Single-tablet regimen shows non-inferior efficacy and strong safety in virologically suppressed adults with HIV-1.
Gilead Sciences, Inc. (NASDAQ: GILD) has announced encouraging topline results from its Phase 3 ARTISTRY-1 clinical trial, marking an important milestone in the company’s ongoing efforts to simplify HIV treatment for people who remain dependent on complex, multi-tablet antiretroviral regimens. The ARTISTRY-1 study examined the outcomes of adults living with HIV-1 who were already virologically suppressed but were managing their condition using multidrug, multi-pill combinations—a burden that often complicates long-term adherence. In this trial, participants transitioned from their existing multi-tablet therapies to Gilead’s investigational once-daily single-tablet regimen combining bictegravir 75 mg and lenacapavir 50 mg (BIC/LEN). According to the company, this experimental fixed-dose regimen successfully met its primary endpoint and demonstrated non-inferior efficacy compared with baseline treatments.
A Major Step Toward Simplifying Treatment for Complex HIV Regimens
ARTISTRY-1 was designed as an open-label, multicenter Phase 2/3 clinical trial to evaluate whether a simplified single-tablet regimen could provide virologically suppressed individuals the same level of control as multi-pill therapies. The study enrolled adults who were stable on their existing regimens but whose treatment required two or more tablets daily—sometimes up to 11 tablets per day—due to factors such as pre-existing drug resistance, tolerability issues, or complex drug–drug interactions. These patients often cannot switch to the guideline-recommended standard single-tablet regimens (STRs) available today. For them, treatment complexity presents a real challenge, contributing to difficulties with adherence, reduced convenience, and potential impacts on overall quality of life.
In this context, Gilead’s investigational combination of bictegravir, an integrase strand transfer inhibitor (INSTI), and lenacapavir, a first-in-class capsid inhibitor, represents a potentially significant advance. By merging the strengths of these two compounds into a once-daily single pill, the BIC/LEN regimen seeks to bring the simplicity of STRs to a patient population that has historically been unable to benefit from them.
Primary Endpoint Achieved: Non-Inferiority Demonstrated
In ARTISTRY-1, the primary efficacy endpoint was the proportion of participants with HIV-1 RNA levels of 50 copies/mL or higher at Week 48, assessed using the U.S. FDA-defined snapshot algorithm. Achieving this benchmark is crucial for demonstrating that patients remain virologically suppressed and that switching therapies does not compromise viral control. Gilead reported that BIC/LEN met the success criterion for non-inferiority compared to participants’ baseline multi-tablet treatment regimens.
The safety profile of the investigational regimen was also encouraging. BIC/LEN was generally well tolerated across the study population, with no new or unexpected safety concerns. This is particularly meaningful given the complexity of medical backgrounds among participants—many of whom have lived with HIV for decades and often manage multiple comorbidities alongside their antiviral treatment.
Expert Perspectives: Addressing an Unmet Need
Chloe Orkin, MBE, Clinical Professor of Infection and Inequities at Queen Mary University of London and a leading HIV researcher, emphasized the importance of advancing simpler treatment options for patients who have historically been overlooked by mainstream regimen innovations. According to Orkin, many of these individuals rely on complex therapeutic combinations due to resistance or prior treatment exposures and are therefore unable to switch to standard STRs. For them, a new simplified regimen could significantly improve daily life.
“Developing new effective, convenient regimens for those left behind by advances in medical research is necessary to close the unmet HIV treatment gap,” Orkin said. She described the ARTISTRY-1 results as particularly meaningful because they demonstrate that a daily single-tablet combination of bictegravir and lenacapavir can maintain viral suppression in individuals who would otherwise be dependent on multi-pill regimens. Orkin also noted that this group tends to include older adults with additional medical conditions, making the complexity of current treatments even more challenging.
