Data on body composition, adipokines and inflammatory markers changes after initial therapy with a nucleos(t)ide reverse transcriptase inhibitor (NtRTI)- sparing or containing regimen are scarce. The effect of tenofovir/emtricitabine (TDF/FTC) vs raltegarvir (RAL), both in association with ritonavir-boosted darunavir (DRV/r) could be relevant for treatment choice.
NEAT001/ANRS143 is a randomised 1:1, open-label, non-inferiority trial comparing DRV/r + RAL or TDF/FTC in 805 ART näive HIV-infected adults. We compared percentage change in lean mass, limb fat mass, trunk fat mass ant total body fat mass assessed by dual energy X-ray absorptiometry scans (DXA) in a substudy of 146 subjects (random sample). Main endpoint was mean % change of limb fat at W96. Secondary endpoints: relationship between changes in body composition variables, and inflammatory/metabolic markers (IL-6, insulin, leptin, adiponectin, FGF-23).
126 (61 DRV/r + RAL and 65 DRV/r + TDF/FTC) had at least one follow-up DXA available. At baseline: 91% male, 14% black, median age 40 years, median BMI 23.2 Kg/m2, HIV-1 RNA load 4.7 log10 copies/mL, CD4 count 338 cells/µL. There was no difference in limb fat mass at W96 between arms (Table). At W96 there was a greater increase in the DRV/r + RAL arm in mean trunk fat mass (15.5% in DRV/r + RAL vs. 8.7% in DRV/r + TDF/FTC; p = 0.026) and total body fat mass (4.1% in DRV/r + RAL vs. 0% in DRV/r + TDF/FTC; p = 0.032). These differences remained robust to adjustment for baseline CD4 count and viral load. Baseline insulin and leptin levels were correlated with baseline limb fat/trunk fat mass [r=0.31 (p=0.0043)/r=0.28 (p=0.0011); r=0.63 (p<0.0001)/r=0.50(p<0.0001), respectively]. Adiponectin was correlated with baseline limb fat mass only [r=0.40 (p<0.0001)]. After adjustment, persons with a 10% increase in leptin between baseline and W48 had a 0.5% (95% CI 0.3-0.7; p<0.0001) and 0.3% (95% CI 0.1-0.6; p=0.013) increase in limb fat mass at W48 and W96 respectively and a 0.4% increase in trunk fat at W96 (95% CI 0.1-0.6; p=0.014). There was no association between baseline IL-6 or insulin and changes in limb or trunk fat mass.
The NtRTI sparing regimen produced a higher increase in total and trunk fat mass than the TDF/FTC containing regimen. These changes were correlated with changes in leptin levels.