Tumor mecrosis factor alpha (TNF-alpha) is produced by monocytes and macrophages during the host response to infection. Excessive TNF-alpha production is associated with the symptoms of infection including fevers, muscle weakness and progressive weight loss. In vitro, TNF-alpha enhances replication of HIV-1 in latently infected cell lines and in cells from HIV-1 infected patients. This activation can be inhibited by the addition of thalidomide which suppresses TNF-alpha production both in vitro and in vivo. Increased TNF-alpha and soluble TNF-alpha receptor levels have been reported in the sera of HIV-1 infected patients. We have shown that in sera of HIV-1 infected patients there is a positive correlation between TNF-alpha levels and HIV-1 viremia. In HIV-1 infected patients with an opportunistic infection such as tuberculosis(TB), both TNF-alpha levels and HIV-1 levels were found to be higher than in patients with HIV-1 infection alone. This relationship between TNF-alpha level and HIV-1 suggested that a reduction in TNF-alpha might not only reduce TNF-alpha associated toxicities, but might also reduce HIV-1 viremia. We have carried out a pilot double-blind study of thalidomide treatment in patients with HIV-1 associated wasting with or without concomitant TB. Thalidomide therapy was associated with a reduction in both plasma TNF-alpha levels and HIV-1 levels in patients dually infected with HIV-1 and TB. A significant weight gain was observed in HIV-1 infected patients treated with thalidomide relative to placebo treated patients. Thalidomide is being investigated for its potential clinical use in reducing TNF-alpha and HIV-1 levels in patients with HIV-1 and concomitant mycobacterial infections.

Double-Blind Method HIV Infections/BLOOD/COMPLICATIONS/VIROLOGY HIV-1/ISOLATION & PURIF/*PHYSIOLOGY Human Macrophages/*METABOLISM Monocytes/*METABOLISM Pilot Projects Receptors, Tumor Necrosis Factor/BIOSYNTHESIS Thalidomide/PHARMACOLOGY Tuberculosis/BLOOD/COMPLICATIONS Tumor Necrosis Factor/*BIOSYNTHESIS/PHYSIOLOGY Virus Replication/PHYSIOLOGY ABSTRACT

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