Background: HIV prevention in women is a major public health priority. Pericoital vaginal application of tenofovir (TFV) gel has been demonstrated to prevent male-to-female HIV transmission in a proof of concept phase IIB trial. However, adherence to product is a critical driver of microbicide effectiveness. Additional data are required for licensure.
Methods: FACTS 001 is a phase III, multi-centre, double-blind, randomised, placebo-controlled trial undertaken in 9 sites in South Africa which evaluated the safety and effectiveness of pericoital TFV 1% gel when using the BAT-24 regimen (before and after sex; no more than 2 doses in 24h). HIV-negative women aged 18-30 years received intensive counselling on product adherence and HIV risk reduction with condom provision. Monthly follow-up visits included HIV and safety testing, return of unused product and used gel applicators, and ongoing counselling on product adherence for up to 27 months. Product adherence was measured by proportion of self-reported sex acts covered by gel. In the primary intent-to-treat analysis, the effectiveness of TFV gel was assessed using a log-rank test stratified by site. A nested case-cohort substudy (n=214) also examined TFV drug levels in quarterly cervicovaginal lavage (CVL) samples in HIV seroconverters vs controls.
Results: Between Oct 2011 and Aug 2014, 3844 participants were screened, 2059 enrolled and 2029 included in the primary analysis. At enrolment, participant mean age was 23 years, most were unmarried (88%), lived with parents (62%), and had earned〈ˆUS$100 in the past 3 months (73%). 3036 person-years of observation were accrued and 7.4% of participants were lost to follow-up. Overall 123 HIV infections occurred (HIV incidence: 4.0/100 women years); 61 in the TFV arm and 62 in the placebo group (incidence rate ratio [IRR], 1.0; 95% CI: 0.7-1.4). TFV gel effectiveness was highest in women who reported product use in〈‰72% of sex acts (IRR 0.43; 95% CI 0.09-1.61); however, this subgroup represented only 20% of participants. In the case-cohort substudy, high TFV in CVL was significantly associated with a reduction in HIV acquisition (HR: 0.52; 95% CI: 0.27-0.99; p=0.04).
Conclusions: In this trial, pericoital vaginal TFV 1% gel was not effective in preventing HIV acquisition. In a stratified analysis, there was an association between adherence based on returned applicators and HIV effectiveness, and a significant association between TFV levels in CVL and reduction in HIV incidence.