title: The effect of thalidomide on the pathogenesis of human immunodeficiency virus type 1 and M. tuberculosis infection.
abstract: Tumor necrosis factor alpha (TNF-alpha), a cytokine produced during the host defense against infection, is associated with fevers, weakness, and progressive weight loss. Thalidomide inhibits the synthesis of TNF-alpha 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-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 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-alpha and HIV-1 levels in patients with HIV-1 and concomitant mycobacterial infections.
authors.affiliation: Department of Medicine, New York University Medical Center, New York, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Klausner
authors.forename: S
authors.initials: S
authors.lastname: Makonkawkeyoon
authors.forename: P
authors.initials: P
authors.lastname: Akarasewi
authors.forename: K
authors.initials: K
authors.lastname: Nakata
authors.forename: W
authors.initials: W
authors.lastname: Kasinrerk
authors.forename: L
authors.initials: L
authors.lastname: Corral
authors.forename: R L
authors.initials: RL
authors.lastname: Dewar
authors.forename: H C
authors.initials: HC
authors.lastname: Lane
authors.forename: V H
authors.initials: VH
authors.lastname: Freedman
authors.forename: G
authors.initials: G
authors.lastname: Kaplan
mesh_terms: D000328:Adult; D001835:Body Weight / Q000187:drug effects; D018791:CD4 Lymphocyte Count; D004311:Double-Blind Method; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010919:Placebos; D013792:Thalidomide / Q000009:adverse effects / Q000627:therapeutic use*; D014397:Tuberculosis, Pulmonary / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D007166:Immunosuppressive Agents; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide