Estimated benefits of providing on-demand pre-exposure prophylaxis options for cisgender women in South Africa: A modeling study

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INTRODUCTION: On-demand oral tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) pre-exposure prophylaxis (PrEP) has been shown to be effective at preventing HIV acquisition among cisgender men and transgender women but is not recommended for cisgender women. On-demand PrEP may improve PrEP uptake, effective use, and persistence in cisgender women. We utilized published oral PrEP adherence-efficacy curves and data from HPTN 067 study to estimate effectiveness of different non-daily PrEP options when used by cisgender women and investigate which sub-groups may benefit most from on-demand PrEP. METHODS: We created a synthetic cohort of PrEP users with data on sex act frequency and pill taking from the HPTN 067 Cape Town site. We simulated PrEP use with three PrEP regimens tested in HPTN 067: daily, time-driven (2 pills/week+1 pill after sex), and event-driven (1 pill before+1 pill after sex) PrEP, and hypothesized 2-1-1 PrEP (2 pills before+1 pill each of the two days after sex) for six months each. We estimated PrEP effectiveness based on the number of pills taken around sex acts. Adherence to 2-1-1 PrEP, which was not tested in the HPTN 067, was informed by observed adherence to event-driven PrEP. Assignment to 2-1-1 PrEP based on daily PrEP adherence and sex act frequency was also analyzed. RESULTS: We estimated median effectiveness of 86% for daily, 47% for time-driven, 42% for event-driven, and 57% for 2-1-1 PrEP. PrEP users with low adherence to daily PrEP (less than 2.8 pills per week) benefited most from on-demand PrEP. In this subgroup, comprising 8% of the cohort, PrEP effectiveness increased from 41% to 44% when switching from daily to 2-1-1 PrEP while pill taking decreased from 2.2 to 1.4 pills per week; population-level effectiveness was unchanged when this subgroup switched to on-demand PrEP. We found no advantage in assigning 2-1-1 PrEP by sex act frequency. CONCLUSIONS: Our model suggests that on-demand PrEP could benefit women with low daily PrEP adherence by decreasing the number of days when pills need to be taken and modestly increasing effectiveness compared to a daily regimen. This would be a valuable and easy-to-implement additional option in places where daily oral PrEP is already available.

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