For pregnant and lactating people in South Africa and Uganda, lenacapavir was efficacious, safe, and well tolerated, with no clinically significant exposure differences in their group and minimal exposure in breastfed infants.
Pregnant and lactating people (PLP) are disproportionately likely to become infected with HIV, but they have historically been excluded from Phase 3 HIV clinical trials. The PURPOSE 1 study was the first pre-exposure prophylaxis (PrEP) trial to intentionally include PLP to address their urgent and unmet need for HIV prevention options.
The researchers engaged community stakeholders, regulatory agencies, ethics committees, and maternal and pediatric health experts to responsibly include PLP in the study. To respect participants’ autonomy and reproductive choice, contraception was offered but not required. Participants who became pregnant were able to remain on the study drug after providing additional informed consent.
Pregnant and lactating people were randomly assigned to twice-yearly subcutaneous lenacapavir at 28 sites up to the primary analysis. Lenacapavir plasma concentrations in PLP during each trimester and postpartum were compared with the concentrations in non-PLP using a population pharmacokinetics (popPK) model. Lenacapavir concentrations in breastmilk and infant plasma were also measured in a subset of participants.
- Among the 2,140 participants receiving lenacapavir, 184 had 193 pregnancies. Of these, 88 (45.6%) were ongoing. The 105 pregnancies with outcomes included 52 (49.5%) live births and 53 (50.5%) losses, including 30 (28.6%) elective or non-elective induced abortions, 20 (19.0%) spontaneous abortions, and three (2.9%) stillbirths.
- Maternal pregnancy-associated adverse events were uncommon, the most reported being four cases of gestational hypertension or pre-eclampsia and three cases of hyperemesis gravidarum.
- No HIV infections occurred among pregnant and lactating people receiving lenacapavir. The population pharmacokinetic analysis predicted lenacapavir exposure was not statistically significantly different by pregnancy trimester or postpartum status compared with non-pregnant and lactating people.
- Although lenacapavir was present in breastmilk (median milk-to-plasma ratio: 0.63 in 8 matched pairs), lenacapavir exposure in infant plasma was minimal (median breastfed-infant-to-mother plasma ratio: 0.05 in 11 matched pairs).
Proactive evaluation of lenacapavir efficacy, safety, and pharmacokinetic data in PLP can support accelerated access to the medication for PLP who need or want PrEP, the researchers concluded.
Reference IAS 2025. Oral abstract session with live Q&A; Program number OAC0504.
