Hong Van Tieu

HIV, alcohol, and noninjection drug use.

Purpose of reviewAlcohol and noninjection drug use has been shown to be associated with increased risk of HIV infection in select populations. In this review, we discuss recent data on the prevalence of alcohol and noninjection drug use and the relationship to HIV acquisition and transmission risk. Recent findingsA strong association between alcohol use and HIV-infection risk has been demonstrated in multiple studies conducted in sub-Saharan Africa. Among men who have sex with men in the USA as well as other countries, substance use is highly prevalent and has been associated with high-risk sexual behavior. Substance use, mental health problems, and sexual risk behaviors conjoin in what is known as a syndemic to increase HIV risk among young men who have sex with men. Only a limited number of intervention studies provide promising results in reducing HIV-infection risk among substance users. SummaryAlcohol and noninjection drug use is prevalent in certain populations. There is a strong association between use of alcohol and noninjecting substances, including methamphetamines, amyl nitrates, cocaine, and other drugs, and HIV-infection risk. This underscores the need for a comprehensive HIV prevention strategy that addresses substance use, including screening and behavioral intervention, among those at risk.

Infrequent HIV testing and late HIV diagnosis are common among a cohort of black men who have sex with men in 6 US cities.

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 <200 cells per cubic millimeter or <350 cells per cubic millimeter at diagnosis. Results:HPTN 061 enrolled 1553 BMSM. HIV testing questions were completed at enrollment by 1284 (98.7%) of 1301 participants with no previous HIV diagnosis; 272 (21.2%) reported no HIV test in previous 12 months (infrequent testing); 155 of whom (12.1% of the 1284 with testing data) reported never testing. Infrequent HIV testing was associated with: not seeing a medical provider in the previous 6 months (relative risk [RR]: 1.08, 95% confidence interval [CI]: 1.03 to 1.13), being unemployed (RR: 1.04, CI: 1.01 to 1.07), and having high internalized HIV stigma (RR: 1.03, CI: 1.0 to 1.05). New HIV diagnoses were more likely among infrequent testers compared with men tested in the previous year (18.4% vs. 4.4%; odds ratio: 4.8, 95% CI: 3.2 to 7.4). Among men with newly diagnosed HIV, 33 (39.3%) had a CD4 cell count <350 cells per cubic millimeter including 17 (20.2%) with CD4 <200 cells per cubic millimeter. Conclusions:Infrequent HIV testing, undiagnosed infection, and late diagnosis were common among BMSM in this study. New HIV diagnoses were more common among infrequent testers, underscoring the need for additional HIV testing and prevention efforts among US BMSM.

Safety and tolerability of long-acting cabotegravir injections in HIV-uninfected men (ECLAIR): a multicentre, double-blind, randomised, placebo-controlled, phase 2a trial

