Effects of thalidomide on HIV-associated wasting syndrome: a randomized, double-blind, placebo-controlled clinical trial.
OBJECTIVE: To evaluate the efficacy of thalidomide in treating wasting syndrome in patients with advanced HIV disease, and to assess the effects of thalidomide on circulating CD4+ T cells, and on HIV viral burden in peripheral blood mononuclear cells (PBMC). DESIGN: Randomized, double-blind placebo-controlled clinical trial. SETTING: Public tertiary care hospital in Mexico City. PATIENTS: Twenty-eight adults with advanced HIV disease being treated with antiretroviral therapy, and who had received antiretrovirals for at least 6 months, who did not have an active opportunistic infection, and who had 10% weight loss in the previous 6 months. INTERVENTIONS: Patients received thalidomide (100 mg by mouth, four times daily) or a matching placebo for the duration of the study (12 weeks). MAIN OUTCOME MEASURES: The main clinical endpoint for efficacy of thalidomide was weight gain or no progression of wasting. Secondary endpoints were Karnofsky performance status, CD4+ cell counts, and HIV viral burden in PBMC. RESULTS: Both groups were comparable in their baseline status. Therapeutic failure occurred in 10 out of 14 patients from the placebo group and in three out of 14 from the thalidomide group (P = 0.021). Weight gain occurred in one patient on placebo and in eight given thalidomide. The Karnofsky index was significantly higher by the end of the study in the thalidomide group (P = 0.003). Mild and transient somnolence and erythematous macular skin lesions were significantly more common in the thalidomide group. CD4+ T cell counts and HIV viral burden in PBMC did not change in either group. CONCLUSIONS: Results suggest that thalidomide not only impeded but also reverted the wasting syndrome, preserving the Karnofsky index in patients with advanced HIV disease. Thalidomide, at the dosage used in this study, had no effect on peripheral CD4+ T cells nor on HIV viral burden in PBMC.