Gilead Unveils New HIV Treatment Data at CROI 2025
Gilead Sciences, Inc. has unveiled a significant array of late-breaking data and multiple oral presentations from its groundbreaking HIV treatment portfolio and pipeline at the Conference on Retroviruses and Opportunistic Infections (CROI) 2025. These findings underscore Gilead’s commitment to innovation in HIV therapy, expanding treatment choices, enhancing patient outcomes, and advancing toward a potential cure for the virus that has affected millions worldwide.
Advancing HIV Treatment with a Transformative Pipeline
Gilead’s leadership in the field of HIV research continues to drive scientific discovery and development of next-generation treatments. “Gilead is fueling the next wave of innovation in HIV to help end the epidemic globally,” stated Jared Baeten, MD, PhD, Senior Vice President, Virology Therapeutic Area Head. “Our contributions to CROI spotlight our dedication to scientific discovery, reflect our commitment to addressing the diverse treatment needs and preferences of communities affected by HIV, and underscore the vital importance of catalyzing research reaching towards a cure.”
Biktarvy’s High Efficacy in HIV/HBV Coinfected Patients
A pivotal study presented at CROI 2025 highlights the efficacy of Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) in patients with HIV and hepatitis B virus (HBV) co-infection. The ALLIANCE trial (NCT03547908), a Phase 3 study, is the first randomized clinical trial comparing tenofovir alafenamide (TAF)- versus tenofovir disoproxil fumarate (TDF)-based regimens in treatment-naïve adults with HIV/HBV co-infection. The study evaluates the effectiveness of these regimens in achieving viral suppression for both viruses, which remains a key challenge in clinical practice.
Newly presented results from the open-label extension phase after 96 weeks of randomized treatment demonstrated that Biktarvy maintained high rates of HIV-1 suppression (95.4%) and HBV suppression (86.6%), reinforcing its efficacy in this patient population. Importantly, study drug-related treatment-emergent adverse events (TEAEs) were reported in only 19% of participants, with most being mild to moderate. The most common TEAEs were weight gain (9%) and increased low-density lipoprotein (LDL) cholesterol (3%), with no participants discontinuing due to TEAEs.
These findings reinforce the potential role of Biktarvy in addressing the needs of HIV/HBV co-infected individuals. However, it is important to note that the use of Biktarvy in this population remains investigational, and its safety and efficacy have not been fully established.
Breakthrough Therapy Designation for Long-Acting, Twice-Yearly HIV Treatment
A key highlight at CROI 2025 was the announcement that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to Gilead’s investigational long-acting, twice-yearly combination regimen of lenacapavir (LEN) with broadly neutralizing antibodies (bNAbs), teropavimab (GS-5423, TAB) and zinlirvimab (GS-2872, ZAB). This designation underscores the regimen’s potential to provide significant benefits over existing therapies and expedites its development.
The Phase 2 study (NCT05729568) evaluating the LEN+TAB+ZAB (LTZ) combination regimen presented promising findings. The study enrolled virologically suppressed individuals and compared outcomes between those who switched to LTZ every six months versus those who remained on a stable baseline oral antiretroviral regimen (SBR). The study met its primary endpoint, with both groups achieving a 96% virologic suppression rate at Week 26. CD4 cell counts also increased in both arms of the study.
The regimen was well tolerated, with the most common adverse events being mild injection site reactions related to subcutaneous LEN administration. Importantly, there were no serious adverse events (AEs) related to LTZ, and no infusion-related reactions occurred with the bNAbs. These results support further clinical development of LTZ as a potentially revolutionary approach to HIV treatment.
It is crucial to note that teropavimab and zinlirvimab are still investigational and have not yet received regulatory approval for use in combination with lenacapavir or any other HIV treatments. Their safety and efficacy continue to be evaluated in clinical trials.
Landmark HIV Cure Clinical Trial in South Africa
In an effort to move closer to an HIV cure, Gilead sponsored a groundbreaking Phase 2a trial (GS-US-382-5445, NCT05281510) in South Africa, marking the first HIV cure trial conducted in the region. This study aimed to assess a novel combination approach involving an investigational toll-like receptor 7 (TLR7) agonist, vesatolimod, along with bNAbs provided by the National Institutes of Health (NIH).
The trial enrolled 20 South African cisgender women from the FRESH (Females Rising through Education, Support, and Health) cohort who had initiated antiretroviral therapy (ART) soon after acquiring HIV and maintained virologic suppression for at least 12 months. Participants received 10 oral doses of vesatolimod every two weeks, coupled with intravenous infusions of bNAbs VRC07-523LS and CAP256V2LS. On Day 35, they began an analytical treatment interruption (ATI), remaining off ART until Week 48 or until meeting ART restart criteria.
The results presented at CROI showed that 70% of participants met ART restart criteria, while 30% remained off ART through Week 48. Four participants remained off ART through Week 60, suggesting that the trial regimen alone is not sufficient for achieving a functional cure but provides valuable insights for future cure strategies. The study was generally well tolerated, with no treatment-related serious adverse events reported.
This pioneering effort demonstrates that complex HIV cure trials can be successfully conducted in resource-limited settings with strong community involvement. The lessons learned from this study will be instrumental in shaping future approaches to HIV cure research.
The Future of HIV Treatment and Cure Research
Gilead’s presentations at CROI 2025 highlight a bold vision for the future of HIV therapy, marked by innovations in both treatment and cure research. The success of long-acting regimens like LTZ could transform HIV management by reducing the burden of daily medication, offering patients more flexibility and improved adherence. Meanwhile, the pursuit of a cure remains a critical priority, with ongoing studies providing valuable insights into novel therapeutic strategies.
Despite the promising advances, there is currently no cure for HIV or AIDS. However, the relentless pursuit of innovative treatments and curative approaches brings hope to the millions of people living with HIV worldwide. Gilead remains at the forefront of this effort, driving scientific breakthroughs that have the potential to change the landscape of HIV care.
As research continues to evolve, Gilead’s commitment to collaboration, inclusivity, and scientific excellence will be key in advancing the fight against HIV. The data presented at CROI 2025 serve as a testament to the progress being made and the unwavering dedication to ending the HIV epidemic.