BACKGROUND Cabotegravir (GSK1265744) is an HIV-1 integrase strand transfer inhibitor with potent antiviral activity and a long half-life when administered by injection that prevented simian-HIV infection upon repeat intrarectal challenge in male macaques. We aimed to assess the safety, tolerability, and pharmacokinetics of long-acting cabotegravir injections in healthy men not at high risk of HIV-1 infection. METHODS We did this multicentre, double-blind, randomised, placebo-controlled, phase 2a trial at ten sites in the USA. Healthy men (aged 18-65 years) deemed not at high risk of acquiring HIV-1 at screening were randomly assigned (5:1), via computer-generated central randomisation schedules, to receive cabotegravir or placebo. Participants received oral cabotegravir 30 mg tablets or matching placebo once daily during a 4 week oral lead-in phase, followed by a 1 week washout period and, after safety assessment, three intramuscular injections of long-acting cabotegravir 800 mg or saline placebo at 12 week intervals. Study site staff and participants were masked to treatment assignment from enrolment through week 41 (time of the last injection). The primary endpoint was safety and tolerability from the first injection (week 5) to 12 weeks after the last injection. We did analysis in the safety population, defined as all individuals enrolled in the study who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov identifier, NCT02076178. FINDINGS Between March 27, 2014, and Feb 23, 2016, we randomly assigned 127 participants to receive cabotegravir (n=106) or placebo (n=21); 126 (99%) participants comprised the safety population. Most participants were men who have sex with men (MSM; n=106 [83%]) and white (n=71 [56%]). 87 (82%) participants in the cabotegravir group and 20 (95%) participants in the placebo group completed the injection phase. Adverse events (n=7 [7%]) and injection intolerability (n=4 [4%]) were the main reasons for withdrawal in the cabotegravir group. The frequency of grade 2 or higher adverse events was higher in participants in the long-acting cabotegravir group (n=75 [80%]) than in those in the placebo group (n=10 [48%]; p=0·0049), mostly due to injection-site pain (n=55 [59%]). No significant differences were noted in concomitant medications, laboratory abnormalities, electrocardiogram, and vital sign assessments. Geometric mean trough plasma concentrations were 0·302 μg/mL (95% CI 0·237-0·385), 0·331 μg/mL (0·253-0·435), and 0·387 μg/mL (0·296-0·505) for injections one, two, and three, respectively, indicating lower than predicted exposure. The geometric mean apparent terminal phase half-life estimated after the third injection was 40 days. Two (2%) MSM acquired HIV-1 infection, one in the placebo group during the injection phase and one in the cabotegravir group 24 weeks after the final injection when cabotegravir exposure was well below the protein-binding-adjusted 90% inhibitory concentration. INTERPRETATION Despite high incidence of transient, mild-to-moderate injection-site reactions, long-acting cabotegravir was well tolerated with an acceptable safety profile. Pharmacokinetic data suggest that 800 mg administered every 12 weeks is a suboptimal regimen; alternative dosing strategies are being investigated. Our findings support further investigation of long-acting injectable cabotegravir as an alternative to orally administered pre-exposure prophylaxis regimens. FUNDING ViiV Healthcare.

Concurrent Partnerships and HIV Risk among Men Who Have Sex with Men in New York City

Background Concurrent partnerships are a significant public health concern among men who have sex with men (MSM). This study describes the prevalence of concurrency and its association with serodiscordant/serostatus unknown unprotected anal or vaginal intercourse (SDUI) among MSM in New York City. Methods A total of 1458 MSM completed a social and sexual network inventory about their male and female sex partners, including concurrency, in the last 3 months. Logistic regression identified factors associated with SDUI. Results Median age was 29 years. The proportion of participants who reported being HIV+ was 23.5%. The men reported a mean of 3.2 male partners in the last 3 months. The proportion of MSM who reported having recent SDUI was 16.6%. More than half (63.2%) described having concurrent sex partners (individual concurrency based on overlapping dates of relationships); 71.5% reported having partners whom they believed had concurrent partners (perceived partner concurrency); and 56.1% reported that both they and their partners had concurrent partners (reciprocal concurrency). Among HIV+ men by self-report, having SDUI was positively associated with individual concurrency, any alcohol use during sex, having more male sex partners, and not having a main partner. Among self-reported HIV− men, having SDUI was positively associated with perceived partner concurrency, lower education level, any alcohol and drug use during sex, having more male sex partners, and having an anonymous partner. Conclusions Concurrency was common among MSM. The association of SDUI with individual and perceived partner concurrency, along with substance use during sex, having an anonymous partner, and having many sex partners likely further increases HIV acquisition and transmission risk among MSM. HIV prevention interventions should address concurrency among MSM.

