Demetre C Daskalakis, M.D.

HIV Diagnostic Testing: Evolving Technology and Testing Strategies
Daskalakis, Demetre
2011 Feb-Mar;19(1):18-22, Topics in antiviral medicine
Detection of acute HIV infection is important to public health because this stage is one of high infectiousness and appears to account for a disproportionate amount of HIV transmission. Newer technologies in HIV testing, including third-generation enzyme immunoassays (EIAs) that detect anti-HIV IgM and IgG antibodies, fourth-generation combination EIAs that detect both anti-HIV antibodies and HIV p24 antigen, and nucleic acid-based testing for HIV RNA, have markedly reduced the interval between infection and detection of infection. Rapid diagnostic tests including assays for IgG and IgM anti-HIV antibodies have high sensitivity and specificity. The availability and wide use of these newer technologies have motivated review of recommended HIV testing algorithms. Individuals' knowledge of their HIV serostatus contributes to reducing transmission risk behaviors. Thus, widespread testing, facilitated by newer technology, allows more individuals to know their serostatus and is the first step in any successful effort to curb the incidence of HIV infection. This article summarizes a lecture by Demetre Daskalakis, MD, at the New York City IAS-USA continuing medical education program held in November 2009 and re-presented in December 2010
— id: 136945, year: 2011, vol: 19, page: 18, stat: Journal Article,

Substance Use in the Bathhouses: Misuse of Prescription and Sex Enhancing Drugs is On Par with Sexual Behavior as an HIV Risk Factor
McNeely, J.; Silvera, R.; Ramos, M.; Bernstein, K.; Gourevitch, M. N.; Aberg, J.; Daskalakis, D. D.
2011 ;32(1):56-57, Substance abuse
— id: 128811, year: 2011, vol: 32, page: 56, stat: Journal Article,

Awareness of post-exposure HIV prophylaxis in high-risk men who have sex with men in New York City
Mehta, Sapna A; Silvera, Richard; Bernstein, Kyle; Holzman, Robert S; Aberg, Judith A; Daskalakis, Demetre C
2011 Jun;87(4):344-348, Sexually transmitted infections
Objectives To understand the factors associated with knowledge of non-occupational post-exposure prophylaxis (nPEP) and pre-exposure prophylaxis (PrEP), bathhouse patrons in New York City (NYC) were surveyed. Methods 554 men who have sex with men (MSM) at two NYC bathhouses were given a standardised survey focused on nPEP and PrEP at the time of HIV testing. Results In the previous 90 days, 63% of respondents reported unprotected sex with a male partner and 7% reported any sex with a known HIV-positive male partner. Less than half reported having a primary provider (primary care practitioner) who was aware of their MSM behaviour. 201 men (36%) were aware of nPEP or PrEP. In univariate analyses, race/ethnicity, previous HIV testing, gay self-identification, higher education level, having a primary provider aware of MSM behaviour, reported interaction with the healthcare system, use of the internet for meeting sex partners, reporting unprotected sex in the previous 90 days, reporting any sex with an HIV-positive male partner in the previous 90 days and having a higher number of sex partners were each significantly associated with being aware of nPEP or PrEP. In multivariate analysis, having a higher number of sex partners was significantly associated (OR 5.10, p=0.02) with post-exposure prophylaxis (PEP)/PrEP knowledge and disclosure to a primary care provider was also associated, although less robustly (OR 2.10, p=0.06). Conclusions Knowledge of nPEP or PrEP among sexually active MSM in NYC is low and is associated with having a primary provider aware of their patient's same-sex behaviours. These findings show the need for improving education about nPEP among high-risk MSM in NYC and the role of providers in these efforts
— id: 132706, year: 2011, vol: 87, page: 344, stat: Journal Article,

REASONS FOR HIV TESTING AMONG MSM ATTENDING A COMMERCIAL SEX VENUE-BASED TESTING PROGRAM IN NEW YORK CITY
Bearnot, B; Silvera, R; Torres, K; Kwan, C; Aberg, J; Daskalakis, D
2010 JUN ;25(9):380-380, Journal of general internal medicine
— id: 111916, year: 2010, vol: 25, page: 380, 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,

Determinants of Protection among HIV-Exposed Seronegative Persons: An Overview
Lederman, Michael M.; Alter, Galit; Daskalakis, Demetre C.; Rodriguez, Benigno; Sieg, Scott F.; Hardy, Gareth; Cho, Michael; Anthony, Donald; Harding, Clifford; Weinberg, Aaron; Silverman, Robert H.; Douek, Daniel C.; Margolis, Leonid; Goldstein, David B.; Carrington, Mary; Goedert, James J.
2010 NOV 1 ;202(5):S333-S338, Journal of infectious diseases
Both clinical experience and a growing medical literature indicate that some persons who have been exposed to human immunodeficiency virus (HIV) infection remain uninfected. Although in some instances this may represent good fortune, cohorts of uninfected persons have been reported who are considered at high risk for infection. In these cohorts a variety of characteristics have been proposed as mediating protection, but to date only the 32-base pair deletion in the chemokine (C-C motif) receptor 5 gene, which results in complete failure of cell surface expression of this coreceptor, has been associated with high-level protection from HIV infection. With this in mind, there are probably many other factors that may individually or in combination provide some level of protection from acquisition of HIV infection. Because some of these factors are probably incompletely protective or inconsistently active, identifying them with confidence will be difficult. Nonetheless, clarifying the determinants of protection against HIV infection is a high priority that will require careful selection of high-risk uninfected cohorts, who should undergo targeted studies of plausible mediators and broad screening for unexpected determinants of protection
— id: 113920, year: 2010, vol: 202, page: S333, stat: Journal Article,

