No women taking long-acting cabotegravir (Apretude) for HIV pre-exposure prophylaxis (PrEP) developed an HIV infection despite short delays before some maintenance injections, according to a U.S. study of routine clinical care.
There were no cases of incident HIV over a median follow-up of 13 months among 315 women who started cabotegravir in 2021-2024 as part of the OPERA longitudinal cohort.
No HIV transmissions occurred despite less-than-perfect adherence to the cabotegravir regimen: 88% of 1,193 maintenance injections overall were delivered on time, with late injections occurring a median 8 days late. Ultimately, 44% of women had at least one delayed maintenance injection, Laura Armas-Kolostroubis, MD, of the AIDS Healthcare Foundation in Dallas, Texas, reported at the International AIDS Conference.
“The great news is that none of the women on cabotegravir PrEP acquired HIV during the study period despite ongoing sexual transmission risk — demonstrating that PrEP works,” Armas-Kolostroubis said. “This study demonstrates the high, real-world effectiveness of cabotegravir for HIV PrEP in cisgender and transgender women in the U.S.”
“We know that the life of our patients, particularly women, is very complicated, and the delays in clinical treatment may be due to family reasons, work, and other factors,” Armas-Kolostroubis said. Despite delays, she said, “don’t discard the possibility of continuing PrEP — stress that this is a very effective method.”
Approved for PrEP in 2021, long-acting injectable cabotegravir is indicated for use in adolescents and adults weighing at least 35 kg (~77.2 lbs) who are at risk for HIV-1 acquisition. Long-acting injectable cabotegravir PrEP is administered as a monthly injection for the first 2 months, then every 2 months afterwards.
Despite the treatment gaps observed, women’s return to cabotegravir suggests a continuing interest in the drug as a PrEP option, Armas-Kolostroubis noted. “This pattern of interruptions and resumptions may reflect how the need for PrEP evolves over time, as true risk — or perception of risk — changes,” she said. “They might feel at risk for a little while, then they trust their partner — and then when they break up, they come back and get back in care.”
Of note, long-acting lenacapavir (Yeztugo) PrEP had not yet been approved during the study. Lenacapavir is positioned to further boost PrEP uptake and persistence given its twice-yearly administration.
The OPERA cohort tracks more than 172,000 people with HIV, 911,000 people without HIV, and 86,000 who’ve received PrEP.
In the present analysis, researchers included cisgender or transgender women age 18 years or older who started PrEP from December 2021 to December 2024. Among 5,330 women who started any PrEP in that period, 6% initiated cabotegravir PrEP; 80% started daily oral tenofovir disoproxil and emtricitabine (Truvada) and 14% started daily oral tenofovir alafenamide fumarate and emtricitabine (Descovy).
The median age of the 315 individuals initiating cabotegravir was 28 years, 43% were Black, 32% were transgender, and 43% had a BMI of at least 30 kg/m2.
Cabotegravir reached a different population than oral PrEP options did, Armas-Kolostroubis observed. A greater percentage of women on cabotegravir were transgender (32%) than among those on oral PrEP (19%), while more women on the long-acting injectable received Medicaid (38%) than those on oral PrEP (8%).
Most women who chose cabotegravir were compliant with the drug’s initiation and maintenance regimen. Among the study’s 315 women, 80% received the cabotegravir initiation sequence of two monthly injections and were followed for a median 13 months afterward. Among the 252 who completed treatment initiation, 83% had at least one maintenance injection, with a median of four maintenance injections among the group.
More than half of women (56%) had all of their subsequent maintenance injections every 2 months on time, and those who didn’t had a median of only one late injection. Additionally, 89% of those who didn’t get a maintenance injection on time had a short delay of less than 31 days that didn’t require a cabotegravir restart.
While 38% of women who received at least one maintenance injection discontinued cabotegravir PrEP therapy, 25% of them resumed injections a median of 31 weeks after their last injection.
