A New Horizon in HIV Prevention: FDA Approves Twice-Yearly Injectable PrEP

 

July 11, 2025 – In a landmark decision poised to revolutionize global efforts in curbing the HIV epidemic, the U.S. Food and Drug Administration (FDA) has granted approval to lenacapavir (brand name Yeztugo) as the first and only twice-yearly injectable medication for HIV pre-exposure prophylaxis (PrEP). This groundbreaking development, announced on June 18, 2025, offers a new, highly effective, and remarkably convenient option for individuals at risk of HIV infection, promising to significantly improve adherence rates and accelerate progress toward ending the epidemic.

For decades, the fight against HIV has seen remarkable scientific advancements, yet challenges in consistent medication adherence for prevention have persisted. Current PrEP options, primarily daily oral pills or a bi-monthly injectable, require regular engagement with healthcare systems and a high degree of personal discipline. Lenacapavir, developed by Gilead Sciences, shatters this paradigm by offering a regimen of just two injections per year, dramatically simplifying the prevention strategy for millions.

The FDA's decision is underpinned by compelling data from two Phase 3 clinical trials, PURPOSE 1 and PURPOSE 2. These trials demonstrated exceptional efficacy, with nearly 100% protection against HIV acquisition among participants receiving lenacapavir. In the PURPOSE 1 trial, which involved cisgender women in Uganda and South Africa, zero HIV infections were observed in the lenacapavir group. The PURPOSE 2 trial, encompassing a broader population across multiple countries, showed similarly impressive results, with a 99.9% protection rate.

"This is a breakthrough moment," stated Winnie Byanyima, Executive Director of UNAIDS, responding to the approval. "Lenacapavir could be the tool we need to bring new infections under control – but only if it is priced affordably and made available to everyone who could benefit."

Lenacapavir distinguishes itself with a novel mechanism of action. Unlike previous antiretrovirals that target a single enzyme, lenacapavir is a first-in-class HIV-1 capsid inhibitor. It interferes with multiple essential stages of the HIV lifecycle, from viral uptake to assembly and release, giving it potent antiviral activity and a distinct advantage against potential drug resistance.

The implications of this approval are far-reaching, particularly for communities facing significant barriers to HIV prevention. The twice-yearly dosing schedule offers:

• Enhanced Adherence: By dramatically reducing the frequency of dosing, lenacapavir addresses a major hurdle in PrEP uptake and effectiveness. This is especially impactful for individuals who struggle with daily pill adherence due to forgetfulness, privacy concerns, or the stigma associated with taking daily medication.
• Increased Discretion: For many, the need for frequent clinic visits or the visible presence of daily pills can lead to discomfort or self-inflicted stigma. A twice-yearly injection offers a more discreet option, potentially empowering more individuals to access PrEP without fear of judgment.
• Expanded Access: This simplified regimen holds immense promise for expanding PrEP access in low- and middle-income countries, where healthcare infrastructure and consistent medication supply chains can be challenging. Gilead has already initiated partnerships with generic manufacturers and the Global Fund to accelerate access to lenacapavir in these regions.

While the excitement surrounding lenacapavir is palpable, discussions continue regarding affordability and equitable global distribution. The current list price in high-income countries presents a challenge, but efforts are underway to ensure that this life-changing prevention tool reaches those who need it most, regardless of their economic circumstances.

The approval of Yeztugo marks a pivotal moment in the ongoing battle against HIV. It represents not just a scientific triumph, but a renewed sense of optimism that, with effective and accessible tools, the global community can truly move closer to ending the HIV epidemic.