CURRENT SUBSTANCE MISUSE AND HIV RISK BEHAVIOR AMONG HIGHLY SEXUALLY ACTIVE MEN WHO HAVE SEX WITH MEN (MSM) ATTENDING COMMERCIAL SEX VENUES, EVENTS AND PARTIES (CSVEP) IN NEW YORK CITY
McNeely, J; Silvera, R; Torres, K; Bernstein, K; Aberg, J; Gourevitch, M; Daskalakis, D
2010 JUN ;25(9):250-250, Journal of general internal medicine
— id: 111910, year: 2010, vol: 25, page: 250, stat: Journal Article,

The Development and Implementation of an Outreach Program to Identify Acute and Recent HIV Infections in New York City
Silvera, Richard; Stein, Dylan; Hutt, Richard; Hagerty, Robert; Daskalakis, Demetre; Valentine, Fred; Marmor, Michael
2010 ;4:76-83, Open AIDS journal
INTRODUCTION: Since 2004, the authors have been operating First Call NYU, an outreach program to identify acute and recent HIV infections, also called primary HIV infections, among targeted at-risk communities in the New York City (NYC) metropolitan area. MATERIALS AND METHODOLOGY: First Call NYU employed mass media advertising campaigns, outreach to healthcare providers in NYC, and Internet-based efforts including search engine optimization (SEO) and Internet-based advertising to achieve these goals. RESULTS: Between October 2004 and October 2008, 571 individuals were screened through this program, leading to 446 unique, in-person screening visits. 47 primary HIV infections, including 14 acute and 33 recent HIV infections, were identified. DISCUSSION: Internet and traditional recruitment methods can be used to increase self-referrals for screening following possible exposure to HIV. CONCLUSION: Community education of at-risk groups, with the goal of increased self-diagnosis of possible acute HIV infection, may be a useful addition to traditional efforts to identify such individuals
— id: 109049, year: 2010, vol: 4, page: 76, 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,

Purified trout egg vitelline envelope proteins VEbeta and VEgamma polymerize into homomeric fibrils from dimers in vitro
Darie, Costel C; Janssen, William G; Litscher, Eveline S; Wassarman, Paul M
2008 Feb;1784(2):385-392, Biochimica & biophysica acta
The rainbow trout egg vitelline envelope (VE) is composed of three proteins, called VEalpha ( approximately 58-60kDa Mr), VEbeta ( approximately 52kDa Mr), and VEgamma ( approximately 47kDa Mr). Each of these proteins is related to mouse egg zona pellucida (ZP) glycoproteins, called ZP1, ZP2, and ZP3, and possesses a ZP domain that has been implicated in the polymerization of the proteins into long, interconnected fibrils or filaments. Here, trout egg VEbeta and VEgamma were purified to homogeneity and analyzed under various experimental conditions (SDS-PAGE, Blue Native-(BN-)PAGE, size-exclusion chromatography, and transmission electron microscopy) to determine whether individual VE proteins would polymerize into fibrils in vitro. Such analyses revealed that in the presence of 6M urea each VE protein is present primarily as monomers and as small oligomers (dimers, tetramers, etc.). However, either a reduction in urea concentration or a complete removal of urea results in the polymerization of VEbeta and VEgamma dimers into very large oligomers. Mixtures of VEbeta and VEgamma also give rise to large oligomers. Under these conditions, VE proteins are visualized by transmission electron microscopy as aggregates of long fibrils, with each fibril composed of contiguous beads located periodically along the fibril. The relationship between the behavior of fish egg VE proteins and mouse ZP glycoproteins, as well as other ZP domain-containing proteins, is discussed
— id: 111669, year: 2008, vol: 1784, page: 385, stat: Journal Article,

Syphilis: continuing public health and diagnostic challenges
Daskalakis, Demetre
2008 May;5(2):72-77, Current HIV/AIDS reports
As the 'great imitator' of disease, syphilis, caused by the bacterium Treponema pallidum, continues to be a conceptually elusive condition that is surrounded by diagnostic ambiguity and clinical misunderstanding. Concurrent HIV infection adds further difficulty by introducing the oldest and most confusing medical conundrum into the socially and biologically complex situation of treating patients with a virus we are still only learning to manage. Syphilis continues to be a challenge to the health of men who have sex with men and people of color as infection rates continue to increase within these substantial subgroups living with HIV. As the resurgence of syphilis continues, a clear understanding of diagnostic testing, disease-staging paradigms, and treatment strategies are necessary for optimal management of the HIV co-infected patient
— id: 111750, year: 2008, vol: 5, page: 72, stat: Journal Article,

