Factors influencing potential use and implementation of long-acting antiretroviral therapy for youth living with HIV in South Africa: a qualitative analysis using the Consolidated Framework for Implementation Research

HIV treatment outcomes among youth living with HIV (YLWH) in South Africa remain suboptimal. Long-acting injectable antiretroviral therapy (LAI-ART) can address individual, social, and structural barriers affecting HIV care engagement among youth, yet data to inform implementation remain limited. In response, we identified determinants of optimal LAI-ART implementation for YLWH. Using semi-structured guides informed by the Consolidated Framework for Implementation Research (CFIR 2.0), we conducted in-depth interviews with youth living with HIV ( n = 16), caregivers ( n = 8), and key informants involved in HIV service delivery and policy, including doctors, nurses, counselors, and HIV governing officials ( n = 8), between April 2023 and May 2024. Youth were recruited using maximum variation sampling, and caregivers and key informants were purposively sampled. We deductively coded the transcripts using CFIR 2.0, systematically identifying implementation determinants across the five CFIR domains. Acceptability and demand for LAI-ART for youth were high across participants, with potential implementation determinants identified across the five CFIR domains (i.e., innovation characteristics, inner setting, outer setting, individual, and process domains). LAI-ART characteristics centered on its relative advantage over oral therapy (i.e., treatment fatigue/burden, social influences, stigma, disclosure), but most key informants worried that the cost would be prohibitive for the health system. Perceptions of who should be prioritized for LAI-ART varied, yet treatment choice was consistently emphasized. Providers preferred initiating LAI-ART implementation at a small number of experienced clinics prior to scale-up, citing the necessity of ensuring feasibility, appropriate training, and provider buy-in. Within inner settings, clinic infrastructure, staffing levels, and access to knowledge and resources were identified as critical for implementation, highlighting relevant strategies to support LAI-ART implementation and retention among youth, including involving caregivers, the need for diverse communication methods, and ensuring provider continuity. While perceptions of LAI-ART for youth were generally positive, successful implementation will require recognizing that LAI-ART may require different delivery strategies across populations and settings to optimize real-world impact. Youth-centered LAI-ART implementation approaches accounting for health system readiness, resource constraints, and youth preferences will be critical.