A Double-Blind Placebo-Controlled Phase II Trial of Thalidomide in Asymptomatic HIV-Positive Patients: Clinical Tolerance and Effect on Activation Markers and Cytokines

A randomized double-blind, placebo-controlled study was performed to determine the safety, efficacy, and effect of thalidomide on a variety of immunological and biochemical parameters in asymptomatic human immunodeficiency virus (HIV)-positive patients. Nineteen male patients with elevated markers of immune activation and CD4 cell counts above 400/mm3 were randomized to either placebo or thalidomide at 100 mg/day for 24 weeks. However, only 3 (of 10) patients receiving thalidomide completed all 24 weeks compared to 6 (of 9) patients receiving placebo. This was mainly due to fatigue (somnolence is a recognized side effect), although this was also seen to a lesser extent in the placebo group and so may not be drug attributable. No significant changes in CD4/CD8 count, activation markers, TNF-α, or TNFR1 were observed. However, a non-significant trend toward inhibition of mitogen-induced TNF-α production was observed in the thalidomide arm. The lack of systemic effect and the lower tolerance of thalidomide (...