Poorer Muscle Quality and Quantity With ART Initiation Is Associated With Greater Inflammation and Immune Activation

J Acquir Immune Defic Syndr. 2021 Dec 1;88(4):399-405. doi: 10.1097/QAI.0000000000002776.

Abstract

Background: We have previously shown that the initiation of antiretroviral therapy (ART) is associated with a decrease in skeletal muscle density (greater fat accumulation), suggesting that gains in lean body mass seen in many ART studies may reflect gains in low quality, fatty muscle. Here, we explore whether skeletal muscle density and area are associated with markers of inflammation and immune activation.

Methods: ART-naïve people with HIV were randomized to raltegravir or ritonavir-boosted atazanavir or darunavir, each with tenofovir disoproxil fumarate/emtricitabine. Abdominal computed tomography scans from baseline and week 96 were reanalyzed for psoas density and area and correlations explored with inflammation [interleukin-6 (IL-6) and high-sensitivity C-reactive protein] and immune activation [soluble CD14 (sCD14), soluble CD163 (sCD163), and %CD38+HLADR+ on CD4+ or CD8+ T cells].

Results: Two hundred twenty-two participants had available inflammation/immune activation markers and paired computed tomography scans. At baseline, lower psoas density (greater fat) correlated with higher IL-6 (r = -0.26, P < 0.001) and sCD163 (r -0.15, P = 0.03) and lower lean psoas area correlated with higher IL-6, high-sensitivity C-reactive protein, sCD14, sCD163, and %CD38+HLADR+ on CD4+ T cells (r = -0.30-0.13; all P ≤ 0.05). From baseline to week 96, greater percent decrease in total psoas density (more fat) correlated with greater increase in IL-6 (r = -0.14; P = 0.04); greater % decrease in lean psoas area correlated greater increases in IL-6, sCD14, sCD163, and %CD38+HLADR+ on CD8+ T cells (r = -0.15 to -0.18; all P < 0.04).

Conclusions: Greater fat infiltration within the psoas muscle (lower density) and greater loss in lean psoas muscle area were associated with higher inflammation and immune activation, which may portend important effects on muscle function and cardiometabolic risk.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HIV Protease Inhibitors / therapeutic use
  • Humans
  • Immune System / drug effects
  • Inflammation*
  • Interleukin-6 / blood
  • Lipopolysaccharide Receptors
  • Muscle, Skeletal*
  • Treatment Outcome

Substances

  • Anti-HIV Agents
  • Biomarkers
  • HIV Protease Inhibitors
  • Interleukin-6
  • Lipopolysaccharide Receptors
  • C-Reactive Protein