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

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 tomog-raphy scans. At baseline, lower psoas density (greater fat) correlated with higher IL-6 (r = 20.26, P , 0.001) and sCD163 (r 20.15, P = 0.03) and lower lean psoas area correlated with higher IL-6, highsensitivity C-reactive protein, sCD14, sCD163, and %CD38 + HLADR + on CD4 + T cells (r = 20.30-0.13; 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 = 20.14; 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 = 20.15 to 20.18; 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.

Associations of Muscle Density and Area With Coronary Artery Plaque and Physical Function

“…56 Among PWH initiating ART, both baseline and change in muscle density and area were associated with greater inflammation. 13 Consistent with the existing literature, in this study, we found strong correlations between muscle density and greater hs-CRP, MCP-1, sTNFR-1, and IIS and correlations between muscle area and greater MCP-1. MCP-1, particularly, is a cytokine that may play a key role in mitochondrial signaling and muscle damage/repair.…”

“…We have previously shown that HIV, in addition to increasing age, may be an important contributor to declines in muscle density and area. 12–16 The health consequences associated with lower muscle density are less well-described, particularly in muscle groups beyond the trunk and thigh, although deposition of ectopic fat in other tissues (eg, liver and pericardium) can have a detrimental impact on cardiometabolic disease risk, driven in part by inflammation. 17…”

“…11 We have previously shown that HIV, in addition to increasing age, may be an important contributor to declines in muscle density and area. [12][13][14][15][16] The health consequences associated with lower muscle density are less well-described, particularly in muscle groups beyond the trunk and thigh, although deposition of ectopic fat in other tissues (eg, liver and pericardium) can have a detrimental impact on cardiometabolic disease risk, driven in part by inflammation. 17 The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE; NCT02344290) is a double-blinded, randomized, controlled trial of pitavastatin calcium (pitavastatin) versus placebo among people with HIV (PWH) with low-to-moderate traditional atherosclerotic cardiovascular disease (ASCVD) risk.…”

The use of non‐invasive imaging modalities for the assessment of skeletal muscle quantity and quality in people with HIV: A narrative review

“…However, the authors postulated that this may be due to fatty muscle, as evidenced by the decreased muscle density, despite similar CSA [12]. Decreased muscle area has been associated with increased inflammatory markers, immune system activation and cardiovascular disease [15, 59] We did not identify studies using CT to quantify the amount of total skeletal muscle mass among PWH.…”

“…This may be due, in part, to ART use and changes in fat distribution (i.e. lipodystrophy) and it has been linked to increased inflammation [14–18].…”