“I didn't think I could get out of the fucking park.” Gay men's retrospective accounts of neighborhood space, emerging sexuality and migrations

Young, African American and Latino gay, bisexual and other men who have sex with men (MSM) are disproportionately represented among new HIV cases according to the most recent national surveillance statistics. Analysts have noted that these racial/ethnic disparities in HIV among MSM exist within the wider context of sexual, mental and physical health disparities between MSM and heterosexuals. The intercorrelation of these adverse health outcomes among MSM, termed syndemics, has been theorized to be socially produced by a heterosexist social system that marginalizes lesbian, gay, bisexual, MSM and other sexual minorities. African American and Latino MSM experience overlapping systems of oppression that may increase their risk of experiencing syndemic health outcomes. In this paper, using data from twenty in-depth qualitative interviews with MSM living in four New York City (NYC) neighborhoods, we present accounts of neighborhood space, examining how space can both physically constitute and reinforce social systems of stratification and oppression, which in turn produce social disparities in sexual health outcomes. By analyzing accounts of emerging sexuality in neighborhood space, i.e. across time and space, we identify pathways to risk and contribute to our understanding of how neighborhood space is experienced by gay men, adding to our ability to support young men as they emerge in place and to shape the social topography of urban areas.

Anal Sex Role Segregation and Versatility among Men Who Have Sex with Men: EXPLORE Study

Abstract:Anal sex role patterns and correlates during unprotected anal sex were examined longitudinally among HIV-negative men who have sex with men. Nearly 9.6% were exclusively receptive, 16.7% exclusively insertive, and 63.0% versatile. Versatility was more likely with primary and HIV-negative/unknown status partners and among younger men and substance users but less likely among Blacks and with higher number of partners. Exclusively receptive role was more likely with HIV-negative/unknown status partners and among younger men and substance users but less likely with higher number of partners. Examining anal sex role patterns helps understand the factors that drive the epidemic among men who have sex with men.

A randomized trial of a behavioral intervention for black MSM: the DiSH study.

Objective:To test a new behavioral intervention for black MSM in reducing sexual risk and increasing social support and intentions to use condoms. Design:A single-site, unblinded randomized trial in New York City with 3-month follow-up. Methods:Participants (n = 283) reporting at least two sexual partners and unprotected anal intercourse with a man in the past 3 months were enrolled and randomized to a social-cognitive theory-based intervention or control comparison. Men in the intervention group participated in five 2-h group sessions focused on creating a group environment with sexual risk-reduction information and exercises woven into joint meal preparation and sharing activities, while exploring self-efficacy perceptions and outcome expectancies. Intervention (n = 142) and control (n = 141) groups received standard HIV counseling and testing at baseline. Results:No significant differences were found between study arms at 3 months in number of male partners, number of unprotected anal intercourse partners, proportion reporting unprotected sex, number of acts protected by condoms, self-efficacy, condom attitudes, condom intentions, social isolation and psychological distress. In both arms combined, declines from baseline to 3 months were observed in sexual risk behaviors, social isolation and psychological distress, whereas self-efficacy, condom attitudes and condom intentions improved. Conclusion:As the HIV epidemic continues to have a dramatic impact on black MSM in the USA, the urgency to design innovative interventions continues.

Safety, pharmacokinetics, and immunological activities of multiple intravenous or subcutaneous doses of an anti-HIV monoclonal antibody, VRC01, administered to HIV-uninfected adults: Results of a phase 1 randomized trial

