A majority of women in the HPTN 084 trial, which compared injectable cabotegravir versus daily oral pre-exposure prophylaxis (PrEP), chose the long-acting option, according to study findings presented at the International AIDS Society Conference on HIV Science (IAS 2023).
“These results suggest that long-acting PrEP could have a huge prevention impact in Africa, where uptake of daily oral PrEP has been disappointingly low,” IAS president Sharon Lewin, MD, of the University of Melbourne, said in a news release. “I hope these findings will accelerate momentum to make long-acting PrEP accessible to all those who need it.”
Cabotegravir is a long-acting integrase inhibitor from ViiV Healthcare. In late 2021, it was approved for HIV prevention in the United States, where it is sold as Apretude. People who wish to use this option first receive two injections administered one month apart, then a shot every two months thereafter. If desired, they can start with an oral lead-in using cabotegravir pills (sold as Vocabria) for the first month. Cabotegravir is also a component of Cabenuva (cabotegravir plus rilpivirine), the only long-acting injectable HIV treatment regimen.
While white gay men in the United States and Europe have eagerly adopted oral PrEP, uptake remains low among Black men and all women. In Africa, adoption of oral PrEP has been slow, and some women who start it do not maintain optimal adherence. Offering more prevention options could increase uptake and encourage consistent use. Injectable PrEP is now being rolled out in Africa, but access remains limited. Last year, ViiV signed a voluntary licensing agreement with the Medicines Patent Pool to allow generic versions of injectable cabotegravir in low- and middle-income countries.
Two large trials showed that injectable cabotegravir works even better than PrEP pills. The HPTN 084 trial enrolled more than 3,000 mostly young cisgender women in sub-Saharan Africa. They were randomly assigned to receive cabotegravir injections every two months or once-daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, or Truvada and generic equivalents). The study was stopped early after an interim analysis found that the injections were more effective. Further follow-up showed that women who received the injections had a 92% lower risk of acquiring HIV compared with those who used daily pills. The higher efficacy was largely attributable to better adherence.
The parallel HPTN 083 trial enrolled more than 4,000 cisgender men and transgender women who have sex with men in the United States, Latin America, Asia and Africa. It was also halted ahead of schedule after an interim analysis showed that the injections worked at least as well as daily pills. As described in The New England Journal of Medicine, the injections were 66% more effective at preventing HIV acquisition. This is remarkable, given that TDF/FTC itself reduces the risk of HIV by around 99% for gay and bisexual men who use it consistently.
In 2022, after completion of the randomized portion of HPTN 084, eligible participants were offered their choice of cabotegravir injections or daily TDF/FTC in an open-label extension of the trial. Mina Hosseinipour, MD, MPH, of the University of North Carolina at Chapel Hill, and colleagues assessed the women’s choice of PrEP and their reasons for it. This analysis included 2,472 women in Botswana, Eswatini, Kenya, Malawi, South Africa, Uganda and Zimbabwe who opted to continue in the open-label extension.
Overall, 1,931 women (78%) chose cabotegravir injections, while 536 (22%) chose daily PrEP pills. Among those initially randomized to TDF/FTC, 67% chose injections, while 33% opted to keep taking the pills. Within this group, 15% chose an oral-lead period and 53% went directly to injections. Among those initially randomized to cabotegravir, most opted to stay on the injections, while only 11% chose to switch to daily pills.
The women who chose long-acting cabotegravir said they preferred injections over daily pills (77%), desired a more convenient or discrete PrEP method (11%) or valued cabotegravir’s high effectiveness (8%); 4% gave other reasons or no reasons. Women who chose TDF/FTC preferred pills over injections (81%), were worried about injection pain or side effects (5%), wanted to get pregnant (1%), wanted efficient clinic visits (1%) or gave no reason (12%).
Women who opted for cabotegravir injections were more likely to be sexually active but not live with a partner, more likely to have experienced recent intimate partner violence and more likely to have been paid for sex. PrEP choice also varied by country. While most participants (66%) reported that their choice was their own, they were influenced by discussions with study staff (20%) or family and friends (11%).
Compared with those who chose TDF/FTC, those opting for the injections “perceived more strongly that they had made a good decision,” the researchers noted.
“Participants were very competent in their decision-making…and this gives us confidence that they may be able to be retained on PrEP more easily,” Hosseinipour said at an IAS press conference. “We really need to cater for the choice that women want to make in their prevention products.”
“[This study] confirms that long-acting PrEP could be a game-changer in Africa, where uptake of daily oral PrEP has been far too low,” especially for vulnerable adolescent girls and young women “for whom prevention interventions have not adequately been taken to scale,” IAS 2023 local chair Charles Gilks, PhD, of the University of Queensland, said at an advance media briefing. “We hope that these findings will increase pressure on companies, governments and other players to make long-acting PrEP accessible quickly to all those who could benefit, not only in Africa but worldwide.”