Macrophage activation and tumor necrosis factor-α (TNF-α) production are critical in tuberculosis immunity but may result in increased human immunodeficiency virus (HIV) expression and accelerated HIV disease progression in HIV-infected persons. Pentoxifylline inhibits expression of TNF-α and HIV. A double-blind, placebo-controlled study of adjunctive therapy with pentoxifylline (1800 mg/day) as a timed-release formulation was done in Ugandan HIV-infected patients with pulmonary tuberculosis. Subjects had early HIV disease (mean CD4 cell count, 380/μL) and did not receive other antiretroviral drugs. Pentoxifylline resulted in decreased plasma HIV RNA and serum β2-microglobulin and, in a subset of moderately anemic patients, improved blood hemoglobin levels. Trends were noted toward reduced TNF-α production in vitro and improved performance scores, but these did not reach statistical significance. No effect was noted on body mass, CD4 cell count, or survival. Additional studies of more potent TNF-α inhibitors in HIV-positive subjects with tuberculosis are warranted.
Bibliographical noteFunding Information:
Received 5 February 1996; revised 15 May 1996. Presented in part: Lancet Conference: Challenge of Tuberculosis, Washington, DC, September 1995 (abstract 107). Informed consent was obtained from study patients in accord with US Department of Health and Human Services guidelines. The protocol was approved by human subjects review committees at Mulago Hospital, Kampala, Uganda, and University Hospitals, Cleveland. Grant support: Hoechst Roussel Pharmaceuticals (now Hoechst Marion Roussel); NIH (AI-45244 and AI-32414). D.O. is employed by Hoechst but has no other interest that would constitute a potential conflict of interest. Reprints or correspondence: Dr. Robert S. Wallis, Division of Infectious Diseases, CWRU School of Medicine, BRB 1037, 10900 Euclid Ave., Cleveland, OH 44106-4984.