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

Abstract

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.

Clinical trials registration: NCT01327651.

Figures

Figure 1.

Consort diagrams for the HIV Prevention Trials Network (HPTN) 067 ADAPT study in Bangkok, Thailand (A) and Harlem, New York (B). Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; DOT, directly observed therapy; HBV, hepatitis B virus; HIV, human immunodeficiency virus; Ser Cr, serum creatinine.

Figure 1.

Consort diagrams for the HIV Prevention Trials Network (HPTN) 067 ADAPT study in Bangkok, Thailand (A) and Harlem, New York (B). Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; DOT, directly observed therapy; HBV, hepatitis B virus; HIV, human immunodeficiency virus; Ser Cr, serum creatinine.

Figure 2.

Coverage of sex events with pre- and postsex preexposure prophylaxis dosing in the HIV Prevention Trials Network (HPTN) 067 study, Bangkok, Thailand (A) and Harlem, New York (B). Error bars represent the 95% confidence interval of the estimate of coverage, based on bootstrap analysis.

Figure 3.

Coverage of sex events with pre- and postsex dosing, the primary outcome, by study site in Bangkok, Thailand (A) and in Harlem, New York (B), showing 4-week period and recommended regimen. Each row represents a different participant. Dark blue represents complete coverage of sex events with pre- and postsex dosing. Lighter blue shades indicate partial coverage. White represents periods where there was no coverage with pre- or postsex dosing. Black periods reflect periods where there was no sexual intercourse reported or data regarding preexposure prophylaxis use or sexual activity was missing.

Figure 4.

Side effects in the HIV Prevention Trials Network (HPTN) 067 study by randomization group in Bangkok, Thailand (A and B) and Harlem, New York (C and D). Neurological side effects include dizziness and headache (A and C). Gastrointestinal side effects include nausea, vomiting, and abdominal cramping (B and D).