Comparable Inflammatory and Metabolic Outcomes After Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide Versus Continuing Dolutegravir/Lamivudine in Virologically Suppressed Adults With HIV (INSTINCT/GESIDA10918 Study).

Abstract

Dual antiretroviral therapy (ART) with dolutegravir/lamivudine (DTG/3TC) is widely used in virologically suppressed individuals. However, data remain limited on potential differential effects of ART regimens on mid-term systemic inflammation and metabolic health. We evaluated whether switching from DTG/3TC to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) modifies systemic inflammation or metabolic parameters. INSTINCT was a phase IV, multicenter, open-label, randomized trial enrolling adults with HIV-1 on stable DTG/3TC and sustained viral suppression. Participants were randomized (1:1) to continue DTG/3TC or switch to BIC/FTC/TAF and followed for 96 weeks. Plasma biomarkers (sCD14, IL-6, sCD163, hsCRP, D-dimer, and kynurenine/tryptophan ratio) were measured at baseline, week 48, and week 96. Secondary outcomes included CD4⁺ and CD4/CD8 ratio, virological suppression, weight, lipid profile, and renal function. Longitudinal changes were analyzed using linear mixed-effects models. A total of 141 participants were randomized. Over 96 weeks, no significant between-group differences were observed in inflammatory biomarkers. CD4⁺ T-cell counts and CD4/CD8 ratio remained stable and comparable across arms. Weight changes were modest and similar; the proportion with ≥5% weight gain did not differ. No relevant differences were found in lipids, glucose, or eGFR. Virological suppression was maintained in >95% of participants. Adverse events were mild and balanced between groups. In virologically suppressed individuals, maintaining DTG/3TC or switching to BIC/FTC/TAF demonstrated equivalent profiles with respect to systemic inflammation, metabolic outcomes, and immunologic markers over 96 weeks.