Background and Design of the ARTISTRY-1 Trial
The ARTISTRY-1 study (NCT05502341) included adults who were virologically suppressed at baseline and receiving multi-tablet antiretroviral therapy. Many were taking multi-tablet regimens because they had developed drug resistance earlier in their treatment history or had other clinical factors necessitating more tailored therapy. At baseline, participants were taking anywhere from 2 to 11 pills daily for their HIV treatment. Notably, approximately 40% of the study population required dosing more than once per day.
The study’s design involved a 2:1 randomization ratio, with two-thirds of participants switching to the BIC/LEN single-tablet regimen and one-third continuing their existing complex regimens. Beyond the primary endpoint at Week 48, the trial also assessed several important secondary endpoints including:
- the proportion of participants achieving virologic suppression (HIV-1 RNA <50 copies/mL)
- changes in CD4 cell counts from baseline
- the incidence of treatment-emergent adverse events (TEAEs)
Collectively, these measures offer a broader view of how well the investigational single-tablet regimen performs in real-world clinical dimensions such as immunologic recovery, tolerability, and overall stability.
Gilead’s Continued Focus on Simplifying HIV Treatment
Jared Baeten, MD, PhD, Senior Vice President of Clinical Development and Virology Therapeutic Area Head at Gilead Sciences, highlighted the company’s long-standing commitment to advancing HIV therapy toward greater simplicity and patient-centered design. Reflecting on Gilead’s history of innovation—which includes developing the first single-tablet HIV regimen in 2006—Baeten positioned BIC/LEN as the next chapter in meeting the diverse needs of people living with HIV.
“People living with HIV who are on complex antiretroviral treatment regimens may experience pill burden, adherence challenges and difficulties with the long-term management of HIV,” Baeten explained. He described the investigational regimen as part of Gilead’s efforts to modernize HIV treatment by offering simpler, effective solutions that support sustained viral suppression over time. The goal is to reduce the complexity of multi-tablet regimens so that more patients can benefit from a streamlined, easy-to-follow daily therapy.
Next Steps: ARTISTRY-2 and Further Clinical Evaluation
The promising results from ARTISTRY-1 are not the end of Gilead’s clinical exploration of the BIC/LEN combination. A second Phase 3 study, ARTISTRY-2 (NCT06333808), is currently underway. This double-blind trial is evaluating the safety and efficacy of switching from Gilead’s widely used BIKTARVY® (bictegravir/emtricitabine/tenofovir alafenamide) to the fixed-dose bictegravir 75 mg/lenacapavir 50 mg combination in virologically suppressed individuals.
The ARTISTRY-2 trial aims to address a broader population of people living with HIV who may benefit from this new regimen. Gilead anticipates releasing topline results from ARTISTRY-2’s primary endpoint analysis before the end of the year, which will help further inform regulatory submissions and potential approval pathways.
Regulatory Plans and Development Status
Gilead has stated its intention to submit the Phase 3 data from the ARTISTRY program to global regulatory authorities. In addition, the company plans to present detailed results from ARTISTRY-1 at an upcoming scientific congress. These steps are important in positioning the investigational BIC/LEN regimen for potential review as a future treatment option.
It is important to note that the combination of bictegravir and lenacapavir in a single-tablet regimen remains investigational and has not been approved by any regulatory authority worldwide. The safety and efficacy of the combination have not been fully established, and further clinical evaluation is required.
Broader Context: The Ongoing Challenge of HIV Treatment
Despite incredible advances in the field, HIV remains an incurable disease. Current antiretroviral therapies (ART) allow individuals living with HIV to achieve long-term viral suppression and lead healthy, productive lives. However, treatment can still be burdensome for certain populations—particularly those with complex medical histories, multi-drug resistance, or challenges accessing simplified, modern regimens.
The development of new therapeutic options such as BIC/LEN is part of a broader global effort to address unmet needs, improve long-term outcomes, support adherence, and enhance quality of life for people living with HIV. Simplifying treatment without compromising efficacy remains a priority for researchers, clinicians, and public health organizations worldwide.
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