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 d etermine the safety, efficacy, and effect of thalidomide on a variety of immunological and biochemical parameters in asymptomatic human immu nodeficiency virus (HIV)-positive patients, Nineteen male patients wit h elevated markers of immune activation and CD4 cell counts above 400/ mm(3) were randomized to either placebo or thalidomide at 100 mg/day f or 24 weeks, However, only 3 (of 10) patients receiving thalidomide co mpleted 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/CD 8 count, activation markers, TNF-alpha, or TNFR1 were observed, Howeve r, a nonsignificant trend toward inhibition of mitogen-induced TNF-alp ha production was observed in the thalidomide arm, The lack of systemi c effect and the lower tolerance of thalidomide (at this dose) in asym ptomatic patients highlights the need for pharmacokinetic analysis to address possible absorption problems and the need for more potent and less toxic TNF-alpha inhibitors to be developed for use in this type o f study.