Lenacapavir does not appear to cause any clinically significant effects in the pharmacokinetics of long-acting hormonal contraceptives or gender-affirming hormone therapy, according to a pair of posters presented at Infectious Disease Week (IDWeek) 2025 Annual Meeting in Atlanta. 

The findings offer reassurance that taking lenacapavir as preexposure prophylaxis (PrEP) while also taking long-acting hormonal contraception will not result in any interactions that affect the effectiveness of the contraception, explained Disebo Potloane, of the Centre for the AIDS Programme of Research in South Africa, the lead author of the study on hormonal contraception. 

“What we see for feminizing hormone therapy, for testosterone, and for DHT [dihydrotestosterone], which is your testosterone metabolite, is no change in hormone therapy concentrations from pre-lenacapavir dosing out to week 52,” Sarah Puryear, MD, director of clinical development at Gilead Sciences, Inc., told Medscape Medical News. “The implication [is] that lenacapavir is not going to interfere with people’s gender-affirming hormone therapy, so they can be co-administered without dose adjustments.”

Data presented last year similarly suggested that there’s no impact from the hormones on lenacapavir’s effectiveness, and more data on that will be presented at an upcoming conference, Puryear said. These findings are particularly important for those who care for transgender people because “concerns about gender-affirming hormone therapy levels being impacted by PrEP are a huge barrier to uptake and to adherence” in gender-diverse populations, she said. “It’s a group that we know is at extremely high risk for HIV acquisition.” 

Both studies explored the potential interactions between hormone-based medications and lenacapavir in subsets of the PURPOSE 1 and PURPOSE 2 phase 3 clinical trials for lenacapavir. The PURPOSE 1 trial enrolled 2140 cisgender women who were offered free contraception but not required to take it. The researchers evaluated the pharmacokinetics of three contraceptive medications — medroxyprogesterone acetate (DMPA), norethindrone enanthate (NET-EN), and etonogestrel — in 226 participants who had uninterrupted long-acting hormonal contraceptive exposure from baseline through week 26. 

They found that plasma concentrations of DMPA and NET-EN through week 52 were similar to those at baseline. Median plasma concentrations of etonogestrel initially showed an upward trend through week 13 and then decreased back to baseline at week 26. In a separate analysis, progestin-type contraceptives did not affect lenacapavir exposures. 

The researchers only looked at adverse events in those taking etonogestrel because it was the only contraceptive to show changes in levels, but adverse events in those taking etonogestrel were similar between those taking lenacapavir and those receiving oral PrEP. 

The PURPOSE 2 trial enrolled 2183 men who have sex with men, transgender women, transgender men, and nonbinary participants, including 22.3% participants who self-identified as gender-diverse and 11.6% who reported receiving gender-affirming hormone therapy during the trial. The researchers evaluated serum estradiol concentrations in 115 participants and plasma testosterone and DHT concentrations in 25 participants at baseline and from week 4 through week 52. They found no significant differences from baseline through week 52.

“This data essentially impacts clinician counseling,” Puryear said. “As a clinician, you can go to someone and tell them that you don’t anticipate any impact on their therapy, that they don’t need to change doses, and that this is a reasonable PrEP option for them when you’re going for options for prevention.” 

Concerns about interference with hormonal contraception was not as substantial a barrier to PrEP uptake as concerns about gender-affirming hormone therapy, Potloane said, but the data confirm what options women have for both PrEP and for contraception. 

“This data is really just reassuring for us to go back and say to them, we had a look at this,” and there are no concerns about interactions, Potloane said. “If you want to continue with your contraceptives, if you don’t want to continue with the contraceptives, and you want to [get] pregnant, that’s fine, too.” 

Previous research has looked at women who became pregnant while taking lenacapavir and found no safety concerns, she added. “Oral PrEP is safe for pregnancy, and now we know that lenacapavir is,” Potloane said.

David Koren, PharmD, MPH, an infectious disease clinical pharmacist at Temple University Hospital and an adjunct clinical professor at Temple University Lewis Katz School of Medicine in Philadelphia, was not involved with either study but told Medscape Medical News that he found the data reassuring.

“From a pharmacist perspective, we know that lenacapavir is a moderate cytochrome P450 3A (CYP3A) inhibitor, as opposed to a strong CYP3A inhibitor, so we’ve always had a question about the relevance of the interactions and how that relates to some of the known interactions we have with medications that we’ve used for many years,” Koren said.

“The two posters that were presented today give us more assurance that the interaction is not as strong as we were expecting, and this is now the data that underlies it,” Koren said. “Since both posters show that the levels were fairly similar, it opens up options so the right person can be on the right dose of the medication, whether it’s for contraception or it’s for gender-affirming therapy.”

Although the gender-affirming hormone therapy poster looks at both feminizing and masculinizing hormones, it was the trans-feminine hormones that initially raised questions about interactions because estradiol undergoes the same pathway as CYP3A4, he said.

“If you know that interaction is there, you worry about the extent,” Koren said. “These posters tell us that the extent is not as clinically significant as we were worried about, so it gives us a lot more confidence.”

The research was funded by Gilead Sciences, and both studies included authors who were employees of Gilead. Puryear reported being an employee of Gilead, and Potloane reported receiving research funding from Gilead. Koren reported receiving research funding from Merck Sharp & Dohme for an unrelated study. 

Tara Haelle is a science/health journalist based in Dallas.