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 Jan 28;14(1):e0209911. doi: 10.1371/journal.pone.0209911. eCollection 2019.

Abstract

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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / blood*
  • Adult
  • Body Composition*
  • Body Mass Index*
  • Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination / administration & dosage*
  • Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination / adverse effects
  • Female
  • Humans
  • Male
  • Raltegravir Potassium / administration & dosage*
  • Raltegravir Potassium / adverse effects
  • Time Factors

Substances

  • Adipokines
  • Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
  • Raltegravir Potassium

Grant support

NEAT is a project funded to the Instituto Superiori di Sanitá-Rome, by the European Union under the Sixth Framework Programme, project number LSHP-CT-2006-037570. This analysis was also partially funded by a grant from the Ministerio de Sanidad y Asuntos Sociales de España (2009/TRA-054). The trial was also supported by Gilead Sciences, Janssen Pharmaceuticals, and Merck Laboratories, and the French National Institute for Health and Medical Research-France Recherche Nord&Sud SIDA-HIV Hépatites (Inserm-ANRS) is the sponsor and a funder of the trial.