HIV interventions across the care continuum for adolescents in high-burden countries: a systematic review and meta-analysis

Background: Adolescents (10-19 years old) have poor outcomes across the prevention-to-treatment HIV care continuum, leading to significant mortality and morbidity. We conducted a systematic review and meta-analysis of interventions that documented HIV outcomes among adolescents in HIV high-burden countries. Methods: We searched PubMed, EMBASE, Scopus, and the Cochrane Library for studies published between January 2015 and September 2024, assessing at least one HIV outcome along the prevention-to-care cascade, including PrEP uptake, HIV testing, awareness of HIV infections, ARV adherence, retention, and virological suppression. We included studies from 37 HIV high-burden countries evaluating interventions with a comparator group. Random-effects meta-analysis was used to pool the effects of the interventions on study outcomes. While the primary focus was on outcomes related to the HIV care cascade, we also evaluated social outcomes and mental health outcomes when sufficient data were available. Adolescent engagement in studies was assessed using Hart's ladder. The study was registered in PROSPERO, CRD42024569203. Findings: We identified 12,411 unique records, of which 99 were included in the final analysis, comprising 57 randomized controlled trials and 42 non-randomized studies, with a total sample size of 441,252 participants. Our analysis found that asset-building interventions significantly improved HIV testing uptake (three studies, RR: 1.38, 95% CI 1.15-1.65) compared to control conditions. Differentiated service delivery interventions were associated with improved ART retention (five studies, RR: 1.18, 95% CI 1.04-1.36) and virological suppression (seven studies, RR: 1.19, 95% CI 1.06-1.33) compared to control conditions. Financial incentives significantly enhanced ART adherence (two studies, RR: 1.52, 95% CI 1.23-1.89) compared to control conditions. Digital interventions, such as mobile phone applications and telehealth services, significantly increased HIV testing uptake (two studies, RR: 1.79, 95% CI 1.23-2.61) compared to control conditions. Positive impacts were also observed for these interventions on social outcomes. Most studies adopted minimal to moderate adolescent engagement. For HIV testing, a stronger effect was seen in studies with moderate to substantial adolescent engagement, yielding an RR of 2.37 (95% CI: 1.43-3.93; nine studies), compared to a lower RR of 1.23 (95% CI: 1.15-1.31; 13 studies) in studies with minimal engagement. Notably, the strength of evidence is moderate to low due to the considerable heterogeneity across studies and limited included studies. Interpretation: Our data demonstrate several evidence-based interventions that can enhance adolescent HIV outcomes across the care continuum. Our findings are relevant in many HIV high-burden countries and can help to inform national and regional adolescent HIV policy. Funding: This study was supported by UNICEF, the Adolescent HIV Prevention and Treatment Implementation Science Alliance (AHISA), and the US NIH (NIAID K24AI143471, NICHD 1UG1HD113156, UM2HD116395).