Since 1996, triple drug antiretroviral therapy (ART) is standard in HIV care. Nowadays, with the increased viral potency of new antiretroviral drugs, dual ART has become a valid and potentially less toxic alternative considering the (present) lifelong need of ART. Metabolic complications such as weight gain have been reported with newer agents such as integrase inhibitors and the nucleoside reverse transcriptase inhibitor tenofovir alafenamide (TAF). We report week 48 results of Rumba, the first open-label randomized clinical trial evaluating effects on metabolic health of switch from 2nd generation integrase inhibitor based triple ART towards dual ART DTG/3TC.
Virally suppressed patients were randomized 2:1 to switch to DTG/3TC or to switch or stay on BIC/FTC/TAF. BMI, weight and waist circumference as well as lipids and insulin resistance (HOMA-IR) were compared among both groups. Body composition and fat distribution were measured by dual-energy x-ray absorptiometry (DXA) scans; liver fibrosis by fibroscans. Primary endpoint analysis on the viral reservoir will be discussed separately. Inflammatory cytokines were measured using commercially available ELISA and Luminex kits. Linear mixed models were built to evaluate changes over time between the groups over baseline, week 24 (if available) and week 48.
From 134 randomized patients, 130 (Nf87 DTG/3TC, Nf43 BIC/FTC/TAF) were included in the intention-to-treat-exposed analysis. The majority is male (118, 90.8%), mean age is 46.5±11.8 years. 102 patients (78.5%) had European and 14 (10.8%) had African ethnicity. Significant changes were observed between the groups from baseline to week 48 (estimated mean difference with 95%CI; BIC/FTC/TAF minus DTG/3TC): ALT (5.37 [0.38, 10.37] U/L; p=0.035), HDL cholesterol (-2.77 [-5.46, -0.08] mg/dL; p=0.044), lean trunk mass (-595.14 [-1121.82,-68.45] g, p=0.027) and fat percentage (1.37 [0.47,2.28] %; p=0.003). The estimated differences in trunk fat mass (617.63 [-43.26, 1278.53] g; p=0.067) and lean body mass (-776.88 [-1684.75, 130.99] g; p=0.093) follow the same trend, yet not significantly different. We did not observe significant divergences in other lipid parameters including triglycerides, LDL and total cholesterol nor in glucose, insulin, HOMA-IR and liver fibrosis.
Our data suggest that treatment with DTG/3TC has a favorable impact on week 48 metabolic outcomes as compared to treatment with BIC/FTC/TAF. More longitudinal data (up to week 144) are being collected.