Helping our patients take HIV pre-exposure prophylaxis (PrEP): a systematic review of adherence interventions

Abstract

Objectives: Adherence is critical for maximizing the effectiveness of pre-exposure prophylaxis (PrEP) in preventing HIV infection. Strategies for promoting adherence to HIV treatment, and their potential application to PrEP adherence, have received considerable attention. However, adherence promotion strategies for prevention medications have not been well characterized and may be more applicable to PrEP. We aimed to identify adherence support interventions that have been effective in other prevention fields and could be applied in the HIV prevention context to support pill taking among PrEP users.

Methods: To identify adherence support interventions that could be evaluated and applied in the PrEP context, we conducted a systematic review across the following prevention fields: hypertension, latent tuberculosis infection, hyperlipidaemia, oral contraceptives, osteoporosis, malaria prophylaxis, and post-exposure prophylaxis for HIV infection. We included randomized controlled trials that evaluated the efficacy of interventions to improve adherence to daily oral medications prescribed for primary prevention in healthy individuals or for secondary prevention in asymptomatic individuals.

Results: Our searches identified 585 studies, of which 48 studies met the eligibility criteria and were included in the review; nine evaluated multiple strategies, yielding 64 separately tested interventions. Interventions with the strongest evidence for improving adherence included complex, resource-intensive interventions, which combined multiple adherence support approaches, and low-cost, low-intensity interventions that provided education or telephone calls for adherence support.

Conclusions: Our review identified adherence interventions with strong evidence of efficacy across prevention fields and provides recommendations for evaluating these interventions in upcoming PrEP studies.

Keywords: HIV; antiretroviral medications; medication adherence; pre-exposure prophylaxis (PrEP); preventive therapy; review.

Figure 1. Identified studies of interventions to support adherence to daily oral medications prescribed in healthy or asymptomatic populations

Eligibility criteria were as follows: 1) randomized controlled trial; 2) at least one adherence outcome; 3) designed to support adherence to a daily oral medication in healthy or asymptomatic populations; 4) conducted in the following clinical fields: hypertension, latent tuberculosis infection, hyperlipidemia, oral contraceptives to prevent pregnancy, osteoporosis, malaria prophylaxis, and post-exposure prophylaxis for HIV infection.

Figure 2. Risk of bias among included studies (N=48)

“Other bias” included bias potentially introduced by using different adherence measures across intervention groups, not accounting for clustering in analysis, contamination of the control group, not accounting for baseline differences between the intervention and control group, and using different outcome measures over the course of study follow-up.