Systemic inflammation in suppressed HIV similar after switch to 3-drug ART

In adults with HIV maintaining viral suppression, switching from dolutegravir plus lamivudine (DTG/3TC) to bictegravir plus emtricitabine and tenofovir alafenamide (BIC/FTC/TAF) does not improve inflammatory or metabolic outcomes over 96 weeks, according to study findings published in Clinical Infectious Diseases.

Researchers conducted a prospective, open-label, multicenter, phase IV randomized clinical trial (INSTINCT/GESIDA10918) across 19 hospitals in Spain to evaluate whether switching from a dual (DTG/3TC) to a triple (BIC/FTC/TAF) antiretroviral therapy regimen would modify systemic inflammation or metabolic parameters. Adults with HIV-1 infection who had plasma HIV-1 ribonucleic acid levels below 50 copies/mL for at least 48 weeks while receiving DTG/3TC were included in the analysis. They were randomly assigned 1:1 to either continue DTG/3TC (n=71) or switch to BIC/FTC/TAF (n=70) and were followed for 96 weeks with clinical and laboratory evaluations.

A total of 141 virologically suppressed adults were included in the final analysis, of whom the median (SD) age was 45 (11.1) years, 86.5% were men, and 78% were Caucasian. The median CD4⁺ count was 790 cells/µL, with a CD4⁺/CD8⁺ ratio of 1.1. The mean body weight was 77 kg, and the mean estimated glomerular filtration rate (eGFR) was 88 mL/min/1.73 m². Both treatment arms were well balanced in demographics, HIV history, and metabolic parameters.

The primary outcome was the change in plasma inflammatory biomarkers, including, interleukin (IL)-6, soluble CD14⁺ (sCD14⁺), sCD163⁺, high-sensitivity C-reactive protein (hsCRP), D-dimer, and the kynurenine/tryptophan (K/T) ratio, from baseline to week 96. Secondary outcomes included changes in CD4⁺ and CD8⁺ T-cell counts, CD4⁺/CD8⁺ ratio, weight, lipid profile, renal function, and virologic suppression rates.

At week 96, no significant between-group differences were observed for any biomarker. Annualized mean changes in sCD14⁺ increased by 2.6% with BIC/FTC/TAF and decreased by 2.9% with DTG/3TC (P =.391). Levels of IL-6, D-dimer, hsCRP, sCD163⁺, and the K/T ratio also remained stable and comparable. Both regimens maintained high rates of virologic suppression (>95%), with no significant differences in viral rebound.

Body weight increased modestly in both groups (+0.3% with BIC/FTC/TAF vs +0.2% with DTG/3TC), and approximately 20% of participants experienced more than 5% weight gain. Lipid parameters, including total cholesterol, low- and high-density lipoprotein, and triglycerides, changed minimally, with no significant between-group differences. Renal function, assessed by eGFR and serum creatinine, remained stable.

Adverse events (AEs) were mostly grade 1 through 2 and occurred at similar rates in both groups. Drug-related AEs were more common in the BIC/FTC/TAF arm (4.8% vs 0.4%), including transient insomnia, fatigue, and gastrointestinal discomfort, all of which were self-limited. No treatment-related serious AEs or discontinuations were reported.

Both regimens were safe, well tolerated, and maintained durable viral suppression through 96 weeks.

Study limitations include a small sample size due to the COVID-19 pandemic, a predominantly male and Caucasian population, the absence of cellular activation markers, and reduced follow-up for long-term inflammatory effects.

“These findings reinforce the notion that, in the setting of sustained virologic suppression, switching between contemporary ART regimens may have limited impact on residual inflammation and highlight the importance of identifying alternative strategies to address inflammation-driven comorbidities,” the researchers concluded.

Disclosure: This research was supported by Gilead Sciences and monitored by Fundación GeSIDA. Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

By Hibah Khaja, PharmD

References:

Serrano-Villar S, Martín-Pedraza L, Tiraboschi J, et al. 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). Clin Infect Dis. Published online October 10, 2025. doi:10.1093/cid/ciaf565.