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Summary Background In DISCOVER, a multinational, randomised controlled trial, emtricitabine and tenofovir alafenamide compared with emtricitabine and tenofovir disoproxil fumarate showed non-inferior efficacy for HIV prevention and improved bone mineral density and renal safety biomarkers at week 48. We report outcomes analysed after all participants had completed 96 weeks of follow-up. Methods This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in Europe and North America. Adult cisgender men and transgender women who have sex with men, both with a high risk of acquiring HIV as determined by self-reported sexual behaviour or recent sexually transmitted infections, were randomly assigned (1:1) to receive either emtricitabine and tenofovir alafenamide (200/25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine and tenofovir disoproxil fumarate (200/300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). The primary efficacy outcome was incident HIV infection. Incidence of HIV-1 infection per 100 person-years was assessed when the last participant had completed 96 weeks of follow-up. This trial is registered with ClinicalTrials.gov , number NCT02842086 . Findings Between Sept 13, 2016, and June 30, 2017, 5387 participants were randomly assigned to receive emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693), contributing 10 081 person-years of follow-up. At 96 weeks of follow-up, there were eight HIV infections in participants who had received emtricitabine and tenofovir alafenamide (0·16 infections per 100 person-years [95% CI 0·07–0·31]) and 15 in participants who had received emtricitabine and tenofovir disoproxil fumarate (0·30 infections per 100 person-years [0·17–0·49]). Emtricitabine and tenofovir alafenamide maintained its non-inferiority to emtricitabine and tenofovir disoproxil fumarate for HIV prevention (IRR 0·54 [95% CI 0·23–1·26]). Approximately 78–82% of participants reported taking study medication more than 95% of the time across all study visits. Rates of sexually transmitted infections remained high and similar across groups (21 cases per 100 person-years for rectal gonorrhoea and 28 cases per 100 person-years for rectal chlamydia). Emtricitabine and tenofovir alafenamide continued to show superiority over emtricitabine and tenofovir disoproxil fumarate in all but one of the six prespecified bone mineral density and renal biomarkers. There was more weight gain among participants who had received emtricitabine and tenofovir alafenamide (median weight gain 1·7 kg vs 0·5 kg, p Interpretation Emtricitabine and tenofovir alafenamide is safe and effective for longer-term pre-exposure prophylaxis in cisgender men and transgender women who have sex with men. Funding Gilead Sciences.

Routine data on vaccine uptake are not disaggregated by lesbian, gay, bisexual, transgender, queer, and other sexual identities (LGBTQ+) populations, despite higher risk of infection and severe disease. We found comparable vaccination uptake patterns among 1032 LGBTQ+ New Yorkers and the general population. We identified critical socioeconomic factors that were associated with vaccine hesitancy in this economically vulnerable population.

IntroductionHIV transmission within serodifferent heterosexual couples plays a key role in sustaining the global HIV pandemic. In the USA, transmission within established mixed-status couples accounts for up to half of all new HIV infections among heterosexuals. Oral HIV pre-exposure prophylaxis (PrEP) is a highly effective prevention method, although underutilised among serodifferent couples. Moreover, there is a dearth of research on US HIV-serodifferent couples’ perspectives and use of PrEP, alone or in combination with other prevention methods. In this paper, we describe the study protocol for the Magnetic Couples Study, designed to fill critical knowledge gaps regarding HIV-serodifferent heterosexual couples’ perspectives, experiences and utilisation of PrEP.Methods and analysisThe Magnetic Couples Study is a mixed methods prospective cohort study designed to describe temporal patterns and identify determinants at multiple levels (individual, couple, HCF) of PrEP outcomes along the care continuum (PrEP awareness, linkage, uptake, retention and medication adherence) among HIV-serodifferent heterosexual couples residing in New York City. The study will also examine clinical management of PrEP, side effects and changes in sexual-related and substance use–related behaviour. A prospective cohort of 230 mixed-status couples already on oral PrEP was recruited, with quarterly assessments over 18 months; in addition, a cross-sectional sample of 150 mixed-status couples not currently on PrEP was recruited. In-depth semistructured qualitative interviews were conducted with a subsample of 25 couples. Actor-partner interdependence modelling using multilevel analysis will be employed for the analysis of longitudinal dyadic data. Framework analysis will be used to analyse qualitative data. A parallel convergent design will be used for mixed methods integration.Ethics and disseminationThe study was approved by the University of Rochester Institutional Review Board (RSRB00052766). Study findings will be disseminated to community members and providers and to researchers and policy makers.

We evaluated the relationship between 2 types of social relationships, ie, (1) external support for use of HIV pre-exposure prophylaxis (PrEP) and related study supplies and (2) participants' disclosure of PrEP use and condom use and HIV PrEP adherence among daily-dosing regimen participants in HIV Prevention Trials Network (HPTN) 067, an open-label trial of oral tenofovir (TFV) disoproxil fumarate (TDF) 300 mg/emtricitabine (FTC) 200 mg.Using HPTN 067 survey data, we developed scales examining (1) Low Perceived External Support for PrEP: low perceived support by others for PrEP use or perceived negative reactions to the pill case (scoring ranges from 0 to 2) and (2) Participant-Staff Disclosure Challenges Scale, which identifies challenges to sharing nonuse of PrEP or condoms to study staff (scoring ranges from 0 to 4); these scales are the primary independent variables. Adherence, the dependent variable, was determined using log-transformed plasma TFV concentrations. generalized estimating equation (GEE) linear regression was used to assess the association between both scales and adherence.Participants (n = 161) included HIV-uninfected women in South Africa, and men who have sex with men and transgender women, in Thailand and the United States. In multivariable analyses, higher scores in the Participant-Staff Disclosure Challenges Scale were significantly associated with lower PrEP adherence [exp(β) = 0.62, 95% CI: (0.46 to 0.84); P = 0.002] as were increased days since the last PrEP dose [exp(β) = 0.73, 95% CI: (0.65 to 0.83); P ≤ 0.001].Given the association with adherence, study staff-participant interactions and participants' disclosure of PrEP challenges may be worthwhile intervention targets for improving PrEP adherence in confirmatory studies.

