequence-based technique that uses low-resolution PCR to select either the simpler Taq or the more demanding T7 sequencing chemistry. One or more DR13 alleles, including DRB1*1301, 1302, and 1303, were found in 31.7% of seroreverting infants and 15.2% of those becoming HIV-infected [OR (odds ratio) = 2.6 (95% confidence interval 1.0-6.8); P = 0.048]. This association was influenced by ethnicity, being seen more strongly among the 80 Black and Hispanic children [OR = 4.3 (1.2-16.4); P = 0.023], with the most pronounced effect among Black infants where 7 of 24 seroreverters inherited these alleles with none among 12 HIV-infected infants (Haldane OR = 12.3; P = 0.037). The previously recognized association of DR13 alleles with some situations of long-term nonprogression of HIV suggests that similar mechanisms may regulate both the occurrence of infection and disease progression after infection. Upon examining for residual associations, only only the DR2 allele DRB1*1501 was associated with seroreversion in Caucasoid infants (OR = 24; P = 0.004). Among Caucasoids the DRB1*03011 allele was positively associated with the occurrence of HIV infection (P = 0.03)
— id: 14557, year: 1995, vol: 92, page: 12374, stat: Journal Article,

Subacute pneumococcal pericarditis in a patient who did not develop tamponade
Arlievsky N; Rigaud M; Pollack H; Borkowsky W; Krasinski K
1994 Dec;19(6):1163-1163, Clinical infectious diseases
— id: 14559, year: 1994, vol: 19, page: 1163, stat: Journal Article,

Correlation of perinatal transmission of human immunodeficiency virus type 1 with maternal viremia and lymphocyte phenotypes
Borkowsky W; Krasinski K; Cao Y; Ho D; Pollack H; Moore T; Chen SH; Allen M; Tao PT
1994 Sep;125(3):345-351, Journal of pediatrics
OBJECTIVE: To determine whether maternal transmission of human immunodeficiency virus (HIV) is correlated with increased quantities of HIV, decreased frequencies of CD4+ T cells, or increased levels of CD8+ T cells in the transmitting mother. METHODS: Peripheral blood obtained from HIV-infected women at different times during pregnancy was used to measure quantitative cell-associated HIV-1 and CD3+CD4+ and CD3+CD8+ proportions; the plasma was used to perform measurements of quantitative viremia by culture and subsequently to measure quantitative HIV-1 ribonucleic acid levels. These measurements were analyzed with respect to their association with HIV transmission to the baby, which occurred in one fourth of the cases. The children were also studied to determine whether HIV-1 was detected near birth or not until 1 to 8 weeks of life. RESULTS: Increased clonal frequencies of HIV-1-infected peripheral blood mononuclear cells were found in mothers of infected children; fivefold fewer cells were required for a positive culture result (median cell numbers of 10(4.5) vs 10(5.2); p = 0.008). Higher frequencies of infected cells were seen in mothers of babies with evidence of infection at birth than in mothers of infected babies without evidence of infection at birth (p < 0.05). Plasma viremia was measured in 10% of cultures without regard to whether the mothers transmitted virus to their babies. Increased levels of ribonucleic acid as detected by the branched-chain DNA method were measurable more often (45% vs 17%) in the mothers of infected children than in mothers of uninfected children. Proportions of CD4+ and CD8+ T cells were indistinguishable in these two groups of women. CONCLUSIONS: Increased viremia was present in mothers who transmitted HIV to their offspring. This variable could be used to select women at highest risk of transmitting HIV to their offspring for treatment to decrease the HIV burden five-fold
— id: 8459, year: 1994, vol: 125, page: 345, stat: Journal Article,

Anti-HIV effect of gramicidin in vitro: potential for spermicide use
Bourinbaiar AS; Krasinski K; Borkowsky W
1994 ;54(1):PL5-PL9, Life sciences
Gramicidin, cation channel forming ionophore with antibacterial properties, was studied in vitro for inhibition of human immunodeficiency virus (HIV) infection of MT-4 lymphocytes. Effective antiviral concentrations required for complete HIV inactivation were three orders of magnitude lower than 10 micrograms/ml cytotoxic dose. Gramicidin, routinely used as a contraceptive agent, should be considered for clinical application as a spermicide with antiviral activity
— id: 7876, year: 1994, vol: 54, page: PL5, stat: Journal Article,

Anti-HIV effect of immunomodulating agent, levamisole, in vitro
Bourinbaiar AS; Lee-Huang S; Krasinski K; Borkowsky W
1994 ;48(7):327-330, Biomedicine & pharmacotherapy
An anthelminthic agent, levamisole, also known as a potent immunomodulator, has been successfully used for adjuvant therapy of malignancies and chronic infections underlined by immunodeficiency. We have tested the effect of this drug on de novo viral infection by exposing MT-4 T lymphocytes to HIV in the presence of serial ten-fold dilutions of levamisole (range 10(-3)-10(-9) M). The results indicate that 50% reduction in viral infectivity (IC50) of levamisole starts from as low as 10(-7) M, whereas even the highest millimolar dose of the drug has not shown any appreciable cytotoxicity. Although the mechanism of levamisole action remains unknown, our observation in vitro suggests that levamisole, a clinically established immunomodulator, can be potentially effective for treatment of HIV infection
— id: 6585, year: 1994, vol: 48, page: 327, stat: Journal Article,

Inhibitory effect of the oral immune response modifier, bestatin, on cell-mediated and cell-free HIV infection in vitro
Bourinbaiar AS; Lee-Huang S; Krasinski K; Borkowsky W
1994 ;48(2):55-61, Biomedicine & pharmacotherapy
The antiviral effect of the immunomodulating anti-cancer agent, bestatin, was examined in vitro by exposing MT-4 lymphocytes to HIV in the presence of 10-fold dilutions of drug (range 100 micrograms-100 pg/ml). The reduction in infectivity was measured by p24 ELISA and compared to the effect of established anti-HIV drugs-azidothymidine (AZT) and dextran sulfate. The results indicate that low doses of bestatin (1 microgram/ml) can completely inhibit viral infection resulting either from inoculation with free virus or coculture with infected lymphocytes. Unlike AZT or dextran sulfate, bestatin prevents HIV infection without interfering with the rate of cell growth. No appreciable decrease in HIV production was observed when chronically infected virus-producing T cell lines ie, H9, MOLT-4, HPB-ALL, 8E5 and MT-2 were treated with bestatin. Bestatin appears to act in the early stages of viral penetration, possibly through inhibition of lymphocyte-associated aminopeptidases
— id: 6586, year: 1994, vol: 48, page: 55, stat: Journal Article,

Streptococcus pneumoniae in human immunodeficiency virus type 1-infected children
Gesner M; Desiderio D; Kim M; Kaul A; Lawrence R; Chandwani S; Pollack H; Rigaud M; Krasinski K; Borkowsky W
1994 Aug;13(8):697-703, Pediatric infectious disease journal
The purpose of this study was to characterize systemic Streptococcus pneumoniae disease in human immunodeficiency virus type 1 (HIV-1)-infected children. All cases of bacteremia and meningitis caused by S. pneumoniae among children less than 18 years old were collected by review of the Microbiology Laboratory records at the Bellevue Hospital Center during the period August 1, 1978, through July 31, 1993. There were 31 bouts of systemic S. pneumoniae disease in 19 of 235 HIV-1-infected children cared for by the Pediatric Infectious Disease staff and 116 bouts in 113 children not known to be HIV-1-infected. Four of the 19 HIV-1-infected children had multiple episodes of S. pneumoniae bacteremia as compared with 3 of 113 in the general population (P = 0.008). The frequency of serotypes and distribution of infections by season of the year did not differ between the 2 groups. The median ages at the time of the S. pneumoniae infection were 1.8 and 1.1 years for the HIV-1-infected children and the general population of children, respectively, when those children with multiple episodes were included for their initial episode only (P = 0.06). In the HIV-1-infected patients, 10 episodes were associated with pneumonia, 5 with pneumonia and otitis media, 5 with otitis media only, 1 with pneumonia and meningitis, 1 with meningitis only and 1 with periorbital cellulitis; 5 had no apparent focus of infection. One episode of pneumonia was complicated by lung abscess and there were 2 deaths. Most HIV-1-infected patients recovered without significant sequelae, and the clinical course of their systemic infections did not appear to be markedly different than that of healthy children
— id: 12935, year: 1994, vol: 13, page: 697, stat: Journal Article,

Increased soluble CD8 (sCD8) in human immunodeficiency virus 1-infected children in the first month and year of life
Gesner M; Di John D; Krasinski K; Borkowsky W
1994 Oct;13(10):896-898, Pediatric infectious disease journal
The purpose of this study was to determine whether soluble CD8 (sCD8) in serum of perinatally human immunodeficiency virus 1 (HIV-1)-infected children during the first year of life differs from that of HIV-1-uninfected control children. Soluble CD8 concentrations in stored plasma and serum samples of children of HIV-1-infected and uninfected mothers were determined using a sandwich immune assay. In the first month of life significantly greater concentrations of sCD8 occurred in 12 HIV-1-infected infants than in 9 uninfected infants born to infected mothers (mean = 1054, SD 540 vs. 589, SD 370 units/ml, P < 0.05), although the CD8+ T cell proportions were not different (21.7 vs. 21.1, P > 0.5). The difference in sCD8 concentrations was most pronounced in 8 infants who were HIV-1 culture positive on initial testing in the first week of life compared with the remaining 4 patients when virus was first detected on subsequent analysis (mean = 1315, SD 446 vs. 529, SD 231 units/ml, P < 0.01). The concentration of sCD8 was also greater in 26 HIV-1-infected children than in either 26 uninfected children born to infected mothers or 25 seronegative children during the first year of life (mean = 1268, SD 529 vs. 630, SD 290 vs. 553, SD 315 units/ml, P < 0.05). Early and persistent elevation in sCD8 probably reflects immune activation resulting from HIV-1 infection. The occurrence of this increase in the neonatal period may reflect prenatal viral transmission, a higher viral inoculum or coinfection with other agents stimulating immune activation
— id: 6626, year: 1994, vol: 13, page: 896, stat: Journal Article,

Alteration in the proportion of CD4 T lymphocytes in a subgroup of human immunodeficiency virus-exposed-uninfected children
Gesner M; Papaevangelou V; Kim M; Chen SH; Moore T; Krasinski K; Borkowsky W
1994 Apr;93(4):624-630, Pediatrics
OBJECTIVE. The age-related changes in the proportion of CD4 and CD8 lymphocytes in human immunodeficiency virus (HIV)-seronegative children born to HIV-infected mothers (seroreverters) were compared with the changes in these lymphocyte subsets in children born to seronegative women to assess a possible effect of exposure to HIV without infection. DESIGN. There were 146 seroreverter and 72 seronegative children. The median CD4 and CD8 percentages for each of these two groups of children were compared retrospectively at 3-month intervals from birth through 27 months and at a tenth interval for the time beyond 27 months. The weighted average of the within-subject rate of change of CD4 and CD8 percentages were also compared between the two groups. Finally, for each subject, the proportion of the subject's CD4 percentage assays which were <10th percentile of the entire study population (30%) was calculated, and the distributions of the subject-specific proportions were then compared between the seronegative and seroreverter groups using the Wilcoxon rank sum test. The proportion of CD8 assays <10th percentile (12%) or > 90th percentile (26%) were also computed for each subject, and the distributions of the proportions were compared similarly. . RESULTS. The median CD4 percentage of seroreverter children was lower than that for the seronegative children at every interval from birth through 27 months and for the last interval for values obtained at greater than 27 months, although the comparison was statistically significant only at the 4- to 6-month period. The weighted average of the within-subject rate of change of CD4 percentage was -0.09 and -3.0 per year (P = .04), and of CD8 percentage was 1.3 and 1.0 (P = .67), for the seroreverter and seronegative children, respectively. There were significantly more children in the seroreverter group than in the seronegative group who had repeated assays in which the CD4 percentage was < 10th percentile for age (P < .00005). In addition, there was a subset of 10 seroreverter children (6.8%) who had CD4 percentages < 30% on > 50% of their assays, as compared with only one (1.4%) seronegative child. The proportion of CD8 assays < 10th percentile or > 90th percentile were not significantly different between the two groups of children. CONCLUSIONS. The CD4 proportions were persistently lower in the seroreverter than in the seronegative population, although only reaching statistical significance in 1 of 10 3-month intervals. This finding may be due to a subgroup of seroreverter children who have persistently low CD4 lymphocyte percentages
— id: 6383, year: 1994, vol: 93, page: 624, stat: Journal Article,

Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome
Koup RA; Safrit JT; Cao Y; Andrews CA; McLeod G; Borkowsky W; Farthing C; Ho DD
1994 Jul;68(7):4650-4655, Journal of virology
Virologic and immunologic studies were performed on five patients presenting with primary human immunodeficiency virus type 1 (HIV-1) infection. CD8+ cytotoxic T lymphocyte (CTL) precursors specific for cells expressing antigens of HIV-1 Gag, Pol, and Env were detected at or within 3 weeks of presentation in four of the five patients and were detected in all five patients by 3 to 6 months after presentation. The one patient with an absent initial CTL response had prolonged symptoms, persistent viremia, and low CD4+ T-cell count. Neutralizing antibody activity was absent at the time of presentation in all five patients. These findings suggest that cellular immunity is involved in the initial control of virus replication in primary HIV-1 infection and indicate a role for CTL in protective immunity to HIV-1 in vivo
— id: 6425, year: 1994, vol: 68, page: 4650, stat: Journal Article,

HIV-1 infected children with severe immunodeficiency: survival and prognostic factors
Papaevangelou V; Pollack H; Kaul A; Lawrence R; Krasinski K; Borkowsky W
1994 Oct 4-7;:35-35, Program & abstracts (Interscience Conference on Antimicrobial Agents & Chemotherapy)
Objective: To study the survival and identify prognostic laboratory indicators for HIV-1 infected children with severe immunodeficiency (CD4 less than 15%). Methods: Kaplan-Meier product-limit analysis, from the time of severe immunodeficiency (i.e. presentation with CD4 less than 15% or persistent levels of CD4 less than 15%), was performed on HIV-1 infected children. Plasma p24 antigen and serial hemoglobin concentrations were reviewed as possible prognostic indicators of survival. Results: (Table: see text.) The presence of plasma p24 antigen at presentation did not appear to affect survival in children with CD4 between 10-15%, however the absence of detectable plasma p24 antigen was associated with increased survival in those with CD4 of less than 10% at presentation (50% survival 4.5y and 3.4y for children with CD4 5-9% and 0-4% respectively). A 15% reduction in serum hemoglobin concentration, was associated with decreased 50% survival only in children with CD4 less than 10% (6.2y vs 2.3y). Conclusions: Children with 9 greater than CD4% less than 15% are considered to be severely immunodeficient by the CDC, yet their 50% survival is significantly better than children who present with CD4 less than 10%. The absence of detectable p24 antigenemia at presentation appeared to be associated with improved survival only in children with CD4 T cells less than 10%, whereas a 15% decrease in serum hemoglobin concentration was associated with lower survival only in those with greater than 10% CD4 T cells
— id: 5994, year: 1994, vol: , page: 35, stat: Journal Article,

Effects of antiviral therapy on the production of anti-human immunodeficiency virus-specific immunoglobulin in infants and children
Pollack H; Zhan MX; Moore T; Tao PZ; Krasinski K; Borkowsky W
1994 Oct;170(4):1003-1006, Journal of infectious diseases
The effect of zidovudine therapy on human immunodeficiency virus (HIV)-specific antibody production was studied in 64 HIV-1-infected infants and children > 6 months old. HIV-specific in vitro antibody production (IVAP) was measured in cultures of peripheral blood mononuclear cells (PBMC). IVAP decreased in 85% of children after zidovudine was initiated (mean decline, 1 log within 2 months). Effects were seen as early as 1 week after starting zidovudine. No change in IVAP was seen in children not treated. In comparison, plasma core (p24) antigen levels declined and CD4+ lymphocytes increased in only 42% and 52%, respectively, of treated subjects. Thus, the production of antibody to HIV-1 decreases rapidly after the initiation of antiretroviral therapy. This response to therapy may provide a simple and sensitive method of monitoring antiretroviral therapy
— id: 6716, year: 1994, vol: 170, page: 1003, stat: Journal Article,

Efficacy of primary chemoprophylaxis against Pneumocystis carinii pneumonia during the first year of life in infants infected with human immunodeficiency virus type 1
Rigaud M; Pollack H; Leibovitz E; Kim M; Persaud D; Kaul A; Lawrence R; John DD; Borkowsky W; Krasinski K
1994 Sep;125(3):476-480, Journal of pediatrics
To evaluate the efficacy of primary chemoprophylaxis in preventing Pneumocystis carinii pneumonia (PCP) in infants with perinatal human immunodeficiency virus-1 infection during the first year of life, we conducted a retrospective chart review of infants with human immunodeficiency virus-1 infection born at New York University Medical Center-Bellevue Hospital Center, in New York. Between March 1989 and March 1993, 24 infants received primary chemoprophylaxis with trimethoprim-sulfamethoxazole in the first year of life and 24 infants did not receive primary prophylaxis. The CD4+ T-lymphocyte counts in the two groups did not differ during the first year of life. The median age at the time of initiation of prophylaxis was 3 months, and the average duration of prophylaxis was 5.5 months. Among the infants who had not received prophylaxis, five cases of PCP were diagnosed at a median age of 5 months; in contrast, no cases of PCP were observed in the infants receiving prophylaxis (log-rank test, p = 0.017). The probability of surviving after 1 year of age was 92% for the children who received prophylaxis and 74% for those who did not (log-rank test, p = 0.035). These data indicate that chemoprophylaxis is highly effective in preventing primary PCP and improving survival time in infants with human immunodeficiency virus-1 infection
— id: 12908, year: 1994, vol: 125, page: 476, stat: Journal Article,

HIV-1 viremia in the first week of life in perinatal infection: effect on CD4% and survival
Zarudsky N; Rigaud M; Pollack H; Kaul A; Kim M; Krasinski K; Borkowsky W
1994 Oct 4-7;:33-33, Program & abstracts (Interscience Conference on Antimicrobial Agents & Chemotherapy)
Objective: To compare survival and CD4+ T cell % (CD4%) in infants with early versus late HIV viremia. Methods: HIV viremia was measured by HIV culture. PCR or P24 ag assay of peripheral blood. Three groups were identified: infants testing positive within the first week of life (X), infants testing negative in the first week and positive within two months (Y), infants tested after the first week but positive within two months (Z). Initial CD4% for all infants in the three groups were compared using the t test. CD4% attrition in the three groups was compared using linear regressions of the last CD4% measured in each infant. Survival times were evaluated by Kaplan-Meier product-limit analyses and compared by log-rank tests. Results: There were nine infants in group X, 12 in group Y, and 20 in group Z. There were no differences in CD4% at birth among these groups. Decline of CD4% in groups X, Y and Z was -0.30, -0.18 and -3.0% per month respectively. These were not significantly different. Survival in the three groups (X vs Y, log-rank p=0.24; Y vs Z, log-rank p=0.42; X vs Z, log-rank p=0.65) was not significantly different. Conclusions: The data suggest that early HIV-1 viremia in perinatal infection is not associated with more rapid decline of CD4% and decreased survival in this small sample. Further studies must be done to determine whether early HIV viremia in perinatal HIV-1 infection can serve as a prognostic indicator
— id: 5997, year: 1994, vol: , page: 33, stat: Journal Article,

Early diagnosis of human immunodeficiency virus type 1-infected infants by plasma p24 antigen assay after immune complex dissociation
Chandwani S; Moore T; Kaul A; Krasinski K; Borkowsky W
1993 Jan;12(1):96-97, Pediatric infectious disease journal
— id: 13308, year: 1993, vol: 12, page: 96, stat: Journal Article,

Human megakaryocytes have a CD4 molecule capable of binding human immunodeficiency virus-1
Kouri YH; Borkowsky W; Nardi M; Karpatkin S; Basch RS
1993 May 15;81(10):2664-2670, Blood
Most human megakaryocytes (MGKs) express the CD4 antigen on their surface. Approximately 25% have a CD4 receptor density comparable to that of CD4+ T cells (Basch et al, Proc Natl Acad Sci USA 87:8085, 1990). In these studies, we show: (1) the presence of mRNA for CD4 in human MGKs; (2) the binding of human immunodeficiency virus-1 (HIV-1) to human MGKs; (3) the inhibition of binding by anti-CD4 (Leu3a) antibody or rCD4; (4) the infection of a human MGK line, CHRF-288 with HIV-1; and (5) inhibition of infection with anti-CD4. Human MGKs have mRNA for CD4 as shown by in situ hybridization with an RNA probe synthesized from a 3-kb cDNA sequence of plasmid pSP65.T4.8 containing the full-length CD4 sequence. MGKs (23% +/- 17%) bound HIV-1, as determined by anti-gp120 and anti-CD41 staining. Binding to human MGKs could be inhibited 55% to 75% with anti-CD4 or rCD4, respectively. Infection of a CD4+ MGK line (CHRF-288) could be accomplished with HIV-1, as determined by proviral DNA polymerase chain reaction and p24 production. Preincubation with anti-CD4 inhibited apparent proviral DNA infection by 100% and p24 production by 65% to 70%. Thus, human MGKs have a CD4 receptor capable of binding HIV-1. Using this receptor, HIV-1 can infect cells representative of the MGK lineage
— id: 13159, year: 1993, vol: 81, page: 2664, stat: Journal Article,

Cholestatic hepatitis in children infected with the human immunodeficiency virus
Persaud D; Bangaru B; Greco MA; Nachman S; Mittal K; Chandwani S; Krasinski K; Borkowsky W; Kaul A
1993 Jun;12(6):492-498, Pediatric infectious disease journal
A distinct clinical syndrome of cholestasis and hepatitis occurred during early infancy in seven infants with perinatally acquired human immunodeficiency virus 1 infection. In five infants hepatitis was the first manifestation of human immunodeficiency virus 1 infection. The median age of onset of hepatitis was 7 months (range, 5 to 10 months). The mean total bilirubin concentration at presentation was 7.4 mg/dl (range, 3.9 to 11 mg/dl), the mean aspartate aminotransferase was 1512 IU/liter (range, 782 to 2960 IU/liter) and the mean alanine amino-transferase 512 IU/liter (range, 92 to 1247 IU/liter). The absolute CD4 count at the time of onset of hepatitis ranged from 191 to 2298 cells/mm3 (mean, 766 cells/mm3). Six of the seven children died within 12 weeks of onset of hepatitis, three as a result of complications of Pneumocystis carinii pneumonia, and two died of complications secondary to cytomegalovirus. In only one infant was the cause of death the direct consequence of liver failure. The seventh infant died 17 months after the onset of hepatitis of dilated cardiomyopathy. No specific etiologic agent has been identified as the cause of cholestatic hepatitis in these infants. In situ hybridization studies to detect human immunodeficiency virus 1 messenger RNA was negative in the liver tissue obtained at biopsy and autopsy in five of the samples tested
— id: 6483, year: 1993, vol: 12, page: 492, stat: Journal Article,

Ontogeny of anti-human immunodeficiency virus (HIV) antibody production in HIV-1-infected infants
Pollack H; Zhan MX; Ilmet-Moore T; Ajuang-Simbiri K; Krasinski K; Borkowsky W
1993 Mar 15;90(6):2340-2344, Proceedings of the National Academy of Sciences of the United States of America
The early serologic response of infants to infection with human immunodeficiency virus type 1 (HIV-1) is normally obscured by the presence of transplacentally acquired maternal HIV antibody. By measuring HIV antibody produced in vitro by lymphocytes isolated from peripheral blood of infants and children of HIV-1-infected mothers, we have been able to study the natural acquisition of humoral immunity to perinatal HIV-1 infection. One hundred ninety-seven infants of HIV-1-infected women were studied prospectively and longitudinally from birth. In the neonatal period, infected infants produced only small amounts of HIV-specific IgG antibodies to a restricted number of antigens. The amount of immunoglobulin to HIV-1 and the number of HIV-1 antigens recognized increased with age. After 6 months of life 85% of infected infants made detectable antibody to two or more viral proteins. Antibody to gp160 appeared first and was the most frequently found at all ages, followed by antibody to the envelope proteins gp120 and gp41. The amount of HIV antibody produced correlated positively with the percentage of CD4+ T lymphocytes in peripheral blood. This assay provides a method of studying the immunogenicity of vaccines against HIV-1 in HIV-1-infected infants and of assessing the effect of early therapeutic interventions on the humoral response to HIV-1
— id: 13214, year: 1993, vol: 90, page: 2340, stat: Journal Article,

