PENTOXIFYLLINE THERAPY IN HUMAN IMMUNODEFICIENCY VIRUS-SEROPOSITIVE PERSONS WITH TUBERCULOSIS - A RANDOMIZED, CONTROLLED TRIAL

Macrophage activation and tumor necrosis factor-alpha (TNF-alpha) prod uction are critical in tuberculosis immunity but may result in increas ed human immunodeficiency virus (HIV) expression and accelerated HIV d isease progression in HIV-infected persons. Pentoxifylline inhibits ex pression of TNF-alpha and HIV, A double-blind, placebo-controlled stud y of adjunctive therapy with pentoxifylline (1800 mg/day) as a timed-r elease formulation was done in Ugandan HIV-infected patients with pulm onary tuberculosis, Subjects had early HIV disease (mean CD4 cell coun t, 380/mu L) and did not receive other antiretroviral drugs. Pentoxify lline resulted in decreased plasma HIV RNA and serum beta(2)-microglob ulin and, in a subset of moderately anemic patients, improved blood he moglobin levels, Trends were noted toward reduced TNF-alpha production in vitro and improved performance scores, but these did not reach sta tistical significance, No effect was noted on body mass, CD4 cell coun t, or survival. Additional studies of more potent TNF-alpha inhibitors in HIV-positive subjects with tuberculosis are warranted.