Background: Oral pre-exposure prophylaxis (PrEP) is highly efficacious but low adherence undermines effectiveness. PrEP implementation programs are working to identify modifiable factors to improve PrEP adherence. Depression has been associated with low PrEP adherence in African women and may affect PrEP use through other psychosocial factors but this has not yet been explored.
Methods: We analyzed data from South African women in HPTN 067, a trial of intermittent and daily open-label oral PrEP from 2011-2013. Participants were randomized to daily, time-driven, or event-driven PrEP regimens. Study visits occurred at weeks 0, 4, 12, and 24 post-randomization. PrEP adherence was measured via Wisepill? adjusted with weekly telephone calls that assessed sexual behavior and dosing. We considered participants “adherent” if adjusted Wisepill? data indicated that ≥80% of expected doses were taken. Depressive symptoms were assessed at screening using the 20-item Center for Epidemiological Studies-Depression (CES-D) scale; scores ≥16 indicate likely depression. We used Markov chain Monte Carlo methods to impute missing data and marginal structural models to estimate the direct effect of likely depression on PrEP adherence after controlling for confounders (age, marital status, education, alcohol use, HIV risk perceptions, sexual behavior) and mediating effects of stigma, social support, and PrEP optimism. We estimated parameters in each imputed dataset and combined the estimates using Rubin''s method. We ran models assessing the direct effect after accounting for each mediator individually.
Results: At screening, 79 (45.4%) of 174 women had likely depression. High PrEP adherence at week 24 was detected among 55.1% (N=87) of participants and occurred less often among women who had likely depression (N=35; 44.3%) compared with those who did not (N=52; 54.7%; adjusted relative risk [aRR]: 0.81; 95% Confidence Interval [CI]: 0.62-1.00). We found a direct effect of depression on adherence in models accounting for the mediating influence of stigma (aRR: 0.74; 95% CI: 0.62-0.88) and PrEP optimism (aRR: 0.75; 95% CI: 0.55-0.98). Estimates were robust to sensitivity analyses.
Conclusions: Depression was common and associated with lower PrEP adherence among South African women after accounting for confounding and mediating variables. Depression screening and services may improve PrEP effectiveness among African women.

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