Daily dosing of emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) pre-exposure prophylaxis (PrEP) leads to protective drug concentrations for most men and transgender women who have sex with men, according to a study published in Clinical Infectious Diseases.
The HIV Prevention Trials Network 067 study was a randomized, open-label, behavioral equivalence, phase 2, pharmacokinetic study of daily and nondaily FTC/TDF PrEP in men and transgender women who have sex with men. Participants were enrolled from a clinical research site in Harlem in New York City and from a clinic and clinical research site in Bangkok, Thailand. Eligibility was based on the following criteria: HIV-antibody negative, assigned male at birth, at least 18 years old, normal renal function, hepatitis B negative, literate in Thai or English, able to give written informed consent, and reported anal or neovaginal sex with a man in the previous 6 months.
Participants were required to have at least 1 of the following risk factors for HIV: history of an acute sexually transmitted disease, sex with more than 1 man or transgender woman, intercourse without a condom with HIV-infected partner or partner with unknown HIV status, and sex in exchange for money, goods, or favors.
The study began with directly observed dosing at enrollment, then one directly observed FTC/TDF dosing per week for the first 4 weeks, to facilitate the interpretation of drug concentration data. Participants were then randomly assigned a dosing regimen: 1 daily FTC/TDF tablet, 1 twice-weekly tablet with post-sex dose (time-driven arm), or 1 tablet taken before and after sex (event-driven arm). Participants self-administered medication from week 5 through 34. An additional 30 tablets of FTC/TDF were provided every 4 weeks, and participants received an electronic drug monitoring device and weekly interviews to determine if an electronically recorded “opening” event reflected an ingested dose or other factors such as device refill.
Of the 431 individuals enrolled in the study, 357 underwent randomization and were included in the analysis. These 357 participants reported 7734 sex events during the self-administered phase, averaging 0.9 sex events per individual per week. Coverage of sex events for participants in Bangkok was 74% for the event-driven arm, 84% for the time-driven arm, and 85% for the daily arm. For Harlem participants, coverage was 52% for the event-driven arm, 47% for the time-driven arm, and 66% for the daily arm. Higher PrEP use in Bangkok may reflect greater familiarity with PrEP, more identification with gay communities, less stigma, more general health literacy, and greater trust in medical services.
Study limitations include the fact that participants were randomly assigned treatment arms rather than choosing a regimen based on their sexual habits and personal preferences, causing a minority of participants to switch regimens during the study. Still, data gathered were sufficient to confirm the importance of offering PrEP to populations at substantial risk for HIV infection and the recommendation of daily dosing, which resulted in protective drug concentrations for the majority of study participants in two very different settings.
Grant RM, Mannheimer S, Hughes JP, et al. 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 [published online February 6, 2018]. Clin Infect Dis. doi:10.1093/cid/cix1086