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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
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July 14, 2026
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Twice-yearly subcutaneous lenacapavir is well tolerated among pregnant, postpartum, and lactating women. Zero HIV infections occurred among participants who received lenacapavir during pregnancy. Pregnant, postpartum, and non-pregnant participants had similar lenacapavir exposure and infant exposure via breastmilk was minimal.
In conclusion, lenacapavir was highly efficacious and well tolerated in pregnant and lactating women, with no clinically significant differences in pharmacokinetics compared with women who did not become pregnant. We demonstrated the feasibility and value of including pregnant and lactating women in phase 3 studies, underscoring the importance of equitable study design in advancing global HIV prevention efforts. Our findings support the use of twice-yearly subcutaneous lenacapavir for PrEP in pregnant and lactating women who want or need PrEP.
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.
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