Randomized trial of clinical safety of daily oral tenofovir disoproxil fumarate among HIV-uninfected men who have sex with men in the United States.

OBJECTIVES: To evaluate the clinical safety of daily tenofovir disoproxil fumarate (TDF) among HIV-negative men who have sex with men. DESIGN: Randomized, double-blind, placebo-controlled trial. Participants were randomized 1:1:1:1 to immediate or delayed study drug (TDF, 300 mg orally per day, or placebo). METHODS: Four hundred healthy HIV-uninfected men who have sex with men reporting anal sex with another man within the previous 12 months enrolled in Atlanta, Boston, and San Francisco. HIV serostatus, clinical and laboratory adverse events (AEs), adherence (pill count, Medication Event Monitoring System, and self-report), and sexual and other sociobehavioral data were assessed at 3-month intervals for 24 months. Primary outcomes were clinical safety, assessed by incidence of AEs and laboratory abnormalities. RESULTS: Study drug was initiated by 373 (93%) participants (186 TDF and 187 placebo), of whom 325 (87%) completed the final study visit. Of 2428 AEs reported among 334 (90%) participants, 2366 (97%) were mild or moderate in severity. Frequencies of commonly reported AEs did not differ significantly between TDF and placebo arms. In multivariable analyses, back pain was more likely among TDF recipients (P = 0.04); these reports were not associated with documented fractures or other objective findings. There were no grade ≥3 creatinine elevations; grades 1 and 2 creatinine increases were not associated with TDF receipt. Estimated percentage of study drug doses taken was 92% by pill count and 77% by Medication Event Monitoring System. Seven seroconversions occurred: 4 on placebo and 3 among delayed arm participants not yet on study drug. CONCLUSIONS: Daily oral TDF was well tolerated, with reasonable adherence. No significant renal concerns were identified.

Sexual risk behavior among HIV-uninfected men who have sex with men participating in a tenofovir preexposure prophylaxis randomized trial in the United States.

OBJECTIVE: To evaluate for changes in sexual behaviors associated with daily pill use among men who have sex with men (MSM) participating in a preexposure prophylaxis trial. DESIGN: Randomized, double-blind, placebo-controlled trial. Participants were randomized 1:1:1:1 to receive tenofovir disoproxil fumarate or placebo at enrollment or after a 9-month delay and followed for 24 months. METHODS: Four hundred HIV-negative MSM reporting anal sex with a man in the past 12 months and meeting other eligibility criteria enrolled in San Francisco, Atlanta, and Boston. Sexual risk was assessed at baseline and quarterly visits using Audio Computer-Assisted Self-Interview. The association of pill taking with sexual behavior was evaluated using logistic and negative-binomial regressions for repeated measures. RESULTS: Overall indices of behavioral risk declined or remained stable during follow-up. Mean number of partners and proportion reporting unprotected anal sex declined during follow-up (P < 0.05), and mean unprotected anal sex episodes remained stable. During the initial 9 months, changes in risk practices were similar in the group that began pills immediately vs. those in the delayed arm. These indices of risk did not differ significantly after initiation of pill use in the delayed arm or continuation of study medication in the immediate arm. Use of poppers, amphetamines, and sexual performance-enhancing drugs were independently associated with one or more indices of sexual risk. CONCLUSIONS: There was no evidence of risk compensation among HIV-uninfected MSM in this clinical trial. Monitoring for risk compensation should continue now that preexposure prophylaxis has been shown to be efficacious in MSM and other populations and will be provided in open-label trials and other contexts.