A novel detection assay for the early diagnosis of HIV-1 infected infants
Pollack H; Zhan MX; Ilmet-Moore T; Tao P; Krasinski K; Borkowsky W
1993 Jun;6(6):582-586, Journal of acquired immune deficiency syndrome
This investigation compares the results of a new method of diagnosing HIV-1 infection in infants < 6 months of age with currently employed techniques including cocultivation, the polymerase chain reaction (PCR), serum p24 antigen, and in vitro antibody production (IVAP) measurements. The new method, called in vitro antigen (IVAG), measures p24 antigen released into culture supernatants of peripheral blood mononuclear cells that are incubated with Epstein-Barr virus (EBV). No activated donor lymphocytes or interleukin 2 (IL-2) are added to the culture. Using this technique, HIV-1 infection was detected in 15 of 17 HIV-1-infected infants < 2 months of age, including 3 of 7 infants tested at birth, and 15 of 15 HIV-1-infected infants between 2 and 6 months of age. None of 83 determinations of 15 uninfected infants were positive. These results were found to be comparable to results obtained by the traditional cocultivation technique and the polymerase chain reaction. Because of its simplicity and reduced cost, this sensitive and specific assay could be a valuable addition to the current methods of diagnosis of HIV-1 infection in young infants
— id: 13146, year: 1993, vol: 6, page: 582, stat: Journal Article,

Opportunistic infections and tumors in immunocompromised children
Ambrosino MM; Genieser NB; Krasinski K; Greco MA; Borkowsky W
1992 May;30(3):639-658, Radiologic clinics of North America
HIV infection is responsible for a major proportion of the immunodeficiency disease seen in the pediatric population. The radiologic findings are varied and generally non-specific. The development of secondary neoplasms may present new diagnostic and therapeutic challenges as therapy for superimposed infections becomes more successful
— id: 13615, year: 1992, vol: 30, page: 639, stat: Journal Article,

Varicella does not appear to be a cofactor for human immunodeficiency virus infection in children
Aronson JE; McSherry G; Hoyt L; Boland M; Oleske J; Connor E; Persaud D; Borkowsky W; Krasinski K; Bakshi S; et al
1992 Dec;11(12):1004-1008, Pediatric infectious disease journal
We performed a retrospective analysis of longitudinal clinical and immunologic data obtained from 22 children in the early stages of infection with human immunodeficiency virus (HIV) when they developed varicella. We studied the course of HIV infection to determine whether clinical deterioration occurred after chickenpox. We examined the following indices: growth and development; neurologic status; helper T lymphocyte counts; blood values of core (p24) antigen of HIV; changes in the stage of HIV infection; and need for administration of zidovudine. We studied children for a mean of 2.8 years and for as long as 9.8 years after onset of varicella. There was little evidence that chickenpox affected HIV infection. Three (14%) children developed clinical zoster, 2 of whom (9%) had evidence of chronic infection with varicella-zoster virus. One additional child (5%) had 2 episodes of chickenpox. These observations suggest that children with early HIV infection could be considered for immunization with live attenuated varicella vaccine, which would be predicted to decrease their morbidity from varicella-zoster virus
— id: 14560, year: 1992, vol: 11, page: 1004, stat: Journal Article,

Perinatal human immunodeficiency virus infection: ruminations on mechanisms of transmission and methods of intervention
Borkowsky W; Krasinski K
1992 Jul;90(1 Pt 2):133-136, Pediatrics
Perinatal human immunodeficiency virus (HIV) infection is undoubtedly a multifactorial process. Neither the quantity of viremia nor the level of neutralizing antibody in the infected mother is alone predictive of HIV transmission to her offspring. Additional cofactors may include the ability of maternal immunity to control the host cell range and rate of viral replication. The placenta probably constitutes an effective barrier to viral transmission unless disrupted by processes such as syphilis. Prevention of such breaks in the trophoblast barrier and efforts to stimulate maternal and newborn HIV-specific immunity may further decrease the perinatal transmission rate
— id: 8458, year: 1992, vol: 90, page: 133, stat: Journal Article,

Early diagnosis of human immunodeficiency virus infection in children less than 6 months of age: comparison of polymerase chain reaction, culture, and plasma antigen capture techniques
Borkowsky W; Krasinski K; Pollack H; Hoover W; Kaul A; Ilmet-Moore T
1992 Sep;166(3):616-619, Journal of infectious diseases
Three techniques were evaluated for their ability to detect human immunodeficiency virus (HIV) in infants from birth to 6 months of age. Polymerase chain reaction (PCR) and HIV cocultivation were of comparable sensitivity, detecting 90% of all positive specimens. Both techniques found positive results in approximately 5% of samples from seroreverting children. Both assays detected HIV in only half of infected newborns, suggesting that this fraction of children was infected during gestation. Plasma p24 antigen was detected in three-fourths of all samples tested but in only half of infected children during the first 2 months of life and 88% of samples from children during the next 4 months. The specificity of p24 antigen detection was 100%
— id: 13452, year: 1992, vol: 166, page: 616, stat: Journal Article,

Evolution of phenotypic memory T cells in HIV-1 infected infants and children
Borkowsky W; Moore T; Krasinski K; Ajuang-Simbiri KO; Holzman R
1992 Jun;63(3):280-284, Clinical immunology & immunopathology
Infants are reported to be devoid of memory T cells at birth but acquired them with time. A cross-sectional study of peripheral blood mononuclear cells from HIV-infected and uninfected infants and children that bear the CD4R0 antigen was undertaken to describe the development of memory T cells. Linear regression lines derived from the data revealed increasing percentages of memory CD4 and CD8 cells in the uninfected children. Memory CD4 cells in the infected children were detected at a frequency equal to or greater than that seen in uninfected children until 6 months of age but subsequently declined with age. In contrast, memory CD8 cells were found to be significantly increased in HIV-infected children early in life with a rate of increase similar to that seen in the uninfected population. This increase in memory CD8 cells may facilitate the early diagnosis of HIV infection
— id: 13589, year: 1992, vol: 63, page: 280, stat: Journal Article,

Cell-mediated and humoral immune responses in children infected with human immunodeficiency virus during the first four years of life
Borkowsky W; Rigaud M; Krasinski K; Moore T; Lawrence R; Pollack H
1992 Mar;120(3):371-375, Journal of pediatrics
OBJECTIVES: To determine whether cell-mediated and humoral immune responses to recall antigens develop in children infected with the human immunodeficiency virus (HIV) and, if so, whether these responses are retained. METHODS: Children infected with HIV and uninfected children born to mothers infected with HIV were compared with respect to lymphoproliferative responses to recall antigens and protective levels of antibody to bacterial toxoids during the first 4 years of life. RESULTS: Children infected with HIV who were enrolled in a prospective study of the natural history of the infection were relatively normal (1) in their lymphoproliferative responses to diphtheria toxoid, tetanus toxoid, and Candida, and (2) in their ability to make protective diphtheria and tetanus antitoxins during the first 2 years of life. During the next 2 years, attrition was noted in both lymphoproliferative and humoral responses. Attrition in response was not necessarily correlated with declining numbers of helper T cells. CONCLUSIONS: These results suggest that both cellular and humoral immune responses develop early in life in most children infected with HIV, while they remain relatively well both clinically and immunologically. Previously reported severe immune deficits in these children were probably attributable to advanced clinical disease when they were first studied
— id: 13680, year: 1992, vol: 120, page: 371, stat: Journal Article,

Pathology of the placenta in HIV-1 infection
Chandwani S; Greco MA; Krasinski K; Borkowsky W
1992 ;3(1):65-81, Progress in AIDS pathology
— id: 13742, year: 1992, vol: 3, page: 65, stat: Journal Article,

Novel deletion and a new missense mutation (Glu 217 Lys) at the catalytic site in two adenosine deaminase alleles of a patient with neonatal onset adenosine deaminase- severe combined immunodeficiency
Hirschhorn R; Nicknam MN; Eng F; Yang DR; Borkowsky W
1992 Nov 1;149(9):3107-3112, Journal of immunology
Mutations at the adenosine deaminase (ADA) locus result in a spectrum of disorders, encompassing a fulminant neonatal onset severe combined immunodeficiency (SCID) and childhood onset immunodeficiency, as well as apparently normal immune function. The extent of accumulation of the toxic metabolite, deoxyATP, correlates directly with severity of disease. We have now determined the mutations on both alleles of a child with fulminant, neonatal onset ADA- SCID and accumulation of extremely high concentrations of deoxyATP. The genotype was consistent with the severely affected phenotype. One allele carried a large deletion that arose by non-homologous recombination and included the first five exons and promoter region. The second allele carried a missense mutation (G649A) resulting in replacement of Glu217, an amino acid involved in the catalytic site, by Lys and predicting a major alteration in charge. Expression of the mutant cDNA in Cos cells confirmed that the mutation abolished enzyme activity. We have previously reported that a missense mutation at the preceding codon is similarly associated with neonatal onset ADA- SCID and accumulation of extremely high deoxyATP. These findings suggest that genotype-phenotype correlations may be apparent for ADA- SCID, despite the role that random variation in exposure to environmental pathogens may play in the initial phenotype. Such genotype-phenotype correlations may be important to consider in evaluating results of ongoing trials of 'gene' and enzyme replacement therapy
— id: 13383, year: 1992, vol: 149, page: 3107, stat: Journal Article,

Chronic varicella zoster in a child infected with human immunodeficiency virus: case report and review of the literature
Leibovitz E; Kaul A; Rigaud M; Bebenroth D; Krasinski K; Borkowsky W
1992 Jan;49(1):27-31, Cutis
Chronic zoster represents an infrequent presentation of varicella zoster virus infection. It is observed with increased frequency in patients infected with human immunodeficiency virus, especially when their lymphocyte counts are depressed. We report a child infected with human immunodeficiency virus who showed a long-standing cutaneous zoster lesion and was treated for a prolonged period of time with acyclovir. The occurrence of resistance to acyclovir by varicella zoster virus was suspected based on the clinical picture. The clinical and laboratory features of this case and a review of the literature are presented
— id: 13718, year: 1992, vol: 49, page: 27, stat: Journal Article,

Lack of predictive value of maternal human immunodeficiency virus p24 antigen for transmission of infection to their children
Papaevangelou V; Moore T; Nagaraj V; Krasinski K; Borkowsky W
1992 Oct;11(10):851-855, Pediatric infectious disease journal
The association of maternal-to-infant transmission of human immunodeficiency virus type 1 (HIV-1) with maternal p24 antigenemia was assessed in 86 HIV-1-infected mothers. We retrospectively examined serum or plasma samples collected in the peripartum period (delivery +/- 11 days; sd 16.89 days; range, delivery +/- 2 months). Immune complexes of p24 antigen and anti-p24 antibody were dissociated using acid hydrolysis (Method A, glycine-HCl buffer; Method B, HCl) in an attempt to increase the sensitivity of the test. The detection of HIV-1 p24 antigenemia in serum was increased from 23 of 86 (26.7%) to 37 of 82 (45.1%) following acid hydrolysis with Method A (chi square = 5.4, P = 0.02) and to 36 of 78 (46.1%) with Method B (chi square = 5.874, P = 0.015). Mothers of HIV-1-infected children were no more likely to have p24 antigenemia than mothers of seroreverted infants when untreated samples were assayed (7 of 23 vs. 10 of 48; chi square = 0.348, P = 0.55). Although acid hydrolysis increased the ability to detect p24 antigen, it did not enhance any association between p24 antigenemia and maternal-to-infant transmission of HIV infection: Method A, 9 of 23 in mothers of infected children vs. 21 of 45 in mothers of seroreverted children (chi square = 0.112, P = 0.738); and Method B, 9 of 22 in mothers of infected children vs. 18 of 42 in mothers of seroreverted children (chi square = 0.014; P = 0.907), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 13417, year: 1992, vol: 11, page: 851, stat: Journal Article,

