Lenacapavir and cabotegravir PrEP supported for use in pregnancy and breastfeeding

New data presented at the 13th International AIDS Society Conference on HIV Science (IAS 2025) yesterday show that two long-acting injectable PrEP options, lenacapavir and cabotegravir, are safe, well tolerated and effective for use during pregnancy and breastfeeding. Both drugs showed minimal transfer to infants through breast milk and no increase in adverse pregnancy or birth outcomes, supporting their use as convenient HIV prevention options for pregnant and lactating people at risk of HIV.

In the PURPOSE 1 trial, lenacapavir maintained blood levels similar to those seen in non-pregnant participants, with no need for dose adjustment during pregnancy. Given its infrequent dosing, high efficacy and safety profile, it is now supported for use in pregnancy by both the US Food and Drug Administration (FDA) and the World Health Organization (WHO).

Professor Linda-Gail Bekker, principal investigator of PURPOSE 1, told the conference that pregnancy outcomes among people receiving lenacapavir were comparable to those seen in participants taking daily oral PrEP and in the general population.

Pregnant and lactating people remain disproportionately vulnerable to HIV, yet have historically been excluded from prevention trials despite their need for additional options. The PURPOSE trials are the first phase III PrEP studies to include pregnant and lactating people, following recommendations made by WHO and the PHASES project.

Participants were not required to use contraception to join, but contraception was provided if pregnancy was not desired. If a participant became pregnant, she could continue lenacapavir after receiving counselling on the potential risks and benefits and repeating the informed consent process.

A pharmacokinetic study nested within PURPOSE 1 measured maternal drug concentrations during pregnancy and postpartum, as well as drug levels in breast milk and infants. The median age of participants was 21 years. Lenacapavir was shown to pass into breast milk at about half the concentration (0.52) found in maternal blood, but only about 2% of this reached the infant’s bloodstream, suggesting minimal exposure in breastfed babies. PK results were consistent whether injections were given in the thigh or abdomen.

Birth outcomes did not differ significantly between the lenacapavir and oral PrEP arms. Among 2140 women receiving lenacapavir, there were 193 pregnancies, compared to 218 in those receiving tenofovir alafenamide / emtricitabine (2135 women) and 98 in those on tenofovir disoporxil / emtricitabine (1070 women). Six cases of birth defects were reported in the lenacapavir arm, which is within the expected background rate. Across these pregnancies, there was no increase in pregnancy-related complications such as hypertension, nausea or foetal distress, or in adverse pregnancy or birth outcomes, and notably, no participants using lenacapavir acquired HIV.

Based on these findings, the researchers suggest that women of reproductive age should not face barriers to accessing lenacapavir, but more research and ongoing safety surveillance during pregnancy remain essential.

Cabotegravir studies provide reassurance for breastfeeding mothers and newborns

Long-acting cabotegravir, given every eight weeks, has already been shown to substantially reduce HIV acquisition in people assigned female at birth. New data from the Tshireletso study in Botswana now offer reassurance about its use immediately after childbirth in a predominantly breastfeeding population.

Twenty-seven mothers, with an average age of 23, were enrolled. Each intended to exclusively breastfeed. The first cabotegravir injection (600 mg) was administered within one to two days of delivery, followed by a second dose at one month and then every two months at maternal and child health clinics.

Maternal blood, infant blood, and breast milk samples were collected at four time points: just before the one-month and five-month injections, and again one week after each. Most infants were exclusively breastfed during the early months, though some began solids or stopped breastfeeding by five months.

At one month, almost 75% of mothers had cabotegravir concentrations above the protective threshold (four times PA-IC90). By one week later and at all subsequent time points, about 97% exceeded this threshold. These levels were comparable to those observed in non-pregnant women, suggesting that pregnancy and delivery do not reduce cabotegravir’s effectiveness. No new HIV infections were recorded among participants.

Cabotegravir concentrations in breast milk were very low, only a small amount transferring from the mother’s blood into breast milk, averaging about 1.4% of maternal blood levels. Measuring drug concentrations in infants’ blood, the relative infant dose was a median of 5%. These findings suggest that cabotegravir is safe for use in breastfeeding mothers.

HPTN 084 data support continued cabotegravir during pregnancy

Similar findings came from the open-label extension of the HPTN 084 study, which allows women who become pregnant to continue cabotegravir for PrEP. Dr Sinead Delany-Moretlwe, the study’s principal investigator, reported that between the start of the extension and 6 June 2024, there were 433 pregnancies, about two-thirds among women who were receiving cabotegravir at the time. The median age of participants taking cabotegravir was 28 years. Most had received 12 to 14 injections before pregnancy and continued with a median of four additional doses during pregnancy.

Pregnancy outcomes were similar across exposure groups. Most pregnancies resulted in full-term births, with no maternal deaths or HIV infections reported. Maternal adverse events occurred most frequently in the cabotegravir group (42 per 100 person years, compared to 35 and 24 in the other two groups, respectively): gestational hypertension was the most common, but serious complications were rare.

There were 290 live births, 75% of which were in the cabotegravir group. The median gestational age at delivery was 37 to 39 weeks, and the median birth weight across all groups was 3kg, with 11% or fewer infants classified as small for gestational age. Two infants in the active cabotegravir group were born with congenital anomalies.

Following these findings, the 2025 WHO guidelines recommend that PrEP should not be discontinued during pregnancy and breastfeeding for women at risk of HIV exposure. The decision to start, continue or stop PrEP during pregnancy should be made by the individual, in consultation with a healthcare provider, after discussion of the benefits and available safety data.