Written By: Pharmacally Medical News Desk
Gilead Sciences has announced positive topline results from the Phase 3 ARTISTRY-2 trial evaluating its investigational single-tablet regimen combining Bictegravir and Lenacapavir for the treatment of HIV-1 infection. The study met its primary endpoint, demonstrating that the novel two-drug regimen was effective in maintaining viral suppression in adults living with HIV.
Eric Meissner, MD, PhD, Associate Professor and Director of HIV and Hepatitis Patient Care and Research, Medical University of South Carolina, said the ARTISTRY-2 results show that the investigational Bictegravir–Lenacapavir regimen delivers efficacy comparable to guideline-recommended HIV therapies, with the potential to expand treatment options for virologically suppressed adults.
Why this regimen matters
Current standard HIV treatment typically relies on three-drug combinations to achieve and sustain viral suppression. While these regimens are highly effective, long-term therapy can be associated with cumulative toxicity, drug–drug interactions, and adherence challenges. Gilead’s approach with Bictegravir plus Lenacapavir aims to simplify treatment while preserving high efficacy by combining two potent agents with complementary mechanisms of action into a single daily tablet.
If approved, this would represent one of the most advanced two-drug, single-tablet regimens designed for long-term HIV treatment.
About the ARTISTRY-2 trial
ARTISTRY-2 (NCT06333808) is a global, randomized, Phase 3 clinical trial conducted in virologically suppressed adults living with HIV-1. Participants were switched from a stable antiretroviral therapy regimen BIKTARVY (Bictegravir 50 mg/Emtricitabine 200 mg/Tenofovir alafenamide 25 mg tablets, B/F/TAF) to the investigational Bictegravir 75 mg/Lenacapavir 50 mg (BIC/LEN) single-tablet regimen or continued on their existing standard-of-care therapy.
The primary endpoint assessed the proportion of participants who maintained viral suppression, typically defined as HIV-1 RNA levels below 50 copies/mL, at a prespecified time point. The trial met this endpoint, showing that the investigational regimen was non-inferior to established HIV treatments.
Efficacy outcomes
According to Gilead, patients receiving the Bictegravir–Lenacapavir regimen maintained high rates of viral suppression comparable to those who remained on standard therapy. These findings support the potential of this two-drug approach as a durable maintenance regimen for people living with HIV who are already virologically controlled.
Key secondary endpoints included the proportion of participants with virologic failure, changes in CD4+ T-cell counts, safety and tolerability outcomes, and treatment discontinuations due to adverse events. Rates of virologic failure were low and comparable between the investigational regimen and the standard-of-care arm, indicating sustained viral control after switching therapy.
Immunologic outcomes remained stable across both treatment groups, with no clinically meaningful declines in CD4+ T-cell counts observed during the study period. This finding is consistent with effective long-term viral suppression.
From a safety perspective, secondary analyses showed similar overall adverse event rates between groups. Most reported events were mild to moderate in severity, and serious adverse events were infrequent. Discontinuations related to adverse events occurred at low rates and were comparable to those seen with established antiretroviral regimens.
These results are consistent with the earlier Phase 3 ARTISTRY-1 trial, which also showed that switching virologically suppressed adults to the Bictegravir–Lenacapavir regimen maintained viral suppression with a favorable safety profile.
Understanding the drugs
Bictegravir is an integrase strand transfer inhibitor (INSTI) widely used in first-line HIV therapy and known for its strong antiviral activity and high barrier to resistance.
Lenacapavir is a first-in-class HIV capsid inhibitor with activity at multiple stages of the viral life cycle. It has already gained attention for its role in heavily treatment-experienced patients and for its long-acting potential.
Together, these agents target HIV through distinct and complementary pathways, which may help sustain viral suppression with fewer drugs.
Jared Baeten, MD, PhD, Senior Vice President, Clinical Development and Virology Therapeutic Area Head at Gilead Sciences, said the data support BIC/LEN as a promising additional treatment option for adults with HIV, and the company plans to present full Phase 3 results and submit the program for regulatory review.
Additional analyses, including longer-term outcomes and subgroup data, may be presented at upcoming medical conferences.
The ARTISTRY-2 Phase 3 trial marks an important milestone in HIV drug development. By meeting its primary endpoint, Gilead’s investigational Bictegravir–Lenacapavir single-tablet regimen demonstrates the potential to redefine maintenance therapy for people living with HIV, balancing treatment simplification with sustained viral control.
References
Gilead’s Investigational Single-Tablet Regimen of Bictegravir and Lenacapavir for HIV Treatment Meets Primary Endpoint in Phase 3 ARTISTRY-2 Trial, 15 October 2025, https://investors.gilead.com/news/news-details/2025/Gileads-Investigational-Single-Tablet-Regimen-of-Bictegravir-and-Lenacapavir-for-HIV-Treatment-Meets-Primary-Endpoint-in-Phase-3-ARTISTRY-2-Trial/default.aspx
Study to Compare Bictegravir/Lenacapavir Versus Current Therapy in People With HIV-1 Who Are Successfully Treated with Biktarvy (ARTISTRY-2), ClinicalTrials.gov ID NCT06333808, https://clinicaltrials.gov/study/NCT06333808
Gilead’s Investigational Single-Tablet Regimen of Bictegravir and Lenacapavir for HIV-1 Treatment Meets Primary Endpoint in Phase 3 ARTISTRY-1 Trial, Pharmacally, 15 November 2025, https://pharmacally.com/gileads-investigational-single-tablet-regimen-of-bictegravir-and-lenacapavir-for-hiv-1-treatment-meets-primary-endpoint-in-phase-3-artistry-1-trial/