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The Effect of Thalidomide on the Pathogenesis of Human Immunodeficiency Virus Type 1 and M. tuberculosis Infection

1996; Lippincott Williams & Wilkins; Volume: 11; Issue: 3 Linguagem: Inglês

10.1097/00042560-199603010-00005

2331-6993

Jeffrey D. Klausner, Sanit Makonkawkeyoon, Pasakorn Akarasewi, Koh Nakata, Watchara Kasinrerk, Laura G. Corral, Robin Dewar, H. Clifford Lane, Victoria H. Freedman, Gilla Kaplan,

Leprosy Research and Treatment

Summary: Tumor necrosis factor alpha (TNF-α), a cytokine produced during the host defense against infection, is associated with fevers, weakness, and progressive weight loss. Thalidomide inhibits the synthesis of TNF-α both in vitro and in vivo and may have clinical usefulness. We therefore initiated a pilot study of thalidomide treatment in patients with human immunodeficiency virus type 1 (HIV-1)-associated wasting with or without concomitant infection with tuberculosis. Thirty-nine patients were randomly allocated to treatment with either thalidomide or placebo in a double-blind manner for 21 days. Thirty-two patients completed the study. In patients with concomitant HIV-1 and tuberculosis infections, thalidomide therapy was associated with a reduction in both plasma TNF-α levels and HIV-1 levels. No significant reduction in either TNF-α or HIV-1 levels was observed in patients with HIV-1 infection only. During the study period, patients receiving thalidomide 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 experienced a higher mean weight gain during thalidomide treatment than the group of patients with HIV-1 infection only. The results of this pilot study suggest that thalidomide may have a clinical role in enhancing weight gain and possibly reducing TNF-α and HIV-1 levels in patients with HIV-1 and concomitant mycobacterial infections.