HLA-B∗46 associates with rapid HIV disease progression in Asian cohorts and prominent differences in NK cell phenotype.

Human leukocyte antigen (HLA) alleles have been linked to HIV disease progression and attributed to differences in cytotoxic T lymphocyte (CTL) epitope representation. These findings are largely based on treatment-naive individuals of European and African ancestry. We assessed HLA associations with HIV-1 outcomes in 1,318 individuals from Thailand and found HLA-B∗46:01 (B∗46) associated with accelerated disease in three independent cohorts. B∗46 had no detectable effect on HIV-specific T cell responses, but this allele is unusual in containing an HLA-C epitope that binds inhibitory receptors on natural killer (NK) cells. Unbiased transcriptomic screens showed increased NK cell activation in people with HIV, without B∗46, and simultaneous single-cell profiling of surface proteins and transcriptomes revealed a NK cell subset primed for increased responses in the absence of B∗46. These findings support a role for NK cells in HIV pathogenesis, revealed by the unique properties of the B∗46 allele common only in Asia.

An Open-Label Pharmacokinetic and Pharmacodynamic Assessment of Tenofovir Gel and Oral Emtricitabine/Tenofovir Disoproxil Fumarate.

The Microbicide Trials Network-017 study was undertaken to characterize the safety, acceptability, pharmacokinetic (PK), and pharmacodynamic profile of the reduced-glycerin (RG) 1% tenofovir (RG-TFV) gel compared to oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF). The study was a Phase 2, three-period, randomized sequence, open-label, expanded safety and acceptability crossover study. In each 8-week study period, HIV-1-uninfected participants were randomized to RG-TFV rectal gel daily or RG-TFV rectal gel before and after receptive anal intercourse (RAI) (or at least twice weekly in the event of no RAI), or daily oral FTC/TDF. A mucosal substudy was conducted at sites in the United States and Thailand. Samples were collected to evaluate PK and ex vivo biopsy challenge with HIV-1. A total of 195 men who have sex with men and transgender women were enrolled in the parent study and 37 in the mucosal substudy. As previously reported, both products were found to be safe and acceptable. Systemic TFV concentrations were significantly higher following oral exposure and daily rectal administration compared to RAI-associated product use (p < .001). All three routes of pre-exposure prophylaxis (PrEP) administration resulted in the inhibition of explant infection (p < .05), and there was a significant inverse correlation between explant HIV-1 p24 and tissue concentrations of TFV and FTC (p < .0001). Despite significant differences in systemic and mucosal drug concentrations, all three PrEP regimens were able to protect rectal explants from ex vivo HIV infection. These data suggest that there is a rationale for co-development of oral and topical antiretroviral PrEP for HIV prevention. Clinical Trial Registration number: NCT01687218.

HIV and syphilis prevalence among transgender women and men who have sex with men, Silom Community Clinic, Bangkok, Thailand, 2017-2019.

We assessed HIV and syphilis infection among MSM and TGW attending Silom Community Clinic from 2017 to 2019. Walk-in and referral clients completed a registration application including a question on gender identity. We compared the prevalence of HIV, syphilis, and HIV and syphilis coinfection among TGW and MSM. In a total of 1050 clients, 276 (26.3%) were TGW and 774 (74.7%) were MSM. Among TGW clients, HIV prevalence was 29.8%, syphilis prevalence was 38.4%, and coinfection prevalence was 18.5%. Comparing prevalence among TGW to MSM, the adjusted prevalence ratio (aPR) for HIV was 1.8 (95% CI:1.4-2.3), for syphilis was 1.2 (95% CI:1.0-1.4), and for HIV and syphilis coinfection was 2.1 (95% CI:1.4-2.9). The prevalence of syphilis was higher than HIV among TGW, with a PR of 1.3 (95% CI:1.1-1.6), and among MSM, with a PR of 1.4 (95% CI:1.2-1.7). TGW age 15-21 years had an HIV prevalence of 16.9% and syphilis prevalence of 30.8%. After adjusting for age, referral, and sexual behaviors, TGW remain significantly associated with HIV and syphilis prevalence. There is a substantial burden of HIV and HIV/syphilis co-infection among TGW. HIV/STI prevention are needed for TGW, including linkage to HIV care.

Antiretroviral treatment initiation among HIV-positive participants in the Bangkok men who have sex with men cohort study, 2006-2016.

