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.

In response to World Health Organization (WHO) guidance recommending oral pre-exposure prophylaxis (PrEP) for all individuals at substantial risk for HIV infection, significant investments are being made to expand access to oral PrEP globally, particularly in sub-Saharan Africa. Some have interpreted early monitoring reports from new programs delivering oral PrEP to adolescent girls and young women (AGYW) as suggestive of low uptake. However, a lack of common definitions complicates interpretation of oral PrEP uptake and coverage measures, because various indicators with different meanings and uses are used interchangeably. Furthermore, operationalising these measures in real-world settings is challenged by the difficulties in defining the denominator for measuring uptake and coverage among AGYW, due to the lack of data and experience required to identify the subset of AGYW at substantial risk of HIV infection. This paper proposes an intervention-centric cascade as a framework for developing a common lexicon of metrics for uptake and coverage of oral PrEP among AGYW. In codifying these indicators, approaches to clearly define metrics for uptake and coverage are outlined, and the discussion on ‘low’ uptake is reframed to focus on achieving the highest possible proportion of AGYW using oral PrEP when they need and want it Recommendations are also provided for making increased investments in implementation research to better quantify the sub-group of AGYW in potential need of oral PrEP.and for improving monitoring systems to more efficiently address bottlenecks in the service delivery of oral PrEP to AGYW so that implementation can be taken to scale.

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