Background The HIV Prevention Trials Network (HPTN) 067/Alternative Dosing to Augment PrEP Pill Taking (ADAPT) Study evaluated the feasibility of daily and nondaily human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) regimens among high-risk populations, including men who have sex with men (MSM) and transgender women, in Bangkok, Thailand and Harlem, New York. We used a mathematical model to predict the efficacy and effectiveness of different dosing regimens. Methods An individual-based mathematical model was used to simulate annual HIV incidence among MSM cohorts. PrEP efficacy for covered sex acts, as defined in the HPTN 067/ADAPT protocol, was estimated using subgroup efficacy estimates from the preexposure prophylaxis initiative (iPrEx) trial. Effectiveness was estimated by comparison of the HIV incidence with and without PrEP use. Results We estimated that PrEP was highly protective (85%–96% efficacy across regimens and sites) for fully covered acts. PrEP was more protective for partially covered acts in Bangkok (71%–88% efficacy) than in Harlem (62%–81% efficacy). Our model projects 80%, 62%, and 68% effectiveness of daily, time-driven, and event-driven PrEP for MSM in Harlem compared with 90%, 85%, and 79% for MSM in Bangkok. Halving the efficacy for partially covered acts decreases effectiveness by 8–9 percentage points in Harlem and by 5–9 percentage points in Bangkok across regimens. Conclusions Our analysis suggests that PrEP was more effective among MSM in Thailand than in the United States as a result of more fully covered sex acts and more pills taken around partially covered acts. Overall, nondaily PrEP was less effective than daily PrEP, especially in the United States where the sex act coverage associated with daily use was substantially higher.

Author(s): Velloza, Jennifer; Bacchetti, Peter; Hendrix, Craig W; Murnane, Pamela; Hughes, James P; Li, Maoji; Curlin, Marcel E; Holtz, Timothy H; Mannheimer, Sharon; Marzinke, Mark A; Amico, K Rivet; Liu, Albert; Piwowar-Manning, Estelle; Eshleman, Susan H; Dye, Bonnie J; Gandhi, Monica; Grant, Robert M; HPTN 067/ADAPT Study Team | Abstract: BackgroundThe effectiveness of oral emtricitabine (FTC)/tenofovir (TFV) disoproxil fumarate-based HIV pre-exposure prophylaxis (PrEP) depends on adherence. Pharmacologic measures help interpret patterns and predictors of PrEP adherence.SettingWe analyzed data from the subsample of men who have sex with men enrolled in HPTN 067/ADAPT in Bangkok, Thailand, and Harlem, NY, U.S.MethodsAfter a 5-week directly observed therapy period, participants were randomized to daily, time-driven, or event-driven PrEP. Follow-up occurred at weeks 4, 12, and 24 after randomization. Plasma and hair FTC/TFV levels indicated short- and long-term PrEP use, respectively. Electronic pill bottle data (Wisepill) were collected weekly. Pearson correlation coefficients between PrEP use measures were calculated; linear mixed models assessed predictors of plasma and hair drug concentrations.ResultsAmong 350 participants (median age: 31 years, interquartile range: 25-38), 49.7% were from Harlem, half had less than college education, and 21% reported heavy alcohol use. In multivariable models, being enrolled in Harlem, being in non-daily arms, and having less than college education were associated with lower hair FTC/TFV concentrations; heavy alcohol use was associated with higher concentrations. Similar results were found for plasma concentrations by site and arm, but older age and greater number of sex partners were associated with higher concentrations. Hair and plasma FTC/TFV concentrations were moderately correlated with Wisepill data (r ≥ 0.29) across visits.ConclusionsIn HPTN067, plasma, hair, and Wisepill data correlated with one another and served as complementary adherence measures. Site, arm, education, age, alcohol, and sexual behavior influenced patterns of adherence.

Accurate HIV risk assessment among men who have sex with men (MSM) is important to help providers assess risk, and target HIV prevention interventions. We sought to develop an evidence-based HIV risk assessment tool for US MSM that is inclusive of Black MSM. Data from four large longitudinal cohorts of MSM were used to develop (EXPLORE), and validate (VAX004, HPTN061, and HVTN505). These data included visits in which participants self-reported HIV risk behavior and underwent HIV testing. We developed a pooled logistic model for incident HIV infection based on self-reported risk behaviors during the 6months before each study visit. A total of 4069 MSM were used for the development cohort, and 8047 MSM in the three validation cohorts through 2013. The final model includes age (

Supplemental Digital Content is available in the text, Objectives: To review the main factors influencing the costs of nondaily oral preexposure prophylaxis (PrEP) with tenofovir (±emtricitabine). To estimate the cost reductions possible with nondaily PrEP compared with daily PrEP for different populations (MSM and heterosexual populations). Design: Systematic review and data triangulation. Methods: We estimated the required number of tablets/person/week for dosing regimens used in the HPTN 067/ADAPT (daily/time-driven/event-driven) and IPERGAY (on-demand) trials for different patterns of sexual intercourse. Using trial data, and behavioural and cost data obtained through systematic literature reviews, we estimated cost savings resulting from tablet reductions for nondaily versus daily oral PrEP, assuming 100% adherence. Results: Among different populations being prioritized for PrEP, the median reported number of days of sexual activity varied between 0 and 2 days/week (0–1.5 days/week for MSM, 1–2 days/week for heterosexual populations). With 100% adherence and two or fewer sex-days/week, HPTN 067/ADAPT nondaily regimens reduced the number of tablets/week by more than 40% compared with daily PrEP. PrEP program costs were reduced the most in settings with high drug costs, for example, by 66–69% with event-driven PrEP for French/US populations reporting on average one sex-day/week. Conclusion: Nondaily oral PrEP could lower costs substantially (>50%) compared with daily PrEP, particularly in high-income countries. Adherence and efficacy data are needed to determine cost-effectiveness.

