Shaffiq Essajee

HIV testing for children in resource-limited settings: what are we waiting for?
Kellerman, Scott; Essajee, Shaffiq
2010 Jul;7(7):e1000285-e1000285, PLoS medicine
— id: 134326, year: 2010, vol: 7, page: e1000285, stat: Journal Article,

Early treatment of HIV: implications for resource-limited settings
Hobbs, Charlotte V; Essajee, Shaffiq M
2009 May;4(3):222-231, Current Opinion in HIV & AIDS
PURPOSE OF REVIEW: We review the current literature supporting adoption of higher CD4 thresholds for initiation of antiretroviral treatment and survey progress in adoption of early treatment policies in resource-limited settings. We highlight some of the challenges and opportunities implementation of early treatment will bring. RECENT FINDINGS: The initial success of combination antiretroviral treatment resulted in the recommendation to treat early all individuals with HIV. However, the gradual realization that antiretroviral treatment was associated with toxicity led to a more tempered approach. Recent cohort studies and some clinical trials have shown that delaying treatment is associated with increased morbidity and mortality. SUMMARY: Early treatment is routinely practiced in developed countries. Now, early treatment is being adopted as a strategy in many resource-limited settings. The implications of this policy shift are not known, but we predict early treatment will have important consequences for the health system, the individual, and the community. Whereas these consequences will bring significant challenges, the increased numbers of HIV-infected individuals on treatment will result in many new opportunities - antiretroviral treatment will become less expensive, systems to deliver chronic care will be strengthened, and the policy shift will focus greater attention on pregnant women and children. Finally, some authors postulate that early treatment may impact HIV transmission
— id: 100201, year: 2009, vol: 4, page: 222, stat: Journal Article,

Monitoring virologic responses to antiretroviral therapy in HIV-infected adults in Kenya: evaluation of a low-cost viral load assay
Sivapalasingam, Sumathi; Wangechi, Beatrice; Marshed, Fatuma; Laverty, Maura; Essajee, Shaffiq; Holzman, Robert S; Valentine, Fred
2009 ;4(8):e6828-e6828, PLoS ONE
BACKGROUND: A key advantage of monitoring HIV viral load (VL) in persons receiving antiretroviral therapy (ART) is the ability to detect virologic failure before clinical deterioration or resistance occurs. Detection of virologic failure will help clarify the need for enhanced adherence counseling or a change to second- line therapy. Low-cost, locally performable alternates to expensive VL assays are needed where resources are limited. METHODOLOGY/PRINCIPAL FINDINGS: We monitored the response to 48-week ART in 100 treatment-naive Kenyan adults using a low-cost VL measurement, the Cavidi reverse transcriptase (RT) assay and gold-standard assays, Roche RNA PCR and Bayer Versant HIV-1 RNA (bDNA) assays. In Altman-Bland plots, the mean difference in viral loads between the three assays was small (<0.5 log(10) copies/mL). However, the limits of agreement between the methods exceeded the biologically relevant change of 0.5 log copies/ml. Therefore, the RT assay cannot be used interchangeably with the other assays to monitor individual patients. The RT assay was 100% sensitive in detecting viral loads of > or =400 copies/ml compared to gold-standard assays. After 24 weeks of treatment, viral load measured by the RT assay was undetectable in 95% of 65 patients with undetectable RNA PCR VL (<400 copies/ml), 90% of 67 patients with undetectable bDNA VL, and 96% of 57 patients with undetectable VL in both RNA PCR and bDNA assays. The negative predictive value of the RT assay was 100% compared to either assay; the positive predictive value was 86% compared to RNA PCR and 70% compared to bDNA. CONCLUSION: The RT assay compared well with gold standard assays. Our study highlights the importance of not interchanging viral load assays when monitoring an individual patient. Furthermore, the RT assay may be limited by low positive predictive values when used in populations with low prevalence of virologic failure
— id: 101963, year: 2009, vol: 4, page: e6828, stat: Journal Article,

A Reverse Transcriptase Assay for Early Diagnosis of Infant HIV Infection in Resource-limited Settings
Sivapalasingam, Sumathi; Patel, Usha; Itri, Vincenza; Laverty, Maura; Mandaliya, Kishorchandra; Valentine, Fred; Essajee, Shaffiq
2007 Oct;53(5):355-358, Journal of tropical pediatrics
Early diagnosis of pediatric HIV infection is confounded by persistence of maternal antibodies until 18 months, necessitating the use of expensive assays such as HIV-1 DNA PCR, an untenable option in resource-limited settings. This is the first report of a low-cost, commercial, reverse transcriptase (RT) assay for the diagnosis of HIV-1 infection in infants. RT assays were performed on 42 samples from 30 HIV-exposed Kenyan infants under 15 months of age. When correlated with serologic testing conducted after 18 months, the sensitivity, specificity, positive and negative predictive values of the RT assay were 92%, 93%, 87% and 96%. A low-cost assay for infant HIV diagnosis is urgently needed, and these results merit further evaluation.
— id: 72999, year: 2007, vol: 53, page: 355, stat: Journal Article,

Human immunodeficiency virus (HIV) reverse transcriptase activity correlates with HIV RNA load: implications for resource-limited settings
Sivapalasingam, Sumathi; Essajee, Shaffiq; Nyambi, Phillipe N; Itri, Vincenza; Hanna, Bruce; Holzman, Robert; Valentine, Fred
2005 Aug;43(8):3793-3796, Journal of clinical microbiology
Measurement of human immunodeficiency virus type 1 (HIV-1) plasma RNA levels using Roche AMPLICOR version 1.5 (HIV RNA) is an integral part of monitoring HIV-infected patients in industrialized countries. These assays are currently unaffordable in resource-limited settings. We investigated a reverse transcriptase (RT) assay as a less expensive alternative for measuring viral burden that quantifies RT enzyme activity in clinical plasma samples. A comparison of RT and HIV RNA assays was performed on 29 paired plasma samples from patients living in the United States and 21 paired plasma samples from patients living in Cameroon. RT levels correlated significantly with plasma HIV RNA viral loads in plasma from U.S. patients (r = 0.898; P < 0.001) and Cameroonian patients, a majority of whom were infected with HIV-1 clade type CRF02_AG (r = 0.669; P < 0.01). Among 32 samples with HIV viral load of >2,000 copies/ml, 97% had detectable RT activity. One Cameroon sample had undetectable RNA viral load but detectable RT activity of 3 fg/ml. The RT assay is a simple and less expensive alternative to the HIV RNA assay. Field studies comparing these assays in resource-limited settings are warranted to assess the practicality and usefulness of this assay for monitoring HIV-infected patients on antiretroviral therapy
— id: 57865, year: 2005, vol: 43, page: 3793, 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,

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,

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,

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,

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,

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,