Body composition and adipokines changes after initial treatment with darunavir-ritonavir plus either raltegravir or tenofovir disoproxil fumarate-emtricitabine: A substudy of the NEAT001/ANRS143 randomised trial.

Jose Bernardino (1) , Amanda Mocroft (2) , Cedrick Wallet (3) , Stéphane de Wit (4, 5) , Christine Katlama (6, 7, 8, 9) , Peter Reiss (10, 11) , Patrick W Mallon (12) , Laura Richert (3) , Jean-Michel Molina (13, 14) , Hernando Knobel (15) , Philippe Morlat (16, 3) , Abdel Babiker (17, 2) , Anton Pozniac (18) , François Raffi (19) , Jose R Arribas (1)

1 Department of Internal Medicine [Madrid, Spain]
2 UCL - University College of London [London]
3 BPH - Bordeaux population health
4 ULB - Université libre de Bruxelles
5 CHU Saint-Pierre
6 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
7 CHU Pitié-Salpêtrière [AP-HP]
8 SU - Sorbonne Université
9 SU FM - Sorbonne Université - Faculté de Médecine
10 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
11 AMC - Academic Medical Center - Academisch Medisch Centrum [Amsterdam]
12 UCD - University College Dublin [Dublin]
13 AP-HP - Hopital Saint-Louis [AP-HP]
14 Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales
15 IMIM-Hospital del Mar
16 Service de médecine interne et maladies infectieuses [Bordeaux]
17 MRC CTU - Medical Research Council Clinical Trials Unit
18 Chelsea and Westminster Hospital
19 Service des maladies infectieuses et tropicales [CHU Nantes]

Background : Comparison of changes in body composition, adipokines and inflammatory markers after initial therapy with a nucleos(t)ide reverse transcriptase inhibitor (N(t)RTI)- sparing or containing regimen are scarce. Design : Randomised Clinical Trial. Methods : This is the body composition substudy of NEAT 001/ANRS 143, a randomised trial comparing darunavir/ritonavir (DRV/r) plus either raltegravir (RAL) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in 805 ART naïve HIV-infected adults. The primary endpoint was percentage change in limb fat at week 96. Secondary endpoints were associations among these changes and metabolic markers (IL-6, insulin, leptin, adiponectin, FGF-23). Results : 126 subjects (61 DRV/r + RAL and 65 DRV/r + TDF/FTC) were included. The rate of change in BMI between groups for RAL versus TDF/FTC at week 96 was 1.5% per 48-week period (p = 0.015). The rate of change in limb fat mass, trunk fat mass, total body fat and total lean mass was for RAL versus TDF/FTC at week 96 was 2.5% (p = 0.38), 7.3% ((p = 0.021), 4.9% (p = 0.061) and 1.3% (p = 0.12) respectively. Baseline insulin and leptin levels were correlated with baseline limb fat and trunk fat mass [r = 0.31 (p = 0.0043)/r = 0.28 (p = 0.0011) for limb fat, and r = 0.63 (p<0.0001)/r = 0.50(p<0.0001) for trunk fat]. After adjustment, a 10% faster increase in leptin between baseline and week 48 was associated with a more rapid increase in limb fat at week 48 (0.5% per 48 weeks, p<0.001), total body fat mass (0.6% per 48 weeks, p<0.001), and trunk fat mass (0.3% per 48 weeks, p = 0.0026). Conclusions : After week 96 a N(t)RTI sparing regimen of DRV/r + RAL produced a numerically greater percentage increase in body composition variables with only change in trunk fat mass and BMI being significant.

Domaines: Sciences du Vivant [q-bio]

Jose Bernardino, Amanda Mocroft, Cedrick Wallet, Stéphane de Wit, Christine Katlama, et al.. Body composition and adipokines changes after initial treatment with darunavir-ritonavir plus either raltegravir or tenofovir disoproxil fumarate-emtricitabine: A substudy of the NEAT001/ANRS143 randomised trial.. PLoS ONE, 2019, 14 (1), pp.e0209911. ⟨10.1371/journal.pone.0209911⟩. ⟨hal-01999822⟩