Resistance to reverse transcriptase and protease inhibitors was frequently detected in HIV from black men who have sex with men (MSM) enrolled in the HIV prevention trials network (HPTN) 061 study. In this study, integrase strand transfer inhibitor (INSTI) resistance was analyzed in black MSM enrolled in HPTN 061 (134 infected at enrollment and 23 seroconverters) and a follow-up study, HPTN 073 (eight seroconverters). The ViroSeq HIV-1 Integrase Genotyping Kit (Abbott Molecular) was used for analysis. Major INSTI resistance mutations were not detected in any of the samples. HIV from 14 (8.4%) of the 165 men, including 4 (12.9%) of 31 seroconverters, had accessory or polymorphic INSTI-associated mutations. The most frequently detected mutation was E157Q. These findings are promising because INSTI-based regimens are now recommended for first-line antiretroviral treatment and because long-acting cabotegravir is being evaluated for pre-exposure prophylaxis.

HPTN 067/ADAPT evaluated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) pre-exposure prophylaxis (PrEP) in women (South Africa) and men who have sex with men (Thailand, US). Participants received once-weekly directly observed TDF/FTC (DOT), and were then randomized to daily, time-driven, or event-driven PrEP. This report describes characterization of 12 HIV seroconversion events in this trial. HIV rapid testing was performed at study sites. Retrospective testing included: 4th generation assays; HIV RNA testing; Western blot; an HIV-1/2 discriminatory assay; resistance testing; and antiretroviral (ARV) drug testing. Six of the 12 seroconverters received TDF/FTC in the DOT phase, but were not randomized (3 were acutely infected at enrollment; 2 were infected during the DOT phase; one was not randomized due to pregnancy). One of the six randomized participants had acute infection at randomization but was not diagnosed for 3-4 months because HIV rapid tests were non-reactive; continued daily PrEP use was associated with false-negative antibody tests and low HIV RNA levels. The five participants infected after randomization included four with low adherence to the PrEP regimen, and one who reported a 7-day period without dosing prior to infection. Three participants had TDF/FTC resistance (M184I, K65R), including two who received only four once-weekly TDF/FTC doses; most TDF/FTC mutations were detected by next generation sequencing only. In HPTN 067/ADAPT, participants who acquired HIV infection had infrequent PrEP dosing or low/suboptimal adherence. Sensitive assays improved detection of HIV infection and drug resistance. Drug resistance was observed with limited PrEP exposure. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

In the United States, little is known about interventions that rely on mobile phones and/or text messaging to improve engagement in HIV care for vulnerable populations. Domestic studies using these technologies as part of the National Institute on Drug Abuse "Seek, Test, Treat, Retain" research initiative were queried regarding intervention components, implementation issues, participant characteristics, and descriptive statistics of mobile phone service delivery. Across five studies with 1,135 predominantly male, minority participants, implementation challenges occurred in three categories: (1) service interruptions; (2) billing/overage issues, and; (3) the participant user experience. Response rules for automated text messages frequently frustrated participants. The inability to reload minutes/texting capacity remotely was a significant barrier to intervention delivery. No study encountered confidentiality breaches. Service interruption was common, even if studies provided mobile phones and plans. Future studies should attend to the type of mobile phone and service, the participant user experience, and human subjects concerns.

INTRODUCTION: Suboptimal ART adherence, despite HIV viral suppression, has been associated with chronic residual inflammation. Whether this association extends to individuals who initiate ART during early HIV infection remains unknown, which was the objective of this study.METHODS: Plasma levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein, serum amyloid A protein (SAA), IL-27, soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, D-dimer and the CD4+/CD8+ T-cell ratio, were analysed at baseline and eight months after ART initiation in treatment-naïve participants with HIV and CD4+ T-cells >500 cells/mm3 enrolled in the immediate arm of START. Adherence was assessed by seven-day self-report. Multivariable linear regression was utilized to analyse the association between ART adherence and each biomarker at the eight-month visit in participants who achieved virologic suppression (RESULTS: We evaluated 1627 participants (422 female) who achieved virologic suppression at the eight-month visit in the period between 2009 and 2013. Median (IQR) CD4+ T-cell count before ART was 651 (585, 769) cells/mm3 . Incomplete adherence was reported in 109 (7%) participants at the eight month visit. After adjusting for covariates, plasma IL-6 was 1.12 (95% CI, 1.00 to 1.26; p = 0.047) fold higher in participants reporting incomplete versus 100% adherence. A similar association for SAA was observed in an exploratory analysis (1.29 (95% CI 1.04 to 1.60); p = 0.02). No significant differences in other biomarkers were observed.CONCLUSIONS: Incomplete ART adherence was associated with higher IL-6 levels in individuals who achieved virologic suppression early after ART initiation in START. A potential similar association for SAA requires confirmation. These findings suggest a role for identifying strategies to maximize ART adherence even during virologic suppression. ClinicalTrials.gov number: NCT00867048.

