(Taken from application) Body wasting, particularly loss of lean body mass (LBM), occurs frequently and impacts survival in HIV infection. Weight loss is most rapid during episodes of secondary infection when decreased energy intake and increased resting energy expenditure (REE) lead to negative energy balance. Nutritional interventions can increase weight but fail to consistently restore LBM. Recombinant human growth hormone (rhGH) increased weight and LBM in stable patients and limited loss of LBM during weight-losing episodes, but other metabolic effects (e.g. increased REE) may negatively impact energy balance in patients with secondary infections. Therapies that blunt immune activation during infection may mitigate the catabolic response, anorexia, and loss of weight and LBM; thalidomide, an inhibitor of TNFa synthesis, caused rapid weight gain in patients co-infected with HIV and M. tuberculosis, but the potential deleterious effects of inhibiting the host defense during secondary infections must be carefully evaluated. To determine the efficacy and safety of rhGH and thalidomide in HIV-infected patients with secondary infections and the mechanisms by which they affect energy balance and protein metabolism, a multicenter clinical trial will be conducted in which two cohorts of HIV+ patients with secondary infections (120 with tuberculosis or fungal infections; 120 with bacterial infections) will be randomly assigned to receive rhGH, thalidomide, or placebo for a four-week period concurrent with initiation of standard antimicrobial therapy. This trial will test the hypotheses that: (1) both rhGH and thalidomide will mitigate weight loss and loss of LBM (dual energy X-ray absorptiometry; bioelectrical impedance); (2) the ameliorative effects of rhGH and thalidomide on body weight and composition will be mediated through different effects on energy balance (energy intake; REE; total energy expenditure); (3) rhGH will conserve LBM in part by increasing protein synthesis and lipid oxidation and thalidomide in part through reduction of protein breakdown (leucine flux; substrate oxidation); (4) thalidomide will blunt the increase in HIV RNA levels and immune activation during secondary infection; (5) when used in conjunction with effective antimicrobial agents, thalidomide and rhGH will have acceptable safety profiles in patients with secondary infections (adverse events, hematologic and biochemical parameters); and (6) interdicting loss of weight and LBM during infection will improve the subsequent clinical course.
| Maia, Bruno S; Engelson, Ellen S; Wang, Jack et al. (2005) Antiretroviral therapy affects the composition of weight loss in HIV infection: implications for clinical nutrition. Clin Nutr 24:971-8 |
| Kaplan, G; Thomas, S; Fierer, D S et al. (2000) Thalidomide for the treatment of AIDS-associated wasting. AIDS Res Hum Retroviruses 16:1345-55 |
| Mulligan, K; Tai, V W; Schambelan, M (1999) Use of growth hormone and other anabolic agents in AIDS wasting. JPEN J Parenter Enteral Nutr 23:S202-9 |
