BACKGROUND: HIV incidence remains high in sub-Saharan Africa (SSA) despite treatment scale-up. Oral pre-exposure prophylaxis (PrEP) is effective when taken as directed, but has had limited impact in SSA, in part due to challenges with daily dosing. Long-acting PrEP (LA-PrEP) formulations that may ameliorate these challenges include (1) two-monthly injections (cabotegravir), (2) six-monthly injections (lenacapavir), and (3) monthly oral pills (islatravir and its potential successors). We estimated the potential impact of each LA-PrEP formulation and maximum cost per dose delivered to be cost-effective in western Kenya (Nyanza region), South Africa, and Zimbabwe.
METHODS: We adapted an HIV network transmission model, EMOD-HIV, to estimate (1) impact of scaling each LA-PrEP product on when incidence falls below 1 per 1,000 adults per year, (2) doses required to avert 1 HIV acquisition or disability-adjusted life-year (DALY), and (3) maximum per-dose cost to avert 1 DALY for US<$500 over 20 years. We assumed PrEP introduction in 2025, coverage rising to 5-20% of adults by 2030, and HIV risk reduction by 95% while using injectable PrEP and 67% while using monthly oral PrEP (to account for sub-optimal adherence with self-dosing). We performed a bounding analysis on user risk profiles: (1) equal distribution among sexually active adults, and (2) “risk-prioritized” distribution from highest-risk (sex workers) to lowest.
RESULTS: Two-monthly or six-monthly injectable PrEP with 20% risk-prioritized coverage could reduce incidence to <1 per 1,000 per adult per year in western Kenya by 2030 (2034 for monthly oral) and Zimbabwe by 2034 (2039 for monthly oral). In South Africa, incidence remained >1 per 1,000 for 20 years, but LA-PrEP was more efficient than in western Kenya and Zimbabwe, requiring 5-7x fewer doses to avert 1 HIV acquisition. LA-PrEP could be cost-effective if delivered at =$24 (two-monthly injectable), =$70 (six-monthly injectable), and =$7 (monthly oral) per dose in the most efficient setting (South Africa) and scenario (5% risk-prioritized coverage). Results were sensitive to prioritization: 1 risk-prioritized dose averted as many HIV acquisitions as 2 non-risk-prioritized doses.
CONCLUSIONS: LA-PrEP has the potential to significantly accelerate HIV incidence declines in SSA. Low-cost suppliers and delivery models will be required for LA-PrEP to be cost-effective.

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