Poorer Muscle Quality and Quantity with ART Initiation is Associated with Greater Inflammation and Immune Activation.

BACKGROUND We have previously shown that 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-naive PWH were randomized to raltegravir or ritonavir-boosted atazanavir or darunavir, each with tenofovir disoproxil fumarate/emtricitabine. Abdominal Computed Tomography (CT) scans from baseline and week 96 were re-analyzed for psoas density and area and correlations explored with inflammation (IL-6, hs-CRP) and immune activation (sCD14, sCD163, %CD38+HLADR+ on CD4+ or CD8+ T-cells). RESULTS 222 participants had available inflammation/immune activation markers and paired CT 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, hs-CRP, sCD14, sCD163, and %CD38+HLADR+ on CD4+ T-cells (r= -0.30 to 0.13); all p≤0.05). From baseline to week 96, greater % 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.