Supplemental Digital Content is Available in the Text., Background: HPTN 067 assessed the feasibility of daily and non-daily dosing of open-label emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)-based pre-exposure prophylaxis (PrEP). Methods: Factors associated with sex-related PrEP adherence were assessed among men who have sex with men (MSM) randomized to one of 3 PrEP dosing arms in HPTN 067 in New York City. Sex-related PrEP adherence was defined per protocol as at least 1 PrEP tablet taken within 4 days pre-sex and at least 1 additional PrEP tablet taken within 24 hours post-sex, assessed via electronic drug monitoring and weekly interviews. Demographic data and behavioral measures were evaluated for association with sex-related PrEP adherence. Logistic regression for clustered data was used to estimate the unadjusted and adjusted odds ratios. Results: Of 176 randomized MSM participants, 59% were Black, 10% White, 25% Hispanic, and 6% other; median age was 31 years. In the multivariable analyses, higher sex-related PrEP adherence was significantly associated with daily dosing arm, older age, employment, and higher PrEP adherence behavioral skills. Lower sex-related PrEP adherence was significantly associated with identifying as Black or Hispanic (compared with White), opiate use, and reporting “I forgot” as an adherence barrier. Conclusions: This analysis identified populations of MSM who might benefit from additional support to optimize PrEP adherence, including those who are younger, unemployed, or opiate users. MSM with lower PrEP behavioral skills may benefit from targeted interventions. Further study is needed to assess racial and ethnic disparities in PrEP adherence, which may reflect broader social and economic inequalities not captured in this study.

Tenofovir (TFV), a nucleotide reverse transcriptase inhibitor, requires two phosphorylation steps to form a competitive inhibitor of HIV reverse transcriptase. Adenylate kinase 2 (AK2) has been previously demonstrated to phosphorylate tenofovir to tenofovir-monophosphate, while creatine kinase, muscle (CKM), pyruvate kinase, muscle (PKM) and pyruvate kinase, liver and red blood cell (PKLR) each have been found to phosphorylate tenofovir-monophosphate to the pharmacologically active tenofovir-diphosphate. In the present study, genomic DNA isolated from dried blood spots collected from 505 participants from Bangkok, Thailand; Cape Town, South Africa; and New York City, USA were examined for variants in AK2, CKM, PKM, and PKLR using next-generation sequencing. The bioinformatics tools SIFT and PolyPhen predicted that 19 of the 505 individuals (3.7% frequency) carried variants in at least one kinase that would result in a decrease or loss of enzymatic activity. To functionally test these predictions, AK2 and AK2 variants were expressed in and purified from E. coli, followed by investigation of their activities towards tenofovir. Interestingly, we found that purified AK2 had the ability to phosphorylate tenofovir-monophosphate to tenofovir-diphosphate in addition to phosphorylating tenofovir to tenofovir-monophosphate. Further, four of the six AK2 variants predicted to result in a loss or decrease of enzyme function exhibited a ≥30% decrease in activity towards tenofovir in our in vitro assays. Of note, an AK2 K28R variant resulted in a 72% and 81% decrease in the formation of tenofovir-monophosphate and tenofovir-diphosphate, respectively. These data suggest that there are naturally occurring genetic variants that could potentially impact TFV activation.

Suboptimal (ie, ClinicalTrials.gov number NCT00027352

Background Assays that detect HIV antigen (Ag) and antibody (Ab) can be used to screen for HIV infection. Objectives To compare the performance of the BioPlex 2200 HIV Ag-Ab assay and two other Ag/Ab combination assays for detection of acute HIV infection. Study design Samples were obtained from 24 individuals (18 from the US, 6 from South Africa); these individuals were classified as having acute infection based on the following criteria: positive qualitative RNA assay; two negative rapid tests; negative discriminatory test. The samples were tested with the BioPlex assay, the ARCHITECT HIV Ag/Ab Combo test, the Bio-Rad GS HIV Combo Ag-Ab EIA test, and a viral load assay. Results Twelve (50.0%) of 24 samples had RNA detected only ( > 40 to 13,476 copies/mL). Ten (43.5%) samples had reactive results with all three Ag/Ab assays, one sample was reactive with the ARCHITECT and Bio-Rad assays, and one sample was reactive with the Bio-Rad and BioPlex assays. The 11 samples that were reactive with the BioPlex assay had viral loads from 83,010 to >750,000 copies/mL; 9/11 samples were classified as Ag positive/Ab negative by the BioPlex assay. Conclusions Detection of acute HIV infection was similar for the BioPlex assay and two other Ag/Ab assays. All three tests were less sensitive than a qualitative RNA assay and only detected HIV Ag when the viral load was high. The BioPlex assay detected acute infection in about half of the cases, and identified most of those infections as Ag positive/Ab negative.

