Targeted deployment of twice-yearly lenacapavir for pregnant and breastfeeding women without HIV in high-incidence districts in sub-Saharan Africa could substantially reduce vertical transmission at a fraction of the cost of universal rollout, according to a modelling study published in the Journal of the International Aids Society. But the authors say LEN should be seen as complementary to, not a substitute for, strengthening existing programmes to prevent the transmission, reports Aidsmap.
In 2024, around 98 000 newborns acquired HIV in sub-Saharan Africa. Among women who were already HIV+, gaps in antiretroviral therapy (ART) access accounted for almost half of paediatric acquisitions, with treatment discontinuation during pregnancy or breastfeeding contributing 20%.
But a further 25% of paediatric acquisitions came from mothers who became infected during pregnancy or breastfeeding. This pathway was more pronounced in countries like South Africa and Zambia, where it accounted for almost 60% and 50% of transmissions, respectively.
Twice-yearly LEN has demonstrated high efficacy in clinical trials and is a potential option for women who face elevated risk of acquiring HIV during pregnancy and breastfeeding.
Anna Yakusik of UNAids and colleagues carried out the modelling study, evaluating the cost-effectiveness of scaling up lenacapavir among pregnant and breastfeeding women without HIV across sub-Saharan Africa. They found that targeted deployment in high-incidence districts could reduce both maternal and paediatric HIV acquisitions, at a net cost of $8 500 per acquisition averted, compared with $85 000 under universal rollout.
The study
The researchers used mathematical modelling to estimate outcomes among a cohort of HIV-negative pregnant and breastfeeding women over 2.2 years, from the first antenatal care visit to the average end of breastfeeding.
The base scenario assumed that 65% of eligible women would take up LEN, and of these, 70% would be retained over the full 2.2 years. Drug costs were based on a projected generic price of US$40 per person per year, plus US$17 for the loading dose of LEN tablets, with service delivery costs of US$50 per person per year drawn from existing oral PrEP costing studies.
They also modelled a best-case scenario assuming 100% uptake and retention with no loss to follow-up.
The researchers tested both scenarios under two approaches: rolling out lenacapavir PrEP to all pregnant and breastfeeding women aged 15 to 49 without HIV across sub-Saharan Africa (universal rollout), or targeting districts where HIV incidence among women was highest.
For the targeted rollout, they further divided it into three tiers: high-priority districts (where at least seven in every 1 000 women acquired HIV annually), intermediate districts (five in 1 000) and expanded districts (three in 1 000).
In each scenario, they measured the number of HIV acquisitions averted among both mothers and infants, the total programme costs, and the net cost per HIV acquisition averted after accounting for lifetime ART savings.
Results
Under universal rollout, the base scenario (65% uptake and 70% retention) reached 25.5m pregnant and breastfeeding women, and averted 56 000 HIV acquisitions (44 500 maternal and 11 600 paediatric) over 2.2 years, at a total programme cost of $5bn. The best-case scenario (100% uptake and retention) reached 39m women and averted 123 000 HIV acquisitions (98 000 maternal and 25 500 paediatric) at a cost of $9bn.
After accounting for lifetime ART savings, the net cost per HIV acquisition averted was US$85 000 under the base scenario and US$68 000 under the best case.
Under geographically targeted rollout at the highest-priority threshold, which primarily included districts in South Africa, Mozambique, Zambia and Eswatini, the base scenario reached roughly 626 000 women and averted 8 500 HIV acquisitions (6 700 among mothers and 1 750 among infants).
Expanding to intermediate-priority districts increased coverage to just more than 1m women and averted 10 400 acquisitions. The broadest tier reached 2m women and averted 11 600 acquisitions.
At the highest-priority threshold, total programme costs were US$126m under the base scenario and US$226m under the best case. Accounting for lifetime ART savings, net costs per acquisition averted were US$8 500 and US$5 750, respectively.
Overall, expanding geographic eligibility increased the total number of HIV acquisitions averted but was associated with progressively higher programme costs and lower efficiency per HIV acquisition averted. The most selective targeting strategy (high-priority districts) consistently yielded the lowest net cost per HIV acquisition averted, whereas universal rollout achieved the greatest overall impact.
The researchers also tested multi-way sensitivity analysis across the combinations of uptake, retention and service delivery costs. Retention in care was by far the most important factor in determining cost-effectiveness. Under the highest-priority strategy, net cost per acquisition averted ranged from roughly US$4 800 under the most favourable assumptions (90% retention, US$35 service delivery cost) to US$15 100 under the least favourable (50% retention, US$75 service delivery cost).
Service delivery costs played a secondary but consistent role, with higher costs leading to worse cost-effectiveness across all scenarios. Uptake had no meaningful impact on cost-effectiveness, because higher uptake increased both the number of women reached and programme costs proportionally.
The researchers conclude that LEN should be seen as complementary to, not a substitute for, strengthening existing programmes to prevent vertical transmission. Gaps in HIV testing, ART initiation and retention among mothers living with HIV still account for the majority of paediatric acquisitions; therefore, addressing those remains the most important priority.
But in high-incidence settings, targeted LEN PrEP for pregnant and breastfeeding women without HIV could provide an important additional layer of prevention.
Study details
Drivers of Vertical HIV Transmission in Sub-Saharan Africa and the Impact and Cost-Effectiveness of Targeted and Universal Lenacapavir Pre-Exposure Prophylaxis
Anna Yakusik, Magdalene K. Walters, Deepak Mattur et al.
Published in the Journal of the International Aids Society on 19 June 2026
Abstract
Introduction
Eliminating vertical HIV transmission remains a major public health priority, particularly in sub-Saharan Africa (SSA), which accounted for 83% of global paediatric HIV acquisitions 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.
Methods
Using 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.
Results
In 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 acquisition 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.
Conclusions
Gaps 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 acquisitions 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.
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