Donald P. Kotler

OBJECTIVE: To determine the effects of whey protein, resistance exercise, and combined protein and exercise treatment on body cell mass (BCM), muscle strength, and quality of life (QOL) in HIV-infected women with reduced BCM. DESIGN AND SETTING: Prospective, randomized, controlled trial at a university hospital in New York City. METHODS: A volunteer sample of 30 HIV-infected women were randomized to whey protein (PRO), progressive resistance exercise (PRE), or combined treatment (PRO-PRE) for 14 weeks after a 6-week control period. The main outcome measures were body weight, BCM, skeletal muscle, fat mass, muscle strength, and QOL. RESULTS: There were no significant changes in BCM, strength, or QOL during the control period. PRO patients gained 3.6 kg (P = 0.001), and 2.5 kg fat (P = 0.002) with no change in BCM (0.5 kg; P = 0.07) or skeletal muscle (0.6 kg; P = 0.12). The PRE group increased BCM (0.74 kg;P = 0.03) and skeletal muscle (1.2 kg; P < 0.001) and decreased fat (1.7 kg; P = 0.02). PRO-PRE increased BCM (0.61 kg; P = 0.01) without change in skeletal muscle (0.6 kg; P = 0.30). Strength increased for both exercise groups (range, 40.6-95.3%; P < 0.001). The QOL physical activity score improved for PRE (P = 0.02) and worsened for PRO (P = 0.01). CONCLUSIONS: Resistance exercise significantly increased BCM, muscle mass, muscle strength, and QOL in HIV-infected women with reduced BCM. Whey protein had little effect on BCM accrual. Combined protein and exercise did not increase BCM in excess of gains achieved by exercise alone.

Nutritional alterations are common in HIV infection. Early studies documented weight loss and protein depletion, a finding associated with body cell mass depletion in untreated patients. The application of highly active antiretroviral therapy has led to a decreased incidence of malnutrition, although altered body fat distribution and metabolic alterations, including hyperlipidemia and insulin resistance, are common sequelae. The development of malnutrition is multifactorial and occurs through changes in caloric intake, nutrient absorption, or energy expenditure. Clinically, malnutrition develops as a result of either starvation or cachexia. Other hormonal and endocrinologic alterations include hypercortisolemia and hypogonadism. The rationale for providing nutritional support to AIDS patients is based upon the assumptions that nutrition status can be improved and that such improvements have clinical benefits. The results of hypercaloric feeding studies, including the use of appetite stimulants, indicate that weight gain is possible but that the weight gained is predominantly fat. In contrast, anabolic agents and resistance training exercise have been shown to promote body cell mass repletion and skeletal muscle gain. Cytokine inhibitors also have been evaluated for the treatment of wasting in HIV infection. Development of combination therapies, preventive therapies, and efficient and cost-effective therapies are current tasks in the field.

HIV-associated wasting is defined as > or = 10% involuntary weight loss and includes declines in both lean and fat mass. This large (757 subjects), randomized, double-blind, placebo-controlled trial investigated the efficacy, safety, and tolerability of recombinant human growth hormone (rhGH) in 2 doses-0.1 mg/kg up to a maximum of 6 mg daily (DD) or alternate days (AD)-in the treatment of wasting and weight loss in highly active antiretroviral therapy (HAART)-treated HIV-infected subjects. The evaluable population for ergometry comprised 555 subjects, 87.6% of whom were receiving HAART. At 12 weeks, median maximum work output increased by 2.4 and 2.6 kJ in the AD and DD groups, respectively. The median treatment difference was 2.9 kJ for DD vs. placebo (P < 0.0001). Body weight increased by 2.2 and 2.9 kg in the AD and DD groups, respectively. Corresponding median treatment differences vs. placebo were 1.5 and 2.2 kg (P < 0.0001). Lean body mass (LBM), by bioelectric impedance spectroscopy, increased by 3.3 and 5.2 kg, respectively (P < 0.0001 vs. placebo; P = 0.0173 DD vs. AD), and fat mass, predominately truncal, decreased. Quality of life (QoL) improved significantly in both rhGH groups. Fluid-retention adverse effects and hyperglycemia were more common in the DD than in the AD group. No significant changes in HIV viral load or CD4 cell count occurred. In conclusion, over the 12-week course of therapy, rhGH, 0.1 mg/kg DD, was superior to placebo in improving physical function, body weight, body composition, and QoL and was superior to AD dosing in restoring LBM.