Lenacapavir, PrEP demand, and the efficacy-effectiveness gap in South African HIV prevention

South Africa has launched a limited, phased rollout of twice-yearly injectable lenacapavir pre-exposure prophylaxis (PrEP) for HIV prevention. Initially supported by donor funding, the medication is positioned as a turning point in the national HIV response. The launch reflects a recurring pattern in biomedical HIV prevention where high efficacy in randomised trials is quickly translated into expectations of population-level impact before real-world effectiveness, sustained demand, affordability, and long-term health-system capacity are demonstrated. While lenacapavir may address one limitation of oral PrEP by eliminating daily pill-taking, previous PrEP experience shows that uptake and continuation are shaped by stigma, mobility, gender power relations, access to services, changing risk perceptions, and the social meanings attached to HIV prevention. Modelling analyses suggest that lenacapavir is most efficient where HIV incidence is high, risk is ongoing, and follow-up systems are strong. However, its broader population-level impact depends on whether programmes can identify, reach, and retain at risk users without diverting scarce resources from interventions with already established epidemiological and economic returns. Lenacapavir is a relevant addition to the HIV prevention repertoire, but its health-system feasibility, affordability and opportunity cost must be assessed cautiously in the context of likely future donor decline.