Background VRC01 is an HIV-1 CD4 binding site broadly neutralizing antibody (bnAb) that is active against a broad range of HIV-1 primary isolates in vitro and protects against simian-human immunodeficiency virus (SHIV) when delivered parenterally to nonhuman primates. It has been shown to be safe and well tolerated after short-term administration in humans; however, its clinical and functional activity after longer-term administration has not been previously assessed. Methods and findings HIV Vaccine Trials Network (HVTN) 104 was designed to evaluate the safety and tolerability of multiple doses of VRC01 administered either subcutaneously or by intravenous (IV) infusion and to assess the pharmacokinetics and in vitro immunologic activity of the different dosing regimens. Additionally, this study aimed to assess the effect that the human body has on the functional activities of VRC01 as measured by several in vitro assays. Eighty-eight healthy, HIV-uninfected, low-risk participants were enrolled in 6 United States clinical research sites affiliated with the HVTN between September 9, 2014, and July 15, 2015. The median age of enrollees was 27 years (range, 18–50); 52% were White (non-Hispanic), 25% identified as Black (non-Hispanic), 11% were Hispanic, and 11% were non-Hispanic people of diverse origins. Participants were randomized to receive the following: a 40 mg/kg IV VRC01 loading dose followed by five 20 mg/kg IV VRC01 doses every 4 weeks (treatment group 1 [T1], n = 20); eleven 5 mg/kg subcutaneous (SC) VRC01 (treatment group 3 [T3], n = 20); placebo (placebo group 3 [P3], n = 4) doses every 2 weeks; or three 40 mg/kg IV VRC01 doses every 8 weeks (treatment group 2 [T2], n = 20). Treatment groups T4 and T5 (n = 12 each) received three 10 or 30 mg/kg IV VRC01 doses every 8 weeks, respectively. Participants were followed for 32 weeks after their first VRC01 administration and received a total of 249 IV infusions and 208 SC injections, with no serious adverse events, dose-limiting toxicities, nor evidence for anti-VRC01 antibodies observed. Serum VRC01 levels were detected through 12 weeks after final administration in all participants who received all scheduled doses. Mean peak serum VRC01 levels of 1,177 μg/ml (95% CI: 1,033, 1,340) and 420 μg/ml (95% CI: 356, 494) were achieved 1 hour after the IV infusion series of 30 mg/kg and 10 mg/kg doses, respectively. Mean trough levels at week 24 in the IV infusion series of 30 mg/kg and 10 mg/kg doses, respectively, were 16 μg/ml (95% CI: 10, 27) and 6 μg/ml (95% CI: 5, 9) levels, which neutralize a majority of circulating strains in vitro (50% inhibitory concentration [IC50] > 5 μg/ml). Post-infusion/injection serum VRC01 retained expected functional activity (virus neutralization, antibody-dependent cellular cytotoxicity, phagocytosis, and virion capture). The limitations of this study include the relatively small sample size of each VRC01 administration regimen and missing data from participants who were unable to complete all study visits. Conclusions VRC01 administered as either an IV infusion (10–40 mg/kg) given monthly or bimonthly, or as an SC injection (5 mg/kg) every 2 weeks, was found to be safe and well tolerated. In addition to maintaining drug concentrations consistent with neutralization of the majority of tested HIV strains, VRC01 concentrations from participants’ sera were found to avidly capture HIV virions and to mediate antibody-dependent cellular phagocytosis, suggesting a range of anti-HIV immunological activities, warranting further clinical trials. Trial registration Clinical Trials Registration: NCT02165267

Analysis of HIV Diversity in HIV-Infected Black Men Who Have Sex with Men (HPTN 061)

Background HIV 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. Methods A 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. Results Men 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. Conclusions HIV 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.

Associations Among Neighborhood Characteristics and Sexual Risk Behavior Among Black and White MSM Living in a Major Urban Area

Identifying neighborhood characteristics associated with sexual HIV risk behavior among gay, bisexual and other men who have sex with men (MSM) living in urban areas may inform the development of policies and programs to reduce risk and subsequently HIV prevalence in urban areas. New York City M2M was a cross-sectional study designed to identify neighborhood-level characteristics associated with sexual risk behaviors among MSM living in New York City. This paper presents results of an analysis of neighborhood-level indicators of three distinct social theories of influence of the neighborhood environment on human behavior: physical disorder, social disorganization and social norms theories. Using multilevel modeling on a sample of 766 MSM stratified by race/ethnicity, we found little support for the role of social disorganization on the sexual risk behavior of MSM, whereas different indicators of physical disorder exerted negative effects across race groups. Our results suggest that the beneficial effects of housing stock maintenance and general neighborhood physical orderliness and cleanliness may have positive effects beyond those traditionally studied for African American MSM and that the field needs novel theorizing regarding whether and how neighborhood or virtual community-level factors relate to sexual behavior among MSM.