Hypermetabolism and progression of HIV infection

Several studies evaluating resting energy expenditure (REE) in HIV-infected patients have been published. This component of energy expenditure, when adjusted for differences in body composition, has been reported as being increased (1–4), decreased (5), or even normal (6, 7) in these patients. The reason for this lack of consensus remains unclear. Given the evidence that viral load is an important predictor of the progression of HIV infection, it is of interest to assess the relation between this variable and the degree of hypermetabolism. A significant relation (r = 0.404, P = 0.011) between plasma viral load and REE was described in 1997 by Mulligan et al (8) in 36 clinically stable HIV-positive men, suggesting that energy expenditure would increase as a part of the host response to viral replication. Recently, Grinspoon et al (9) evaluated the probable determinants of energy expenditure in 33 ambulatory HIV-infected female patients. In the accompanying editorial, Kotler and Heymsfield (10) found it surprising that there was not a significant relation between REE and viral burden in the study by Grinspoon et al. They hypothesized that such a relation would have been statistically significant had the study sample size been increased or had the viral load variable been log-transformed in the statistical analyses. Our experience suggests that such a relation does not exist. We studied 85 HIV-infected patients (20 women, 65 men) ranging in age from 24 to 65 y. They were recruited from 2 different hospitals [Hospital Universitari de Sant Joan de Reus (n = 50) and Hospital Virgen del Rocio de Sevilla (n = 35)] at different stages of HIV infection. Thirty-three patients were free of any acute opportunistic infection and the rest (n = 52) had clinical evidence of an active secondary infection. After an overnight fast, body composition was estimated by bioelectrical impedance analysis (Human-Im Scan; Dietosystem, Milano, Italy) and REE was estimated by 30-min indirect calorimetry (Deltatrac; Datex, Instrumentarium, Finland). Subjects rested for 30 min before the testing began. Blood samples were taken the same day of the study to determine CD4 cell counts and viral load (Amplicor HIV-1 Monitor; Roche Molecular Systems, Inc, Branchburg, NJ). The malabsorption and nutritional status of some of the patients included in this letter were reported previously (7). Nutritional status varied a great deal between patients. The body mass index (in kg/m2) of our patients ranged from 14.03 to 30.78 and mean changes in body weight over the previous 3and 1-mo periods were 5.4 ± 5.1 and 3.5 ± 3.3, respectively. REE ranged from 84.7% to 143.0% of the value predicted by the Harris-Benedict equation in patients free of opportunistic infection and from 84.8% to 152.4% in patients with active opportunistic infection. As did Grinspoon et al (9), we found no significant relation between REE and CD4 cell counts (r = 20.07) or plasma concentrations of HIV RNA (r = 0.02) even when the viral RNA load in the total study population was log-transformed. These relations were not significant in the group of subjects free of opportunistic infections or in the rest of patients. The relation between REE and plasma viral load was consistent when patients from either hospital were analyzed separately. The lack of a significant relation between REE and progression markers of HIV infection is, perhaps, not so surprising. After all, a considerable number of factors known to be present in HIV-infected patients are able to modulate energy expenditure and although the effects of energy intake, malabsorption, weight loss, and physical activity on energy expenditure have been studied in these patients, the considerable variability in the degree of hypermetabolism between subjects remains unexplained. Furthermore, the effects of proinflammatory cytokines, which affect intermediary metabolism, as well as those of antiretroviral therapies and other factors need to be explored.