Gilead Sciences recently announced positive topline results from its Phase 3 ARTISTRY-1 trial, which evaluated an investigational single-tablet regimen combining Bictegravir and Lenacapavir for the treatment of HIV-1. This novel once-daily therapy demonstrated statistical non-inferiority to existing complex multi-tablet antiretroviral regimens in Virologically suppressed adults with HIV-1. The primary endpoint was met, confirming that the single-tablet regimen effectively maintained viral suppression at Week 48. Gilead, the marketing authorization holder (MAH), plans to submit these Phase 3 data for regulatory approvals and further scientific presentation.

The ARTISTRY-1 trial (ClinicalTrials.gov identifier NCT05502341) is a multicenter, open-label, Phase 2/3 study designed to assess the efficacy and safety of switching Virologically suppressed adults from complex multi-tablet regimens to a fixed-dose single tablet containing Bictegravir 75 mg and Lenacapavir 50 mg. Participants were randomized 2:1 to either switch to the investigational single-tablet regimen or continue their existing complex regimens. The primary efficacy endpoint was the proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48 as defined by the FDA snapshot algorithm. Key secondary endpoints included virologic suppression rates (HIV RNA <50 copies/mL), change in CD4+ cell count, and treatment-emergent adverse events (TEAEs). Results indicated that the investigational Bictegravir/Lenacapavir regimen maintained viral suppression comparable to baseline therapies, with high rates of virologic control maintained at Week 48. The regimen was generally well tolerated, and no new significant safety signals were observed, offering a convenient once-daily oral therapy option for adults living with HIV-1 on complex regimens.​

Regarding safety, the Bictegravir/Lenacapavir combination demonstrated a favorable profile in the ARTISTRY-1 trial. Treatment-emergent adverse events were consistent with expectations based on the individual drugs’ known profiles. No new safety concerns or significant warnings emerged, and the regimen was well tolerated among the diverse participant population, which included older adults and those with comorbidities such as chronic kidney disease. This safety profile supports its potential as a simplified alternative to reduce pill burden and complexity in HIV treatment.​

Bictegravir is an HIV-1 integrase strand transfer inhibitor (INSTI) that works by specifically targeting the integrase enzyme, which is crucial for HIV replication. The integrase enzyme catalyzes the insertion of the viral DNA into the host cell’s genome, a necessary step for the virus to replicate and propagate. Bictegravir binds to the active site of this enzyme and blocks the strand transfer step, which is the integration of HIV viral DNA into the host DNA genome. Lenacapavir, the HIV-1 capsid inhibitor, is already approved by the FDA under the brand name Yeztugo® as a twice-yearly injectable option for HIV pre-exposure prophylaxis (PrEP) in adults and adolescents weighing at least 35 kg. The fixed-dose combination is administered orally once daily, with Bictegravir dosed at 75 mg and Lenacapavir at 50 mg per tablet. Both drugs are under clinical development to offer potent antiviral activity with convenient dosing

Lenacapavir is also a recognized as best medical invention and best pharma product by TIME magazine and Prix Galien USA in 2025.

Chloe Orkin, MBE, Clinical Professor at Queen Mary University of London, stated that developing effective, convenient regimens is crucial to address the unmet HIV treatment gap and that the ARTISTRY-1 results show how the Bictegravir and Lenacapavir combination maintains viral suppression in people who otherwise face complex multi-tablet regimens, especially those with long-term HIV and aging comorbidities. Jared Baeten, MD, PhD, Senior VP at Gilead Sciences, emphasized that reducing pill burden with innovative single-tablet regimens like this is key to modernizing HIV treatment, improving adherence, and sustaining viral suppression for better health outcomes.