Dysregulated energy expenditure in HIV-infected patients: a mechanistic review

Metabolic abnormalities are common in patients with human immunodeficiency virus (HIV) infection and range from protein catabolism to lipodystrophy and dyslipidemia associated with the use of highly active antiretroviral therapy. One abnormality is increased resting energy expenditure, which even occurs in clinically stable HIV-infected patients. Increased resting energy expenditure may aggravate the tendency towards weight loss and wasting, which are independent predictors of mortality. Despite much investigation, the factors associated with altered resting energy expenditure remain unclear; viral load, CD4 cell count, use of antiretroviral drugs, body composition, hormones, and proinflammatory cytokines have been imputed. Mechanisms that could explain increased resting energy expenditure include the HIV accessory protein viral protein R, antiretroviral drugs that affect mitochondrial function, and futile cycling within adipocytes. Other components of energy expenditure are also important to overall energy balance and may also be affected. Identifying unifying mechanisms will be an important step to finding effective treatments for HIV-related alterations in energy expenditure and to reversing metabolic risks in patients with HIV infection.