Pedro Gonzales

Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial

BACKGROUND Daily preexposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) decreases the risk of human immunodeficiency virus (HIV) acquisition. Initiation of TDF decreases bone mineral density (BMD) in HIV-infected people. We report the effect of FTC/TDF on BMD in HIV-seronegative men who have sex with men and in transgender women. METHODS Dual-energy X-ray absorptiometry was performed at baseline and 24-week intervals in a substudy of iPrEx, a randomized, double-blind, placebo-controlled trial of FTC/TDF PrEP. Plasma and intracellular tenofovir concentrations were measured in participants randomized to FTC/TDF. RESULTS In 498 participants (247 FTC/TDF, 251 placebo), BMD in those randomized to FTC/TDF decreased modestly but statistically significantly by 24 weeks in the spine (net difference, -0.91% [95% confidence interval {CI}, -1.44% to -.38%]; P = .001) and hip (-0.61% [95% CI, -.96% to -.27%], P = .001). Changes within each subsequent 24-week interval were not statistically significant. Changes in BMD by week 24 correlated inversely with intracellular tenofovir diphosphate (TFV-DP), which was detected in 53% of those randomized to FTC/TDF. Net BMD loss by week 24 in participants with TFV-DP levels indicative of consistent dosing averaged -1.42% ± 29% and -0.85% ± 19% in the spine and hip, respectively (P < .001 vs placebo). Spine BMD tended to rebound following discontinuation of FTC/TDF. There were no differences in fractures (P = .62) or incidence of low BMD. CONCLUSIONS In HIV-uninfected persons, FTC/TDF PrEP was associated with small but statistically significant decreases in BMD by week 24 that inversely correlated with TFV-DP, with more stable BMD thereafter. CLINICAL TRIALS REGISTRATION NCT00458393.

Alcohol use disorders negatively influence antiretroviral medication adherence among men who have sex with men in Peru

As international guidelines increase access to antiretroviral therapy (ART) globally, ART adherence becomes increasingly important to achieve HIV treatment as prevention (TasP) goals. In the concentrated HIV epidemic among men who have sex with men (MSM) and transgendered women (TGW) in Lima, Peru, the independent correlates of ART nonadherence were examined to inform treatment intervention priorities. Cross sectional survey of HIV-infected MSM and TGW who are engaged in clinical care in Lima, Peru. From June to August 2012, 302 HIV-infected Peruvian MSM/TGW from three clinical care sites were recruited using convenience sampling to participate in a cross-sectional computer-assisted adherence survey. Several standardized screening measures associated with ART nonadherence were examined in order to determine the independent correlates of optimal (≥90%) and perfect (100%) adherence, which were assessed using logistic regression. Of the 302 participants recruited, 263 (87.1%) were prescribed ART. Among those prescribed ART, 229 (87.1%) reported optimal and 146 (55.5%) reported perfect adherence. The prevalence of alcohol use disorders (AUD; 43.2%), alcohol dependence (5.3%), recent drug use (6.0%), and depression (44.5%) was high, and most participants had some evidence of neurocognitive impairment. Meeting criteria for having an AUD and depression were collinear (p < 0.001). On multivariate analysis, having an AUD was inversely related and the only independent correlate of optimal (AOR = 0.427; 95% CI = 0.187–0.976) and perfect (AOR = 0.552; 95% CI = 0.327–0.930) ART adherence. AUDs are highly prevalent among Peruvian HIV-infected MSM and contribute significantly to ART nonadherence. These findings support the need for screening and treating underlying AUDs. In order to meet HIV TasP goals, evidence-based strategies targeting AUDs are likely to directly improve ART adherence and indirectly improve overall individual health, HIV treatment engagement, and reduce transmission to sexual partners among this vulnerable and disproportionally affected population.

Screening for Drug and Alcohol Use Disorders and Their Association with HIV-Related Sexual Risk Behaviors among Men Who Have Sex with Men in Peru

Background Perus HIV epidemic is concentrated among men who have sex with men (MSM). The contribution of alcohol use disorders (AUDs) to known high-risk behaviors associated with HIV transmission in this context has not been well characterized. Methods Between June and October 2011, 5,148 sexually active MSM were recruited using convenience sampling in five cities to participate in a cross-sectional bio-behavioral survey. Five high-risk sexual criteria previously associated with incident HIV infection in this setting were selected a priori as the dependent outcomes. Screening for AUDs used the validated Alcohol Use Disorders Identification Test (AUDIT) and AUDS were stratified by severity. Unadjusted and adjusted odds ratios (AOR) were computed to establish the independent correlates of the five dependent outcomes. Results The majority (62.8%) of participants met screening criteria for having an AUD, which were independently correlated with each of the following high-risk sexual risk behaviors in the previous 6 months: 1) >5 sexual partners [AOR = 1.76; (1.54–2.02)]; 2) sex with an HIV-infected partner [AOR = 1.29; (1.03–1.62)]; 3) having a sexually transmitted infection [AOR = 1.38; (1.13–1.68)]; 4) being a sex worker [AOR = 1.61; (1.40–1.87)]; and 5) unprotected sex during last encounter [AOR = 1.22; (1.09–1.38)]. Recent drug use was also correlated with having >5 sexual partners [AOR = 1.42 (1.19–1.71)], sex work [AOR = 1.97 (1.63–2.39)] and unprotected sex during last encounter [AOR = 1.31 (1.11–1.54)]. For each dependent variable, the association with AUDs significantly increased with increasing AUD severity. Conclusions AUDs are highly prevalent among MSM in Peru and are associated with increased HIV risk-taking behaviors that are associated with HIV transmission. Strategies that target problematic drinking such as medication-assisted therapy, behavioral counseling and structural interventions could potentially reduce risky behaviors and ultimately reduce HIV transmission among MSM in Peru.