BACKGROUND: Nondaily dosing of oral preexposure prophylaxis (PrEP) may provide equivalent coverage of sex events compared with daily dosing. METHODS: At-risk men and transgender women who have sex with men were randomly assigned to 1 of 3 dosing regimens: 1 tablet daily, 1 tablet twice weekly with a postsex dose (time-driven), or 1 tablet before and after sex (event-driven), and were followed for coverage of sex events with pre- and postsex dosing measured by weekly self-report, drug concentrations, and electronic drug monitoring. RESULTS: From July 2012 to May 2014, 357 participants were randomized. In Bangkok, the coverage of sex events was 85% for the daily arm compared with 84% for the time-driven arm (P = .79) and 74% for the event-driven arm (P = .02). In Harlem, coverage was 66%, 47% (P = .01), and 52% (P = .01) for these groups. In Bangkok, PrEP medication concentrations in blood were consistent with use of ≥2 tablets per week in >95% of visits when sex was reported in the prior week, while in Harlem, such medication concentrations occurred in 48.5% in the daily arm, 30.9% in the time-driven arm, and 16.7% in the event-driven arm (P < .0001). Creatinine elevations were more common in the daily arm (P = .050), although they were not dose limiting. CONCLUSIONS: Daily dosing recommendations increased coverage and protective drug concentrations in the Harlem cohort, while daily and nondaily regimens led to comparably favorable outcomes in Bangkok, where participants had higher levels of education and employment. CLINICAL TRIALS REGISTRATION: NCT01327651.

We describe the sexual behaviors of women at elevated risk of HIV acquisition who reside in areas of high HIV prevalence and poverty in the US. Participants in HPTN 064, a prospective HIV incidence study, provided information about participants’ sexual behaviors and male sexual partners in the past 6 months at baseline, 6- and 12-months. Independent predictors of consistent or increased temporal patterns for three high-risk sexual behaviors were assessed separately: exchange sex, unprotected anal intercourse [UAI] and concurrent partnerships. The baseline prevalence of each behavior was >30% among the 2,099 participants, 88% reported partner(s) with > one HIV risk characteristic and both individual and partner risk characteristics decreased over time. Less than high school education and food insecurity predicted consistent/increased engagement in exchange sex and UAI, and partner's concurrency predicted participant concurrency. Our results demonstrate how interpersonal and social factors may influence sustained high-risk behavior by individuals and suggest that further study of the economic issues related to HIV risk could inform future prevention interventions.

Little is known about HIV treatment optimism and risk behaviors among Black men who have sex with men (BMSM). Using longitudinal data from BMSM in the HPTN 061 study, we examined participants’ self-reported comfort with having condomless sex due to optimistic beliefs regarding HIV treatment. We assessed correlates of treatment optimism and its association with subsequent risk behaviors for HIV acquisition or transmission using multivariable logistic regression with generalized estimating equations. Independent correlates of treatment optimism included age ≥35 years, annual household income

Introduction Black men who have sex with men and transgender women are at high risk for HIV infection, but are more likely to be unaware of their infection or not in care for diagnosed HIV compared to other races. Respondent driven sampling has been advanced as a method to reach stigmatized and hidden populations for HIV testing. We compared strategies to recruit black, substance‐using men who have sex with men and transgender women to identify newly diagnosed HIV infection, or those previously diagnosed but not in care. Methods The STAR (Seek, Test, and Retain) study (ClinicalTrials.gov NCT01790360) used several recruitment strategies to identify black, substance‐using men who have sex with men and transgender women with undiagnosed HIV infection or with previously diagnosed HIV infection but who were not in HIV care. Respondent‐driven sampling, community‐based recruitment and online advertising were used to recruit participants. Incentivized peer referral was integrated into all recruitment strategies. Participants completed interviewer‐administered questionnaires and HIV testing. Demographic and HIV risk‐related characteristics and recruitment strategy were summarized and stratified by HIV status. Associations were tested using Pearson's chi‐squared, Fisher's exact, and Wilcoxon rank sum tests. Factors associated with HIV‐positive diagnosis at p

Substance use is associated with HIV sexual risk behaviors, yet few studies have examined substance use patterns longitudinally. We evaluated the types and frequency of substances used over a six-month period among U.S. women at risk for HIV acquisition.Women reporting unprotected sex with a man in the previous six months and at least one other personal or partner HIV risk characteristic enrolled in a multisite cohort study and completed interviews about substance use at study visits. Prevalence and frequency of substance use at the baseline and six-month visits were compared and correlates of decreased substance use at the six-month visit were assessed.Of 2099 women enrolled, 1882 had substance use data at baseline and six-months. Of these, 76.1% reported using at least one drug or binge drinking in the previous six months; 37.5% were frequent and 38.6% non-frequent substance users. Binge drinking was most frequently reported (63.3%), followed by cocaine (25.0%) and opioids (16.5%). Fifty-five percent of opiate users and 30% of cocaine users reported daily/almost daily use. At the six-month visit, 40.5% reported a decrease in frequency of use. Adjusting for income and type of drug used, poly-substance users were less likely to decrease frequency of use compared to those who only used one substance.A substantial decrease in frequency of substance use over time was observed in this cohort. Poly-substance users were less likely to reduce frequency of use over time, suggesting that specific substance use interventions targeting these users are warranted.

Background: In the HIV Prevention Trials Network (HPTN) 061 study, 8 (2.3%) of 348 HIV-infected participants identified as HIV uninfected at study enrollment using a single HIV rapid test for screening were found to be HIV infected after additional testing. Objectives: To evaluate the performance of different HIV assays for detection of HIV infection in HPTN 061 participants with missed infection and individuals with viral suppression. Methods: Plasma samples from 8 HPTN 061 participants, 17 elite controllers, and 101 individuals on antiretroviral treatment (ART) were tested for HIV with 3 rapid tests, 2 laboratory-based immunoassays, and a Western blot assay. The HPTN 061 samples were also tested with 2 HIV RNA assays and an antiretroviral drug assay. Results: Of the 8 HPTN 061 participants with missed infection, 1 was an elite controller, 1 was taking ART, 2 were missed because of testing or clerical errors, 1 had recent HIV infection (identified using a multi-assay algorithm), and 3 had acute HIV infection. Two (1.7%) of 118 individuals with viral suppression (both taking ART) had at least 1 false-negative test. Conclusions: In clinical trials, HIV infections can be missed for a variety of reasons. Using more than one assay to screen for HIV infection may reduce the number of missed infections. © 2014 Thomas Land Publishers, Inc.