INTRODUCTION: Data on HIV antiretroviral therapy (ART) initiation among key-affected populations will support reaching the UNAIDS goal to end AIDS by 2030. METHODS: We assessed ART initiation among HIV-positive participants of the Bangkok Men Who Have Sex with Men (MSM) Cohort Study, which enrolled sexually experienced MSM aged ≥ 18 years and included visits every four months for a period of 3-5 years, from 2006-2016. At each visit, participants had HIV testing and completed computer-assisted self-interviewing on demographics and HIV risk behaviors. If they acquired HIV infection during the study, they received active referral for HIV treatment, continued in the cohort, and were asked about ART initiation. We used logistic regression to determine factors associated with ART initiation. RESULTS: Overall, 632 (36.2%) participants were diagnosed with HIV infection; 463 (73%) had a follow-up visit reporting information about ART, of those 346 (74%) reported ART initiation, with 323 (93%) on ART initiating ART through their registered national health benefit program. Only 70 (11%) were eligible for ART at time of diagnosis, and 52 (74%) initiated ART, on average, within six months of diagnosis. Multivariable analysis evaluating factors associated with ART initiation demonstrated that low CD4 cell count at time of diagnosis was the only independent factor associated with ART initiation. CONCLUSIONS: Most HIV-positive participants in the cohort reported ART initiation through the national health benefit program but limited data suggests there could be improvements in length of time to initiation of ART. Efforts should focus on ART start in MSM and transgender women soon after HIV diagnosis.

Spatial characteristics of men who have sex with men and transgender women attending HIV voluntary counselling and testing in Bangkok, Thailand, 2005-2015.

Spatiotemporal analyses can support Human Immuno-deficiency Virus (HIV) prevention programmes by identifying locations of at-risk populations in space and time, and their proximity to HIV testing and prevention services. We assessed residential proximity to HIV testing venues for Men who have Sex with Men (MSM) and Transgender Women (TGW) attending Voluntary Counselling and Testing (VCT) at a large urban MSM clinic in Bangkok, Thailand in the period 2005-2015. We mapped clientprovided spatial data and HIV testing venues, calculating distance from residence to venues for VCT clients between i) September 2005-December 2009; ii) January 2010-September 2013; and iii) October 2013-May 2015. We assessed spatial characteristics across times, evaluating autocorrelation of HIV prevalence and visit density using Moran's I. Among 8,758 first-time VCT clients reporting geographic information from 2005-2015 (by period: 2737, 3917, 2104), 1329 (15.2%) lived in postal codes ≤5 km from the clinic. Over time, the proportion living in areas covered by Bangkok postal codes ≤2 km from any MSM HIV testing venue increased from 12.6% to 41.0% (p<0.01). The proportion living ≤5 km from the clinic decreased from 16.6% to 13.0% (p<0.01). HIV prevalence and clinic visit density demonstrated statistically significant non-random spatial patterning. Significant non-random patterning of prevalent infection and client visits highlighted Bangkok's urban HIV epidemic, clinic proximity to clients, and geographic reach. Clients lived closer to testing venues, yet farther from the urban MSM clinic, over time. Spatiotemporal characteristics of VCT clients can help assess service accessibility and guide targeted prevention planning.

Facilitators and barriers affecting PrEP adherence among Thai men who have sex with men (MSM) in the HPTN 067/ADAPT Study.

The HPTN 067/ADAPT Study evaluated the feasibility, acceptability, patterns of adherence and coverage for three randomly assigned oral FTC/TDF pre-exposure prophylaxis (PrEP) dosing regimens to prevent HIV infection. Using qualitative methods, we explored facilitators and barriers among a subset of men who have sex with men (MSM) participants in Bangkok, Thailand. Between August 2013 and March 2014, 32 HPTN 067/ADAPT participants joined in 6 focus group discussions, and 6 attended key informant interviews. Facilitators of PrEP adherence included use of strategies to have PrEP available when needed, simplicity in regimen requirements with recognition that more complex regimens may take some time to master, ability to plan for sex, receipt of social and technology support, ability to use a PrEP regimen that best matches to one's own patterns of sex, and experiences with PrEP as a part of health and well-being. Challenges to PrEP adherence included perceptions of no or low HIV risk, difficulties following regimens when intoxicated, concerns about side effects, experience of HIV stigma, and affordability of PrEP outside of study context influencing uptake and use in the community. Preferences for regimens varied, suggesting that multiple PrEP effective regimen options should be available to fit those with different needs.

