Modelling study backs targeted, not universal, lenacapavir PrEP for pregnancy and breastfeeding

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 lenacapavir should be seen as complementary to, not a substitute for, strengthening existing programmes to prevent vertical transmission.

In 2024, an estimated 98,000 newborns acquired HIV in sub-Saharan Africa. Among women already living with 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 acquired HIV during pregnancy or breastfeeding. This pathway was more pronounced in countries such as South Africa and Zambia, where it accounted for almost 60% and 50% of transmissions, respectively.

Twice-yearly lenacapavir 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. Because it is given as an injection every six months, it reduces reliance on daily pill-taking, addressing one of the key barriers to oral PrEP.

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 US$8,500 per acquisition averted, compared to US$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 lenacapavir, 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 lenacapavir 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 7 in every 1,000 women acquired HIV annually), intermediate districts (5 in 1,000) and expanded districts (3 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 25.5 million 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 US$5 billion. The best-case scenario (100% uptake and retention) reached 39 million women and averted 123,000 HIV acquisitions (98,000 maternal and 25,500 paediatric) at a cost of US$9 billion.

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 over a million women and averted 10,400 acquisitions. The broadest tier reached two million women and averted 11,600 acquisitions.

At the highest-priority threshold, total programme costs were US$126 million under the base scenario and US$226 million 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 lenacapavir 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 lenacapavir PrEP for pregnant and breastfeeding women without HIV could provide an important additional layer of prevention.