Delayed recognition of human immunodeficiency virus infection in preadolescent children
Persaud D; Chandwani S; Rigaud M; Leibovitz E; Kaul A; Lawrence R; Pollack H; DiJohn D; Krasinski K; Borkowsky W
1992 Nov;90(5):688-691, Pediatrics
Thirty-two (18%) of 181 children cared for at our institution who were infected with the human immunodeficiency virus type 1 (HIV-1) were first seen, and HIV was diagnosed, when they were 4 years of age and older. Initial complaints or diagnoses for these children included the following: hematologic disorders (5) (3 idiopathic thrombocytopenic purpura, 1 neutropenia, 1 anemia); recurrent bacterial infections (10); Pneumocystis carinii pneumonia (3); developmental delay (1); skin disorders (2) (1 genital wart, 1 chronic zoster); weight loss (3); malignancy (1); and nephropathy (1). Eight children were referred for evaluation because of maternal HIV-1 infection. The risk factors for HIV-1 infection included maternal/perinatal exposure (22), perinatal blood transfusion (6), blood transfusion during infancy (2), and sexual abuse (2). Ten (31%) of the 32 children have subsequently died. The longest survival from perinatal infection was 12 years. HIV-1 infection in children can result in a prolonged clinical latency and can masquerade as other pathologic conditions. The absence of clinical symptoms in older children at risk for HIV-1 infection should not deter HIV testing
— id: 13381, year: 1992, vol: 90, page: 688, stat: Journal Article,

Fatal disseminated infection with human herpesvirus-6
Prezioso PJ; Cangiarella J; Lee M; Nuovo GJ; Borkowsky W; Orlow SJ; Greco MA
1992 Jun;120(6):921-923, Journal of pediatrics
A 13-month-old immunocompetent girl had fever, rash, and multisystem disease, and she eventually died of cardiac failure. Autopsy revealed intracellular viral inclusions of the herpesvirus group, with results of in situ hybridization positive for human herpesvirus-6. This is apparently the first case of fatal disseminated herpesvirus-6 infection
— id: 13591, year: 1992, vol: 120, page: 921, stat: Journal Article,

Pathology and human immunodeficiency virus expression in placentas of seropositive women
Chandwani S; Greco MA; Mittal K; Antoine C; Krasinski K; Borkowsky W
1991 May;163(5):1134-1138, Journal of infectious diseases
The pathology of term placentas from seropositive human immunodeficiency virus (HIV)-infected and seronegative women was investigated by routine histologic, immunocytochemical, and in situ hybridization techniques. Placentas were evaluated for evidence of villitis, chorioamnionitis, and funisitis. Membranes, trophoblast, and decidua were also examined by immunohistochemistry using monoclonal HIV p24 antibody. Twenty placentas were evaluated by combined immunochemical and in situ hybridization techniques, using a 35S-labeled RNA probe complementary to the 3' long terminal repeat and envelope region of HIV-1. HIV-seropositive placentas did not show significant villitis; however, the incidence of chorioamnionitis increased (P less than .01). HIV antigens and nucleic acids were identified in the trophoblast of 10% of the placentas that also showed chorionitis. Term HIV-positive placentas may show histologic changes that may or may not be directly related to the virus. Analysis of tissues from earlier gestational placentas may prove more informative in clarifying the mechanism of maternal-fetal HIV transmission
— id: 14042, year: 1991, vol: 163, page: 1134, stat: Journal Article,

Laboratory diagnosis of HIV infection
Krasinski K; Borkowsky W
1991 Feb;38(1):17-35, Pediatric clinics of North America
Laboratory diagnosis of human immunodeficiency virus (HIV) infection is complicated by absence of data on sensitivity, specificity and predictive value of the various tests as they apply to children. The presence of maternal anti-HIV passively transmitted across the placenta also confounds diagnosis. The authors review currently available data on the detection of HIV, HIV genome, and HIV gene products, as well as the diagnostic value of detecting serologic and cellular responses to HIV in infants and children
— id: 14145, year: 1991, vol: 38, page: 17, stat: Journal Article,

A multicenter trial of oral zidovudine in children with advanced human immunodeficiency virus disease. The Protocol 043 Study Group
McKinney RE Jr; Maha MA; Connor EM; Feinberg J; Scott GB; Wulfsohn M; McIntosh K; Borkowsky W; Modlin JF; Weintrub P; et al
1991 Apr 11;324(15):1018-1025, New England journal of medicine
BACKGROUND AND METHODS. Zidovudine has been shown to be an effective antiretroviral treatment in adults with human immunodeficiency virus (HIV) infection. We examined the safety of zidovudine and the tolerance of and therapeutic response to the drug in 88 children with advanced HIV disease. During a 24-week outpatient trial, zidovudine (180 mg per square meter of body-surface area per dose) was given by mouth every six hours and serial measurements were made of clinical, immunologic, and virologic indexes. Children who completed 24 weeks of treatment were permitted to continue receiving zidovudine. RESULTS. Of the 88 children (mean age, 3.9 years; range, 4 months to 11 years), 61 completed the initial 24-week trial, and 49 continued to receive zidovudine for up to 90 weeks (median follow-up, 56 weeks). The patients generally tolerated zidovudine well. One or more episodes of hematologic toxicity occurred in 54 children (61 percent)--anemia (hemoglobin level, less than 75 g per liter) in 23 children (26 percent) and neutropenia (neutrophil count, less than 0.75 x 10(9) per liter) in 42 (48 percent). Many of these abnormalities resolved spontaneously, but 30 children required transfusions or a modification of the dose of zidovudine. Only three children had to stop receiving the drug because of hematologic toxicity. Kaplan-Meier analysis demonstrated that the probability of survival was 0.89 after 24 weeks and 0.79 after 52 weeks. There was marked improvement in weight gain, cognitive function (mainly in children less than 3 years old), serum and cerebrospinal fluid concentrations of p24 antigen, and the proportion of cerebrospinal fluid cultures negative for HIV. CD4+ lymphocyte counts (mean at base line, 0.263 x 10(9) per liter) improved during the first 12 weeks, although the improvement was not sustained through the 24th week. CONCLUSIONS. Zidovudine in a dose of 180 mg per square meter every six hours can be safely administered to children with advanced HIV disease. The resultant clinical, immunologic, and virologic improvements in children are similar to those reported with zidovudine in adults
— id: 14561, year: 1991, vol: 324, page: 1018, stat: Journal Article,

Lymphocyte proliferative responses to HIV-1 envelope and core antigens by infected and uninfected adults and children
Borkowsky W; Krasinski K; Moore T; Papaevangelou V
1990 May;6(5):673-678, AIDS research & human retroviruses
Lymphocytes derived from children and adults infected with the human immunodeficiency virus (HIV-1), as well as from seronegative children and adults, were tested for their ability to proliferate in response to recombinant HIV envelope (env) and core (cor) peptides. Proliferative responses to env were seen in 9% of control children compared with 27% of infected children (p less than 0.02). There was no difference in the response rates of seropositive and seronegative adults (17% and 16%, respectively). Proliferative responses to cor were seen more frequently in children and adults (22% and 28%, respectively) than their seronegative cohorts (11% and 12%, respectively). Also, the proliferative response to env and cor was seen in 27% and 37%, respectively, of seronegative children who were born to seropositive mothers and then subsequently seroreverted. These results suggest that sensitization to HIV recombinant antigens has resulted in a cell-mediated immune response in some HIV-infected individuals. Furthermore, the significant cell-mediated immune response to these antigens in seroreverting children raises the possibility that they may have been sensitized to this antigen by previous HIV infection
— id: 14565, year: 1990, vol: 6, page: 673, stat: Journal Article,

Respiratory syncytial virus infection in human immunodeficiency virus-infected children
Chandwani S; Borkowsky W; Krasinski K; Lawrence R; Welliver R
1990 Aug;117(2 Pt 1):251-254, Journal of pediatrics
— id: 14563, year: 1990, vol: 117, page: 251, stat: Journal Article,

PATHOLOGY AND HIV EXPRESSION IN TERM PLACENTAS FROM SEROPOSITIVE WOMEN
Chandwani, S; Greco, MA; Mittal, K; Antoine, C; Krasinski, K; Borkowsky, W
1990 ;62(Suppl 1):A17-A17, Laboratory investigation
— id: 32016, year: 1990, vol: 62, page: A17, stat: Journal Article,

Very late onset of group B streptococcal disease in infants infected with the human immunodeficiency virus
Di John D; Krasinski K; Lawrence R; Borkowsky W; Johnson JP; Schieken LS; Rennels MB
1990 Dec;9(12):925-928, Pediatric infectious disease journal
— id: 14247, year: 1990, vol: 9, page: 925, stat: Journal Article,

Pneumocystis carinii pneumonia in infants infected with the human immunodeficiency virus with more than 450 CD4 T lymphocytes per cubic millimeter
Leibovitz E; Rigaud M; Pollack H; Lawrence R; Chandwani S; Krasinski K; Borkowsky W
1990 Aug 23;323(8):531-533, New England journal of medicine
— id: 14562, year: 1990, vol: 323, page: 531, stat: Journal Article,

CD-4 T-CELL COUNT ARE NOT PREDICTIVE OF ACQUIRING PNEUMOCYSTIS- CARINII PNEUMONITIS IN HIV-INFECTED CHILDREN
Leibovitz, E; Rigaud, M; Chandwani, S; Lawrence, R; Krasinski, K; Borkowsky, W
1990 Apr;27(4):A176-A176, Pediatric research
— id: 31992, year: 1990, vol: 27, page: A176, stat: Journal Article,

A controlled trial of bovine dialyzable leukocyte extract for cryptosporidiosis in patients with AIDS
McMeeking A; Borkowsky W; Klesius PH; Bonk S; Holzman RS; Lawrence HS
1990 Jan;161(1):108-112, Journal of infectious diseases
Cryptosporidial infection causes severe diarrheal disease in patients with AIDS. Fourteen patients with AIDS and symptomatic cryptosporidiosis were treated with a specific bovine dialyzable leukocyte extract (immune DLE) prepared from lymph node lymphocytes of calves immunized with cryptosporidia or a nonspecific (nonimmune) DLE prepared from nonimmunized calves. Six of 7 patients given immune DLE gained weight and had a decrease in bowel movement frequency, with eradication of oocysts from stool in 5 patients. Six of 7 patients given nonimmune DLE showed no decrease in bowel movement and 4, no clearing of oocytes from stool; 5 continued to lose weight. Subsequently, 5 of these 7 were treated with immune DLE; 4 had a decrease in bowel movement frequency and significant weight gain, with eradication of oocytes from stool in 2 patients. Immune DLE produces sustained symptomatic improvement in patients with AIDS and active cryptosporidiosis, but lack of an appropriate cryptosporidial antigen allows only postulation that an augmentation of cellular immunity to Cryptosporidium parvum induced by immune DLE resulted in the microbiologic and clinical improvement observed
— id: 14566, year: 1990, vol: 161, page: 108, stat: Journal Article,

Outcome after assisted ventilation in children with acquired immunodeficiency syndrome
Notterman DA; Greenwald BM; Di Maio-Hunter A; Wilkinson JD; Krasinski K; Borkowsky W
1990 Jan;18(1):18-20, Critical care medicine
Twenty-two pediatric patients with AIDS required assisted ventilation during 27 pediatric ICU (PICU) admissions. Patients were retrospectively divided on the basis of whether they required assisted ventilation for acute respiratory failure (ARF) or for another reason. Sixteen (59%) courses of assisted ventilation were for ARF. The PICU mortality rate was 81% for the ARF group. Eleven (41%) courses of assisted ventilation were for reasons not involving ARF. The PICU mortality rate for the group without ARF was 9%, significantly lower (p less than .01) than for the ARF group. Pneumocystis carinii pneumonia (PCP) was documented during 48% of admissions. Occurrence of PCP did not affect mortality, nor was it more likely in those with than without ARF. Two patients with ARF survived to discharge from the hospital. Both died within 1 yr of ARF. Thus, the short-term prognosis for pediatric AIDS patients requiring assisted ventilation for ARF is extremely poor
— id: 14567, year: 1990, vol: 18, page: 18, stat: Journal Article,

