WHO welcomes the news that long-acting injectable lenacapavir as pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV acquisition in women. This represents a significant breakthrough in HIV prevention.
The full results of the PURPOSE 1 trial, presented at the 25th International AIDS Conference, demonstrate the safety and efficacy of the long-acting injectable antiretroviral drug lenacapavir (LEN) for PrEP in HIV-negative cisgender women. LEN is a HIV-1 capsid inhibitor that is delivered by subcutaneous injection twice a year for HIV prevention. The PURPOSE 1 study showed zero new infections among those taking LEN.
Women in countries where the PURPOSE 1 trial was conducted, and across East and southern Africa, continue to experience high HIV incidence. Additional effective and acceptable HIV prevention choices for women are needed, including PrEP choices.
LEN has the potential to further increase the range of effective and acceptable prevention choices available to women, overcome challenges including those related to effective use of oral tablets and improve uptake and use of prevention.
While WHO is excited by these results, there remain several important issues to address, including safety of LEN in pregnancy and breastfeeding, best approaches for HIV testing to confirm infection, potential drug resistance, safety and effectiveness among groups not included in PURPOSE 1, and the real-world implementation of LEN.
WHO is eagerly awaiting the results from PURPOSE 2, which is evaluating lenacapavir for PrEP among cisgender men, transgender men, transgender women and gender non-binary individuals. Having these data will allow WHO to convene experts, ministries, partners and communities to develop and issue guidelines and to prepare for stringent regulatory authorities (SRAs) and WHO pre-qualification.
WHO has recommended a range of options for women who could benefit from PrEP, including oral PrEP containing TDF (2015), the dapivirine ring (DVR) (2021) and long-acting cabotegravir (CAB-LA) (2022). WHO has also developed implementation tools to support safe, effective, and acceptable implementation of these products.
About the PURPOSE 1 trial
Study design
PURPOSE 1 enrolled 5345 adolescent girls and young women aged 16–26 years at 25 sites in South Africa and three in Uganda. The median age of all trial participants was 21 years.
The study randomized participants to one of three arms:
- Arm A – LEN (as a subcutaneous injection every 6 months) and placebo daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) or placebo daily oral tenofovir alafenamide fumarate/emtricitabine (TAF/FTC).
- Arm B – Daily oral TAF/FTC and placebo subcutaneous LEN every 6 months.
- Arm C – Daily oral TDF/FTC and placebo subcutaneous LEN every 6 months.
Results
Fifty-five women in the trial acquired HIV. Sixteen (16/1068) were randomized to the daily, oral TDF/FTC arm (1.69/100 person-years; 95% CI, 0.96 to 2.74) and 39 (39/2136) were randomized to the daily, oral TAF/FTC arm (2.02/100 person-years; 95% CI, 1.44 to 2.76). There were zero (0/2138) infections in the LEN arm.
Overall adherence to TDF/FTC and TDF/TAF was poor. Among the 55 women in the TDF and TAF arms who acquired HIV, most had low to no tenofovir detected in their blood.