Immune Driven Recombination Leads to Loss of Control Following HIV Superinfection
Streeck, H; Li, B; Poon, AF; Schneidewind, A; Gladden, AD; Power, K; Daskalakis, D; Bazner, S; Zuniga, R; Brander, C; Rosenberg, ES; Frost, SD; Allen, TM
2008 OCT ;24(1):79-79, AIDS research & human retroviruses
— id: 91417, year: 2008, vol: 24, page: 79, stat: Journal Article,

Immune-driven recombination and loss of control after HIV superinfection
Streeck, H; Li, B; Poon, AFY; Schneidewind, A; Gladden, AD; Power, KA; Daskalakis, D; Bazner, S; Zuniga, R; Brander, C; Rosenberg, ES; Frost, SDW; Altfeld, M; Allen, TM
2008 AUG 4 ;205(8):1789-1796, Journal of experimental medicine
After acute HIV infection, CD8(+) T cells are able to control viral replication to a set point. This control is often lost after superinfection, although the mechanism behind this remains unclear. In this study, we illustrate in an HLA-B27(+) subject that loss of viral control after HIV superinfection coincides with rapid recombination events within two narrow regions of Gag and Env. Screening for CD8(+) T cell responses revealed that each of these recombination sites (similar to 50 aa) encompassed distinct regions containing two immunodominant CD8 epitopes (B27-KK10 in Gag and Cw1-CL9 in Env). Viral escape and the subsequent development of variant-specific de novo CD8(+) T cell responses against both epitopes were illustrative of the significant immune selection pressures exerted by both responses. Comprehensive analysis of the kinetics of CD8 responses and viral evolution indicated that the recombination events quickly facilitated viral escape from both dominant WT- and variant-specific responses. These data suggest that the ability of a superinfecting strain of HIV to overcome preexisting immune control may be related to its ability to rapidly recombine in critical regions under immune selection pressure. These data also support a role for cellular immune pressures in driving the selection of new recombinant forms of HIV
— id: 86812, year: 2008, vol: 205, page: 1789, stat: Journal Article,

Another perfect storm: Shigella, men who have sex with men, and HIV
Daskalakis, Demetre C; Blaser, Martin J
2007 Feb 1;44(3):335-337, Clinical infectious diseases
— id: 78759, year: 2007, vol: 44, page: 335, stat: Journal Article,

Sequence variation occurs in CD4 epitopes during early HIV infection
Rychert, Jenna; Saindon, Suzanne; Placek, Sarah; Daskalakis, Demetre; Rosenberg, Eric
2007 Nov 1;46(3):261-267, Journal of acquired immune deficiency syndromes. JAIDS
OBJECTIVE: To determine whether viral sequence variation occurs in HIV-specific CD4 epitopes during early HIV infection. METHODS: Gag, Nef, and integrase (Int) sequences were obtained from the plasma of 7 subjects identified during acute HIV-1 infection. Changes in the viral sequence were determined based on comparison of sequences obtained at 2 time points during early infection. Peptide-specific CD4+ T-cell responses were measured at matched time points using interferon-gamma enzyme-linked immunosorbent spot assays to identify CD4 epitopes. RESULTS: An average of 4 mutations were identified per subject. The majority of the mutations were nonsynonymous and resulted in a total of 6 amino acid changes in Gag, 7 changes in Nef, and 6 changes and a deletion in Int. Half of the sequence changes were within recognized CD4 epitopes. Mutations within CD4 epitopes were coincident with changes in the peptide-specific CD4 response. CONCLUSION: These data indicate that sequence variation occurs within recognized CD4 epitopes during early HIV infection. Furthermore, it suggests that mutations within HIV-specific CD4 epitopes may affect T helper cell function
— id: 78758, year: 2007, vol: 46, page: 261, stat: Journal Article,

Challenging cases in HIV medicine from Bellevue Hospital: HIV and syphilis--diagnostic and therapeutic approach
Trevejo-Nunez, Giraldina; Daskalakis, Demetre C
2007 ;9(2):42-42, MedGenMed: Medscape General Medicine
— id: 75396, year: 2007, vol: 9, page: 42, stat: Journal Article,

HIV as an emerging chronic disease: the challenge of "living with living"
Daskalakis, Demetre C
2006 ;19(1):8-13, Body Positive
— id: 78761, year: 2006, vol: 19, page: 8, stat: Journal Article,

When your new diagnosis is with HIV
Daskalakis, Demetre C
2006 ;19(1):13-14, Body Positive
— id: 78760, year: 2006, vol: 19, page: 13, stat: Journal Article,

Case files from the Bellevue Hospital Center at New York University--lipoatrophy following long-term antiretroviral therapy
Daskalakis, Demetre; Aberg, Judith A
2005 ;7(4):9-9, MedGenMed: Medscape General Medicine
— id: 64585, year: 2005, vol: 7, page: 9, stat: Journal Article,