Switching from complex HIV regimens to bictegravir–lenacapavir STR: Phase 3 ARTISTRY-1 results

Complex antiretroviral regimens often involve multiple tablets taken several times a day, sometimes with food and occasionally with auxiliary booster agents to maintain virologic suppression. The complexity of these regimens can lead to high pill burden, inconvenient dosing schedules and multiple drug–drug interactions, and represents a significant clinical challenge for the long-term treatment of HIV.

Q. What was the rationale for evaluating a bictegravir-lenacapavir STR in ARTISTRY-1, and could you briefly outline the study design and primary endpoints?

Finding new effective STRs is key to optimising treatment and ensuring that more people can benefit from recent advances in medical research, such as bictegravir and lenacapavir. The significant burden of complex treatment regimens on the lives of people with HIV was apparent in the ARTISTRY-1 trial, where participants were taking between two and eleven pills daily at baseline, and 40% were taking antiretroviral therapies more than once a day.

ARTISTRY-1 compared the safety and efficacy of an investigational single-tablet combination regimen of bictegravir and lenacapavir (BIC/LEN) with complex, multi-tablet antiretroviral regimens in adults with HIV who were virologically suppressed. Trial participants were randomized 2:1 to receive BIC/LEN or continue their stable baseline complex antiretroviral regimen. The primary endpoint was the proportion of patients with HIV-1 RNA ≥50 copies/mL at Week 48, as determined by the US Food and Drug Administration (FDA)-defined snapshot algorithm.

Q. What were the key findings from the study, and how should clinicians interpret these findings when considering regimen simplification in virologically suppressed patients?

Bictegravir and lenacapavir in combination are investigational and are not approved for clinical use anywhere globally. The safety and efficacy of this combination have not been established by the US FDA.

The data presented at CROI and simultaneously published in The Lancet support the potential of the BIC/LEN regimen to optimize treatment for people with HIV who are virologically suppressed on complex multi-tablet regimens, expanding treatment options and patient choice.

In ARTISTRY-1, BIC/LEN was shown to be non-inferior to complex multi-tablet regimens in maintaining virologic suppression, and the combination was generally well tolerated with no significant or new safety concerns identified.

• After 48 weeks of treatment, 0.8% of participants receiving BIC/LEN had HIV-1 RNA levels ≥50 copies/mL compared with 1.1% who remained on their complex antiretroviral regimen.
• CD4 cell counts remained stable in both treatment groups.
• The switch from complex multi-tablet regimens to BIC/LEN was also associated with broader benefits at Week 48, including improvements in fasting lipid parameters and patient-reported treatment satisfaction.

Q. Following these results, how should clinicians balance tolerability, safety and patient preference when switching stable patients from complex regimens to a novel STR?

Advances in antiretroviral therapy and a better understanding of drug resistance have made it possible to consider switching people with HIV from one effective regimen to another. Clinicians must keep several key principles in mind to maintain viral suppression while addressing concerns with the current regimen.

It is essential that antiretroviral regimens offer efficacy alongside a tolerable safety profile and meet the unmet needs, expectations and preferences of people with HIV.

Q. Treatment satisfaction improved significantly among participants who switched to BIC/LEN. In your view, how should patient-reported outcomes influence treatment decisions in long-term HIV management, particularly for ageing populations with multimorbidity?

Patient-reported outcomes are an important component of the ARTISTRY-1 trial, particularly in relation to adherence, patient preference and treatment satisfaction. For people with HIV, treatment needs can change over time, especially with age, when adults with HIV may develop chronic medical conditions that complicate treatment, increase pill burden and heighten the risk of drug–drug interactions.

As HIV treatment increasingly spans decades, durable treatment strategies are needed that both clinicians and people with HIV can rely on over time.

Read Q&A with Dr Eric Meissner on the Phase 3 ARTISTRY-2 findings

Q. Beyond this presentation, what were the most important therapeutic and treatment updates presented at CROI 2026?

Exciting HIV treatment research data were presented involving a range of drugs from different classes, including third-generation long-acting integrase inhibitors and novel long-acting capsid inhibitors.

In HIV prevention research, very encouraging data were presented on the roll-out of cabotegravir for pre-exposure prophylaxis (PrEP), as well as updated results from the PURPOSE-1 and PURPOSE-2 studies evaluating lenacapavir as PrEP. Across these studies, only three additional HIV acquisitions were reported, with similar safety profiles and strong persistence.