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M94A2833.TXT
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1994-10-25
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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).