Acceptability and feasibility of HIV self-testing among men who have sex with men in Peru and Brazil.

HIV self-testing has the potential to increase testing frequency and uptake. This pilot study assessed the feasibility and acceptability of HIV self-testing in a sample of sexually active men who have sex with men (MSM) in Peru and Brazil. Participants were trained to use a whole blood rapid HIV self-test and instructed to use the self-test monthly during this three-month study. Test acceptability was measured with self-reported use of the test at the one-month and three-month study visits, and test feasibility was assessed by direct observation of self-test administration at the final three-month visit. A total of 103 participants (52 in Peru and 51 in Brazil) were enrolled, and 86% completed the three-month study. Nearly all participants reported use of the self-test (97% at one-month and 98% at three-month visit), and all participants correctly interpreted the self-administered test results when observed using the test at the final study visit. HIV self-testing with a blood-based assay was highly acceptable and feasible. HIV self-testing may have the potential to increase testing frequency and to reach high-risk MSM not currently accessing HIV-testing services.

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.

Client and provider perspectives on new HIV prevention tools for MSM in the Americas.

Men who have sex with men (MSM) in the Americas require targeted, combination HIV prevention approaches. We solicited client and provider perspectives on emerging prevention interventions including HIV pre-exposure prophylaxis (PrEP) and HIV self-tests through focus groups and in-depth interviews with 130 MSM and 41 providers across four sites: New York, San Francisco, Lima, and Rio de Janeiro. Among the MSM participants, we identified three prevention typologies: non-condom users, inconsistent condom users, and consistent condom users. Northern and Southern MSM differed in the variety of harm reduction strategies utilized: where U.S. MSM relied on condom use as well as disclosure and seroadaptive behaviors for prevention, condom use without disclosure or serostatus discussions was the norm in South America. Interest in new prevention technologies was shaped by the social context. U.S. MSM preferences differed by typology, such that non-condom users were interested in taking PrEP and using home HIV tests. MSM in Brazil, regardless of typology, were interested in exploring new prevention options. MSM in Peru demonstrated moderate interest but were less comfortable with adopting new strategies. MSM and providers’ opinions differed substantially with respect to new prevention options. Across sites, most providers were reticent to engage with new prevention options, though some NGO-based providers were more supportive of exploring new prevention tools. Both clients and providers will need to be engaged in developing integrated prevention strategies for MSM.

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.

Men Who Have Sex With Men in Peru: Acceptability of Medication-Assisted Therapy for Treating Alcohol Use Disorders.

In Peru, the HIV epidemic is concentrated in men who have sex with men (MSM) and transgender women (TGW). Multiple studies correlate alcohol use disorders (AUDs) with risky sexual behaviors among Peruvian MSM. Qualitative research was used to inform a clinical trial on the acceptability of medication-assisted therapies to assist management of AUDs and improve antiretroviral therapy (ART) adherence among MSM/TGW in Peru. Three focus groups involving HIV-infected or HIV-uninfected MSM/TGW (n = 26) with AUDs (AUDIT ≥ 8) were transcribed, translated from Spanish into English, and analyzed using thematic content analysis. Despite having an AUD, participants considered themselves “social” drinkers, minimized their drinking behaviors, and differed about whether or not alcohol problems could be treated. Participants expressed skepticism about medication for treating AUDs. Three concepts emerged as necessary components of a treatment program for alcohol problems: cost, family support, and the potential to drink less alcohol without attaining total abstinence. This study reveals important areas of education to increase potential acceptability of a medication for treating AUDs among MSM/TGW. Given the social conditions and knowledge base of the participants, medication-assisted therapies using naltrexone may be a beneficial strategy for MSM with AUDs.

Using conjoint analysis to determine the impact of product and user characteristics on acceptability of rectal microbicides for HIV prevention among Peruvian men who have sex with men

Objectives Men who have sex with men (MSM) are in need of novel and acceptable HIV prevention interventions. In Peru, a Phase II clinical trial was recently completed evaluating rectally applied tenofovir gel among Peruvian MSM and transgender women. If deemed safe and acceptable, the product could move into efficacy testing, but acceptability data for similar products are needed now in order to prepare for future implementation. Peru is in need of expanded, national acceptability data among likely users. Methods Using conjoint analysis of an online cross-sectional survey taken by 1008 Peruvian MSM and transgender women, we tested the acceptability of eight hypothetical rectal microbicide (RM) products comprising six, dual-value attributes. We also assessed the relationship of select product attributes with sample characteristics. Results Highest acceptability was found for a RM that was 90% effective, used before and after sex, without side effects, costing approximately

Active syphilis and its association with HIV and sexual risk behaviours in a multicity sample of men who have sex with men and transgender women in Peru

0.30, had no prescription requirement and had a single-use applicator. Product effectiveness and presence of side effects were the factors most likely to drive RM acceptance and use. Education, sexual orientation, sexual role and concern for HIV infection were also related to aspects of RM acceptability. Conclusion RM acceptability was high, confirming the results of earlier, smaller studies and placing confidence in the acceptability of RMs. Analysis of the relationships with product attributes and sample characteristics underscore the need to consider the impact of factors such as sexual orientation, sexual role, level of education and concern for HIV acquisition on RM acceptability.