Decreased limb muscle and increased central adiposity are associated with 5-year all-cause mortality in HIV infection

Abstract

Background: Unintentional loss of weight and muscle due to aging and disease has been associated with increased mortality. Wasting and weight loss occur in HIV infection even in the modern era of effective antiretroviral therapy.

Methods: We determined the association of MRI-measured regional and total skeletal muscle and adipose tissue with 5-year, all-cause mortality in 922 HIV-infected persons in the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM).

Results: After 5 years of follow-up, HIV-infected participants with arm skeletal muscle in the lowest tertile had a mortality rate of 23%, compared with 11 and 8% for those in the middle and highest tertiles. After multivariable adjustment for demographics, cardiovascular risk factors, HIV-related factors, inflammatory markers, and renal disease, we found that lower arm skeletal muscle, lower leg skeletal muscle and higher visceral adipose tissue (VAT) were each independently associated with increased mortality. Those in the lowest tertile of arm or leg skeletal muscle had higher odds of death [arm: odds ratio (OR) = 2.0, 95% confidence interval (CI) 0.96-4.0; leg: OR = 2.4, 95% CI 1.2-4.8] compared with the highest respective tertiles. Those in the highest tertile of VAT had 2.1-fold higher odds of death (95% CI 1.1-4.0) compared with the lowest VAT tertile.

Conclusion: Lower muscle mass and central adiposity appear to be important risk factors for mortality in HIV-infected individuals. A substantial proportion of this risk may be unrecognized because of the current reliance on body mass index in clinical practice.

Trial registration: ClinicalTrials.gov NCT00331448.

Fig. 1. Multivariable adjusted associations of MRI-measured skeletal muscle and adipose tissue with 5-year mortality in HIV-infected FRAM participants

The x-axis is on log10 scale. Estimates from multivariable adjusted models controlling for age, sex, race, traditional CVD risk factors, HIV-related factors, CRP, fibrinogen, eGFRcys, albuminuria, arm SM, leg SM, and VAT. Reference category is tertile 1, those with the lowest amount of muscle or adipose tissue. CI, confidence interval; SM, skeletal muscle; VAT, visceral adipose tissue.

Fig. 2. Association of arm skeletal muscle and visceral adipose tissue with 5-year mortality in HIV-infected FRAM participants

The y-axis gives unadjusted prevalence of death. Tertile 1, lowest SM or AT. **P<0.001 and ***P<0.0001 for comparison with VAT tertile 1 in fully adjusted model. CI, confidence interval; SM, skeletal muscle; VAT, visceral adipose tissue.