Defining success with HIV pre-exposure prophylaxis: a prevention-effective adherence paradigm

Abstract

Clinical trial data have shown that oral pre-exposure prophylaxis (PrEP) is efficacious when taken as prescribed; however, PrEP adherence is complex and must be understood within the context of variable risk for HIV infection and use of other HIV prevention methods. Different levels of adherence may be needed in different populations to achieve HIV prevention, and the optimal methods for achieving the necessary adherence for both individual and public health benefits are unknown. Guidance for PrEP use must consider these questions to determine the success of PrEP-based HIV prevention programs. In this article, we propose a new paradigm for understanding and measuring PrEP adherence, termed prevention-effective adherence, which incorporates dynamic HIV acquisition risk behaviors and the use of HIV alternative prevention strategies. We discuss the need for daily PrEP use only during periods of risk for HIV exposure, describe key issues for measuring and understanding relevant behaviors, review lessons from another health prevention field (i.e., family planning), and provide guidance for prevention-effective PrEP use. Moreover, we challenge emerging calls for sustained, near perfect PrEP adherence regardless of risk exposure and offer a more practical and public health-focused vision for this prevention intervention.

Figure 1. Adherence success by adherence paradigm

The paradigm of consistently high adherence for all individuals applies to ART and PrEP in clinical trials (panel A). The prevention-effective paradigm applies to PrEP in demonstration projects and wider implementation (panel B).

Figure 2. Prevention-effective execution and persistence of adherence

Execution refers to adherence during the time that an individual is at risk for HIV acquisition and is intending to rely upon it for protection. Persistence describes the duration of PrEP use during periods of HIV risk and should reference the absolute time of use. As an example for individuals taking PrEP during periods of HIV risk, the striped shape represents 100% executed adherence for the first three months of PrEP use, followed by 50% adherence for the next three months of use, with a persistence of 100%. The dotted shape represents 80% executed adherence with a persistence of three months.