Bictegravir/Lenacapavir Well Tolerated in HIV With Comorbidities

Switching to the once-daily single-tablet regimen of bictegravir and lenacapavir (BIC/LEN; Gilead Sciences) produced adverse event rates similar to comparator regimens across people with HIV with dyslipidemia, hypertension, or diabetes.^1,2 Metabolic outcomes, including lipids, glucose, and weight, remained stable through 48 weeks. Moti Ramgopal, MD, of Midway Immunology and Research Center in Fort Pierce, Florida, presented subanalyses of the phase 3 ARTISTRY-1 and ARTISTRY-2 trials at IDWeek 2026, held October 21-24 in Washington, DC.^1,2

Comorbidities are more common among people with HIV than in the general population, and prevalence rises with age.² BIC/LEN combines bictegravir, an integrase strand transfer inhibitor, with lenacapavir, a first-in-class capsid inhibitor with no documented de novo resistance in the absence of prior exposure.¹

ARTISTRY-1 Safety Outcomes by Comorbidity in People With HIV on Complex Regimens

ARTISTRY-1 (NCT05502341) randomized virologically suppressed adults on complex antiretroviral regimens 2:1 to switch to BIC/LEN (n = 371) or continue their regimen (n = 186).¹ Median age was 60 years in both groups, and participants had received HIV treatment for a median of 28 years. In the BIC/LEN group, the median regimen involved 3 pills per day, 41% dosed twice daily, and 75% took a protease inhibitor.¹

At baseline, 66% of the BIC/LEN group had dyslipidemia, 51% had hypertension, and 25% had diabetes, and 64% took at least 2 select concomitant medications.¹ The investigators noted bictegravir inhibits OCT2 and MATE1 in vitro and lenacapavir moderately inhibits CYP3A and P-glycoprotein, with drug interaction guidance provided to clinicians.¹

Through week 48, adverse events occurred in 82% of the BIC/LEN group vs 84% of the complex regimen group, and grade 3 or higher events occurred in 14% of each.¹ Within comorbidity groups, adverse event rates were 81% vs 88% among those with dyslipidemia, 82% vs 87% with hypertension, and 79% vs 95% with diabetes. Adverse events leading to BIC/LEN discontinuation occurred in 2% or fewer of patients.¹

"People with HIV have a high comorbidity and concomitant medication burden," Ramgopal said in a recorded presentation accompanying the posters. "This study has enrolled the oldest known population of people with HIV in a registrational trial for antiretrovirals, and most of the participants had comorbidities they were taking medications for."

ARTISTRY-2 Metabolic Outcomes After Switching From B/F/TAF to BIC/LEN

ARTISTRY-2 (NCT06333808) randomized 574 virologically suppressed adults 2:1 to switch to BIC/LEN (n = 383) or remain on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF; Biktarvy; Gilead Sciences) (n = 191) in double-blind fashion.² At baseline, 41% had dyslipidemia, 36% had hypertension, 17% had hyperglycemia or diabetes, and 6% had chronic kidney disease.² Median age was 47 years with BIC/LEN and 51 years with B/F/TAF, and 30% of participants had at least 2 of these comorbidities.²

At week 48, median change in fasting LDL cholesterol was 1 mg/dL with BIC/LEN vs 3 mg/dL with B/F/TAF, and median change in fasting total cholesterol was 0 vs 1 mg/dL.² Median weight change was −0.2 kg vs 0.0 kg, and median hemoglobin A1c rose 0.1% in both groups. Among patients with hyperglycemia or diabetes, hemoglobin A1c changed 0.1% vs 0.0%.²

Use of lipid-lowering, antihypertensive, antidiabetic, and GLP-1 receptor agonist medications remained stable and comparable between groups over 48 weeks.² Rates of adverse events were generally similar between groups within each baseline comorbidity group, with very few discontinuations.² Among participants with dyslipidemia, median LDL cholesterol change was −1 mg/dL with BIC/LEN vs 1 mg/dL with B/F/TAF.²

"Overall, these results continue to support BIC/LEN single tablet regimen as a treatment option for people with HIV, including those who are older, who have comorbidities, and are taking concomitant medications," Ramgopal said.

References

1. Ramgopal M, Losso MH, Trottier B, et al. Safety analysis of BIC/LEN single-tablet regimen in people with HIV who have comorbidities of dyslipidemia, hypertension, and diabetes mellitus from phase 3 of ARTISTRY-1. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC. Poster P-24.

2. Ramgopal M, Hung C-C, Mills AM, et al. Metabolic and safety outcomes with BIC/LEN single-tablet regimen in people with HIV and comorbidities in ARTISTRY-2. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC. Poster P-23.