title: Randomized trial of clinical safety of daily oral tenofovir disoproxil fumarate among HIV-uninfected men who have sex with men in the United States.
abstract: OBJECTIVE
  To evaluate the clinical safety of daily tenofovir disoproxil fumarate (TDF) among HIV-negative men who have sex with men.
  
  
  METHODS
  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.
authors: Epidemiology Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA. lkg6@cdc.gov
authors: Lisa A
authors: LA
authors: Grohskopf
authors: Kata L
authors: KL
authors: Chillag
authors: Roman
authors: R
authors: Gvetadze
authors: Albert Y
authors: AY
authors: Liu
authors: Melanie
authors: M
authors: Thompson
authors: Kenneth H
authors: KH
authors: Mayer
authors: Brandi M
authors: BM
authors: Collins
authors: Sonal R
authors: SR
authors: Pathak
authors: Brandon
authors: B
authors: Oʼhara
authors: Marta L
authors: ML
authors: Ackers
authors: Charles E
authors: CE
authors: Rose
authors: Robert M
authors: RM
authors: Grant
authors: Lynn A
authors: LA
authors: Paxton
authors: Susan P
authors: SP
authors: Buchbinder
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001900:Boston / Q000453:epidemiology; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D005500:Follow-Up Studies; D005845:Georgia / Q000453:epidemiology; D015658:HIV Infections / Q000453:epidemiology / Q000517:prevention & control*; D018023:HIV Seronegativity; D018451:Homosexuality, Male / Q000706:statistics & numerical data*; D006801:Humans; D017674:Hypophosphatemia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage* / Q000494:pharmacology; D012495:San Francisco / Q000453:epidemiology; D000068698:Tenofovir; D016896:Treatment Outcome; D016903:Drug Monitoring
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine