Can pregnant, lactating people use lenacapavir to prevent HIV infection?

The use of lenacapavir is highly efficacious in pregnant and lactating people (PLP), with zero participants acquiring HIV, as shown by the results of the PURPOSE 1 study.

“Lenacapavir was safe and well tolerated in PLP,” said lead author Dr Linda-Gail Bekker, The Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa. “PLP receiving lenacapavir had similar pregnancy outcomes to the general population and to participants receiving oral PrEP.”

A total of 2,140 participants received lenacapavir, of whom 184 had 193 pregnancies. Among these pregnancies, 88 (45.6 percent) were ongoing. [IAS 2025, abstract OAC0504]

Overall, 105 pregnancy outcomes were documented, including 52 live births (49.5 percent) and 53 losses (50.5 percent), which consisted of 30 induced/elective abortions (28.6 percent), 20 spontaneous abortions (19.0 percent), and three stillbirths (2.9 percent).

Adverse events (AEs) related to maternal pregnancy were rare. The most common AEs reported were gestational hypertension/pre-eclampsia (n=4) and hyperemesis gravidarum (n=3). None of the PLP receiving lenacapavir acquired HIV infections.

In the population pharmacokinetics (pop-PK) analysis, the predicted exposure to lenacapavir was not statistically significantly different by pregnancy trimester or postpartum status relative to non-PLP.

Lenacapavir was also found in breastmilk (median milk-to-plasma ratio, 0.63; n=8 matched pairs), but exposure to the study drug in infant plasma was minimal (median breastfed-infant-to-mother plasma ratio, 0.05; n=11 matched pairs).

“Blood levels of lenacapavir in pregnant and postpartum people were generally similar compared with those in nonpregnant people; lenacapavir is transferred to breastmilk, but breastfed infants have very low levels of lenacapavir in their blood,” Bekker said.

“Proactively including PLP in PURPOSE I yielded valuable data about blood levels of lenacapavir and safety, which support the use of [the study drug] for PrEP in this important population,” she added.

PURPOSE 1

Bekker and her team engaged community stakeholders, regulatory agencies, ethics committees, and maternal/paediatric health experts to include PLP in PURPOSE 1. They offered, but did not require, the use of contraception to respect autonomy and reproductive choice. Furthermore, participants who became pregnant were permitted to remain on lenacapavir following additional informed consent.

Bekker and colleagues described pregnancy outcomes, AEs, and HIV infections in PLP who were randomly allocated to twice-yearly subcutaneous (SC) lenacapavir up to the primary analysis. They then compared study drug plasma concentrations in PLP during each trimester/postpartum with non-PLP using a pop-PK model and measured concentrations in breastmilk and infant plasma.

“Lenacapavir is a first-in-class, multistage HIV-1 capsid inhibitor with high potency and a long half-life, supporting twice-yearly SC injection,” Bekker said. “Preclinical studies do not indicate harmful effects of lenacapavir on fertility, pregnancy, foetal development, or postnatal development.”

PLP have a disproportionate vulnerability to HIV-1 infection. Unfortunately, they have been “historically excluded” from phase III trials on HIV despite an “urgent unmet need” for HIV prevention options, according to Bekker.

The use of lenacapavir for PrEP in pregnancy is supported by the US Food and Drug Administration and the 2025 WHO Guidelines.