Pediatric human immunodeficiency virus infection: an otolaryngologist's perspective
Sculerati N; Borkowsky W
1990 Jun;19(3):182-188, Journal of otolaryngology
Children with human immunodeficiency virus (HIV) frequently have recurrent otitis media, chronic rhinorrhea, parotitis, cough and other common pediatric otolaryngologic problems. As these complaints often occur before more unusual opportunistic infections or pulmonary conditions prompt a diagnosis of acquired immunodeficiency syndrome (AIDS), members of our specialty are liable to see HIV-positive children before infection with the virus has been recognized. Children with HIV infection are also likely to be referred to us after diagnosis, as is any immunosuppressed child with otolaryngologic infections. These children may require procedures such as bronchoscopy, sinus irrigations or tympanocentesis. The subject of this review is the natural history of pediatric HIV infection with special emphasis on otolaryngologic manifestations and recommendations for safe techniques of examination and treatment
— id: 14564, year: 1990, vol: 19, page: 182, stat: Journal Article,

Human immunodeficiency virus type 1 antigenemia in children
Borkowsky W; Krasinski K; Paul D; Holzman R; Moore T; Bebenroth D; Lawrence R; Chandwani S
1989 Jun;114(6):940-945, Journal of pediatrics
Human immunodeficiency virus type 1 (HIV-1) core antigen was assayed in the plasma of children at risk for infection with HIV to determine its usefulness in the diagnosis of infection and to correlate it with the clinical stage of disease. Antigen was detected in the plasma of all children less than 15 months of age with acquired immunodeficiency syndrome (AIDS). Two thirds of children with AIDS-related illnesses and half of children with asymptomatic infection had antigen. Although 53% of plasma specimens originating from HIV-infected children younger than 6 months of age contained antigen, only 25% of plasma specimens from children younger than 6 months who had no symptoms and none of the 10 specimens from HIV-infected newborn infants contained antigen. Half of the specimens containing core antigen also contained anticore antibody. Quantitative mean antigen levels were more likely to be elevated in children with AIDS (516 pg/ml) than in children with AIDS-related illnesses (295 pg/ml) or in those who had no symptoms (70 pg/ml). Antigen levels tended to increase over time in children with advancing clinical illness, but they tended to decrease over time after a diagnosis of AIDS was made. Antigen was detected in the plasma of 4 of 14 children without symptoms who subsequently reverted to an HIV seronegative state. We conclude that the detection of core antigen occurs with high frequency in children, even young infants, with symptomatic HIV infection. Plasma core antigen was less frequent in children without symptoms and was not detected in 10 infected children when they were tested at birth
— id: 10595, year: 1989, vol: 114, page: 940, stat: Journal Article,

Antibodies to human immunodeficiency virus type 1 in the urine specimens of HIV-1-seropositive individuals
Cao YZ; Hosein B; Borkowsky W; Mirabile M; Baker L; Baldwin D; Poiesz BJ; Friedman-Kien AE
1989 Jun;5(3):311-319, AIDS research & human retroviruses
Specific antibodies to human immunodeficiency virus type 1 (HIV-1) were detected in 200-fold concentrated urine samples, but none were detected in unconcentrated urine specimens, from 100 randomly selected HIV-1--seropositive individuals by enzyme-linked immunosorbent assay (ELISA) and Western blot techniques using the manufacturer's recommended procedures. Using modified methods for both the ELISA and Western blot tests, antibodies to HIV-1 have also been detected in the unconcentrated urine specimens from the same HIV-1--seropositive individuals. No difference in the frequency of antibodies to HIV-1 were found between unconcentrated and 200-fold concentrated urine samples when tested by the modified methods. HIV-1 core antigen (p24) was not detected in either the concentrated or the unconcentrated HIV-1--seropositive adult urine samples; none of these individuals showed overt clinical or laboratory evidence of renal dysfunction. The titer of the antibodies to HIV-1 found in the urine specimens was found to be parallel with the titer of antibodies to HIV-1 in the corresponding individual's serum. Further elucidation of the pathophysiology and the nature of the specific antibodies to HIV-1 observed in the urine of HIV-1--seropositive individuals is under investigation in our laboratories
— id: 10608, year: 1989, vol: 5, page: 311, stat: Journal Article,

Varicella-zoster virus infections in children infected with human immunodeficiency virus [see comments]
Jura E; Chadwick EG; Josephs SH; Steinberg SP; Yogev R; Gershon AA; Krasinski KM; Borkowsky W
1989 Sep;8(9):586-590, Pediatric infectious disease journal
Primary varicella-zoster (VZ) infection in eight children with perinatally acquired human immunodeficiency virus infection tended to be severe, prolonged, complicated by bacterial infections and in one case fatal. Depletion of CD4-lymphocytes was associated with chronic and recurrent VZ infection. In some patients convalescent VZ antibody titers were low and did not correlate with recurrence of VZ lesions. Administration of acyclovir appeared to be beneficial in suppressing VZ in human immunodeficiency virus-infected children with primary or recurrent VZ infection
— id: 10495, year: 1989, vol: 8, page: 586, stat: Journal Article,

Measles and measles immunity in children infected with human immunodeficiency virus
Krasinski K; Borkowsky W
1989 May 5;261(17):2512-2516, JAMA
The development of measles vaccination recommendations for immunodeficient children infected with human immunodeficiency virus requires assessment of disease risk and the risks and benefits of vaccination. Measles in 4 such children resulted in 3 severe pneumonias and 1 death despite previous immunization in 2. Antibody to measles as determined by enzyme-linked immunosorbent assay was present in 3 (12.5%) of 24 children studied retrospectively and developed in only 2 (25%) of 8 children immunized and followed up prospectively. The sera of 9 of 24 children had antibody when tested by sensitive hemagglutination inhibition. Measles developed in 2 of 6 children who had negative enzyme-linked immunosorbent assay results and positive hemagglutination inhibition results. No adverse consequences of measles immunization were detected. Although the immunogenicity of measles vaccine in children infected with human immunodeficiency virus was low and vaccine failure occurred, the apparent safety provides the rationale for immunization in the face of a potentially fatal disease. Since neither documented immunization nor low-level antibody guaranteed immunity to measles, we recommend passive postexposure immunoglobulin prophylaxis for all children infected with human immunodeficiency virus
— id: 10621, year: 1989, vol: 261, page: 2512, stat: Journal Article,

Prognosis of human immunodeficiency virus infection in children and adolescents
Krasinski K; Borkowsky W; Holzman RS
1989 Apr;8(4):216-220, Pediatric infectious disease journal
The prognosis of 111 children and adolescents (from 2.5 months to 19.5 years of age) infected with human immunodeficiency virus (HIV) was assessed by survival analysis based on risk factors and clinical status. Risk factors included: maternal HIV infection 93; transfusion 12; both maternal HIV infection and transfusion 2; sexual abuse 1; and intravenous drug use and/or sexual activity 3. Children with perinatal infection survived from 2.5 months to 10.25 years (median, 1.87 years) and had inapparent infection from 6 weeks to 7.3 years (median, 0.75 years). Children who acquired HIV infection via transfusion had inapparent infection from 4 months to 5.7 years (median, 3.6 years). Actuarial survival following infection was not significantly different from maternally and transfusion-acquired infection; however, survival from infection was longer for children infected by transfusion beyond 2 years of age (mean, 7.5 years) than for children infected perinatally (mean, 5.6 years). The case-fatality ratio was 32%, with 25% of subjects succumbing within 1 year of developing an HIV-associated illness. Opportunistic infection was the most common acquired immunodeficiency syndrome-defining illness and the cause of death in 22 of the 35 children who died. Pneumocystis carinii and fungal pneumonias had the worst prognosis. Cryptosporidiosis and other opportunistic infections had a better prognosis. Because of difficulties in case finding, diagnosis of infection and variable survival of HIV-infected children, arge longitudinal studies and pooling of data among centers will be necessary to have an accurate understanding of the prognosis of individual clinical syndromes.(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 10675, year: 1989, vol: 8, page: 216, stat: Journal Article,

The nature and functions of inducer factor and suppressor factor in T cell dialysates
Lawrence HS; Borkowsky W
1989 Apr;21(1):75-80, Immunology letters
— id: 10672, year: 1989, vol: 21, page: 75, stat: Journal Article,

THE PRODUCTION OF ANTI-HIV ANTIBODIES INVITRO IN CHILDREN AND ADULTS
Pollack, H; Moore, T; Krasinski, K; Xia, ZM; Borkowsky, W
1989 Apr;25(4):A167-A167, Pediatric research
— id: 31731, year: 1989, vol: 25, page: A167, stat: Journal Article,

CARDIAC DISEASE IN CHILDREN WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION
Rigaud, M; Avnisinger, J; Presti, S; Lawrence, R; Krasinski, K; Borkowsky, W
1989 Apr;25(4):A188-A188, Pediatric research
— id: 31732, year: 1989, vol: 25, page: A188, stat: Journal Article,

IMMUNIZATION OF HIV-INFECTED CHILDREN - REPLY
Borkowsky, W
1988 Feb;112(2):334-334, Journal of pediatrics
— id: 31547, year: 1988, vol: 112, page: 334, stat: Journal Article,

Failure of voluntary testing for human immunodeficiency virus to identify infected parturient women in a high-risk population
Krasinski K; Borkowsky W; Bebenroth D; Moore T
1988 Jan 21;318(3):185-185, New England journal of medicine
— id: 14568, year: 1988, vol: 318, page: 185, stat: Journal Article,

Bacterial infections in human immunodeficiency virus-infected children
Krasinski K; Borkowsky W; Bonk S; Lawrence R; Chandwani S
1988 May;7(5):323-328, Pediatric infectious disease journal
A retrospective review of 71 children infected with human immunodeficiency virus cared for over a 3.5-year period revealed that 44 of 71 (63%) required a bacterial culture and 27 of 71 (37%) had bacteriologically documented infection. There were 125 episodes in 27 patients. Pneumonia (24 of 125 (19%)), upper respiratory tract syndromes (23 of 125 (19%)), urinary tract infection (24 of 125 (19%)) and wound infection (12 of 125 (10%)) were the most common syndromes identified. Bacteremic infections occurred in 35 of 125 (28%), and in 17 of 125 (14%) no other primary source could be identified. Pneumococci (11 of 35 (31%)) and Salmonella (4 of 35 (11%)) were the most common blood isolates; however, a wide spectrum of Gram-positive and Gram-negative pathogens were recovered. Bacterial pneumonia directly contributed to the death of 4 patients, in whom pneumonia caused by Pneumocystis carinii (2), cytomegalovirus (1) or varicella-zoster virus (1) also coexisted, respectively. Absolute T4 counts less than 400 and depressed lymphocyte-proliferative responses to diphtheria and tetanus toxoids, Candida antigen and pokeweed mitogen correlated with the occurrence of bacterial infection in human immunodeficiency virus-infected children. Although bacterial infections are a frequent cause of morbidity in human immunodeficiency virus-infected children, they are usually treatable
— id: 11118, year: 1988, vol: 7, page: 323, stat: Journal Article,

CONTROLLED TRIAL OF BOVINE TRANSFER-FACTOR THERAPY FOR CRY
Mcmeeking, A; Borkowsky, W; Klesius, PH; Bonk, S; Haynes, TB; Holzman, RS; Lawrence, HS
1988 Apr;36(3):A621-A621, Clinical research
— id: 31519, year: 1988, vol: 36, page: A621, stat: Journal Article,

