Gilead Advances HIV Treatment Pipeline, Focusing on Long-Acting Therapies

Gilead Selects GS-3242 as Partner for Lenacapavir in Twice-Yearly HIV Treatment

Gilead Sciences has announced a significant development in its HIV treatment pipeline, selecting GS-3242 as the partner compound for lenacapavir in its pursuit of a twice-yearly injectable HIV treatment. This decision, revealed during the company's third-quarter earnings call on October 30, 2025, marks a pivotal step in Gilead's strategy to develop low-frequency treatment options for people living with HIV.

The selection of GS-3242 came after a comparative evaluation with another phase 1 integrase strand transfer inhibitor, GS-1219. As a result of this decision, Gilead has terminated a phase 1 study of GS-1219 in HIV patients. Dr. Dietmar Berger, Gilead's Chief Medical Officer, explained the company's approach: "Our strategy has been to set up our pipeline for multiple shots on goal and then choose the best option for each dosing frequency."

Lenacapavir's Growing Role in HIV Treatment and Prevention

Lenacapavir, Gilead's capsid inhibitor, has been making waves in the HIV treatment landscape. In June 2025, it received approval for HIV prevention under the brand name Yeztugo, a development that Gilead CEO Daniel O'Day described as "one of the most important scientific breakthroughs of our time." This sentiment was echoed by the scientific community, with Science magazine naming lenacapavir its 2024 Breakthrough of the Year following its impressive performance in a large phase 3 trial, where it demonstrated 100% efficacy.

The compound first gained approval in 2022 as Sunlenca, a treatment for patients with multi-drug resistant HIV. Now, Gilead is expanding lenacapavir's potential through various combination therapies:

1. Twice-yearly injectable treatment: Pairing lenacapavir with GS-3242
2. Weekly oral treatment: Combining lenacapavir with Merck's islatravir in a phase 3 trial
3. Daily oral treatment: Testing lenacapavir with Gilead's bictegravir (part of the Biktarvy regimen) in a phase 3 study
4. Quarterly injectable treatment: Evaluating lenacapavir with GS-1614, a prodrug of islatravir, in phase 1 trials

Challenges and Ongoing Research in Gilead's HIV Pipeline

While Gilead advances its lenacapavir-based therapies, the company faces challenges with other compounds in its HIV pipeline. Two phase 2/3 trials testing investigational treatments GS-1720 and GS-4182 were placed on hold by the FDA in June due to safety concerns. As of the October 30 presentation, these holds remain in effect, underscoring the complexities and risks inherent in HIV drug development.

Gilead continues to prioritize its HIV research, with plans to share more details about GS-3242 at a virology conference in 2026. This ongoing commitment to innovation in HIV treatment reflects the company's broader strategy of developing multiple treatment options with varying dosing frequencies to meet the diverse needs of people living with HIV.