Ketotifen in HIV infected patients: Effects on body weight and release of TNF-alpha

Objective: Tumor necrosis factor alpha (TNF-alpha) is involved in the genesis of HIV-associated malnutrition. We performed an open-label trial on the effects of ketotifen, an in vitro inhibitor of TNF-alpha release from peripheral blood mononuclear cells (PBMCs), on the nutritional status and TNF-alpha release of HIV-infected subjects. Patients: Six HIV-infected subjects received oral ketotifen 4 mg per day for 84 days and were followed up for an additional 70-day period. Body composition was measured by bioelectrical impedance analysis. TNF-alpha plasma levels, TNF-alpha release from PBMCs, and plasma concentration of soluble TNF receptors were measured repeatedly during the study and control period. Results: During ketotifen intake, TNF-alpha release from stimulated PBMCs significantly decreased (68 vs 155 pg ml(-1)), but not TNF-alpha and soluble TNF receptor plasma concentrations. Subjects gained weight (+ 2.7 kg), whereas weight loss was observed after cessation of treatment (- 1.6 kg). Conclusion: Ketotifen inhibits TNF-alpha release from stimulated PBMCs and might thus be useful in the management of HIV-associated malnutrition.