Health and budget impact, and price threshold for cost-effectiveness of lenacapavir for PrEP in Eastern and Southern Africa: a modeling analysis

SUMMARY Background Six-monthly injectable lenacapavir is a promising product for HIV pre-exposure prophylaxis (PrEP). However, health and budget impacts and threshold price at which lenacapavir could be cost-effective in Eastern and Southern Africa is unknown. Methods We adapted an agent-based model, EMOD-HIV, to simulate lenacapavir scale-up in Zimbabwe, South Africa, and western Kenya from 2026-2036; uptake assumptions were informed by a literature review of PrEP product preferences. In the main analysis, we varied lenacapavir coverage by subgroup: female sex workers (32%), male clients of FSWs (30%), adolescent girls/young women >1 partner (32%), older females with >1 partner (36%), and males >1 partner (32%). We also assessed a higher coverage scenario (64-76% across subgroups) and scenarios of expanding lenacapavir use, varying from concentrated among those with highest HIV risk to broader coverage. We estimated maximum per-dose lenacapavir price that achieved cost-effectiveness (90% of the budget impact. In the higher coverage scenario, lenacapavir distribution reached 2. 7-6. 9% population coverage and averted 21-33% of HIV infections across setting; price thresholds were 10-18% lower: 88. 34 in South Africa, 17. 71 in Zimbabwe, and 14. 78 in western Kenya. Expanding lenacapavir coverage resulted in higher HIV incidence reductions but lower price thresholds. Interpretation Lenacapavir can avert substantial HIV incidence; price thresholds and budget impacts vary by setting and coverage. Results can inform policy deliberations regarding lenacapavir pricing and resource planning. RESEARCH IN CONTEXT Evidence before this study We searched PubMed for modelling studies published through July 31, 2024 that assessed the health or economic impact of long-acting PrEP scale-up in Africa using the terms: “HIV” AND “lenacapavir” OR “pre-exposure prophylaxis” OR “PrEP” AND (a list of terms indicating health impact), “cost*”, “budget impact”, “economic evaluation” and (a list of countries in sub-Saharan Africa), “sub-Saharan” AND “model*”, OR “mathematical model*”. We did not find modeling studies evaluating the maximum cost or budget impact of lenacapavir for PrEP. However, several modelling studies evaluated the cost-effectiveness of other long-acting injectable PrEP products in South Africa. Two studies found that CAB-LA was cost-effective when used by populations at substantial HIV risk, while another found it was not cost-effective when delivered to heterosexual men. Five more recent modelling studies evaluating CAB-LA (four parameterized to South Africa and one to sub-Saharan Africa), found that CAB-LA is not cost-effective when targeted to those at highest risk unless the price is reduced. One compartment model evaluated the price threshold at which CAB-LA would be similarly cost-effective to oral PrEP in South Africa and found a per-dose cost ranging from 9. 05-14. 47. We found a lack of studies evaluating LA-PrEP in other African settings aside from South Africa, which has a considerably higher gross domestic product than other countries in the region. Added value of this study We evaluate the health impact and budget impact and maximum price threshold of lenacapavir in three African settings (South Africa, Zimbabwe, and Kenya) using an individual-based network transmission model. We find that lenacapavir scale up to 1. 4-3. 5% population coverage across settings can avert 12. 3-18. 0% of infections and can be cost-effectively implemented at a price per-dose of 106. 30 (South Africa), 21. 10 (Zimbabwe), and 16. 60 (western Kenya) in our main analysis based on PrEP preference data. Price threshold, volume of doses needed, and budget impact, varied by setting and coverage. Implications of all the available evidence LA PrEP formulations have the potential to substantially reduce HIV burden in low- and middle-income countries, but costs will likely need to be reduced to enable equitable implementation. Our findings can inform price negotiations and public health planning regarding adoption of novel PrEP products.