HIV Infection Is Associated with Increased Fatty Infiltration of the Thigh Muscle with Aging Independent of Fat Distribution

Abstract

BackgroundLower muscle density on computed tomography (CT) provides a measure of fatty infiltration of muscle, an aspect of muscle quality that has been associated with metabolic abnormalities, weakness, decreased mobility, and increased fracture risk in older adults. We assessed the cross-sectional relationship between HIV serostatus, age, thigh muscle attenuation, and thigh muscle cross-sectional area (CSA).MethodsMean CT-quantified Hounsfield units (HU) of the thigh muscle bundle and CSA were evaluated in 368 HIV-infected and 145 HIV-uninfected men enrolled in the Multicenter AIDS Cohort Study (MACS) Cardiovascular Substudy using multivariable linear regression. Models all were adjusted for HIV serostatus, age, race, and body mass index (BMI); each model was further adjusted for covariates that differed by HIV serostatus, including insulin resistance, hepatitis C, malignancy, smoking, alcohol use, and self-reported limitation in physical activity.ResultsHIV-infected men had greater thigh muscle CSA (p<0.001) but lower muscle density (p<0.001) compared to HIV-uninfected men. Muscle density remained lower in HIV-infected men (p = 0.001) when abdominal visceral adiposity, and thigh subcutaneous adipose tissue area were substituted for BMI in a multivariable model. Muscle density decreased by 0.16 HU per year (p<0.001) of increasing age among the HIV-infected men, but not in the HIV-uninfected men (HIV x age interaction -0.20 HU; p = 0.002).ConclusionHIV-infected men had lower thigh muscle density compared to HIV-uninfected men, and a more pronounced decline with increasing age, indicative of greater fatty infiltration. These findings suggest that lower muscle quality among HIV-infected persons may be a risk factor for impairments in physical function with aging.

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

“…Several studies [7, 33, 34] have shown associations between less dense thigh musculature with poorer lower limb performance, which may contribute to mobility impairment. Although most prior studies of muscle density and area have focused on thigh musculature, Goodpaster et al observed that trunk muscle density (our primary outcome) was strongly correlated with thigh density (r=0.65–0.77; p<0.01) [26].…”

“…PLWH with lipodystrophy had significantly lower median muscle density (55.0 HU; IQR 51.0–58.3) compared to PLWH without lipodystrophy (57.0 HU; IQR 55.0–59.0) and HIV-uninfected men (59.5 HU: IQR 57.3–64.8) [39]. 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].…”

“…Due to the successes of antiretroviral therapy, persons living with human immunodeficiency virus infection (PLWH) are living longer [1] and experiencing conditions commonly associated with aging (i.e., cardiovascular disease [2–4], neurocognitive dysfunction [5, 6], physical function impairments [7, 8], and falls [7, 9]). Although multiple factors contribute to the development of these disease processes, an accumulation of visceral adipose tissue (VAT) may play a central role [10–12].…”

Geriatric syndromes

“…We recently reported that ART initiation is associated with significant increases in skeletal muscle fat with minimal gains in skeletal muscle lean area [65] . In a cross-sectional study within the MACS, we found more skeletal muscle fat with increasing age among HIV-infected men, independent of body fat distribution, compared to HIV-uninfected men [66] . A small study of 40 community-dwelling HIV-infected individuals in Rochester, NY reported an association between impaired physical function and the ratio of intramuscular to total body fat [61] .…”

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

“…Few studies have described the changes in skeletal muscle fat that occur with HIV infection; to the best of our knowledge, no studies have described changes in skeletal muscle fat with ART initiation. Compared to HIV-uninfected men, HIV-infected men had lower density (greater fatty infiltration) of the mid-thigh muscle bundle and lower muscle quality with age, even after multivariable adjustment including VAT and SAT [16]. Among younger HIV-infected persons with body fat changes (previously referred to as lipodystrophy), decreased psoas muscle density was more strongly associated with insulin resistance than BMI, subcutaneous fat, lean body mass, or ART [17].…”