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.
†Quantitative Sciences and Data Management Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA;
‡Bridge HIV, San Francisco Department of Public Health, San Francisco, CA;
§AIDS Research Consortium of Atlanta, Atlanta, GA;
‖Fenway Health, Beth Israel Deaconess Medical center, Harvard Medical School, Boston, MA;
¶Northrop Grumman Corporation, Falls Church, VA; and
#Gladstone Institutes; Department of Medicine, University of California, San Francisco, CA.
Correspondence to: Lisa A. Grohskopf, MD, MPH, Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mailstop A-20, Atlanta, GA 30333 (e-mail: email@example.com).
Supported by US Department of Health and Human Services, Centers for Disease Control and Prevention, Contracts #200-2003-03003, #200-2003-03007, and #200-2004-09853.
Use of trade names and commercial sources is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention or the US Department of Health and Human Services. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. L. Grohskopf reports that study medication was provided for the submitted work by Gilead Sciences. A. Liu reports funding to his institution from CDC for the submitted work and consultancy for Clinical Care Options, employment by the San Francisco Department of Public Health, and grants/pending grants with the National Institutes of Health outside the submitted work. M. Thompson reports funding from CDC for the submitted work and board membership with Tibotec Therapeutics, Board membership with ViiV Healthcare, consultancy with Kowa Research Institute, consultancy with Gilead Sciences, and Consultancy with GeoVax outside the submitted work. K. Mayer reports funding from Gilead, Bristol Meyer-Squibb, and Merck for the submitted work. R. Grant reports support from CDC and Gilead for the submitted work and grants/grants pending from Gilead, speaking relationships with Clinical Care Options and WebMD, and payment for development of educational presentations from Viraled outside the submitted work. S. Buchbinder reports support from CDC for the submitted work and consultancy with Clinical Care Options, Employment by the San Francisco Department of Public Health, and grants/grants pending from CDC, NIH, and the Bill and Melinda Gates Foundation outside the submitted work.
Preliminary analyses of limited data from this study were presented at the XVIIIth International AIDS Conference, Vienna, Austria, 2010—Grohskopf et al., Abstract FRLBC102, Preliminary analysis of biomedical data from the phase II clinical safety trial of tenofovir disoproxil fumarate for HIV-1 preexposure prophyalxis among US men who have sex with men.
L.A. Grohskopf and K.L. Chillag are co-first authors.
Received November 30, 2012
Accepted February 21, 2013