Interventions to Improve Adherence to Oral Pre-exposure Prophylaxis: A Systematic Review and Network Meta-analysis

For people at risk of HIV infection, pre-exposure prophylaxis (PrEP) can reduce the risk of infection in anticipation of exposure to HIV. The effectiveness of PrEP relies upon a user's adherence to their PrEP regimen. We sought to assess the effect of PrEP adherence interventions compared to usual care or another intervention for people at risk of HIV. We searched electronic databases from 2010 onwards for randomized controlled trials (RCTs) involving persons at risk of HIV randomized to an adherence promoting intervention vs usual care or another intervention. We used network meta-analyses to compare PrEP adherence for all participant populations. Certainty of evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). 21 trials (N = 4917) were included in qualitative analysis (19 in network meta-analyses (N = 4101)). HIV self-testing interventions with adherence feedback elements improved adherence compared to usual care (risk ratio (RR): 1.83, 95%CI 1.19, 2.82). In contrast, HIV self-testing alone was inferior to HIV self-testing with adherence feedback (RR: 0.58, 95%CI 0.37-0.92). Reminders alone also were inferior to HIV self-testing with adherence feedback on adherence (RR: 0.53, 95%CI 0.34-0.84) and had similar effects on adherence as usual care (RR: 0.98, 95%CI: 0.86-1.11). Interventions with only one component were inferior for adherence than those with two components (RR: 0.74, 95%CI 0.62-0.88) and those with three components (RR: 0.78, 95%CI 0.65-0.93). The certainty of evidence was moderate for HIV self-testing plus adherence feedback and interventions with two or three components. When designing future PrEP adherence interventions, we recommend strategies with more than one but no more than three components.