In The HIV Prevention Trials Network 061 study, 155 human immunodeficiency virus (HIV)-infected men reported no prior HIV diagnosis; 83 of those men had HIV RNA levels of

Author(s): Chen, Iris; Chau, Gordon; Wang, Jing; Clarke, William; Marzinke, Mark A; Cummings, Vanessa; Breaud, Autumn; Laeyendecker, Oliver; Fields, Sheldon D; Griffith, Sam; Scott, Hyman M; Shoptaw, Steven; Del Rio, Carlos; Magnus, Manya; Mannheimer, Sharon; Tieu, Hong-Van; Wheeler, Darrell P; Mayer, Kenneth H; Koblin, Beryl A; Eshleman, Susan H | Abstract: BackgroundHIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study.MethodsA high resolution melting (HRM) diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified using a multi-assay algorithm), and for 21 men who seroconverted during the study. HIV diversification was analyzed in a paired analysis for 62 HIV-infected men using plasma samples from the enrollment and 12-month (end of study) visits.ResultsMen with acute or recent infection at enrollment and seroconverters had lower median HRM scores (lower HIV diversity) than men with non-recent infection in all six regions analyzed. In univariate analyses, younger age, higher CD4 cell count, and HIV drug resistance were associated with lower median HRM scores in multiple regions; ARV drug detection was marginally associated with lower diversity in the pol region. In multivariate analysis, acute or recent infection (all six regions) and HIV drug resistance (both gag regions) were associated with lower median HRM scores. Diversification in the pol region over 12 months was greater for men with acute or recent infection, higher CD4 cell count, and lower HIV viral load at study enrollment.ConclusionsHIV diversity was significantly associated with duration of HIV infection, and lower gag diversity was observed in men who had HIV drug resistance. HIV pol diversification was more pronounced in men with acute or recent infection, higher CD4 cell count, and lower HIV viral load.

HIV Prevention Trials Network (HPTN) 061 enrolled black men who have sex with men in the United States. Some men with low/undetectable HIV RNA had unusual patterns of antiretroviral (ARV) drug use or had drugs detected in the absence of viral suppression. This report includes a comprehensive analysis of ARV drug use and drug resistance among men in HPTN 061 who were not virally suppressed.The analysis included 169 men who had viral loads400 copies per milliliter at enrollment, including 3 with acute infection and 13 with recent infection. By self-report, 88 were previously diagnosed, including 31 in care; 137 men reported no ARV drug use. Samples from these 169 men and 23 seroconverters were analyzed with HIV genotyping and ARV drug assays.Forty-eight (28%) of the 169 men had ≥ 1 drug resistance mutation (DRM); 19 (11%) had multiclass resistance. Sixty men (36%) had ≥ 1 ARV drug detected, 42 (70%) of whom reported no ARV drug use. Nine (23%) of 39 newly infected men had ≥ 1 DRM; 10 had ≥ 1 ARV drug detected. Unusual patterns of ARV drugs were detected more frequently in newly diagnosed men than previously diagnosed men. The rate of transmitted drug resistance was 23% based on HIV genotyping and self-reported ARV drug use but was 12% after adjusting for ARV drug detection.Many men in HPTN 061 had drug-resistant HIV, and many were at risk of acquiring additional DRMs. ARV drug testing revealed unusual patterns of ARV drug use and provided a more accurate estimate of transmitted drug resistance.

Antiretroviral therapy (ART) adherence remains critical for achieving successful outcomes. Factors affecting ART adherence can occur at the individual level or be related to the treatment regimen, daily schedule, and/or interpersonal relationships. While treatment-related barriers have diminished with recent simplified ART regimens, guidelines still recommend considering regimen simplicity. ART readiness should be assessed prior to starting ART, with follow-up adherence assessments once ART is initiated, and at all subsequent clinical visits. Adherence interventions work best when multifaceted, targeted for at-risk and nonadherent participants, and tailored to individuals' needs. Successful interventions have included education and counseling, provision of social support, directly observed therapy, and financial incentives. Pillboxes and two-way short-text messaging service (SMS) reminders have been shown to be effective and are widely recommended tools for promoting ART adherence. Further research is needed to determine the optimal combination of adherence interventions, as well as generalizability, implementation, and cost-effectiveness.

Objectives. We determined the prevalence of recent emotional, physical, and sexual violence against women and their associations with HIV-related risk factors in women living in the United States. Methods. We performed an assessment of women ages 18 to 44 years with a history of unprotected sex and 1 or more personal or partner HIV risk factors in the past 6 months from 2009 to 2010. We used multivariable logistic regression to examine the association of experiencing violence. Results. Among 2099 women, the prevalence of emotional abuse, physical violence, and sexual violence in the previous 6 months was 31%, 19%, and 7%, respectively. Nonmarried status, food insecurity, childhood abuse, depression symptomology, and posttraumatic stress disorder were significantly associated with multiple types of violence. All types of violence were associated with at least 3 different partner or personal HIV risk behaviors, including unprotected anal sex, previous sexually transmitted infection diagnosis, sex work, or partner substance abuse. Conclusions. Our data suggested that personal and partner HIV risk behaviors, mental illness, and specific forms of violence frequently co-occurred in the lives of impoverished women. We shed light on factors purported to contribute to a syndemic in this population. HIV prevention programs in similar populations should address these co-occurring issues in a comprehensive manner.

