THE EFFECT OF THALIDOMIDE ON THE PATHOGENESIS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND MYCOBACTERIUM-TUBERCULOSIS INFECTION

Tumor necrosis factor alpha (TNF-alpha), a cytokine produced during th e host defense against infection, is associated with fevers, weakness, and progressive weight loss. Thalidomide inhibits the synthesis of TN F-alpha both in vitro and in vivo and may have clinical usefulness. We therefore initiated a pilot study of thalidomide treatment in patient s with human immunodeficiency virus type 1 (HIV-1)-associated wasting with or without concomitant infection with tuberculosis. Thirty-nine p atients were randomly allocated to treatment with either thalidomide o r placebo in a double-blind manner for 21 days. Thirty-two patients co mpleted the study. In patients with concomitant HIV-1 and tuberculosis infections, thalidomide therapy was associated with a reduction in bo th plasma TNF-alpha levels and HIV-1 levels. No significant reduction in either TNF-alpha or HIV-1 levels was observed in patients with HIV- 1 infection only. During the study period, patients receiving thalidom ide treatment (n = 16) showed a significant weight gain (mean +/- SEM: 6.5 +/- 1.2%; p < 0.02) relative to placebo-treated patients (n = 16) . Patients with simultaneous HIV-1 and tuberculosis infections experie nced a higher mean weight gain during thalidomide treatment than the g roup of patients with HIV-1 infection only. The results of this pilot study suggest that thalidomide may have a clinical role in enhancing w eight gain and possibly reducing TNF-alpha and HIV-1 levels in patient s with HIV-1 and concomitant mycobacterial infections.