HPTN 067/ADAPT: Correlates of Sex-Related Pre-exposure Prophylaxis Adherence, Thai Men Who Have Sex With Men, and Transgender Women, 2012-2013.

BACKGROUND: We identified correlates of sex-related pre-exposure prophylaxis (PrEP) adherence in HPTN067/ADAPT, a phase 2, open-label feasibility study of daily and nondaily regimens of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)-based PrEP, among Thai men who have sex with men (MSM), and transgender women (TGW), Bangkok. METHODS: Participants were randomly assigned to one of three self-administered dosing regimens for 24 weeks: daily, time-driven, or event-driven. Demographic and behavioral information was obtained at screening. Pill-container opening was recorded with electronic dose monitoring, and self-reported information on PrEP use, sex events, and substance use was obtained during weekly interviews to confirm dose data. Sex-related PrEP adherence was calculated as the proportion of sex events covered by PrEP use (at least one tablet taken within 4 days before sex and at least one tablet taken within 24 hours after sex) to total sex events. We used multivariate modeling with sex event as the unit of analysis to evaluate correlates associated with sex-related PrEP adherence. RESULTS: Among 178 MSM and TGW, sex-related PrEP adherence was similar in the daily and time-driven arms (P = 0.79), both significantly greater than the event-driven arm (P = 0.02 compared to daily). Sex-related PrEP adherence by those reporting stimulant use (74.2%) was similar to those reporting other nonalcohol drug use (76.3%, P = 0.80), but lower than those reporting no substance use (84.6%, P = 0.04). In a multivariable model, randomization to the event-driven arm, a higher prestudy number of reported sex events, and use of stimulant drugs were associated with significantly lower sex-related PrEP adherence. CONCLUSION: Adherence was influenced by treatment schedule and adversely affected by nonalcoholic substance use. Regardless of these factors, Thai MSM and TGW maintained high adherence levels to oral PrEP dosing regimens and coverage of sexual exposures.

Brief Report: Routine Use of Oral PrEP in a Phase 2 Rectal Microbicide Study of Tenofovir Reduced-Glycerin 1% Gel (MTN-017).

BACKGROUND: As daily oral preexposure prophylaxis (PrEP) becomes standard for HIV prevention, routine use of PrEP is likely to increase within clinical trials of novel preventive agents. We describe the prevalence and characteristics of participants reporting nonstudy oral PrEP use within Microbicide Trials Network-017 (MTN-017), a phase 2 trial of a rectal microbicide. SETTING AND METHODS: One hundred ninety-five HIV-uninfected men who have sex with men and transgender women were enrolled and followed in MTN-017 across 8 sites in the United States, Thailand, South Africa, and Peru from 2013 to 2015. Nonstudy oral PrEP use was recorded on case report forms and progress notes. Characteristics of PrEP users and non-PrEP users were compared using tests of statistical significance. RESULTS: Overall, 11% of participants reported nonstudy oral PrEP use, all from the San Francisco (SF) site, accounting for 58% (22/38) of participants enrolled in SF. There was a higher median number of sex partners reported in the past 8 weeks before enrollment among oral PrEP users vs. nonusers (7 vs. 2, P = 0.02). Most PrEP users (18/22, 82%) began PrEP treatment during screening/after enrollment, and most (19/22, 86%) decided to continue oral PrEP after study completion. CONCLUSION: Nonstudy oral PrEP use in the first phase 2 study of tenofovir reduced-glycerin 1% gel was high at a single site in SF where community PrEP availability and use was expanding. Investigators should consider the evolving context of nonstudy oral PrEP use across trial sites when designing and interpreting trials of novel biomedical prevention modalities.

Low Disclosure of PrEP Nonadherence and HIV-Risk Behaviors Associated With Poor HIV PrEP Adherence in the HPTN 067/ADAPT Study.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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(ß) = 0.62, 95% CI: (0.46 to 0.84); P = 0.002] as were increased days since the last PrEP dose [exp(ß) = 0.73, 95% CI: (0.65 to 0.83); P ≤ 0.001]. CONCLUSIONS: 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.

Risk Behaviors Among Young Men Who Have Sex With Men in Bangkok: A Qualitative Study to Understand and Contextualize High HIV Incidence.

