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Adherence is a critical component of the success of antiretroviral-based pre-exposure prophylaxis (PrEP) in averting new HIV-infections. Ensuring drug availability at the time of potential HIV exposure relies on self-directed product use. A deeper understanding of how to best support sustained PrEP adherence remains critical to current and future PrEP efforts. This paper provides a succinct synthesis of the adherence support experiences from four pivotal PrEP trials--Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004, FEM-PrEP, Iniciativa Prophylaxis (iPrEx), and Vaginal and Oral Interventions to Control the Epidemic (VOICE). Notwithstanding variability in the design, population/cohort, formulation, drug, dosing strategy, and operationalization of adherence approaches utilized in each trial, the theoretical basis and experiences in implementation and monitoring of the approaches used by these trials provide key lessons for optimizing adherence in future research and programmatic scale-up of PrEP. Recommendations from across these trials include participant-centered approaches, separating measurement of adherence from adherence counseling, incorporating tailored strategies that go beyond education, fostering motivation, and addressing the specific context in which an individual incorporates and negotiates PrEP use.

Adherence Support Approaches in Biomedical HIV Prevention Trials: Experiences, Insights and Future Directions from Four Multisite Prevention Trials