A multilevel health system intervention for virological suppression in adolescents and young adults living with HIV in rural Kenya and Uganda (SEARCH-Youth): a cluster randomised trial

Background: Social and cognitive developmental events can disrupt care and medication adherence among adolescents and young adults living with HIV in sub-Saharan Africa. We hypothesised that a dynamic multilevel health system intervention helping adolescents and young adults and their providers navigate life-stage related events would increase virological suppression compared with standard care. Methods: We did a cluster randomised, open-label trial of young individuals aged 15–24 years with HIV and receiving care in eligible clinics (operated by the government and with ≥25 young people receiving care) in rural Kenya and Uganda. After clinic randomisation stratified by region, patient population, and previous participation in the SEARCH trial, participants in intervention clinics received life-stage-based assessment at routine visits, flexible clinic access, and rapid viral load feedback. Providers had a secure mobile platform for interprovider consultation. The control clinics followed standard practice. The primary, prespecified endpoint was virological suppression (HIV RNA <400 copies per mL) at 2 years of follow-up among participants who enrolled before Dec 1, 2019, and received care at the study clinics. This trial is registered with ClinicalTrials.gov, NCT03848728, and is closed to recruitment. Findings: 28 clinics were enrolled and randomly assigned (14 control, 14 intervention) in January, 2019. Between March 14, 2019, and Nov 26, 2020, we recruited 1988 participants at the clinics, of whom 1549 were included in the analysis (785 at intervention clinics and 764 at control clinics). The median participant age was 21 years (IQR 19–23) and 1248 (80·6%) of 1549 participants were female. The mean proportion of participants with virological suppression at 2 years was 88% (95% CI 85–92) for participants in intervention clinics and 80% (77–84) for participants in control clinics, equivalent to a 10% beneficial effect of the intervention (risk ratio [RR] 1·10, 95% CI 1·03–1·16; p=0·0019). The intervention resulted in increased virological suppression within all subgroups of sex, age, and care status at baseline, with greatest improvement among those re-engaging in care (RR 1·60, 95% CI 1·00–2·55; p=0·025). Interpretation: Routine and systematic life-stage-based assessment, prompt adherence support with rapid viral load testing, and patient-centred, flexible clinic access could help bring adolescents and young adults living with HIV closer towards a goal of universal virological suppression. Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development, US National Institutes of Health.