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

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

Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology: 1 March 1996 - Volume 11 - Issue 3 - pp 247-257
Clinical Science

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.

Departments of Medicine and Pulmonary and Critical Care Medicine, New York University Medical Center, New York, New York, U.S.A.; *Department of Microbiology and Faculty of Medicine, Chiang Mai University, and Chiang Mai Anti-TB Association, Chiang Mai, Thailand; Celgene Corporation, Warren, New Jersey; §NIAID, National Institutes of Health, Bethesda, Maryland; and Rockefeller University, Laboratory of Cellular Physiology and Immunology, New York, New York, U.S.A.

Address correspondence and reprint requests to Dr. Gilla Kaplan, Rockefeller University, 1230 York Avenue, New York, N.Y. 10021, U.S.A.

Manuscript received April 10, 1995; accepted November 20, 1995.

© Lippincott-Raven Publishers.