Author(s): Scott, Hyman M; Irvin, Risha; Wilton, Leo; Van Tieu, Hong; Watson, Chauncey; Magnus, Manya; Chen, Iris; Gaydos, Charlotte; Hussen, Sophia A; Mannheimer, Sharon; Mayer, Kenneth; Hessol, Nancy A; Buchbinder, Susan | Abstract: BackgroundBlack men who have sex with men (MSM) have a high prevalence of bacterial sexually transmitted infections (STIs), and individual risk behavior does not fully explain the higher prevalence when compared with other MSM. Using the social-ecological framework, we evaluated individual, social and sexual network, and structural factors and their association with prevalent STIs among Black MSM.MethodsThe HIV Prevention Trials Network 061 was a multi-site cohort study designed to determine the feasibility and acceptability of a multi-component intervention for Black MSM in six US cities. Baseline assessments included demographics, risk behavior, and social and sexual network questions collected information about the size, nature and connectedness of their sexual network. Logistic regression was used to estimate the odds of having any prevalent sexually transmitted infection (gonorrhea, chlamydia, or syphilis).ResultsA total of 1,553 Black MSM were enrolled in this study. In multivariate analysis, older age (aOR = 0.57; 95% CI 0.49-0.66, pl0.001) was associated with a lower odds of having a prevalent STI. Compared with reporting one male sexual partner, having 2-3 partners (aOR = 1.74; 95% CI 1.08-2.81, pl0.024) or more than 4 partners (aOR = 2.29; 95% CI 1.43-3.66, pl0.001) was associated with prevalent STIs. Having both Black and non-Black sexual partners (aOR = 0.67; 95% CI 0.45-0.99, p = 0.042) was the only sexual network factor associated with prevalent STIs.ConclusionsAge and the number and racial composition of sexual partners were associated with prevalent STIs among Black MSM, while other sexual network factors were not. Further studies are needed to evaluate the effects of the individual, network, and structural factors on prevalent STIs among Black MSM to inform combination interventions to reduce STIs among these men.

Although studies have consistently demonstrated that women at high risk for HIV and non-HIV sexually transmitted infections (STIs) tend to underestimate their individual risk, little is known about how women at risk perceive their community’s HIV/STI risk. We explored perceptions of community HIV/ STI risk among U.S. women living in areas with high poverty and HIV prevalence rates as part of a qualitative substudy of the Women’s HIV SeroIncidence Study. Semi-structured focus groups were conducted. Data were coded and analyzed using the constant comparative method. Participants expressed the perception that their communities were at elevated HIV/STI risk, mostly due to contextual and structural factors such as lack of access to health care and education. Findings suggest that HIV prevention messages that target U.S. women at high risk for HIV may be strengthened by addressing the high perceived community HIV/ STI risk driven by structural factors.

Copyright © 2014 by Lippincott Williams & Wilkins. HIV RNA levels are usually high early in HIV infection. In the HPTN 061 study, men were tested for HIV infection every 6 months; 6 (21.4%) of 28 men who acquired HIV infection during the study had low or undetectable HIV RNA at the time of HIV diagnosis. Antiretroviral drugs were not detected at the time of HIV diagnosis. False-negative HIV test results were obtained for 2 men using multiple assays. Antiretroviral drug resistance mutations were detected in HIV from 1 man. Additional studies are needed to identify factors associated with low HIV RNA levels during early HIV infection.

Drug-induced lupus (DIL) is a rare adverse reaction to medications with features resembling idiopathic systemic lupus erythromatosis. Rifabutin/rifamycins have only rarely been reported as a cause of DIL, and no cases have been reported in blacks. A 55-year-old African American woman with HIV presented with severe generalized arthralgias and recurrent oral ulcers while receiving treatment for tuberculous meningitis. Arthralgias, which began in her knees after 5 weeks of antituberculous therapy, progressed to involve the joints in the ankles, wrists, and hands. She had no associated fever or rash. When she had these symptoms her antinuclear antibody (ANA) was 1:1280 homogenous pattern, antidouble stranded DNA was negative, antihistone antibody was strongly positive, anti-smith and antiribonucleoprotein (anti-RNP) were negative. Her symptoms resolved within 2 months of stopping rifabutin while continuing other antituberculous medications and her ANA titer started to decrease. We review the existing literature on this subject.

OBJECTIVE US guidelines recommend at least annual HIV testing for those at risk. This analysis assessed frequency and correlates of infrequent HIV testing and late diagnosis among black men who have sex with men (BMSM). METHODS HIV testing history was collected at enrollment from participants in HPTN 061, an HIV prevention trial for at-risk US BMSM. Two definitions of late HIV diagnosis were assessed: CD4 cell count

Women at high-risk for HIV acquisition often face challenges that hinder their retention in HIV prevention trials. These same challenges may contribute to missed clinical care visits among HIV-infected women. This article, informed by the Gelberg-Andersen Behavioral Model for Vulnerable Populations, identifies factors associated with missed study visits and describes the multifaceted retention strategies used by study sites. HPTN 064 was a multisite, longitudinal HIV seroincidence study in 10 US communities. Eligible women were aged 18-44 years, resided in a census tract/zipcode with high poverty and HIV prevalence, and self-reported ≥1 personal or sex partner behavior related to HIV acquisition. Multivariate analyses of predisposing (e.g., substance use) and enabling (e.g., unmet health care needs) characteristics, and study attributes (i.e., recruitment venue, time of enrollment) identified factors associated with missed study visits. Retention strategies included: community engagement; interpersonal relationship building; reduction of external barriers; staff capacity building; and external tracing. Visit completion was 93% and 94% at 6 and 12 months. Unstable housing and later date of enrollment were associated with increased likelihood of missed study visits. Black race, recruitment from an outdoor venue, and financial responsibility for children were associated with greater likelihood of attendance. Multifaceted retention strategies may reduce missed study visits. Knowledge of factors associated with missed visits may help to focus efforts.

