Targeted Deployment of Long-Acting HIV Pre-Exposure Prophylaxis in sub-Saharan Africa: Modelled Impact on Infections and Programme Costs to 2050

Background Long-acting HIV pre-exposure prophylaxis (LAP) could transform HIV prevention in sub-Saharan Africa, but its public-health impact and value-for-money will depend on whether programmes can reach people at greatest risk. We quantified the potential impact and efficiency of targeted LAP deployment across sub-Saharan Africa. Methods We developed a deterministic, age-structured compartmental model of HIV among adults aged 15 years or older in African countries accounting for 98% of adults living with HIV in sub-Saharan Africa. Antiretroviral therapy (ART) was assumed to reach 95% coverage by 2030 in all countries. LAP was assumed to reduce HIV acquisition by 96%. In model analyses, LAP was allocated according to rules that specify the degree to which programmes can effectively allocate it to those at greatest risk of acquiring HIV, including using a person's district, sex and age-group, and other signals of risk. Findings Across 34 countries, allocating a fixed quantity of LAP by district, sex and age averted 2 - 21 times as many infections as uniform allocation; perfect identification of within-group risk, an upper bound, raised this to 5 - 32 times. Multipliers were largest in low-prevalence countries, where absolute impact was smallest; in higher burden settings, they were 2 - 6 and 5 - 11, respectively. If 3 million people used LAP from 2028 in the 11 countries currently receiving Global Fund-supported lenacapavir, uniform allocation would avert about 41,000 infections by 2050, targeting by district, sex and age about 601,000 (range 360,000 - 1,660,000), and perfect risk targeting about 972,000 (490,000 - 3,570,000). Discounted averted ART costs fully offset LAP costs by 2050 at a total cost of up to ~US$50 per person-year with perfect risk targeting, $30 with targeting by district, sex and age, and $2 with uniform allocation. Expansion to 15 million users by 2035 brought modelled adult incidence across sub-Saharan Africa below 0.1 per 1000 person-years in 2049, about a decade earlier than projected without LAP, under the assumption that ART coverage reaches 95% in every country by 2030. Interpretation Targeting determines both the impact and the net cost of LAP. Allocation by district, sex and age is feasible now and multiplies the infections averted by each person-year of LAP. LAP offsets its cost through averted treatment only when it is targeted and its fully loaded cost is near the low end of current estimates. Better identification of people at highest risk within demographic groups, and sustained use among them, could add substantially to impact. The same approach could guide the allocation of LAP in other settings where HIV risk is concentrated.