The Bangkok Men Who Have Sex With Men (MSM) Cohort Study has shown high HIV incidence (8-12/100 person-years) among 18-21-year-old MSM. These data led to a further study using qualitative methods among young (18-24 years old) MSM in order to understand the factors driving the HIV epidemic among YMSM. We conducted eight focus group discussions and 10 key informant interviews among YMSM in Bangkok, Thailand. Sociodemographic and behavioral data were collected using a questionnaire. We audio-recorded, transcribed, and analyzed qualitative and questionnaire data using computer software. The categories relating to risk behavior were (1) the use of social networks for seeking sexual partners and the marketing promotions of MSM entertainment venues, (2) social influence by peers and older MSM, (3) easy access to high parties and group sex, (4) easy access to club drugs, (5) conceptions related to HIV risk, and (6) sexual preferences of YMSM. Increased HIV testing, same-sex education, and YMSM-specific HIV prevention efforts are urgently needed for YMSM in Bangkok.

Selling and buying sex in the city: men who have sex with men in the Bangkok men who have sex with men Cohort Study.

We describe participants in the Bangkok Men who have sex with men Cohort Study (BMCS) who sold or bought sex. Men who have sex with men (MSM) and transgender women aged ≥18 years had HIV testing and behavioral data collected at enrollment and every four months. We evaluated report of receiving money or goods for sex (selling sex) or giving money or goods for sex (buying sex) at enrollment using logistic regression models; we also describe sex work over time, and HIV and syphilis incidence among those who report sex work. At enrollment, 511 (29.3%) of 1744 participants reported buying or selling sex. Factors associated with selling sex were young age, lower education, living alone or living with a friend, being unemployed, higher HIV knowledge, binge drinking and club drug use, a higher number of casual male partners, meeting sex partners at specific venues, having a foreign sex partner, and being HSV-1 seropositive. MSM aged 18-21 years who sold sex had an HIV incidence of 11.1 per 100 person-years (95% CI: 6.7-17.4). Almost one-third of participants from BMCS reported sex work at enrollment. Young men who sold sex had high HIV incidence and HIV prevention interventions are needed for this at-risk population in Bangkok, Thailand.

Estimating recent HIV incidence among young men who have sex with men: Reinvigorating, validating and implementing Osmond's algorithm for behavioral imputation.

HIV incidence information is essential for epidemic monitoring and evaluating preventive interventions. However, reliable HIV incidence data is difficult to obtain, especially among marginalized populations, such as young men who have sex with men (YMSM). Here we evaluate the reliability of an alternative HIV incidence assessment method, behavioral imputation, as compared to serologically estimated HIV incidence. Recent HIV incidence among YMSM (aged 18 to 21 and 18 to 24 years) enrolled in a cohort study in Bangkok from 2006 to 2014 was estimated using two mid-point methods for seroconversion: 1) between age of first anal intercourse and first HIV-positive test (without previous HIV-negative test) (behavioral imputation) and 2) between the date of last negative and first positive HIV test (serological estimation). Serologically estimated HIV incidence was taken as the "gold standard" to evaluate between-method agreement. At baseline, 314 YMSM age 18 to 21 years accumulated 674 person-years (PY) of follow-up since first anal intercourse. Considering that 50 men had prevalent HIV infection, the behaviorally imputed HIV incidence was 7.4 per 100 PY. Of the remaining 264 HIV-negative men, 54 seroconverted for HIV infection during the study, accumulating 724 PY of follow-up and a serologically estimated HIV incidence of 7.5 per 100 PY. At baseline, 712 YMSM age 18 to 24 years (including 18 to 21-year-old men analyzed above) accumulated 2143 PY of follow-up since first anal intercourse. Considering that 151 men had prevalent HIV infection, the behaviorally imputed HIV incidence was 7.0 per 100 PY. Of the remaining 561 HIV-negative men, 125 seroconverted for HIV infection during the study, accumulating 1700 PY of follow-up and a serologically estimated HIV incidence of 7.4 per 100 PY. Behavioral imputation and serological estimation are in good agreement when estimating recent HIV incidence in YMSM.

In what circumstances could nondaily preexposure prophylaxis for HIV substantially reduce program costs?

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.

Daily and Nondaily Oral Preexposure Prophylaxis in Men and Transgender Women Who Have Sex With Men: The Human Immunodeficiency Virus Prevention Trials Network 067/ADAPT Study.