Human-immunodeficiency-virus infections in infants negative for anti-HIV by enzyme-linked immunoassay
Borkowsky W; Krasinski K; Paul D; Moore T; Bebenroth D; Chandwani S
1987 May 23;1(8543):1168-1171, Lancet
Of 85 children with human-immuno-deficiency-virus (HIV) infection based on clinical (opportunistic infection), epidemiological (mother a drug addict or known to be HIV infected), and immunological (helper-T-cell deficiency and impaired proliferative response to pokeweed mitogen) features, 9 were found to lack antibody to HIV as measured by a commercial enzyme-linked immunoassay (ELISA). All 9 children had detectable levels of HIV antigen in simultaneous plasma specimens, measured by a sensitive antigen-capture ELISA. The use of the western blot assay and an ELISA with recombinant HIV antigens was able to identify HIV infection in 4 of the 9 children
— id: 14570, year: 1987, vol: 1, page: 1168, stat: Journal Article,

Antibody responses to bacterial toxoids in children infected with human immunodeficiency virus
Borkowsky W; Steele CJ; Grubman S; Moore T; La Russa P; Krasinski K
1987 Apr;110(4):563-566, Journal of pediatrics
— id: 14572, year: 1987, vol: 110, page: 563, stat: Journal Article,

RETROVIRAL ANTIGENEMIA IN CHILDREN WITH HIV-INFECTION
Borkowsky, W; Krasinski, K; Paul, D; Lawrence, R; Moore, T; Chandwani, S
1987 Apr;21(4):A322-A322, Pediatric research
— id: 31243, year: 1987, vol: 21, page: A322, stat: Journal Article,

Dilemmas in infectious diseases
Gershon AA; Borkowsky W; Gerety RJ
1987 May;17(5):289-343, Current problems in pediatrics
— id: 14571, year: 1987, vol: 17, page: 289, stat: Journal Article,

RESPONSE TO POLIO VACCINATION IN CHILDREN INFECTED WITH HUMAN- IMMUNODEFICIENCY-VIRUS
Krasinski, K; Borkowsky, W
1987 Apr;21(4):A328-A328, Pediatric research
— id: 31244, year: 1987, vol: 21, page: A328, stat: Journal Article,

PNEUMOCYSTIS-CARINII PNEUMONIA IN CHILDREN WITH HIV-INFECTION
Lawrence, R; Horwitz, D; Barrow, K; Rogan, D; Chandwani, S; Krasinski, K; Borkowsky, W
1987 Apr;21(4):A329-A329, Pediatric research
— id: 31245, year: 1987, vol: 21, page: A329, stat: Journal Article,

Treatment of cryptosporidiosis with oral bovine transfer factor
Louie E; Borkowsky W; Klesius PH; Haynes TB; Gordon S; Bonk S; Lawrence HS
1987 Sep;44(3):329-334, Clinical immunology & immunopathology
Cryptosporidia are intestinal protozoans long known to cause diarrhea in humans, especially those with acquired immune deficiency syndrome (AIDS). When transfer factor prepared from calves which possessed delayed-type hypersensitivity to Eimeria bovis was given to nonimmune calves and mice it conferred protection against clinical infection (coccidiosis). Recent studies with oral bovine transfer factor have shown that it can confer cell-mediated immunity to humans. Based on these findings we decided to treat eight AIDS patients suffering from Cryptosporidium-associated diarrhea with transfer factor prepared from calves immune to Cryptosporidium. Prior to treatment with transfer factor, three patients had been treated with spiramycin, one patient with alpha-difluoromethylornithine (DFMO), and one patient with furazolidone for greater than 1 month without clinical or laboratory improvement. Following administration of transfer factor, five or eight patients exhibited a decrease in the number of bowel movements and the development of formed stools. Cryptosporidium was eradicated from the stools of four patients but two of these patients subsequently relapsed and one patient continued to have diarrhea despite the absence of Cryptosporidium in the stool. One patient has been free of diarrhea and Cryptosporidium for 2 years after discontinuation of transfer factor therapy
— id: 14569, year: 1987, vol: 44, page: 329, stat: Journal Article,

RESIDUAL CELL-MEDIATED-IMMUNITY TO RECALL ANTIGENS IN PEDIATRIC AIDS-RELATED DISEASE
Borkowsky, W; Krasinski, K
1986 Apr;20(4):A292-A292, Pediatric research
— id: 31069, year: 1986, vol: 20, page: A292, stat: Journal Article,

THE EFFECTS OF DIALYZABLE LEUKOCYTE EXTRACTS IN THE IMMUNOMODULATION OF A MURINE MODEL OF DIABETOGENESIS
Borkowsky, W; Pilson, R; Fazzini, E; Lawrence, HS
1986 Apr;20(4):A327-A327, Pediatric research
— id: 31070, year: 1986, vol: 20, page: A327, stat: Journal Article,

IMPACT OF AIDS RELATED DISEASE IN CHILDREN
Krasinski, K; Borkowsky, W; Holzman, RS
1986 Apr;20(4):A229-A229, Pediatric research
— id: 31068, year: 1986, vol: 20, page: A229, stat: Journal Article,

IMMUNE STATUS TO VARICELLA-ZOSTER VIRUS AND THE PRESENCE OF ANTIBODY TO SPECIFIC VIRAL GLYCOPROTEINS
LARUSSA, PS; GERSHON, AA; BORKOWSKY, W; STEINBERG, SP; KELLER, PM; ELLIS, RW
1986 APR ;20(4):A314-A314, Pediatric research
— id: 41462, year: 1986, vol: 20, page: A314, stat: Journal Article,

EFFICACY OF BOVINE LEUKOCYTE DIALYSATES CONTAINING TRANSFER- FACTOR (TF) IN THE THERAPY OF THE ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS)
Borkowsky, W; Klesius, P; Gordon, S; Larussa, P; Lawrence, HS
1985 ;19(4):A270-A270, Pediatric research
— id: 30941, year: 1985, vol: 19, page: A270, stat: Journal Article,

A multicentre trial of live attenuated varicella vaccine in children with leukaemia in remission
Gershon AA; Steinberg S; Gelb L; Galasso G; Borkowsky W; LaRussa P; Ferrara A
1985 ;61 Suppl 4:73-78, Postgraduate medical journal
Two hundred forty children with acute leukaemia in remission for at least 1 year were immunized with live attenuated varicella vaccine. All were susceptible to varicella before immunization. There was a seroconversion to varicella-zoster virus in approximately 85% after 1 dose, and in 97% after 2 doses. The major side effect was mild to moderate rash, seen mainly in children with maintenance chemotherapy suspended for 1 week before and 1 week after vaccination. Vaccinees with rash were at some risk (10%) to transmit vaccine virus to varicella susceptibles with whom they had close contact. Twenty-nine vaccinees were subsequently exposed to varicella in their households. The attack rate of clinical varicella in these vaccinees was 21%, which is significantly lower than the 80%-90% attack rate occurring in varicella susceptibles after household exposure. All these breakthrough cases of varicella were mild, even in leukaemics receiving chemotherapy. Varicella vaccine was approximately 80% effective in preventing clinical varicella in children with leukaemia and completely effective in preventing severe varicella in this high-risk group
— id: 14573, year: 1985, vol: 61 Suppl 4, page: 73, stat: Journal Article,

Viral infections in immunocompromised children
Borkowsky W
1984 Sep;13(9):682-3, 686, Pediatric annals
— id: 14575, year: 1984, vol: 13, page: 682, stat: Journal Article,

Leukocyte migration inhibition of buffy coats from patients with autoimmune thrombocytopenic purpura when exposed to normal platelets: modulation by transfer factor
Borkowsky W; Karpatkin S
1984 Jan;63(1):83-87, Blood
Cellular-mediated immunity was studied in autoimmune thrombocytopenic purpura (ATP) patients by investigating leukocyte migration inhibition (LMI) following the interaction of normal platelets with patients' lymphocytes. When normal platelets were incubated with leukocyte buffy coats of ATP patients, the migration index (MI) was significantly impaired compared to buffy coats from normal subjects, employing 4 different concentrations of platelets. At the highest platelet concentration (10(9)/ml), MI was 0.87 +/- 0.04 (SEM) for ATP lymphocytes compared to 1.05 +/- 0.05 (p less than 0.01) for normal lymphocytes. Nine of 21 patients had an MI less than 0.80, whereas all control subjects had MIs greater than 0.85. Similar results were obtained at 2 different platelet membrane concentrations. At 500 micrograms/ml, the MI for ATP lymphocytes was 0.74 +/- 0.04, compared to 0.98 +/- 0.08 (p less than 0.01) for normal lymphocytes (12 experiments). An inverse relationship was noted between platelet count and lymphokine production in ATP patients (r = 0.815, p less than 0.001, 10 experiments). Transfer factor from an ATP patient in remission converted an abnormal LMI response of 0.68 +/- 0.04 from a patient with severe thrombocytopenia to 0.84 +/- 0.07 (p less than 0.005, 8 experiments). Similar results were obtained with transfer factor from 2 other patients in remission. Transfer factor from a patient with severe thrombocytopenia converted a normal response of 1.04 +/- 0.05 of normal subjects to a lower response of 0.88 +/- 0.04 (p less than 0.03, 12 experiments). Thus, lymphocytes of ATP patients are primed to recognize and be perturbed by normal platelets, whereas normal lymphocytes are not. This indicates specificity of the antigen-lymphocyte reaction in ATP patients. Transfer factor is capable of modulating this response in vitro
— id: 14578, year: 1984, vol: 63, page: 83, stat: Journal Article,

Juvenile laryngeal papillomatosis with pulmonary spread. Regression following transfer factor therapy
Borkowsky W; Martin D; Lawrence HS
1984 Jul;138(7):667-669, American journal of diseases of children
A 6-year-old girl with a history of juvenile laryngeal papillomatosis since 6 months of age and progressing pulmonary extension of the tumor for two years was treated with transfer factor prepared from her mother. Within one month of the onset of therapy, she exhibited marked clinical improvement. A computed tomographic scan performed after four months of therapy revealed almost complete resolution of her pulmonary lesions
— id: 14577, year: 1984, vol: 138, page: 667, stat: Journal Article,

Live attenuated varicella vaccine in children with leukemia in remission
Gershon AA; Steinberg S; Galasso G; Borkowsky W; Larussa P; Ferrara A; Gelb L
1984 Sep;27(2-3):77-81, Biken journal
One-hundred-ninety-one children with acute leukemia in remission for at least one year were immunized with 1 or more doses of live attenuated varicella vaccine. All were susceptible to varicella prior to vaccination. The only significant side effect was mild to moderate rash, seen especially in children with maintenance chemotherapy temporarily suspended for one week before and one week after vaccination. Children with rash were at some risk (10%) to transmit vaccine virus to varicella susceptibles with whom they had close contact
— id: 14574, year: 1984, vol: 27, page: 77, stat: Journal Article,

Live attenuated varicella vaccine. Efficacy for children with leukemia in remission
Gershon AA; Steinberg SP; Gelb L; Galasso G; Borkowsky W; LaRussa P; Farrara A
1984 Jul 20;252(3):355-362, JAMA
One hundred ninety-one varicella-susceptible children with leukemia in remission were immunized with live attenuated varicella vaccine. There was serological evidence of an immune response in approximately 80% after one dose and in more than 90% after two doses. The major side effect was mild to moderate rash, seen especially in children with maintenance chemotherapy suspended for one week before and one week after vaccination. Children with rash had higher antibody titers than those without rash, but those with rash were also at risk (10%) to transmit vaccine virus to others. Twenty-two vaccinees subsequently had household exposures to varicella or zoster. The attack rate of clinical varicella in these vaccinees was 18%, significantly lower than the attack rate of approximately 90% in varicella-susceptible persons with household exposures. All cases of clinical illness were extremely mild, with an average of about 50 vesicles. The mild character of the illness was clearly different than varicella in unimmunized children receiving chemotherapy for leukemia. Varicella vaccine was approximately 80% effective in preventing clinical varicella in children with leukemia and completely effective in preventing severe varicella in this high-risk group
— id: 14576, year: 1984, vol: 252, page: 355, stat: Journal Article,

