Antiretroviral initiation is associated with increased skeletal muscle area and fat content

Abstract

Objective: A greater burden of physical function impairment occurs in HIV-infected adults; the impact of antiretroviral therapy (ART) initiation on muscle density (less dense = more fat), a measure of muscle quality, is unknown.

Design: AIDS Clinical Trials Group Study A5260s, a cardiometabolic substudy of A5257, randomized HIV-infected, ART-naive adults to ritonavir-boosted atazanavir, darunavir, or raltegravir with tenofovir/emtricitabine backbone. Single-slice abdominal computed tomography scans from baseline and week 96 were reanalyzed for total and lean muscle area and density.

Methods: Two-sample t-tests described the differences between baseline and week 96 variables. Linear regression analysis was used to explore the role of a priori identified variables and potential confounders.

Results: Participants (n = 235) were mostly men (90%); 31% were Black non-Hispanic; 21% were Hispanic. Over 96 weeks, small but significant increases were seen in oblique/transverse abdominal, rectus, and psoas muscle total area (range 0.21-0.83 cm; P < 0.05) but not the lean muscle component (all P ≥ 0.33). Significant decreases in overall density, consistent with increases in fat, were seen in all muscle groups (range -0.87 to -2.4 HU; P < 0.01); for the lean muscle component, only decreases in oblique/transverse abdominal and rectus reached statistical significance (P < 0.05). In multivariable analyses, Black race was associated with increased muscle density and female sex with decreased density; treatment arm was not associated with changes in mass or density.

Conclusion: The ART-associated increase in muscle area, regardless of regimen, is likely a reflection of increased fat within the muscle. The consequences of fatty infiltration of muscle on subsequent muscle function require further investigation.

Figure 1

Change in total (a) and lean (b) muscle area from week 0 to 96 with antiretroviral initiation. * p<0.05, ** p <0.01, *** p<0.001

Figure 2

Change in total (a) and lean (b) muscle density (HU) from week 0 to 96 with antiretroviral initiation. * p<0.05, ** p <0.01, *** p<0.001