We examined parameters of sexual partnerships, including respondents' participation in concurrency, belief that their partner had concurrent partnerships (partners' concurrency), and partnership intervals, among the 2099 women in HIV Prevention Trials Network 064, a study of women at high risk for HIV infection, in 10 U.S. communities.We analyzed baseline survey responses about partnership dates to determine prevalence of participants' and partners' concurrency, intervals between partnerships, knowledge of whether recent partners had undergone HIV testing, and intercourse frequency during the preceding 6 months.Prevalence of participants' and partners' concurrency was 40% and 36%, respectively; 24% respondents had both concurrent partnerships and nonmonogamous partners. Among women with1 partner and no concurrent partnerships themselves, the median gap between partners was 1 month. Multiple episodes of unprotected vaginal intercourse with ≥2 of their most recent partners was reported by 60% of women who had both concurrent partnerships and nonmonogamous partners, 50% with only concurrent partners and no partners' concurrency, and 33% with only partners' concurrency versus 14% of women with neither type of concurrency (P0.0001). Women who had any involvement with concurrency were also more likely than women with no concurrency involvement to report lack of awareness of whether recent partners had undergone HIV testing (participants' concurrency 41%, partners' concurrency 40%, both participants' and partners' concurrency 48%, neither 17%; P0.0001).These network patterns and short gaps between partnerships may create substantial opportunities for HIV transmission in this sample of women at high risk for HIV infection.

Background: The challenge of identifying and recruiting U.S. women at elevated risk for HIV acquisition impedes prevention studies and services. HIV Prevention Trials Network (HPTN) 064 was a U.S. multisite, longitudinal cohort study designed to estimate HIV incidence among women living in communities with prevalent HIV and poverty. Venue-based sampling (VBS) methodologies and participant and venue characteristics are described. Methods: Eligible women were recruited from 10 U.S. communities with prevalent HIV and poverty using VBS. Participant eligibility criteria included age 18–44 years, residing in a designated census tract/zip code, and self-report of at least one high-risk personal and/or male sexual partner characteristic associated with HIV acquisition (e.g., incarceration history). Ethnography was conducted to finalize recruitment areas and venues. Results: Eight thousand twenty-nine women were screened and 2,099 women were enrolled (88% black, median age 29 years) over 14 months. The majority of participants were recruited from outdoor venues (58%), retail spaces (18%), and social service organizations (13%). The proportion of women recruited per venue category varied by site. Most participants (73%) had both individual and partner characteristics that qualified them for the study; 14% were eligible based on partner risk only. Conclusion: VBS is a feasible and effective approach to rapidly recruit a population of women at enhanced risk for HIV in the United States. Such a recruitment approach is needed in order to engage women most at risk and requires strong community engagement.

Considering higher morbidity and mortality associated with HIV/HBV coinfected patients compared to monoinfected patients, it is imperative to determine the prevalence of occult HBV (OHB) infection, in such population.630 unique HIV-infected patients, during the defined study period, were screened for evidence of occult HBV infection serology. 82 patients (13%) were found to have evidence suggestive of OHB infection of which 57 had HBV DNA testing available and comprised the final study population. Data on demographic variables, Hepatitis C antibody status, antiretroviral therapy (ARV), CD4 count and HIV viral load was also collected. Among the final study population, 7% (n=4) patients met the OHB definition. All 4 (100%) with OHB had HIV RNA levels > 50 copies/ml. OHB was found in 4 (22%) of 18 patients not on ARV, but in none of 39 patients on ARV (p=0.007). All patients on ARV were on a regimen with anti HBV activity. 75% of patients with OHB tested positive for HCV compared to 47% in isolated anti HBc positive but HBV DNA negative population (p= 0.58). With an OHB prevalence of 7% in our community clinic, clinicians should have a high index of suspicion for OHB among HIV patients whose hepatitis panel is positive only for anti HBc only and start them on HAART regimen containing ARVs with anti-HBV activity.

Performing rapid HIV testing in nontraditional clinical settings such as dental clinics is a potential method for targeting high-risk individuals who may not otherwise access health care settings that offer HIV testing. In March 2008, Harlem Hospital Center, located in New York City, launched a counselor-based rapid HIV testing initiative in its on-site dental clinic. A full-time, trained counselor consented and tested patients as they waited for their appointments. HIV screening was performed using a whole-blood, finger-stick rapid HIV test. Through this initiative, 3864 HIV tests were performed from March 1, 2008 to December 31, 2009, representing 3565 unique individuals and 97.6% of dental patients approached for testing. Of those tested, the mean age was 38.5 years, with 47.1% female, 75.5% black, and 20.6% Hispanic. Self-reported HIV risk behaviors included 73.5% with recent unprotected heterosexual intercourse, 4.6% with recent or past injection drug use, and 2.6% who identified as men who have sex with men. Nineteen previously undiagnosed individuals (0.53%) were confirmed HIV positive. Of these individuals, mean age was 38.3 years with males representing 84.2%. Fifteen newly diagnosed patients (78.9%) were linked to care. Of those linked to care, median initial CD4 cell count was 317 cells/mm(3); 6 of these individuals (40%) had CD4 cell counts below 200 cells/mm(3). Our results demonstrate that a counselor-based rapid HIV testing program with linkage to specialized HIV care can be successfully integrated into the dental clinic setting.