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-naïve adults to ritonavir-boosted atazanavir, darunavir, or raltegravir with tenofovir/emtricitabine backbone. Single-slice abdominal computed tomography (CT) scans from baseline and week 96 were reanalyzed for 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 muscles total area (range 0.21 to 0.83 cm2; 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. Conclusions 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.

The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults With Hiv

“…In the Multicenter AIDS Cohort Study, men with HIV (~57 years old) on antiretroviral therapy had lower thigh muscle density (by 1 HU), compared to their HIV-uninfected peers (~54 years old), and lower thigh muscle density was correlated with greater VAT area and weaker grip strength [7]. We have previously shown that antiretroviral therapy initiation was associated with a decrease in trunk muscle density (−0.87 to −2.4 HU across muscle groups) over 96 weeks [40]. Lastly, in a three month intervention of metformin with or without aerobic + resistance exercise among lipodystrophic men and women with HIV (n=25), participants in the exercise + metformin arm experienced greater increase in thigh muscle attenuation (median change 2.0; IQR 0.5, 5.0 HU) compared to metformin only arm (−1.0, IQR −3.5, 0; p=0.04) [41].…”

Benefits and Risks of Statin Therapy in the HIV-Infected Population

“…However, given the recent animal model of enhanced cholesterol excretion in the gut following statin therapy exposure [4], it is likely that future additional studies in the interaction between statin and gut dysbiosis in the HIV-infected population will ensue. Because HIV infection is also associated with increased frailty[49], and particularly decrease in lean body mass [50, 51] and physical strength [52], statin therapy has been evaluated address these problems. For instance, in a study of 147 HIV-infected adults on ART followed for 96 weeks, rosuvastatin 10mg was associated with a non-statistically significant increase in lean body mass [53], indicating a potential role of statin therapy in decreasing muscle frailty and its associated complications in this population.…”

Assessing skeletal muscle radiodensity by computed tomography: An integrative review of the applied methodologies

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