In the phase 3 ARTISTRY-2 trial, switching people with virologically suppressed HIV from B/F/TAF to a once-daily bictegravir/lenacapavir single-tablet regimen maintained viral suppression through week 48 with comparable safety and tolerability.
Single-tablet regimens (STRs) have reshaped HIV care by simplifying treatment and supporting long-term adherence, yet there remains a need for new options with novel mechanisms of action to address the diverse and evolving needs of people with HIV. A new investigational STR combining bictegravir (an integrase strand transfer inhibitor) with lenacapavir (a first-in-class capsid inhibitor) is being evaluated as a potential next-generation option for individuals who already have virological suppression.
ARTISTRY-2 is a double-blind, multicenter phase 3 study that enrolled adults with HIV who had maintained virologic suppression on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for at least 6 months prior to screening. Participants were randomly assigned 2:1 to switch to once-daily oral bictegravir/lenacapavir (75 mg/50 mg) or to continue B/F/TAF. The primary end point assessed the proportion of participants with HIV-1 RNA of 50 copies/mL or more at week 48 using the US Food and Drug Administration Snapshot algorithm, with a noninferiority margin of 4%.
A total of 574 participants were randomly assigned and treated, with 383 switching to bictegravir/lenacapavir and 191 continuing B/F/TAF. The study population had a median age of 49 years and included 19% women, with 27% Black and 27% Hispanic or Latino participants.
Switching to bictegravir/lenacapavir maintained viral suppression through 48 weeks at rates comparable to continued B/F/TAF.
Adverse events, drug-related events, and discontinuation rates were similar between the investigational regimen and standard of care.
The combination of an integrase inhibitor with a capsid inhibitor introduces a novel STR option that could broaden switching strategies for people with virologically suppressed HIV.
At week 48, HIV-1 RNA of 50 copies/mL or more occurred in 1.3% of participants in the bictegravir/lenacapavir group and 1.0% in the B/F/TAF group, meeting the predefined criteria for noninferiority. Virologic suppression below 50 copies/mL was maintained in more than 90% of participants in both arms.
Immunologic outcomes were similar between groups, with small median changes in CD4 cell counts from baseline at week 48. Safety findings were also comparable, with overall adverse event rates of approximately 75% in both groups, the majority of which were mild or moderate. Drug-related adverse events were infrequent, serious events were rare, and discontinuations due to adverse events were low and identical between arms.
