TOPLINE:

Among treatment-naive patients with advanced HIV disease, bictegravir/emtricitabine/tenofovir alafenamide was noninferior to darunavir/cobicistat/emtricitabine/tenofovir alafenamide over 48 weeks and resulted in faster viral suppression and fewer adverse events.

METHODOLOGY:

• Researchers conducted a randomized trial in seven European countries to compare the efficacy and safety of an integrase inhibitor-containing antiretroviral regimen vs a boosted protease inhibitor-containing antiretroviral regimen in patients with advanced HIV disease.
• Overall, 442 treatment-naive patients (median age, 43 years; 81% men; median CD4 count, 41 cells per µL) were treated for 48 weeks with either once-daily bictegravir/emtricitabine/tenofovir alafenamide (n = 220; integrase inhibitor group) or once-daily darunavir/cobicistat/emtricitabine/tenofovir alafenamide (n = 222; boosted protease inhibitor group).
• The primary composite outcome was the first occurrence of virologic failure or a clinically relevant adverse outcome over 48 weeks. Virologic failure was defined as having an insufficient virologic response at week 12, more than 50 HIV-1 RNA copies/mL at week 48, or a confirmed viral rebound.
• Key secondary outcomes included immunologic and virologic responses, tolerability, and therapy discontinuation.
• Noninferiority was concluded if the upper bound of the 95% CI of the adjusted hazard ratio (aHR) was < 1.606.

TAKEAWAY:

• In the modified intention-to-treat analysis, which analyzed patients as assigned who received at least one dose of the drug, the primary composite outcome occurred in 22% of patients on the integrase inhibitor regimen vs 32% of those on the boosted protease inhibitor regimen at week 48 (aHR, 0.70; P = .052), meeting the noninferiority criteria.
• Results were similar in the per-protocol analysis, which focused on patients who remained on their assigned regimen and censored outcomes after treatment discontinuation (aHR, 0.69; P = .051).
• A higher proportion of patients in the integrase inhibitor group than in the boosted protease inhibitor group achieved an HIV viral load of < 50 copies/mL at weeks 4, 8, and 12 (P < .0001 for all); no significant difference in CD4 cell counts was seen between treatment groups from baseline to week 48 (P = .085).
• Drug-related adverse events of grade 2 or higher occurred in 7% of patients in the integrase inhibitor group vs 14% of those in the protease inhibitor group (P = .043); rates of serious adverse events and treatment discontinuation were similar between groups.

IN PRACTICE:

“These findings support high-barrier integrase inhibitor-based regimens as preferred evidence-based first-line therapy in advanced HIV disease, in line with global antiretroviral therapy trends,” the authors wrote.

SOURCE:

This study was led by Georg M.N. Behrens, MD, Hannover Medical School, Hanover, Germany. It was published online on December 01, 2025, in The Lancet Infectious Diseases.

LIMITATIONS:

The open-label design may have introduced bias in reporting adverse events. The 48-week follow-up duration was short, limiting the ability to draw long-term conclusions. The trial excluded patients with tuberculosis or cryptococcal meningitis, limiting generalizability to these patients.

DISCLOSURES:

This study was funded by Gilead Sciences and Janssen Pharmaceuticals. Several authors reported receiving grants, contracts, consulting fees, honoraria, or advisory-board payments from the study funders and other pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.