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.

Screening for Chlamydia trachomatis and Neisseria gonorrhoeae infection among asymptomatic men who have sex with men in Bangkok, Thailand.

We report positivity rates of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection at each anatomic site among asymptomatic men who have sex with men (MSM). We calculated the number needed to screen (NNS) to detect CT and NG infection at each anatomic site. From 2006 to 2010, we enrolled Thai MSM, age ≥ 18 years into the Bangkok MSM Cohort Study. Participants underwent physical examination and had rectal, urethral, and pharyngeal screening for CT and NG infection using nucleic acid amplification tests (NAATs). Of 1744 enrollees, 1696 (97.2%) had no symptoms of CT and NG infection. The positivity rates of CT and NG infection at any site were 14.3% (rectum, urethra, pharynx) and 6.4% (rectum, urethra), respectively. The NNS to detect rectal CT and rectal NG infections was 10 and 16, respectively (p < 0.05). For urethral infection, the NNS of CT was lower than the NNS of NG (22, 121: p < 0.05). The lowest NNS found for rectal CT infection was in HIV-infected MSM (6, 5-8). Asymptomatic CT and NG infection were common among MSM in Bangkok, Thailand and frequently detected in the rectum. In setting where screening in all specimens using NAAT is not feasible, rectal screening should be a priority.

Preference of Oral Tenofovir Disoproxil Fumarate/Emtricitabine Versus Rectal Tenofovir Reduced-Glycerin 1% Gel Regimens for HIV Prevention Among Cisgender Men and Transgender Women Who Engage in Receptive Anal Intercourse with Men.

Oral pre-exposure prophylaxis (PrEP) can prevent HIV transmission. Yet, some may prefer not to take systemic daily medication. MTN-017 was a 3-period, phase 2 safety and acceptability study of microbicide gel applied rectally either daily or before and after receptive anal intercourse (RAI), compared to daily oral tablet. At baseline, cisgender men and transgender women who reported RAI (N = 187) rated the daily oral regimen higher in overall liking, ease of use, and likelihood of future use than the gel regimens. After trying all three, 28% liked daily oral the least. Gel did not affect sexual enjoyment (88%) or improved it (7-8%). Most partners had no reaction to gel use. Ease of gel use improved significantly between the first and the last few times of daily use. A rectal gel used before and after RAI may constitute an attractive alternative to daily tablet. Experience with product use may increase acceptability.

High levels of adherence to a rectal microbicide gel and to oral Pre-Exposure Prophylaxis (PrEP) achieved in MTN-017 among men who have sex with men (MSM) and transgender women.

Trials to assess microbicide safety require strict adherence to prescribed regimens. If adherence is suboptimal, safety cannot be adequately assessed. MTN-017 was a phase 2, randomized sequence, open-label, expanded safety and acceptability crossover study comparing 1) daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), 2) daily use of reduced-glycerin 1% tenofovir (RG-TFV) gel applied rectally, and 3) RG-TFV gel applied before and after receptive anal intercourse (RAI)-if participants had no RAI in a week, they were asked to use two doses of gel within 24 hours. Product use was assessed by mixed methods including unused product return count, text messaging reports, and qualitative plasma TFV pharmacokinetic (PK) results. Convergence interviews engaged participants in determining the most accurate number of doses used based on product count and text messaging reports. Client-centered adherence counseling was also used. Participants (N = 187) were men who have sex with men and transgender women enrolled in the United States (42%), Thailand (29%), Peru (19%) and South Africa (10%). Mean age was 31.4 years (range 18-64 years). Based on convergence interviews, over an 8-week period, 94% of participants had ≥80% adherence to daily tablet, 41% having perfect adherence; 83% had ≥80% adherence to daily gel, 29% having perfect adherence; and 93% had ≥80% adherence to twice-weekly use during the RAI-associated gel regimen, 75% having perfect adherence and 77% having ≥80% adherence to gel use before and after RAI. Only 4.4% of all daily product PK results were undetectable and unexpected (TFV concentrations <0.31 ng/mL) given self-reported product use near sampling date. The mixed methods adherence measurement indicated high adherence to product use in all three regimens. Adherence to RAI-associated rectal gel use was as high as adherence to daily oral PrEP. A rectal microbicide gel, if efficacious, could be an alternative for individuals uninterested in daily oral PrEP.

