Daily and non-daily pre-exposure prophylaxis in African women (HPTN 067/ADAPT Cape Town Trial): a randomised, open-label, phase 2 trial

Abstract

Summary Background The relative feasibility and acceptability of daily versus non-daily dosing of oral HIV pre-exposure prophylaxis (PrEP) among women are unknown. We aimed to investigate the feasibility of non-daily PrEP regimens in adult women. Methods We did a randomised, open-label, phase 2 clinical trial (HPTN 067/ADAPT) of oral PrEP with emtricitabine plus tenofovir disoproxil fumarate at a research centre in Cape Town, South Africa. Participants were adult women (age ≥ 18 years) who received directly observed dosing once a week for 5 weeks followed by random assignment (1:1:1) at week 6 to one of three unblinded PrEP regimens for self-administered dosing over 24 weeks: daily; time-driven (twice a week plus a post-sex dose); or event-driven (one tablet both before and after sex). Primary outcomes were PrEP coverage (at least one dose within the 4 days before sex and one dose within 24 h after sex), pills needed or used to achieve regimen-specific adherence and coverage, and symptoms and side-effects. All analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01327651; the trial is completed and this report presents the final analysis. Findings Between Sept 12, 2011, and Oct 3, 2012, 191 women were enrolled to the trial. 178 (93%) completed directly observed dosing and were randomly assigned one of the three PrEP regimens for the self-administered phase: 59 were allocated the daily regimen, 59 the time-driven regimen, and 60 the event-driven regimen. Median age of women was 26 years (IQR 21–37; range 18–52). In women allocated the daily regimen, 1459 (75%) of 1952 sex events were covered by PrEP, compared with 599 (56%) of 1074 sex events among those assigned the time-driven regimen (odds ratio [OR] 2·35, 95% CI 1·43–3·83; p=0·0007) and 798 (52%) of 1542 sex events among those allotted the event-driven regimen (2·76, 1·68–4·53; p<0·0001). Fewer pills were needed for complete adherence in women allocated non-daily regimens (vs daily regimen, relative mean 2·53 [95% CI 2·39–2·69] for the time-driven regimen and 4·16 [3·59–4·82] for the event-driven regimen; p<0·0001). Side-effects were uncommon. Eight HIV seroconversions occurred overall, with four documented during the self-administered phase (two with the time-driven regimen and two with the event-driven regimen). Adherence to the assigned regimen was 75% (7283 of 9652 doses taken) for women allocated the daily regimen compared with 65% for those assigned the time-driven regimen (2367 of 3616 doses taken; p=0·0028) and 53% for those allotted the event-driven regimen (1161 of 2203 doses taken; p<0·0001). When sex was reported in the previous week, PrEP drugs were detected (above the lower limits of quantification) more frequently in women assigned the daily regimen (73 [68%] of 107 samples) than in those allocated the time-driven regimen (42 [58%] of 72 samples) and the event-driven regimen (41 [41%] of 99 samples). Interpretation Daily PrEP dosing resulted in higher coverage of sex events, increased adherence...

Daily and event‐driven pre‐exposure prophylaxis for men who have sex with men in Belgium: results of a prospective cohort measuring adherence, sexual behaviour and STI incidence

“…In our study, we found a proportion of covered sex days of 67% while on event‐driven and 96% while on daily PrEP. In the Adapt study, the proportion covered sex acts was 74% and 85% among MSM in Bangkok and 52% and 75% among women in Capetown, for event‐driven and daily PrEP respectively . It should be noted however that participants of the Adapt study were randomly assigned to a PrEP regimen, as opposed to our study, where participants self‐selected and could switch between daily and event‐driven, according their preference, during the entire follow‐up period.…”

Factors associated with the informal use of HIV pre‐exposure prophylaxis in Germany: a cross‐sectional study

“…Interestingly, we did not find this association for on-demand/intermittent users, indicating that daily PrEP use without health insurance coverage is likely too expensive for some, and the high cost prevents access to all people who could benefit from it. This is noticeable in light of recent results indicating that in some populations daily PrEP might allow for more intercourse events to be protected against HIV [35,36]. In contrast, about half of the informal PrEP users indicated that generic PrEP would be affordable to them.…”

Global implementation of PrEP for HIV prevention: setting expectations for impact

“…Setting programmatic benchmarks for adherence is essential for identifying shortfalls for further evaluation and intervention. Daily adherence will be the goal for most individuals , but perfection need not be a barrier to potential users ; event‐driven and seasonal use of PrEP present additional challenges for assessing adherence that require consideration. Given programmatic constraints, adherence should be measured through the most reasonably accessible and preferably objective measure .…”