Researchers have said that the data from a phase 3 study, published in The Lancet and which assessed more than 5 000 women and 500 pregnancies, support the use of long-acting lenacapavir (LEN) as HIV pre-exposure prophylaxis among pregnant, postpartum and lactating women, reports Healio.
The PURPOSE 1 trial was conducted among cisgender women in two countries in which none of the participants who received lenacapavir acquired HIV.
Linda-Gail Bekker, MBChB, PhD, director of the Desmond Tutu HIV Centre at the University of Cape Town, told Healio that the researchers had planned to run two phase 3 trials to assess the efficacy of LEN: one among women who have sex with men in South Africa and Uganda – PURPOSE 1 – and one in other populations who have sex with men at sites all around the world. (That second trial, PURPOSE 2, also demonstrated lenacapavir’s high potency.)
While designing PURPOSE 1, Bekker and colleagues asked for advice from the community and received suggestions that the researchers ensure that pregnant and lactating women and adolescent girls be included.
They ultimately enrolled 5 345 cisgender women and adolescent girls aged 16 to 25 between 28 September 2021 and 15 September 2023, and randomly assigned them in a 2:2:1 ratio to receive subcutaneous LEN every 26 weeks following a 600 mg oral loading dose on days 1 and 2, or one of two daily PrEP drugs manufactured by Gilead: oral emtricitabine-tenofovir alafenamide or emtricitabine-tenofovir disoproxil fumarate.
They observed the women for HIV infections, pregnancy outcomes and adverse events during pregnancy and postpartum.
Women who became pregnant were allowed to remain in the trial if they provided additional consent, the researchers noted. Bekker said they decided they could assess lenacapavir’s efficacy in pregnant women by testing participants every 13 weeks.
“That way, if someone became pregnant or was lactating, we would have (pharmacokinetic) read-outs,” she said. “This meant we had drug levels in non-pregnant, first, second and third trimester and lactating/postpartum people.”
In total, 487 participants had one or more pregnancies for a total of 509 pregnancies and 512 pregnancy outcomes recorded during the study.
The majority of pregnancies resulted in live births: 66% in the lenacapavir arm, 54% from women receiving emtricitabine-tenofovir alafenamide and 57% from women receiving emtricitabine-tenofovir disoproxil fumarate. Pregnancy loss occurred in 31%, 41% and 42% of pregnant women enrolled in each arm, respectively.
Additionally, the study found that lenacapavir was present in breastmilk (median breastmilk-to-plasma ratio: 0.52; interquartile range [IQR], 0.38-0.77), although exposure in infant plasma was minimal (median breastfed-infant-to-maternal-plasma ratio: 0.02; IQR, 0.01-0.05).
The researchers also noted that there were no statistically significant differences in LWN exposure by pregnancy trimester or postpartum vs. non-pregnant participants.
Based on the data, Bekker said lenacapavir appears to be safe and effective for PrEP in pregnant and lactating women, although she added that women should always be counselled on the known risks and benefits of any drug during pregnancy.
She also said that LEN as PrEP appears to be safe in offspring but added that “there may be very rare abnormalities which we may not yet have seen due to relatively small numbers still.
“Therefore, it is always good to continue to report pregnancies and outcomes to the antiretroviral registries and report and continue surveillance even after the lenacapavir for PrEP rolls out more widely,” she added.
Study details
HIV acquisitions, safety, and pharmacokinetics of lenacapavir for HIV pre-exposure prophylaxis in pregnant and lactating women (PURPOSE 1): a substudy of a phase 3, randomised controlled trial
Linda-Gail Bekker, Dhayendre Moodley, Dazon Dixon Diallo, Ishana Harkoo, Godfrey Kigozi, Noah Kiwanuka et al.
Published in The Lancet in September 2026
Summary
Background
Lenacapavir demonstrated high efficacy and safety as pre-exposure prophylaxis (PrEP) in cisgender women, but its use during pregnancy and lactation when women are disproportionately vulnerable to HIV acquisition has not previously been described. We aimed to evaluate HIV acquisition, safety, and pharmacokinetics of lenacapavir for PrEP in pregnant and lactating women.
Methods
The randomised, double-blind, multicentre, active-controlled, phase 3 PURPOSE 1 study compared twice-yearly subcutaneous lenacapavir with daily oral emtricitabine–tenofovir alafenamide or emtricitabine–tenofovir disoproxil fumarate in women who were not pregnant at enrolment. Cisgender adolescent girls and young women aged 16–25 years were randomly assigned (2:2:1) to receive subcutaneous lenacapavir (927 mg, in two 1·5 mL injections) every 26 weeks following a 600 mg oral loading dose on days 1 and 2, daily oral emtricitabine (200 mg)–tenofovir alafenamide (25 mg), or daily oral emtricitabine (200 mg)–tenofovir disoproxil fumarate (300 mg). Participants who became pregnant could continue study drug in a planned substudy after providing additional written informed consent. We describe HIV infections, pregnancy outcomes, and adverse events during pregnancy and postpartum, and observed and model-derived lenacapavir plasma concentrations by pregnancy trimester and postpartum period. Pregnancy outcomes and infant congenital anomalies were determined by participant report and medical record review. Lenacapavir concentrations were measured in maternal plasma, breastmilk, and breastfed infant plasma.
Findings
Among 5345 women enrolled between Sept 28, 2021, and Sept 15, 2023, 487 participants (184 allocated to lenacapavir, 208 allocated to emtricitabine–tenofovir alafenamide, and 95 allocated to emtricitabine–tenofovir disoproxil fumarate) had one or more pregnancies, resulting in 509 total pregnancies with 512 pregnancy outcomes, including three sets of twins. Median age was 21 years (IQR 19–23). Most pregnancies resulted in livebirths (128 [66%] of 195 on lenacapavir, 119 [54%] of 219 on emtricitabine–tenofovir alafenamide, and 56 [57%] of 98 on emtricitabine–tenofovir disoproxil fumarate). Numbers of pregnancy losses were similar across groups (60 [31%] of 195 on lenacapavir, 89 [41%] of 219 on emtricitabine–tenofovir alafenamide, 41 [42%] of 98 on emtricitabine–tenofovir disoproxil fumarate). Adverse events during pregnancy and postpartum were balanced across groups, with 44 (33%) of 132 reporting injection site reactions on lenacapavir; all were grade 1 or 2 and none led to discontinuation. Population pharmacokinetic analysis showed no statistically significant differences in lenacapavir exposure by pregnancy trimester or postpartum versus non-pregnant participants. Lenacapavir was present in breastmilk (median breastmilk-to-plasma ratio 0·52 [IQR 0·38–0·77] in 102 mother–infant pairs); however, exposure in infant plasma was minimal (median breastfed-infant-to-maternal plasma ratio: 0·02 [IQR 0·01–0·05] in 98 pairs).
Interpretation
These data support accelerated access for lenacapavir in pregnant and lactating women.
Healio article – Trial backs use of lenacapavir for pregnant, postpartum women (Open access)
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