WHO welcomes the latest findings from the PURPOSE-2 trial on long-acting injectable lenacapavir (LEN) for HIV prevention. An interim analysis, announced on 12 September 2024, demonstrated the drug's remarkable efficacy in preventing HIV. LEN, an HIV-1 capsid inhibitor delivered by subcutaneous injection twice a year, was shown to be highly effective in preventing HIV among cisgender men, transgender men, transgender women, and gender non-binary individuals who have sex with partners assigned male at birth.
The PURPOSE 2 trial reported a 96% reduction in the risk of acquiring HIV among study participants, with 99.9% of individuals using LEN not acquiring HIV. Only two new HIV cases were recorded among 2180 participants receiving LEN twice-yearly, compared to nine new cases among the 1087 participants receiving daily oral TDF/FTC (tenofovir disoproxil fumarate/emtricitabine). Lenacapavir demonstrated a 96% reduction in HIV incidence compared to background HIV incidence (2.37 per 100 person-years) and was 89% more effective than daily oral TDF/FTC in preventing HIV acquisition. Both LEN and daily oral TDF/FTC were well tolerated, with no significant or new safety concerns identified.
These findings build upon the earlier results from the PURPOSE 1 trial, which demonstrated LEN's efficacy in preventing HIV among cisgender women in sub-Saharan Africa, with zero infections among women receiving the injectable.
Together, the results from PURPOSE 1 and PURPOSE 2 provide compelling evidence for the potential of LEN to transform HIV prevention globally, across diverse populations. It is important to note that oral PrEP is safe and effective in preventing HIV when taken as indicated. LEN's twice-yearly dosing offers a significant advantage for people who face challenges with adhering to daily oral PrEP, including stigma and discrimination, pill fatigue, and challenges with consistent access to medication.
WHO next steps
WHO eagerly awaits the full publication of findings from the PURPOSE 2 trial following scientific peer review. Meanwhile, WHO is working rapidly to convene a guideline development group with experts, ministries, partners and communities. This group will develop and issue guidelines based on a rigorous assessment of the potential of LEN for HIV prevention, evaluating key aspects such as efficacy, safety, cost-effectiveness, values and preferences from stakeholders and communities, and global scalability, among others.
In parallel, WHO is working alongside international partners, pharmaceutical companies, and generic manufacturers to create an enabling environment for LEN scale-up, to ensure affordable and sufficient supply and equitable access. A crucial early step in this process is the pharmaceutical company's application to a stringent regulatory authority (SRA) to obtain WHO prequalification of medical products.
The addition of lenacapavir to the growing list of HIV prevention options, including oral PrEP containing TDF (2015), the dapivirine ring (DVR) (2021) and long-acting cabotegravir (CAB-LA) (2022), can expand the toolkit for global HIV prevention efforts, especially for regions and communities with high HIV incidence.
About the PURPOSE 2 trial
Study design
PURPOSE 2 enrolled 3267 participants, including cisgender men, transgender men, transgender women, and gender non-binary individuals aged 16 and older, who have sex with partners assigned male at birth. The trial was conducted at 88 sites in Argentina, Brazil, Mexico, Peru, South Africa, Thailand, and the United States.
Participants were randomized in a 2:1 ratio to receive either twice-yearly subcutaneous injections of LEN or daily oral TDF/FTC. The trial did not use a placebo group due to the established efficacy of available PrEP options. Instead, it compared LEN with background HIV incidence (bHIV) and daily oral TDF/FTC as comparators.
