Drivers of Vertical HIV Transmission in Sub-Saharan Africa and the Impact and Cost-Effectiveness of Targeted and Universal Lenacapavir Pre-Exposure Prophylaxis.

introductionEliminating vertical HIV transmission remains a major public health priority, particularly in sub-Saharan Africa (SSA), which accounted for 83% of global paediatric HIV acquistions in 2024. Despite expanded antiretroviral therapy (ART) coverage, gaps in maternal ART access, retention and HIV acquisition during pregnancy and breastfeeding continue to drive paediatric HIV acquisitions. Long-acting injectable (LAI) lenacapavir pre-exposure prophylaxis (PrEP) may reduce paediatric HIV acquisitions by preventing maternal HIV acquisition. We evaluated drivers of vertical transmission in SSA and assessed the impact and cost-effectiveness of LAI lenacapavir PrEP among pregnant and breastfeeding women (PBW) without HIV.

methodsUsing 2025 UNAIDS estimates, Spectrum AIM and Naomi model outputs, we decomposed vertical HIV transmission pathways by maternal HIV acquisition timing and ART status. We modelled universal and geographically targeted rollout strategies using district-level HIV incidence thresholds among women aged 15-49 years (≥0.7%, ≥0.5% and ≥0.3%). Base-case assumptions included 65% uptake, 70% retention over 2.2 years, drug costs of US$40 per person-year plus a US$17 loading dose and service delivery costs of US$50 per person-year. Upper-bound scenarios and deterministic sensitivity analyses evaluated implementation uncertainty.

resultsIn 2024, an estimated 98,000 new paediatric HIV acquisitions occurred in SSA. Lack of maternal ART access accounted for 46% of vertical transmissions, while ART discontinuation during pregnancy or breastfeeding contributed 19%. Maternal HIV acquisition during pregnancy or breastfeeding accounted for 25% of paediatric HIV acquisitions, reaching 59% in South Africa and 46% in Zambia. Under base-case assumptions, universal LAI lenacapavir PrEP rollout averted approximately 56,100 HIV acquisitions at a net cost of US$85,200 per HIV acqusition averted. Geographic targeting at ≥0.7% incidence was more cost-effective, averting approximately 8450 acquisitions at a net cost of US$8530 per acquisition averted. Retention and service delivery costs were the primary determinants of cost-effectiveness.

conclusionsGaps in maternal ART access and retention remain the dominant drivers of vertical HIV transmission in SSA, while maternal HIV acquisition contributes substantially in high-incidence settings. Targeted LAI lenacapavir PrEP rollout among PBW without HIV could reduce maternal and paediatric HIV acquistions more efficiently than universal rollout, although outcomes remain highly sensitive to implementation conditions. LAI lenacapavir PrEP should complement strengthened maternal ART programmes, not replace them.