MTN-017: A Rectal Phase 2 Extended Safety and Acceptability Study of Tenofovir Reduced-Glycerin 1% Gel.

Background: Human immunodeficiency virus (HIV) disproportionately affects men who have sex with men (MSM) and transgender women (TGW). Safe and acceptable topical HIV prevention methods that target the rectum are needed. Methods: MTN-017 was a phase 2, 3-period, randomized sequence, open-label, expanded safety and acceptability crossover study comparing rectally applied reduced-glycerin (RG) 1% tenofovir (TFV) and oral emtricitabine/TFV disoproxil fumarate (FTC/TDF). In each 8-week study period participants were randomized to RG-TFV rectal gel daily, or RG-TFV rectal gel before and after receptive anal intercourse (RAI; or at least twice weekly in the event of no RAI), or daily oral FTC/TDF. Results: MSM and TGW (n = 195) were enrolled from 8 sites in the United States, Thailand, Peru, and South Africa with mean age of 31.1 years (range 18-64). There were no differences in ≥grade 2 adverse event rates between daily gel (incidence rate ratio [IRR], 1.09; P = .59) or RAI gel (IRR, 0.90; P = .51) compared to FTC/TDF. High adherence (≥80% of prescribed doses assessed by unused product return and Short Message System reports) was less likely in the daily gel regimen (odds ratio [OR], 0.35; P < .001), and participants reported less likelihood of future daily gel use for HIV protection compared to FTC/TDF (OR, 0.38; P < .001). Conclusions: Rectal application of RG TFV gel was safe in MSM and TGW. Adherence and product use likelihood were similar for the intermittent gel and daily oral FTC/TDF regimens, but lower for the daily gel regimen. Clinical Trials Registration: NCT01687218.

Subtypes and Risk Behaviors Among Incident HIV Cases in the Bangkok Men Who Have Sex with Men Cohort Study, Thailand, 2006-2014.

HIV-1 incidence and prevalence remain high among men who have sex with men (MSM), and transgender women (TGW), in Thailand. To examine the link between epidemiologic factors and HIV-1 subtype transmission among Thai MSM, we compared covariates of infection with HIV CRF01_AE and other HIV strains among participants in the Bangkok MSM Cohort Study (BMCS). The BMCS was an observational cohort study of Thai MSM and TGW with up to 60 months of follow-up at 4 monthly intervals. Participants underwent HIV/sexually transmitted infections testing and provided behavioral data at each visit. Infecting viral strain was characterized by gene sequencing and/or multiregion hybridization assay. We correlated behavioral/clinical variables with infecting strain using Cox proportional hazards. Among a total of 1372 HIV seronegative enrolled participants with 4,192 person-years of follow-up, we identified 215 seroconverters between April 2006 and December 2014, with 177 infected with CRF01_AE and 38 with non-CRF01_AE subtype. Age 18-21 years (adjusted hazard ratio [AHR] 2.2, 95% confidence interval [CI]: 1.4-3.5), age 22-29 (AHR 1.6, 95% CI: 1.1-2.3), living alone (AHR 1.5, 95% CI: 1.1-2.1), drug use (AHR 2.2, 95% CI: 1.4-3.5), intermittent condom use (AHR 1.7, 95% CI: 1.3-2.3), any receptive anal intercourse (AHR 1.7, 95% CI: 1.2-2.4), group sex (AHR 1.5, 95% CI: 1.1-2.2), anti-herpes simplex virus type 1 (AHR 1.5, 95% CI: 1.1-2.1), and Treponema pallidum antibody positivity (AHR 2.5, 95% CI: 1.4-4.4) were associated with CRF01_AE infection. Age 18-21 years (AHR 5.1, 95% CI: 1.6-16.5), age 22-29 (AHR 3.6, 95% CI: 1.3-10.4), drug use (AHR 3.1, 95% CI: 1.3-7.5), group sex (AHR 2.4, 95% CI: 1.1-5.0), and hepatitis B virus surface antigen (AHR 3.6, 95% CI: 1.3-10.2) were associated with non-CRF01_AE infection. We observed several significant biological and behavioral correlates of infection with CRF01_AE and other HIV strains among Thai MSM. Divergence in correlates by strain may indicate differences in HIV transmission epidemiology between CRF01_AE and other strains. These differences could reflect founder effects, transmission within networks distinguished by specific risk factors, and possibly biological differences between HIV strains.