A new basis for the immunoregulatory activities of transfer factor--an arcane dialect in the language of cells
Lawrence HS; Borkowsky W
1983 Nov;82(1):102-116, Cellular immunology
— id: 14579, year: 1983, vol: 82, page: 102, stat: Journal Article,

T-lymphocyte cycling in human cyclic neutropenia: effects of lithium in vitro and in vivo
Borkowsky W; Shenkman L; Rausen A
1982 Jun;23(3):586-592, Clinical immunology & immunopathology
— id: 14580, year: 1982, vol: 23, page: 586, stat: Journal Article,

Clinical trial of live attenuated Varicella vaccine in high risk susceptibles--a preliminary report
Gershon AA; Steinberg S; Borkowsky W
1982 ;52:391-397, Developments in biological standardization
— id: 14583, year: 1982, vol: 52, page: 391, stat: Journal Article,

IgM to varicella-zoster virus: demonstration in patients with and without clinical zoster
Gershon AA; Steinberg SP; Borkowsky W; Lennette D; Lennette E
1982 May-Jun;1(3):164-167, Pediatric infectious disease
Antibody to varicella-zoster (VZ) virus of the IgM type was detected in sera from 50% of persons with clinical zoster, 67% of asymptomatic varicella immunes with a recent intimate exposure to VZ virus and 22 to 40% of varicella immunes with no symptoms of zoster or known exposure to the virus. No VZ IgM was found in newborn sera or in sera from persons susceptible to varicella, demonstrating specificity of the VA IgM assay. Since development of specific IgM is associated with acute infection, these data suggest that reinfection with VA virus occurs and also that antigenic stimulation due to exposure to endogenous VZ virus may occur. We hypothesize that during reactivation of VZ virus, persons with intact VZ cell-mediated immunity (CMI) remain asymptomatic but that those with depressed VZ CMI may develop clinical zoster. These data suggest that there is an unstable relationship between VZ virus and the human host
— id: 14581, year: 1982, vol: 1, page: 164, stat: Journal Article,

The histopathology of cervical lymphadenitis caused by Mycobacterium avium-Mycobacterium intracellulare complex in an immunocompromised host
Mufarrij AA; Greco MA; Antopol SC; Borkowsky W
1982 Jan;13(1):78-81, Human pathology
— id: 14582, year: 1982, vol: 13, page: 78, stat: Journal Article,

Deletion of antigen-specific activity from leukocyte dialysates containing transfer factor by antigen-coated polystyrene
Borkowsky W; Lawrence HS
1981 Feb;126(2):486-489, Journal of immunology
We have reported finding antigen-specific activity in human leukocyte dialysates (DLE) containing TF in the leukocyte migration inhibition (LMI) assay. To analyze this activity further, we have used polystyrene bound to antibody or to antigen as immunoadsorbent for DLE before pulsing nonimmune cells in the LMI assay. Candida-(CAN) immune or diphtheria toxoid-(TOX) immune DLE were depleted of all antigen-specific activity after absorption with specific antigen but not affected by absorption with specific antibody, respectively, and depletion of activity with antigen was abrogated by coating bound antigen with specific antibody before absorption of DLE. CAN-immune, TOX-immune DLE was selectively depleted for either CAN activity or TOX activity after absorption with CAN- or TOX-coated polystryrene, respectively, retaining its CAN-activity when absorbed with TOX and conversely retaining its TOX activity when absorbed with CAN; thus the antigen-specific activity binds to related but not unrelated antigen. The polystyrene-bound antigen-specific activity could be recovered by treatment with 8 M urea. We interpret these findings to suggest that such antigen-specific activity may be either a dialysable fragment of a T cell antigen receptor site, or a portion of the V-region, or a unique Ir gene product that assists in antigen presentation to other T cells
— id: 14587, year: 1981, vol: 126, page: 486, stat: Journal Article,

An immunodeficient child with inflammatory bowel disease: involvement of cyclic nucleotides and effects of lithium
Borkowsky W; Shenkman L; Suleski P; Sansaricq C; Siegal F; Hirschhorn R; Smithwick E; Shopsin B; Snyderman S
1981 ;3(2):116-128, Developmental pharmacology & therapeutics
A 3-year-old male with inflammatory bowel disease and hypogammaglobulinemia was found to have decreased T lymphocyte function. His serum was shown to depress normal T cell proliferative responses to phytohemagglutinin. Incorporation of lithium chloride to in vitro cultures enhanced autologous lymphocyte responses to phytohemagglutinin. Since lithium acts by inhibiting cAMP production, the child's lymphocytes were postulated to have increased levels of cAMP. Both lymphocytes and serum were shown to contain elevated levels of cAMP. In vivo therapy with lithium citrate was initiated and enhanced T cell numbers and function were observed concomitantly. Serum cAMP was also reduced to normal levels. The patient showed initially marked clinical improvement as assessed by mood, weight gain, and diminution of diarrhea. This clinical improvement was unfortunately not sustained despite the continued improvement in immune parameters and cAMP levels
— id: 14588, year: 1981, vol: 3, page: 116, stat: Journal Article,

Antigen-specific activity of murine leukocyte dialysates containing transfer factor on human leukocytes in the leukocyte migration inhibition (LMI) assay
Borkowsky W; Suleski P; Bhardwaj N; Lawrence HS
1981 Jan;126(1):80-82, Journal of immunology
We report on the extension of the direct leukocyte migration inhibition (LMI) test as an assay for antigen-specific activity in human leukocyte dialysates (DLE) containing transfer factor to an evaluation of antigen-specific activity in DLE prepared from inbred mice. Murine DLE was observed to cause antigen-dependent and antigen-specific effects on the inhibition of migration of nonimmune human leukocyte populations. Pulsing of nonimmune human leukocyte with DLE preparations from BALB/c and SJL mice immunized with Candida, diphtheria toxoid, and SK-SD resulted in their inhibition of migration in the presence of the respective antigens. The antigen-specific activity in murine DLE was found to be present in lymph node cell preparations and to be absent from spleen cell preparations of the same donors. The activity of DLE in lymph node cells was found to be present in the theta-cell enriched subpopulation of nonadherent lymphocytes after passage through nylon wool columns. The antigen-specific activity of murine DLE, as we have reported for human DLE, was found to reside in the < 3500 dalton dialysis fraction and not in the < 3500 dalton fraction. We conclude that nonimmune human leukocytes in the LMI test provide a suitable assay for the detection of antigen-specific activity in murine DLE as well as that in human DLE. Additionally, murine DLE is active across species barriers and appears to share properties with human DLE
— id: 14589, year: 1981, vol: 126, page: 80, stat: Journal Article,

LEUKOCYTE MIGRATION-INHIBITION (LMI) BY LYMPHOCYTES OF PATIENTS WITH AUTOIMMUNE THROMBOCYTOPENIC PURPURA (ATP) WHEN EXPOSED TO NORMAL PLATELETS
Borkowsky, W; Karpatkin, S
1981 ;29(2):A363-A363, Clinical research
— id: 30260, year: 1981, vol: 29, page: A363, stat: Journal Article,

ANTIGEN-SPECIFIC INDUCER ACTIVITY IN HUMAN-LEUKOCYTE DIALYSATES BINDS TO ANTI-VH BUT NOT ANTI-VL CHAIN ANTIBODY WHILE ANTIGEN SPECIFIC SUPPRESSOR ACTIVITY BINDS TO ANTI-VL CHAIN ANTIBODY
BORKOWSKY, W; LAWRENCE, HS
1981 ;15(4):592-592, Pediatric research
— id: 40235, year: 1981, vol: 15, page: 592, stat: Journal Article,

Fatal reaction to dapsone during treatment of leprosy
Frey HM; Gershon AA; Borkowsky W; Bullock WE
1981 Jun;94(6):777-779, Annals of internal medicine
A Burmese boy being treated with dapsone (diaminodiphenylsulfone [DDS]), 100 mg daily, for lepromatous leprosy had a fatal reaction to the drug 3 weeks after therapy was started. The clinical symptoms and progression of illness conform well to a 'DDS syndrome' first described in the early 1950s. Although the syndrome clinically resembles infectious mononucleosis, neither Epstein-Barr virus nor cytomegalovirus was implicated as an etiologic agent in this case. The syndrome has been recognized during initiation of dapsone therapy for lepromatous leprosy and has led to the use of a prolonged induction period with initial dosages as low as 25 mg/week. However, because dapsone resistance has been recognized in some strains of Mycobacterium leprae, slow induction of therapy has been replaced with the schedule used for this patient. This report of a fatal reaction to dapsone emphasizes the need for caution when initiating therapy with the drug at full dosage
— id: 14585, year: 1981, vol: 94, page: 777, stat: Journal Article,

SUB-CLINICAL ZOSTER - IDENTIFICATION BY SERUM IGM TO VARICELLA-ZOSTER (VZ) VIRUS
GERSHON, A; STEINBERG, S; BORKOWSKY, W; LENNETTE, D; LENNETTE, E
1981 ;15(4):610-610, Pediatric research
— id: 40236, year: 1981, vol: 15, page: 610, stat: Journal Article,

Transfer factor: recent developments in the pursuit of an idea
Lawrence HS; Borkowsky W
1981 Aug;62(2):301-308, Cellular immunology
— id: 14584, year: 1981, vol: 62, page: 301, stat: Journal Article,

Adjuvant effects of lithium chloride on human mononuclear cells in suppressor-enriched and suppressor-depleted systems
Shenkman L; Wadler S; Borkowsky W; Shopsin B
1981 Feb;3(1):1-8, Immunopharmacology
Lithium enhances several in vitro indices of immune function, including thymidine uptake by mitogen-stimulated human mononuclear cells. To further characterize the mechanism of action of lithium and to determine whether it acts by abrogating suppressor cell activity or by enhancing helper cell function, we have compared the effects of lithium on the mitogenic response of normal, suppressor-depleted and suppressor-enriched mononuclear cell preparations. In normal cultures, lithium enhanced thymidine uptake in response to concanavalin A (Con A) and phytohemagglutinin (PHA). In the suppressor-depleted cultures, thymidine uptake after Con A stimulation was significantly higher than in normal cultures, and was further enhanced by lithium. In the suppressor-enriched system, response to PHA was significantly lower than in normal cultures, and addition of lithium reversed the observed suppression. These results indicate that lithium may be enhancing thymidine uptake in response to mitogen at least in part by abrogating suppressor cell activity. The observed increase in thymidine incorporation in the suppressor-depleted cultures suggests that lithium may also have a direct stimulatory effect on helper cell activity
— id: 14586, year: 1981, vol: 3, page: 1, stat: Journal Article,

Adenosine deaminase deficiency without immunodeficiency: clinical and metabolic studies
Borkowsky W; Gershon AA; Shenkman L; Hirschhorn R
1980 Jul;14(7):885-889, Pediatric research
A child diagnosed at birth as deficient in red blood cell adenosine deaminase (ADA) but with substantial residual lymphocyte ADA has been evaluated for two and one-half years. The only immunologic abnormality observed was hypogammaglobulinemia during the fifth month of life. This was unexpected because children with total ADA deficiency either have severe combined immunodeficiency or selectively greater impairment of cellular than humoral immunity. The absence of severe combined immunodeficiency in this child was associated with normal lymphocyte content of ATP, dATP, and cyclic 3'5'-adenosine monophosphate, potentially toxic metabolites which are elevated in ADA-deficient immunodeficient children
— id: 14590, year: 1980, vol: 14, page: 885, stat: Journal Article,

Adjuvant-like effects of lithium on peripheral blood mononuclear cells
Borkowsky W; Shenkman L; Wadler S; Holzman RS; Shopsin B
1980 ;127:417-427, Advances in experimental medicine & biology
— id: 14593, year: 1980, vol: 127, page: 417, stat: Journal Article,

ANTIGEN-SPECIFIC ACTIVITY IN MURINE LEUKOCYTE DIALYSATES CONTAINING TRANSFER-FACTOR ASSAYED ON MIGRATING HUMAN-LEUKOCYTES
BORKOWSKY, W; BHARDWAJ, N; LAWRENCE, HS
1980 ;28(2):A500-A500, Clinical research
— id: 98663, year: 1980, vol: 28, page: A500, stat: Journal Article,

