More Fat May Explain Increased Muscle Area After ART Begins

Total truncal muscle area rose in 235 HIV-positive adults after they began antiretroviral therapy (ART) in AIDS Clinical Trials Group (ACTG) protocol A5260s. But, overall, muscle density fell, a result suggesting that fat accounted for the total muscle gain.

Compared with the general population, aging people with HIV run an increased risk of frailty and impaired physical function. The quality and quantity of skeletal muscle are critical determinants of physical function. As people age, fat accumulation around and within muscles contributes to declining muscle quality.

ACTG investigators conducted this study to assess changes in truncal muscle area and density after ART begins. Less muscle density indicates more fat. The analysis involved participants in ACTG A5260s, a cardiometabolic substudy of ACTG 5257, which compared initial therapy with raltegravir (Isentress), or ritonavir (Norvir)-boosted atazanavir (Reyataz) or darunavir (Prezista) -- each with tenofovir/emtricitabine (Truvada). The investigators evaluated body composition with single-slice CT scans taken at baseline and treatment week 96. CT density at or below 30 Hounsfield units (HU) indicates fatty infiltration of muscle. The researchers used linear regression analysis to identify variables associated with changes in muscle area or density.

The analysis involved 235 people with a median age of 36 years (interquartile range 28 to 45), 90% of them men. While 43% of participants were white, 31% were black and 21% Hispanic. Median baseline CD4 count stood at 349 cells/mm3 and median body mass index at 24.5 kg/m2.

Total muscle area increased significantly through 96 weeks in abdominal, rectus and psoas muscle (range 0.21 to 0.83 cm2, P < .05). Lean muscle mass did not change significantly through 96 weeks. Muscle density decreased significantly in all muscle groups over 96 weeks (range -0.87 to -2.4 HU, P < .01). This finding is consistent with increased muscle fat.

Multivariate analysis linked black race to increased overall muscle density (less fat) in abdominal and psoas muscles and to increased lean muscle density of the rectus, psoas and spinalis. The same analysis found a significant association between female sex and greater declines in overall muscle density of the psoas and decreased lean muscle density of the rectus. The ACTG 5257 treatment arm did not predict changes in overall or lean muscle density.

Further analysis identified a weak but significant negative correlation between change in glucose and change in abdominal lean muscle density (r = -0.13, P = .0499). There were moderate negative correlations between change in visceral adipose tissue and change in abdominal total density (r = -0.289, P < .0001) and lean muscle density (r = -0.210, P = .0013).

This 96-week analysis offers the first evidence that ART-associated gains in the truncal muscle area are explained by increased fat within muscle rather than by "an improvement in high-quality, dense skeletal muscle." The authors note that the muscle groups they studied "are particularly important in everyday activities, contribute to balance, and provide compensatory support in fall prevention." Thus, weakness in these muscles could pose clinical risks.

The ACTG team adds that decreased fatty muscle in blacks and increased fatty muscle in women require further study to discern possible reasons for this difference, such as variations in physical activity, diet, hormonal changes or genetic factors.