ARTISTRY-1 supports switch from complex HIV regimen to a novel single pill

The phase II/III open-label ARTISTRY-1 trial shows that people living with HIV (PWH) may simplify their complex regimen (CR) by switching to a novel daily single-tablet regimen (STR) comprising bictegravir and lenacapavir (BIC+LEN).

“The trial population was older than other registrational HIV programmes, with a high prevalence of comorbidities, polypharmacy, and prior antiretroviral (ARV) resistance. Despite this, the BIC+LEN STR maintained high levels of virologic suppression (VS) and was noninferior to the CR at week 48,”  said presenting author Dr Chloe Orkin from Queen Mary University of London, UK, at CROI 2026.

The STR and CR arms had similar proportions of participants who achieved the primary endpoint of HIV-1 RNA ≥50 c/mL at week 48 (0.8 percent and 1.1 percent). The investigators used the US FDA Snapshot algorithm, with a noninferiority margin of 4 percent.

“All three participants with a detectable viral load were able to resuppress on the BIC+LEN STR or had low-level viraemia without the need to change the assigned treatment. There were no treatment-emergent resistant mutations with BIC+LEN,” Orkin said.

There was also no significant difference between groups in the percentage of participants with HIV-1 RNA <50 c/mL (96 percent and 93.5 percent), and CD4 cell count remained stable in both arms through week 48. [CROI 2026, abstract 181]

Other outcomes

Despite the higher incidence of drug-related adverse events (DRAEs) with the STR vs the CR (14.3 percent vs 1.6 percent), both groups had similarly low rates of grade ≥3 (0.5 percent vs 0 percent) and serious DRAEs (0.3 percent vs 0 percent). AEs leading to premature treatment discontinuation were infrequent (1.6 percent vs 0.5 percent).

The mean change in the HIV Treatment Satisfaction Questionnaire score from baseline was greater in the STR vs CR group at all timepoints (+7 vs 0; p<0.0001).

Switching from the CR to the STR also yielded greater median improvements from baseline in total cholesterol (TC; –15 vs +2; p<0.0001), LDL-C (–9 vs +2; p<0.0001), triglycerides (–15 vs +4; p=0.0008), and TC:HDL-C ratio (–0.3 vs 0; p<0.0001). “These changes were largely driven by removing the protease inhibitors,” Orkin said.

The BIC+LEN STR was generally well-tolerated and was associated with increased treatment satisfaction and improvements in fasting lipid parameters, Orkin noted.

Key to optimizing treatment

STRs revolutionized HIV treatment, improving adherence and clinical outcomes. However, PWH on CRs cannot take the available STRs due to viral resistance, intolerance, contraindications, or drug-drug interactions, noted Orkin.

“[These] may prevent many PWH from benefiting from guideline-recommended ARV STRs … They may experience a high pill burden and challenges with adherence and long-term HIV management, especially older individuals with multiple comorbidities and concomitant medications,” she said.

“Therefore, this is a clear unmet need, and a novel drug such as the BIC+LEN STR could optimize treatment for individuals with VS on CRs who are unable to use the available STRs,” Orkin continued.

In ARTISTRY-1, 557 PWH with VS on a stable CR (median age 60 years, 82 percent men) were randomized 2:1 to either switch to an oral STR of BIC 75 mg + LEN 50 mg (with a LEN loading dose of 600 mg on days 1 and 2) QD or continue their CR.

The most common comorbidity was dyslipidaemia (67.7 percent), followed by hypertension (50.3 percent) and diabetes (23.9 percent). Approximately 54 percent of participants had ≥2 comorbidities.

The median treatment duration was 28.3 years. Participants were taking a median of three ARV pills daily. Of note, about a quarter of participants were taking ≥5 pills daily. Eighty percent of participants were taking a CR due to a history of ARV resistance.

“CRs can pose a significant burden on people’s lives as seen in ARTISTRY-1, where participants were taking between two and 11 pills daily at baseline, with ~40 percent taking ARV therapy more than once a day,” said Orkin. “Finding new effective and convenient dosing with STRs is key to optimizing treatment, ensuring that more people can benefit from recent advances in medical research like bictegravir and lenacapavir.”

Sustained viral suppression through week 96

Participants who reached week 48 and completed the randomized treatment phase were invited to enrol in the extension phase and receive the STR (no LEN loading dose). Of the 52 PWH (median age 62 years, 86.5 percent men) originally randomized to the STR, 47 entered the extension phase. [CROI 2026, abstract 518]

At week 96, 95.7 percent of participants had HIV-1 RNA <50 c/mL (missing=excluded), and the median change in CD4 count from baseline was –6 cells/µL.

According to the investigators, both participants who had HIV-1 RNA ≥50 c/mL at week 96 had low-level viraemia and later resuppressed to HIV-1 RNA <50 c/mL without treatment modification.

Approximately 90 percent of participants had AEs (25 percent grade ≥3). Of the three participants who reported DRAEs, one prematurely discontinued treatment due to grade 3 worsening of vomiting. There were no serious DRAEs. One patient died due to coronary artery disease, but this was deemed unrelated to treatment.

These longer-term data demonstrate that, after almost 2 years of taking the STR, the participants still had low levels of HIV in their blood and few side effects.

Taken together, the results support the continued evaluation of the BIC+LEN STR to optimize treatment in PWH with VS on a CR.