PENTOXIFYLLINE DECREASES TUMOR-NECROSIS-FACTOR EXPRESSION AND SERUM TRIGLYCERIDES IN PEOPLE WITH AIDS

Tumor necrosis factor-alpha (TNF)-cachectin increases the expression o f the human immunodeficiency virus (HIV), reverses the therapeutic eff icacy of zidovudine (ZDV), and may contribute to the wasting syndrome. Pentoxifylline (Trental) decreases TNF activity; in cell culture, it decreases HIV replication and down-regulates expression of the HIV lon g terminal repeat (LTR). Therefore, pentoxifylline was administered to 25 patients with advanced AIDS in this AIDS Clinical Trial Group stud y (ACTG # 160), the goal of which was to investigate the ability of th e drug to decrease TNF expression and HIV replication in this patient population. One patient discontinued drug treatment because of toxicit y. Data were analyzed on the 17 patients who completed the 8-week stud y treatment with pentoxifylline, 400 mg, thrice daily. The median pret reatment CD4+ lymphocyte count was 32 cells/mm3. Fasting serum triglyc erides, which have previously been shown to correlate with levels of i nterferon-alpha and/or TNF, fell on average by 66 mg/dl (p = 0.06). TN F mRNA levels in peripheral blood mononuclear cells fell in 10 of 16 p atients (p = 0.02). HIV load decreased and increased significantly in four and one patients, respectively, but did not change in the group a s a whole. This study demonstrates the safety of pentoxifylline in AID S patients and its ability to decrease triglycerides and TNF mRNA leve ls.