DELETION OF ANTIGEN-SPECIFIC ACTIVITY FROM LEUKOCYTE DIALYSATES CONTAINING TRANSFER-FACTOR BY ANTIGEN-COATED POLYSTYRENE
Borkowsky, W; Lawrence, HS
1980 ;28(2):A550-A550, Clinical research
— id: 28123, year: 1980, vol: 28, page: A550, stat: Journal Article,

CYCLIC ALTERATIONS IN LYMPHOCYTE FUNCTION DURING CYCLIC NEUTROPENIA
Borkowsky, W; Shenkman, L; Suleski, P; Rausen, A; Amorosi, E
1980 ;14(4):531-531, Pediatric research
— id: 28132, year: 1980, vol: 14, page: 531, stat: Journal Article,

EFFECTS OF LITHIUM (LI) THERAPY OF A CHILD WITH IMMUNODEFICIENCY
Borkowsky, W; Shenkman, L; Suleski, P; Sansaricq, C; Snyderman, S
1980 ;14(4):544-544, Pediatric research
— id: 28133, year: 1980, vol: 14, page: 544, stat: Journal Article,

EFFECTS OF LITHIUM-CHLORIDE (LI) ON INVITRO IGG PRODUCTION BY ADULT AND CORD BLOOD MONONUCLEAR-CELLS
Borkowsky, W; Shenkman, L; Suleski, P; Wadler, S
1980 ;14(4):544-544, Pediatric research
— id: 28134, year: 1980, vol: 14, page: 544, stat: Journal Article,

ENHANCEMENT OF IMMUNOGLOBULIN PRODUCTION BY LITHIUM-CHLORIDE IN HUMAN MONONUCLEAR CELL-CULTURES
Borkowsky, W; Wadler, S; Shenkman, L
1980 ;28(2):A341-A341, Clinical research
— id: 28007, year: 1980, vol: 28, page: A341, stat: Journal Article,

Live attenuated rubella virus vaccine: comparison of responses to HPV-77-DE5 and RA 27/3 strains
Gershon AA; Frey HM; Borkowsky W; Steinberg S
1980 Mar-Apr;279(2):95-97, American journal of the medical sciences
The responses of seronegative adults to two live attenuated rubella virus vaccines were compared. Of 50 women who received the HPV-77-DE5 strain, 49 (98%) had an antibody response; the geometric mean antibody titer (GMT) was 1:38 at two to five months and 1:59 at six to 14 months. Of 66 women and three men who received the RA 27/3 strain all (100%) had an antibody response; the GMT was 1:55 at two to five months and 1:75 at six to 14 months. The incidence of mild to moderate transient clinical reactions, occurring in approximately one-fourth of those vaccinated, was similar for both groups. The serologic response to both vaccines was excellent
— id: 14592, year: 1980, vol: 279, page: 95, stat: Journal Article,

EARLY EXPERIENCES WITH VARICELLA VACCINE
Gershon, AA; Borkowsky, W; Brown, A; Frey, HM; Steinberg, S
1980 ;14(4):558-558, Pediatric research
— id: 28025, year: 1980, vol: 14, page: 558, stat: Journal Article,

Effects of lithium on polymorphonuclear leukocyte chemotaxis
Perez HD; Kaplan HB; Goldstein IM; Shenkman L; Borkowsky W
1980 ;127:357-370, Advances in experimental medicine & biology
— id: 14594, year: 1980, vol: 127, page: 357, stat: Journal Article,

Reversal of an abnormality of polymorphonuclear leukocyte chemotaxis with lithium
Perez HD; Kaplan HB; Goldstein IM; Shenkman L; Borkowsky W
1980 Jul;16(3):308-315, Clinical immunology & immunopathology
— id: 14591, year: 1980, vol: 16, page: 308, stat: Journal Article,

Lithium as an immunologic adjuvant
Shenkman L; Borkowsky W; Shopsin B
1980 Jan;6(1):1-6, Medical hypotheses
Lithium, an adenylate cyclase inhibitor, stimulates a variety of in vitro indices of immune function, including proliferation of lymphocytes in response to mitogens, rosette formation by T-cells and phagocytosis by macrophages. Lithium enhances these immunologic responses at concentrations comparable to those achieved in patients receiving lithium for treatment of manic-depressive disorders. Lithium may prove to have important therapeutic applications as an immune adjuvant, particularly in immune deficiency states associated with excessive C-AMP production
— id: 14595, year: 1980, vol: 6, page: 1, stat: Journal Article,

AN IMMUNOSUPPRESSIVE FACTOR WHOSE EFFECT IS REVERSED BY LITHIUM IN A PATIENT WITH XERODERMA PIGMENTOSA (XP)
Wadler, S; Borkowsky, W; Perez, HD; Shenkman, L
1980 ;28(2):A254-A254, Clinical research
— id: 28004, year: 1980, vol: 28, page: A254, stat: Journal Article,

Effects of human leukocyte dialysates containing transfer factor in the direct leukocyte migration inhibition (LMI) assay
Borkowsky W; Lawrence HS
1979 Oct;123(4):1741-1748, Journal of immunology
— id: 14596, year: 1979, vol: 123, page: 1741, stat: Journal Article,

The proliferative response of human lymphocytes to antigen is suppressed preferentially by lymphocytes precultured with the same antigen
Borkowsky W; Valentine FT
1979 May;122(5):1867-1873, Journal of immunology
Human blood lymphocytes activated in vitro with antigen to which the donor is reactive are capable of suppressing the secondary proliferative response of autochthonous fresh cells to antigen. Both antigen-specific and antigen-nonspecific suppression can be detected in each experiment. These suppressor cells act by decreasing the number of lymphocytes entering the proliferative response rather than by slowing or otherwise inhibiting ongoing proliferation. The suppressor cells must be added soon after fresh cells are stimulated with antigen to be effective, but the suppressor cells themselves need not proliferate to exert their effect. Suppressor cells are optimally effective when added in numbers equal to those of the responding population, but still exert a significant effect at one-eighth that number
— id: 14599, year: 1979, vol: 122, page: 1867, stat: Journal Article,

EFFECTS OF LITHIUM-CHLORIDE ON LYMPHOCYTE-RESPONSES IN A CHILD WITH IMMUNODEFICIENCY AND INFLAMMATORY BOWEL-DISEASE
Borkowsky, W; Shenkman, L; Sansaricq, C; Snyderman, S
1979 ;13(4):446-446, Pediatric research
— id: 30110, year: 1979, vol: 13, page: 446, stat: Journal Article,

Differential inhibition of adenosine deaminase deficient peripheral blood lymphocytes and lymphoid line cells by deoxyadenosine and adenosine
Hirschhorn R; Bajaj S; Borkowsky W; Kowalski A; Hong R; Rubinstein A; Papageorgiou P
1979 Feb;42(2):418-423, Cellular immunology
— id: 14600, year: 1979, vol: 42, page: 418, stat: Journal Article,

Erythrocyte adenosine deaminase deficiency without immunodeficiency. Evidence for an unstable mutant enzyme
Hirschhorn R; Roegner V; Jenkins T; Seaman C; Piomelli S; Borkowsky W
1979 Oct;64(4):1130-1139, Journal of clinical investigation
— id: 14597, year: 1979, vol: 64, page: 1130, stat: Journal Article,

REVERSAL OF AN ABNORMALITY OF POLYMORPHONUCLEAR LEUKOCYTE CHEMOTAXIS WITH LITHIUM
Perez, HD; Kaplan, H; Shenkman, L; Borkowsky, W; Goldstein, IM
1979 ;27(2):A353-A353, Clinical research
— id: 30121, year: 1979, vol: 27, page: A353, stat: Journal Article,

Purine and phosphoribosylpyrophosphate metabolism of lymphocytes and erythrocytes of an adenosine deaminase deficient immunocompetent child
Reem GH; Borkowsky W; Hirschhorn R
1979 May;13(5 Pt 1):649-653, Pediatric research
Purine metabolism and phosphoribosylpyrophosphate content of lymphocytes and erythrocytes were studied in an immunocompetent black male child with a total deficiency of erythrocyte and partial deficiency of lymphocyte adenosine deaminase. The partial genetic deficiency of adenosine deaminase was demonstrated in intact lymphocytes, and was approximately one third of the deaminating activity of control lymphocytes. Intact lymphocytes of the patient did not incorporate adenosine at a faster rate than those of control lymphocytes. The patient's erythrocytes deaminating activity was low and adenine ribonucleotide synthesis from adenosine was increased several fold, while adenine incorporation into purine ribonucleotides was comparable to that of control erythrocytes. Transfusion with packed erythrocytes temporarily improved the deaminating capacity of circulating erythrocytes, but did not reduce the elevated incorporation of adenosine into purine ribonucleotides. Phosphoribosylpyrophosphate content of the patient's lymphocytes and erythrocytes was not diminished. Incubation of erythrocytes with adenosine lowered phosphoribosylpyrophosphate content while incubation with phosphate increased phosphoribosylpyrophosphate content to the same extent in mutant and control erythrocytes
— id: 14598, year: 1979, vol: 13, page: 649, stat: Journal Article,

EFFECTS OF LITHIUM ON SUPPRESSOR-ENRICHED AND SUPPRESSOR- DEPLETED MONONUCLEAR CELL PREPARATIONS
Wadler, S; Shenkman, L; Borkowsky, W
1979 ;27(3):A608-A608, Clinical research
— id: 30080, year: 1979, vol: 27, page: A608, stat: Journal Article,

EFFECTS OF LITHIUM ON SUPPRESSOR-ENRICHED AND SUPPRESSOR- DEPLETED MONONUCLEAR CELL PREPARATIONS
Wadler, S; Shenkman, L; Borkowsky, W
1979 ;27(2):A339-A339, Clinical research
— id: 30120, year: 1979, vol: 27, page: A339, stat: Journal Article,

ADENOSINE-DEAMINASE DEFICIENCY WITHOUT IMMUNODEFICIENCY
Borkowsky, W; Gershon, AA; Hirschhorn, R
1978 ;12(4):478-478, Pediatric research
— id: 29939, year: 1978, vol: 12, page: 478, stat: Journal Article,

ADENOSINE-DEAMINASE DEFICIENCY IN A NORMAL CHILD - IMMUNOLOGICAL AND BIOCHEMICAL STUDIES
Hirschhorn, R; Borkowsky, W; Bajaj, S; Gershon, A
1978 ;26(3):A552-A552, Clinical research
— id: 29932, year: 1978, vol: 26, page: A552, stat: Journal Article,

ADENOSINE-DEAMINASE DEFICIENCY AND IMMUNODEFICIENCY - COMPARISON OF CLINICAL PHENOTYPE AND RESIDUAL ENZYME-ACTIVITY
Hirschhorn, R; Roegner, V; Borkowsky, W
1978 ;30(6):A30-A30, American journal of human genetics
— id: 30050, year: 1978, vol: 30, page: A30, stat: Journal Article,

Enhancement of lymphocyte and macrophage function in vitro by lithium chloride
Shenkman L; Borkowsky W; Holzman RS; Shopsin B
1978 Jun;10(2):187-192, Clinical immunology & immunopathology
— id: 14601, year: 1978, vol: 10, page: 187, stat: Journal Article,

SEXUAL ABUSE AND HERPETIC GENITAL INFECTION IN CHILDREN
Gershon, AA; Fish, I; Borkowsky, W
1976 ;89(2):338-338, Journal of pediatrics
— id: 28747, year: 1976, vol: 89, page: 338, stat: Journal Article,

LITHIUM-CHLORIDE, AN IMMUNOLOGICAL ADJUVANT
SHENKMAN, L; BORKOWSKY, W; HOLZMAN, RS; SHOPSIN, B
1976 ;24(5):A634-A634, Clinical research
— id: 98705, year: 1976, vol: 24, page: A634, stat: Journal Article,

Myelitis associated with genital herpes in a child
Shturman-Ellstein R; Borkowsky W; Fish I; Gershon AA
1976 Mar;88(3):523-523, Journal of pediatrics
— id: 14602, year: 1976, vol: 88, page: 523, stat: Journal Article,