Non-daily PrEP dosing is a strategy that may be effective if sufficient PrEP doses correspond with sexual exposure. HPTN 067 ADAPT compared the feasibility of non-daily PrEP dosing regimens in populations at high risk. We modeled the reduction in HIV incidence and the number of pills that would be needed under different dosing regimens.
We used a stochastic mathematical model informed by South African data to simulate one year of sexual behavior of a female cohort (average 1.2 sex-days/week) under three PrEP regimens from the trial: daily (DD), time-driven (TDD, two regular pills/week 3-4 days apart plus one pill within 2h after sex) and event-driven (EDD, pills taken within 2 days before and 2h after sex) dosing. We explored a wide range of PrEP efficacy per sex act defined as fully covered if pills were taken within 2 days before and 1 day after an act and partially covered if only one of these pills were taken. Regimen effectiveness was estimated as 1 minus the ratio of HIV incidence when PrEP is used vs not used. As a proxy for costs saved, the number of pills required for each regimen was compared across different frequencies and distribution of sexual intercourse assuming perfect adherence.
Data from the South African site suggest that 72% (21%), 36% (53%) and 42% (46%) of sex acts were fully (partially) covered with DD, TDD and EDD, respectively. At reported coverage, predicted PrEP effectiveness was 39%, 18%, 21% with DD, TDD and EDD, respectively, assuming 70% PrEP efficacy only for fully covered sex acts (see Figure). Regimens’ effectiveness increased to 47% (DD), 33% (TDD) and 35% (EDD) assuming 35% PrEP efficacy for partially covered sex acts. Assuming perfect adherence, 2, 3-4, and 4-5 pills/week are required with EDD for 1, 2 and 3 sex-days/week, respectively compared to 2-3, 2-4 or 3-5 pills/week with TDD and 7 pills/week for DD. Fewer pills are needed with EDD if sex-days are successive and with TDD if sex-days coincide with regular pill-taking days.
Non-daily PrEP may substantially reduce the number of pills required for the level of sexual activity observed in the HPTN 067 ADAPT trial. However, non-daily PrEP is unlikely to be as effective as daily PrEP in reducing HIV incidence among women in South Africa due to higher sex act coverage observed in the daily use arm. The significant proportion of sex acts partially covered by PrEP implies that the effectiveness of non-daily PrEP depends on the protection provided with partial dosing.