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

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

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 non-daily pre-exposure prophylaxis for HIV substantially reduce program costs?

Objectives: To review the main factors influencing the costs of nondaily oral pre- exposure prophylaxis (PrEP) with tenofovir ( emtricitabine). To estimate the cost reductions possible with nondaily PrEP compared with daily PrEP for different popula- tions (MSM and heterosexual populations). Design: Systematic review and data triangulation. Methods: We estimated the required number of tablets/person/week for dosing regi- mens 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 2days/week (0–1.5days/week for MSM, 1–2days/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