AIDSWEEKLY Plus, 01 April 1996 issue; Published by Charles Henderson, Publisher. Editorial & Publishing Office: P.O. Box 5528, Atlanta, GA 30307-0528 / Telephone: (800) 633-4931; Subscription Office: P.O. Box 830409, Birmingham, AL 35283-0409 / FAX: (205) 995-1588
Salynn Boyles, Senior Editor

Adjunctive therapy with pentoxifylline appears to be marginally beneficial in HIV positive tuberculosis patients, according to a report from Cleveland, Ohio's Case Western University.

In a recent study R.S. Wallis and colleagues found that adjuvant treatment with pentoxifylline resulted in statistically significant improvements in plasma HIV RNA and (beta)2 microglobulin, but did not increase survival times in a cohort of HIV positive tuberculosis patients.

This study was reported at the IBC Biennial International Conference on Mycobacterial Infection, held in Washington D.C. March 7-8, 1996.

Excess deaths in HIV positive tuberculosis patients appear to reflect accelerated progression of HIV disease, but this has not yet been confirmed. Tumor necrosis factor alpha (TNF- (alpha)), a macrophage product, promotes HIV expression by infected lymphocytes and macrophages, and may accelerate HIV disease progression.

Pentoxifylline inhibits TNF(alpha) synthesis, its effects on target cells, and HIV expression in vitro. Clinical trials of pentoxifylline in AIDS have shown only a minimal effect on markers of HIV disease activity. However, TNF(alpha) inhibition may have a greater impact on HIV disease in conditions in which the cytokine is highly expressed, such as in TB.

In this study 109 patients with newly diagnosed smear positive pulmonary TB were recruited at Mulago Hospital, Kampala. All were started on standard short course chemotherapy and were randomly assigned to pentoxifylline 600 mg TID, or placebo, in a double-blind fashion, for four months.

Baseline clinical, immunologic, virologic, and hematologic characteristics of subjects in the two arms were recorded. Six subjects left the study voluntarily. The mean duration of survivor follow-up for the remaining patients was 522 days.

Plasma HIV RNA was measured in a random subset of 40 purified protein derivative-positive subjects. Both the time- weighted average and maximum change from baseline in log10 RNA were greater in the control arm (p=.049 and .053). Values at 12 months (eight months after completion of pentoxifylline) did not indicate a trend toward convergence of the arms. The time-weighted change in (beta)2m of pentoxifylline subjects was significantly less than in the control arm (p=.036). A trend was also seen for reduced neopterin in the pentoxifylline arm (p=.07). A trend toward reduced TNF(alpha) production in vitro was observed in the pentoxifylline arm (p=.27), and there was no effect on INFgamma production, serum TNF(alpha), or CD4 count.

Hemoglobin increased to a greater degree in anemic subjects assigned to pentoxifylline (p=.04). There was no effect on body mass (1.03 versus 0.975 kg/mo., respectively). No significant toxicity was seen and sputum cultures converted to negative equally in the two arms during the first three months. Seven treatment failures were identified (growth of M. tuberculosis after six months): five pentoxifylline, and two placebo (p=.17). All relapses occurred three or more months after completion of anti-TB therapy.

"The degree to which TNF(alpha) and HIV can be suppressed with pentoxifylline appears to be limited," Wallis et al. wrote in an abstract presented at the conference.

"Other TNF(alpha) inhibitors, such as rolipram TNF(alpha) convertase inhibitors, soluble TNF(alpha) receptors, thalidomide derivatives, or prednisone are considerably more potent than pentoxifylline or thalidomide in vitro. Clinical trials with these drugs may help to define the potential role for TNF(alpha) inhibition in HIV disease and in tuberculosis."

The corresponding author for this study is R.S. Wallis, Case Western Reserve University, Cleveland, Ohio.

Copyright (c) 1995 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.

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Copyright © 1996 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.