Infectious Disease
RCT
● RCT
Bictegravir-lenacapavir single-tablet regimen non-inferior to complex regimens for HIV-1 suppression at 48 weeks
Lancet (London, England)
Published March 30, 2026
Orkin Chloe, Ruane Peter J, Hedgcock Malcolm, Gaultier Cyril, Losso Marcelo H, Trottier Benoit, Lutz…
PubMed ↗
NCT05502341 ↗
DOI ↗
This phase 3, open-label, randomized controlled trial enrolled 557 virologically suppressed adults with HIV-1 who were on complex regimens (median 3 pills/day) across hospitals and clinics in 15 countries. Participants were randomized to switch to once-daily oral bictegravir-lenacapavir 75 mg/50 mg single-tablet regimen (n=371) or continue their complex regimen (n=186) for 48 weeks.
The primary outcome was the proportion with HIV-1 RNA ≥50 copies/mL at week 48 using the FDA Snapshot algorithm. The bictegravir-lenacapavir regimen was non-inferior to continued complex regimens, with 1% (3/371) versus 1% (2/186) meeting this endpoint (difference -0.3%, 95.002% CI -2.3 to 1.8, non-inferiority margin 4%). No treatment-emergent resistance was reported.
Safety and tolerability profiles were similar between groups. Discontinuations due to adverse events occurred in 2% (6/371) of the bictegravir-lenacapavir group and 1% (1/186) of the complex regimen group. Five deaths occurred in the intervention group, none deemed drug-related by investigators. Key limitations include the open-label design and lack of long-term safety data beyond 48 weeks. The study was funded by Gilead Sciences.
Imagine taking multiple pills every day for decades to keep a chronic condition in check. For many people with HIV, that's been the reality. A new study asked if a simpler, single daily pill could work just as well for those who have already achieved viral suppression on more complex regimens.
The trial involved 557 adults, mostly in their 60s who had been on HIV treatment for a median of 28 years. They were either switched to a new single-tablet regimen called bictegravir-lenacapavir or stayed on their current multi-pill treatment. After 48 weeks, both groups had the same result: only 1% of people in each group saw their viral load rise above a detectable level. The new pill was just as effective at keeping the virus suppressed. Rates of side effects were similar between the two groups.
It's important to note that the study was open-label, meaning both participants and doctors knew which treatment they were on, which can sometimes influence how people report their experiences. While the results are promising for simplifying treatment, the study only followed people for 48 weeks. We don't yet know the long-term safety profile of this new combination. Five people in the single-pill group died during the study, though none of the deaths were judged to be related to the study drug.
What this means for you: A single daily pill kept HIV suppressed as well as complex multi-pill regimens for one year.
View Original Abstract ↓
BACKGROUND: Single-tablet regimens (STRs) revolutionised HIV-1 treatment, improving adherence and clinical outcomes; however, many people cannot take these due to resistance, contraindications, or drug-drug interactions, instead relying on complex multi-tablet regimens. Novel STRs are therefore needed. We aimed to evaluate the efficacy and safety of a novel STR, bictegravir-lenacapavir, in people with HIV-1.
METHODS: ARTISTRY-1 was a randomised, open-label, active-controlled, non-inferiority phase 3 trial conducted at hospitals and clinics across 15 countries that enrolled people with HIV-1 with virological suppression on complex regimens. Participants were randomly assigned (using interactive technology, 2:1, stratified by geographical region) to switch to once-daily oral bictegravir-lenacapavir 75 mg/50 mg STR or continued complex regimen. The primary outcome was the proportion of participants with an HIV-1 RNA viral load of 50 copies per mL or higher at week 48 (US Food and Drug Administration Snapshot algorithm), assessed in all randomly assigned participants who received any dose of assigned treatment. This trial (active; enrolment complete) was registered with ClinicalTrials.gov (NCT05502341).
FINDINGS: Between Jan 29 and Sept 26, 2024, 729 participants were screened; 557 were randomly assigned and treated (bictegravir-lenacapavir n=371; complex regimen n=186). At baseline, median age was 60 years (range 22-84), HIV treatment duration was 28 years (IQR 22-32); participants were taking a median of three antiretroviral pills per day (range 2-11). At week 48, an HIV-1 RNA viral load of 50 copies per mL or higher was observed in three (1%) participants receiving bictegravir-lenacapavir and two (1%) receiving a complex regimen (difference -0·3%; 95·002% CI -2·3 to 1·8), meeting the non-inferiority margin of 4%. No resistance emerged. Adverse event rates were similar between groups. Six (2%) participants discontinued bictegravir-lenacapavir and one (1%) discontinued their complex regimen due to adverse events. There were five deaths in the bictegravir-lenacapavir group, none of which were deemed related to study drug. Participants reported increased treatment satisfaction after switching to bictegravir-lenacapavir.
INTERPRETATION: Bictegravir-lenacapavir STR demonstrated non-inferior efficacy to complex regimens, with a similar safety profile and increased treatment satisfaction. Bictegravir-lenacapavir offers new opportunities for HIV-1 treatment optimisation for people taking complex regimens.
FUNDING: Gilead Sciences.
