Document 2833
 DOCN  M94A2833
 TI    Pentoxifylline decreases TNF in AIDS patients.
 DT    9412
 AU    Dezube BJ; Lederman M; Spritzler J; Ahlers C; Pardee AB; Crumpacker CS;
       Beth Israel Hosp, Boston, MA 02115.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):214 (abstract no. PB0285). Unique
       Identifier : AIDSLINE ICA10/94369742
 AB    OBJECTIVES: To ascertain if pentoxifylline (Trental, PTX), a tumor
       necrosis factor (TNF) synthesis inhibitor, can decrease TNF and HIV
       expression in AIDS patients. METHODS: AIDS patients, on AZT, ddI, ddC or
       a combination thereof for > 2 months, received PTX 400 mg (Cohort I) or
       800 mg (Cohort II) thrice daily for 8 weeks. Analysis was restricted to
       patients who received 8 weeks of PTX. Viral assays included ICD p24
       antigen and quantitative coculture (changes of > 0.5 log10 considered
       meaningful). TNF assays included TNF mRNA levels in peripheral blood
       mononuclear cells (PBMCs) and inducible TNF protein levels in the
       supernatant of PBMCs cultured in the presence of 0.1 microgram/ml
       lipopolysaccharide (LPS). AZT levels were measured on day 0 (patients on
       AZT alone) and days 7 & 28 (patients on combination AZT & PTX). This is
       an original report representing the final analysis of the data from both
       cohorts. RESULTS: Cohort I-Results of this Cohort only reported in J.
       AIDS, 6:787 (1993). 17 patients completed treatment. The median change
       in TNF mRNA was a 29% decrease. HIV load decreased in 4 patients and
       increased in 1 patient, but did not change in the group as a whole.
       Cohort II--16 patients completed treatment. The median change in TNF
       mRNA was a 34% decrease. There was a median 40% decrease in the
       production of TNF by PBMCs cultured in the presence of LPS (p = 0.016).
       HIV load decreased in 6 patients and increased in 3 patients, but did
       not change in the group as a whole. p24 antigen level did not change.
       PTX did not alter AZT pharmacokinetics (AUC, Cmax). 13% of all enrolled
       patients in this Cohort discontinued PTX early due to gastrointestinal
       toxicity. CONCLUSIONS: PTX at 400 mg, thrice daily, is safe and
       well-tolerated, whereas 800 mg, thrice daily, is not as well-tolerated
       because of gastrointestinal side effects. PTX may decrease PBMC TNF mRNA
       levels or LPS-induced TNF production. PTX may be of value in instances
       where TNF expression is predictably elevated (e.g., TB complicating HIV
       infection) or in selected HIV-infected patients with heightened TNF
       expression.
 DE    Acquired Immunodeficiency Syndrome/BLOOD/*DRUG THERAPY  Cells, Cultured
       Cohort Studies  Comparative Study  Depression, Chemical
       Didanosine/ADMINISTRATION & DOSAGE/THERAPEUTIC USE  Gastrointestinal
       Diseases/CHEMICALLY INDUCED  Human  Leukocytes, Mononuclear/*DRUG
       EFFECTS/METABOLISM  Pentoxifylline/ADVERSE
       EFFECTS/*PHARMACOLOGY/THERAPEUTIC USE  RNA, Messenger/BIOSYNTHESIS
       Tumor Necrosis Factor/*BIOSYNTHESIS  Zalcitabine/ADMINISTRATION &
       DOSAGE/THERAPEUTIC USE  Zidovudine/ADMINISTRATION & DOSAGE/THERAPEUTIC
       USE  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).