The World Health Organization (WHO) has hailed the findings from the PURPOSE 1 trial, revealing that long-acting injectable lenacapavir (LEN) as pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV acquisition among cisgender women. This breakthrough was presented at the 25th International AIDS Conference, underscoring LEN’s safety and efficacy as a game-changer in HIV prevention.
LEN, a HIV-1 capsid inhibitor administered via subcutaneous injection twice yearly, demonstrated zero new infections among trial participants. Conducted in multiple sites across South Africa and Uganda, the PURPOSE 1 trial enrolled 5,345 adolescent girls and young women aged 16–26. The median age of participants was 21 years.
Participants were randomized into three arms:
Arm A received LEN injections every 6 months and daily oral placebo tablets.
Arm B received daily oral tenofovir alafenamide fumarate/emtricitabine (TAF/FTC) and placebo LEN injections every 6 months.
Arm C received daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) and placebo LEN injections every 6 months.
Among those who acquired HIV during the trial, 39 were in the TAF/FTC arm (2.02/100 person-years) and 16 in the TDF/FTC arm (1.69/100 person-years), whereas zero infections occurred in the LEN arm (0/2138).
While LEN, TDF/FTC, and TAF/FTC were generally well-tolerated, injection site reactions (ISRs) were the most common adverse events observed, affecting 68.8% of LEN recipients compared to 34.9% in the placebo group. Notably, no serious ISRs were reported among those receiving lenacapavir, although four participants discontinued the drug due to ISRs.
Despite these promising results, WHO acknowledges critical considerations moving forward, including safety during pregnancy and breastfeeding, optimal HIV testing protocols, potential for drug resistance, and broader demographic applicability beyond cisgender women. Anticipated results from PURPOSE 2, assessing lenacapavir’s efficacy among other gender identities, will inform future guidelines and regulatory processes.
LEN joins WHO’s roster of recommended PrEP options, alongside oral TDF/FTC, the dapivirine ring (DVR), and long-acting cabotegravir (CAB-LA), with implementation tools designed to facilitate safe and effective usage.
As global efforts intensify to expand HIV prevention choices, lenacapavir stands out as a promising addition to empower women in the fight against HIV/AIDS.
