Use of lenacapavir injections for long-acting preexposure prophylaxis (PrEP) in female adolescents and women in Africa resulted in no HIV acquisitions over a 1-year period, according to findings from the open-label extension of the PURPOSE 1 study presented at the annual meeting of AIDS 2026 in Rio de Janeiro.

“I must say it has been a good experience to see as we moved from seeing multiple women, getting infected with HIV in the randomized blinded phase to zero HIV infections in the open-label phase,” Noah Kiwanuka, MB ChB, MPH, PhD, a senior lecturer and infectious diseases epidemiologist at the Makerere University College of Health Sciences in Kampala, Uganda, told attendees.

An estimated 45% of all new HIV infections in 2024 occurred among girls and women, including 63% in sub-Saharan Africa, Kiwanuka noted. In the US, Black women are among the higher risk groups for HIV, making up half of all new infections among women in 2024.

The PURPOSE 1 study enrolled 5338 cisgender females, aged 16-25 years, from Uganda (16%) and South Africa (84%) to assess the effectiveness of lenacapavir compared to two oral PrEP methods. During the randomized controlled phase of the study, 2134 participants received lenacapavir injections every 26 weeks while taking an oral placebo. The other two groups received a placebo injection every 26 weeks and took daily emtricitabine/tenofovir alafenamide (Descovy; n = 2136) or emtricitabine/tenofovir disoproxil fumarate (Truvada; n = 1068).

After 52 weeks of the first phase, the open-label extension assessed effectiveness for another 52 weeks in all participants who chose to continue taking lenacapavir. Among the 4417 participants who completed the randomized, controlled phase and were therefore eligible for the open-label extension, 94% of the 1791 receiving lenacapavir and 95% of the 2626 taking an oral PrEP agent opted to receive lenacapavir every 26 weeks.

No new HIV acquisitions occurred during the year of the open-label extension among those taking lenacapavir, with data encompassing more than 7000 person-years. The safety and tolerability of lenacapavir remained similar to previous reports in both those continuing the drug and in those who switched to it from oral PrEP. Serious adverse events occurred in 7% of those continuing lenacapavir and in 5% of those who switched, both of which resulted in less than 1% discontinuing the drug.

Adherence remained high in both those who remained on lenacapavir (97%) and those who switched to it (97%). Participants receiving twice-yearly lenacapavir reported preferring the convenience of the drug’s dosing and how well it fit into their lifestyle, according to qualitative findings presented by Thandeka Nkosi, MPH, a clinical researcher at the Desmond Tutu HIV Centre at the University of Cape Town in Cape Town, South Africa.

“Participants consistently described the long-acting protection and practicality of lenacapavir as important advantages over daily oral prep,” Nkosi said. “They viewed the injection as reducing the burden of daily pill taking, particularly if they were socializing with friends.

The findings came from in-depth interviews conducted with 35 participants on the first day of the open-label extension and 50 participants within the first 3 months of the extension. The randomly selected participants came from one of the five PURPOSE 1 study sites in South Africa and were representative of the overall South African cohort in the study, including girls and women from urban, semi-urban, and rural settings in the Cape Town, Durban, and Johannesburg areas.

They were a median 20 years old, and 87% had completed secondary school. Nearly all (99%) had never been married, and only 1.2% were living with a husband or partner. Nearly a third (30%) had ever had a sexually transmitted infection, and 13% had previously used any form of PrEP.

Although some participants reported the injection as helpful because they might otherwise forget to take the pill, the convenience went beyond remembering pills, Nkosi said.

“Participants viewed injectable lenacapavir as fitting naturally into busy and active lifestyles, allowing them the flexibility to not worry about scheduling logistics and taking medication every day,” she said. “As another participant shared, if you are busy or moving around, you won’t have to stress that you need to go back home or you must keep the pills here. So you become stress-free because you know you got the injection for 6 months. So you’re sorted.”

The advantages of twice-yearly lenacapavir outweighed concerns about injections, with injection site reactions considered an “acceptable trade-off” for the long-acting protection, Nkosi reported. Some participants reported the injection as painful at the beginning but becoming more tolerable over time.

“Participants also describe practical ways of managing discomfort after the injection, including ice packs, painkillers, warm compressors, or simply resting,” Nkosi said. “Overall, participants highly favored lenacapavir because its demonstrated efficacy, long-acting protection, and convenience gave them confidence, freedom from the burden of taking daily pill, and peace of mind that HIV prevention could fit seamlessly into their everyday lives.”

Many participants reported receiving encouragement from partners, family members, and others in taking lenacapavir, but they also expressed strong themes of autonomy and personal choice in making the decision, including informing their partners rather than asking permission.

“I didn’t discuss it with anyone,” one participant said. “It was my choice because it is for my safety.”

Nkosi reported that some participants expected to continue taking lenacapavir if they got married while others expected they would discontinue it if they entered what they perceived to be a stable relationship.

Monica Gandhi, MD, MPH, a professor of medicine at the University of California, San Francisco, told Medscape Medical News that the confidence revealed among girls and women in PURPOSE 1 in taking lenacapavir reflected similar sentiments among those taking it in the US, especially among key populations like transgender women and men who have sex with men.

“There were some other interesting findings in this abstract, including reported pain with injections but the tolerability increasing with the use of ice pre-and-post injections,” Gandhi said. “We are seeing the utility of icing to decrease adverse reactions in the US as well.”

Overall, Gandhi said, “the interest seen in the interviews of alternative injection sites, such as the buttocks or arms, is also mirrored here in the US as injections in these areas are more familiar than injections in the abdomen.”

The PURPOSE 1 study was funded by Gilead Sciences Inc. Nkosi and Kiwanuka had no other disclosures beyond the study funding.

Tara Haelle has covered science and medicine for nearly two decades and is author of Vaccination Investigation and The Informed Parent: A Science-Based Resource for Your Child's First Four Years. She is based in Dallas.