HIGH-DOSE PENTOXIFYLLINE IN PATIENTS WITH AIDS - INHIBITION OF TUMOR-NECROSIS-FACTOR PRODUCTION

Tumor necrosis factor-alpha (TNF) may activate human immunodeficiency virus (HIV), antagonize zidovudine activity, and contribute to AIDS wa sting syndrome. Pentoxifylline decreases TNF production. In cell cultu re, pentoxifylline decreases HIV replication and gene expression, Sinc e an AIDS Clinical Trial Group study suggested that pentoxifylline (40 0 mg thrice daily) is safe in AIDS patients and decreases TNF mRNA lev els in peripheral blood mononuclear cells (PBMC), a second cohort rece ived 800 mg thrice daily for 8 weeks, During treatment, the median dec rease in TNF production by PBMC cultured with 0.1 mu g/mL lipopolysacc haride (LPS) was 40%. The median change in TNF mRNA was a 34% decrease , Pentoxifylline did not affect HIV levels as detected by quantitative microculture or serum p24 antigen measurements, nor did it alter zido vudine pharmacokinetics. The most common toxicity was gastrointestinal . Pentoxifylline at dosages of less than thrice-daily 800 mg is well t olerated and may decrease TNF mRNA levels and LPS-induced TNF producti on.