Dysregulated Energy Expenditure in HIV-Infected Patients: A Mechanistic Review

Abstract

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.

Metabolic complications and selected cytokines in HIV‑infected individuals

“…The available data on the effect of the HAART on RMR are conflicting. 22,23 Increased RMR is positively correlated with the TNF-α concentration; therefore, a continuous decrease of the serum TNF-α level observed in the present study with therapy duration can partially explain the reported changes of RMR.…”

“…22 In another study, we reported that ARV therapy ameliorated mitochondrial dysfunction. 5 Not all metabolic disturbances can be linked directly to ARV therapy.…”

Decreased respiratory quotient in relation to resting energy expenditure in HIV-infected and noninfected subjects

“…Shevitz et al suggested that antiviral medications might directly stimulate metabolism or that metabolic demand might increase from a rejuvenated immune system in subjects on HAART (30). More recently, it has been postulated that mitochondrial dysfunction may contribute to increased REE and the effects of HAART or the HIV virus may lead to altered energy regulation (34). …”

Stress Biomarkers as Outcomes for HIV+ Prevention: Participation, Feasibility and Findings Among HIV+ Latina and African American Mothers

“…Equivocal directionality of other primary neuroendocrine biomarkers and secondary outcomes is cited as the rationale for scoring all biomarkers with bidirectional risk (Glei et al 2007; Seplaki et al 2005). Such a strategy seems warranted in HIV+ samples, where PSS symptoms may be prevalent (Gaynes et al 2008; Israelski et al 2007; Myers et al 2006; Whetten et al 2006, 2008) and lipodystrophy or other metabolic disturbances are known sequelae of HIV+ infection, antiviral medications, or both (Chang et al 2007). …”