Background
Background: Switching to DTG/3TC (DOV) or BIC/FTC/TAF (BIK) in the PASO-DOBLE trial (ClinicalTrials.gov NCT04884139) showed noninferior efficacy of DOV vs. BIK and weight gain in both groups, which was significantly greater for BIK at 48 weeks. We aimed to know how switching to DOV or BIK affects body composition and whether there are differences between the two regimens.
Methods
Participants in the PASO-DOBLE trial underwent whole-body DXA scans to assess total mass (TM), fat mass [total (FM) and regional, including abdominal (ABFM), visceral (VFM), and appendicular (LFM)], and lean mass [total (LM), and appendicular (ALM)] and a single abdominal CT scan at L4 level to measure subcutaneous (SAT), visceral (VAT), and total (TAT) fat area at baseline and 48 weeks. Mean changes in the pooled population were used to estimate the impact of switching to DOV or BIK on body composition. Linear regression adjusted by sex, TAF at baseline, age and race was used to assess differences in compartments between DOV or BIK. DXA-defined obesity (FM >25% men; >32% women) was assessed at baseline and 48 weeks.
Results
Out of 553 participants in the trial, 447 (81%) (DOV, n=223; BIK, n=224) had paired DXA and CT scans available and were analyzed. At baseline, mean (IQR) age was 50 (40-57) years, 27% were women, 35% on TDF, and 26% on EFV. In the pooled population, there were significant mean (95% CI) increases in DXA-derived TM +1.2% (0.7, 1.7), FM +17.9% (14.6, 21.2), ABFM +23.9% (18.6, 29.2), VFM +82.4% (29.7, 135.3), LFM +21.7% (17.9, 25.5); decreases in DXA-derived LM -2.6% (-3.2, -2.0), and ALM -2.8% (-3.6, -2.1); and increases in CT-derived VAT +21.2% (14.5, 27.8) and TAT +1.5% (0.0, 2.9), but no changes in SAT 0.0% (-1.4, 1.4). Adjusted mean treatment differences (95% CI) BIK minus DOV in changes from baseline are shown in the table; in general, total and fat mass increased more and lean mass decreased less with BIK vs. DOV. DXA-defined obesity increased from baseline (DOV 57.7%, BIK 57.0%) to 48 weeks (DOV 71.3%, BIK 73.5%) [adjusted OR (95% CI) for treatment difference 1.31 (0.76; 2.23)] in both arms. Changes in all fat compartments were positively correlated with changes in insulin resistance (p<0.04).
Conclusions
Switching to DOV or BIK was associated with fat gain, which was relatively greater at the visceral compartment, and lean mass loss. Increases in TM and LFM were significantly greater with BIK than with DOV. Fat gain in any compartment was associated with insulin resistance.