Lenacapavir: The Twice-Yearly Injectable That Is Redefining HIV Prevention and Why Brazil Is Watching Closely

In June 2025, the United States Food and Drug Administration approved injectable lenacapavir for HIV pre-exposure prophylaxis (PrEP), marking the first time a twice-yearly option became available in the US for people seeking protection from HIV. Marketed as Yeztugo by Gilead Sciences, lenacapavir is the first HIV-1 capsid inhibitor approved for HIV prevention, and its clinical trial data are among the most compelling ever seen in a prevention study.

The evidence base comes from two landmark Phase 3 trials. PURPOSE 1, conducted in South Africa and Uganda, enrolled 2,134 HIV-negative cisgender adolescent girls and young women. Zero of the participants who received twice-yearly lenacapavir injections acquired HIV during the study period, a 100 percent risk reduction compared to background HIV incidence. PURPOSE 2, which enrolled 3,265 participants including men who have sex with men, transgender women, and non-binary individuals across Brazil, South Africa, and five other countries, recorded only two infections in the lenacapavir arm, equating to a 96 percent risk reduction. The journal Science named lenacapavir its 2024 Breakthrough of the Year.

The significance of these numbers cannot be overstated in the context of the global HIV prevention challenge. Daily oral PrEP has been available since 2012 and is highly effective when taken consistently. But adherence is a persistent barrier. Studies show that approximately half of people who start daily oral PrEP discontinue it within six to twelve months. The reasons are well-documented: pill burden, HIV-related stigma, difficulty sustaining long-term motivation, and access constraints. A twice-yearly subcutaneous injection eliminates the daily adherence requirement entirely.

Brazil has a direct stake in this technology. PURPOSE 2 included trial sites in Brazil, meaning Brazilian data contributed to the efficacy record that supported FDA approval. In April 2025, Gilead Sciences submitted a registration request to ANVISA, Brazil's health regulatory agency, under the priority review pathway. As of December 2025, real-world implementation studies of lenacapavir for PrEP had commenced in Brazil, supported by Unitaid and conducted in partnership with Fiocruz.

The WHO issued formal guidelines recommending twice-yearly lenacapavir as an additional PrEP option in July 2025 at the International AIDS Society Conference in Kigali. The Gates Foundation and Unitaid announced partnerships in September 2025 with two generic manufacturers to make injectable lenacapavir available for approximately 40 US dollars per person per year in up to 120 countries from 2027.

For Brazil, which currently distributes oral PrEP free of charge through the SUS and recorded 109,000 PrEP users in 2023, lenacapavir represents both an opportunity and a pricing challenge. Brazil is not currently included in the low-income generic licensing agreements, and negotiations on access pricing for middle-income countries remain ongoing. The clinical trials and public health community is watching Brazil's regulatory and access timeline carefully, given the country's unique position as a certified eliminator of mother-to-child HIV transmission and a major contributor to the lenacapavir trial evidence base.

Sources: Gilead Sciences Press Release June 2025 | FDA Approval Documentation June 2025 | CDC MMWR September 2025 | WHO Guidelines July 14, 2025 | ANVISA Submission April 2025 | Wits RHI/Unitaid December 2025 | PrEP Watch | PMC Review Articles