Interventions to increase adherence to antiretroviral therapy in people living with HIV - what works? A systematic review and meta-analysis.

The Perceptions and Practicalities Approach (PaPA) is a recommended framework for designing medication adherence interventions. Little is known about the utility of the PaPA framework in improving antiretroviral therapy (ART) adherence. This systematic review evaluates the efficacy of interventions to improve ART adherence according to the extent to which they apply principles from the PaPA framework. Electronic databases were searched in October 2024. Interventions were classified using the PaPA and whether they were delivered in a low-middle-income country (LMIC) or high-income country (HIC). 85 randomised trials were included (N = 16,401). Interventions classed as PaPA Level 3 improved adherence in both LMICs (k  =  16, (SMD) = 0.44, 95%CI:[0.27;0.62]) and HICs (k = 31, SMD = 0.33, 95%CI:[0.17; 0.49]). PaPA Level 1 interventions (k = 47) did not demonstrate an improvement in adherence compared to usual care in HICs but did in LMICs. Overall, interventions (k = 50, N = 10,004) were associated with greater odds of virological suppression (OR =  1.17, 95%CI:[1.02;1.33], Q = 104.19, p = 0.001;  = 50.58%). PaPA Level 3 interventions were more likely to be associated with suppressed viral load than PaPA Level 1 or 2 interventions. These results suggest that PaPA is an efficacious approach to increasing adherence to ART in HICs. RCTs evaluating the efficacy and acceptability of PaPA-informed interventions in the LMIC context are needed.