Cardiometabolic Parameters 3 Years After Switch to Dolutegravir/Lamivudine vs Maintenance of Tenofovir Alafenamide-Based Regimens

Abstract

Background: Cardiometabolic outcomes were investigated 3 years after switching to the 2-drug regimen dolutegravir/lamivudine (DTG/3TC) vs continuing 3-/4-drug tenofovir alafenamide (TAF)-based regimens in a multicenter phase 3 noninferiority study based on an open-label randomized design. Method: Adults with virologically suppressed HIV-1 switched to once-daily DTG/3TC (n = 369) or continued TAF-based regimens (n = 372). Cardiometabolic health parameters were assessed through week 144 via mixed-model repeated measures or logistic regression analyses, adjusting for baseline variables. Results: At week 144, 13% (42/316) of the DTG/3TC group and 12% (37/303) of the TAF-based regimen group had ≥10% weight gain from baseline (adjusted odds ratio, 1.11; 95% CI,. 68-1.80). Adjusted change from baseline in serum leptin, a surrogate marker of adiposity, was similar between groups (treatment ratio, 1.00; 95% CI,. 89-1.13). The lipid profile generally favored DTG/3TC in the baseline boosted subgroup. Adjusted odds revealed no clinically meaningful differences between groups: homeostatic model assessment of insulin resistance ≥2 (adjusted odds ratio, 0.79; 95% CI,. 50-1.26), metabolic syndrome (International Diabetes Federation criteria, 0.99;. 59-1.68), hepatic fibrosis (fibrosis-4 index score ≥1.45, 1.39;. 63-3.06), and coronary artery disease risk (Framingham risk score ≥10%, 0.92;. 56-1.49). Baseline variables and characteristics associated with odds of each cardiometabolic parameter outcome were consistent with known risk factors, including age, sex, race, and some disease characteristics. Conclusions: Cardiometabolic health 3 years after switching to DTG/3TC was comparable to that for individuals continuing TAF-based regimens, further supporting DTG/3TC as a robust switch option with a stable metabolic profile. Trial registration: ClinicalTrials.gov NCT03446573