Discontinuation, suboptimal adherence, and reinitiation of oral HIV pre-exposure prophylaxis: a global systematic review and meta-analysis

Background Poor adherence to oral HIV pre-exposure prophylaxis (PrEP) diminishes its clinical and public health benefits. This study synthesises evidence regarding discontinuation, adherence, and reinitiation of PrEP among geographically diverse PrEP users. Methods We did a systematic review and meta-analysis evaluating studies published in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to Dec 18, 2020. We included longitudinal studies that presented data for PrEP discontinuation, defined as investigator-reported loss to follow-up or participant self-reported PrEP stoppage. Data were extracted from published reports and assessed for risk of bias. We used a random-effects meta-analysis to pool estimates of discontinuation and I-2 and t(2) to evaluate heterogeneity. This study is registered with PROSPERO, CRD42020155675. Findings We identified 4129 records, of which 59 articles were included (n=43 917 participants). 41 center dot 0% (95% CI 18 center dot 8-63 center dot 5) of participants discontinued PrEP within 6 months, with the highest rates in observational studies. The discontinuation rate in sub-Saharan Africa (47 center dot 5%, 95% CI: 29 center dot 4-66 center dot 4%) was higher than in other regions (p<0 center dot 001). Discontinuation rates were lower in studies with adherence interventions than in those without (24 center dot 7% vs 36 center dot 7%, p=0 center dot 015). Gay or bisexual men who have sex with men and transgender women offered daily or non-daily dosing options had lower discontinuation rates than those offered daily dosing alone (21 center dot 6% vs 31 center dot 5%; p<0 center dot 001). The pooled suboptimal adherence within 6 months was 37 center dot 7% (95% CI 8 center dot 4-66 center dot 9). Among people who discontinued PrEP, 47 center dot 3% (95% CI 31 center dot 5-63 center dot 2) reinitiated PrEP within 1 year of PrEP initiation. The included studies had poor quality in terms of study design, with a moderate risk of bias. Interpretation Strategies to encourage reinitiating PrEP for new or persistent risk should be a focus of future PrEP implementation strategies. Copyright (c) 2022 Elsevier Ltd. All rights reserved.