Document Detail


Parallel decrease in neurotoxin quinolinic acid and soluble tumor necrosis factor receptor p75 in serum during highly active antiretroviral therapy of HIV type 1 disease.
MedLine Citation:
PMID:  10957719     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The chronic immune activation state in HIV disease leads to increased activity of the rate-limiting tryptophan-kynurenine pathway enzyme indoleamine 2,3-dioxygenase (2,3-IDO), thereby increasing the formation of neurotoxic tryptophan metabolites such as kynurenine and quinolinic acid. We investigated whether highly active antiretroviral therapy (HAART) (median duration, 100 days; range, 50-188 days) lowers serum levels of these metabolites in HIV-infected individuals and if so, whether this was paralleled by changes in a surrogate marker for immune activation, i.e., soluble tumor necrosis factor receptor p75 (sTNFR p75) concentrations. Baseline quinolinic acid (848 nM, 95% CI 567-1130 vs. 303 nM, 95% CI 267.1-339.5) and kynurenine (4.1 microM, 95% CI 3.3-4.9 vs. 2.7 microM, 95% CI 2.4-2.9) concentrations as well as the mean kynurenine-to-tryptophan ratio (108.2, 95% CI 76.1-140.4 vs. 51.4, 95% CI 47.6-55.3) in 17 HIV-1-infected outpatients (7 with AIDS) were significantly higher than those in 55 healthy age-matched controls (p < 0.01), respectively. Serum quinolinic acid concentrations in 14 of 17 patients decreased (mean, -44.4%) during HAART in comparison with baseline (471.2 nM, 95% CI 288-654.3; p = 0. 022). Thirteen of these 14 patients also had decreases in sTNFR p75 concentrations. Overall, the mean sTNFR p75 concentration decreased by 36.3% (13.5 ng/ml, 95% CI 9.3-17.8 vs. 8.6 ng/ml, 95% CI 5.9-11. 4; p = 0.01, n = 17). Reduction in viral load through HAART and subsequent mitigation of the pathological immune activation state in HIV disease may have reduced 2,3-IDO over activation. This eventually led to a decrease in quinolinic acid formation. The parallel reduction of the immune activation marker sTNFR p75 supports this hypothesis.
Authors:
M P Look; M Altfeld; K A Kreuzer; R Riezler; S P Stabler; R H Allen; T Sauerbruch; J K Rockstroh
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Publication Detail:
Type:  Clinical Trial; Journal Article    
Journal Detail:
Title:  AIDS research and human retroviruses     Volume:  16     ISSN:  0889-2229     ISO Abbreviation:  AIDS Res. Hum. Retroviruses     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2000-09-27     Completed Date:  2000-09-27     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  8709376     Medline TA:  AIDS Res Hum Retroviruses     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1215-21     Citation Subset:  IM; X    
Affiliation:
Department of General Internal Medicine, University of Bonn, Germany. Look@Uni-Bonn.de
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Anti-HIV Agents / therapeutic use*
Antigens, CD / blood*
Drug Therapy, Combination
Female
HIV Infections / drug therapy*
HIV-1 / physiology
Humans
Kynurenine / blood
Male
Middle Aged
Quinolinic Acid / blood*
RNA, Viral / blood
Receptors, Tumor Necrosis Factor / blood*
Receptors, Tumor Necrosis Factor, Type II
Reverse Transcriptase Inhibitors / therapeutic use*
Treatment Outcome
Tryptophan / blood
Viral Load
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Antigens, CD; 0/RNA, Viral; 0/Receptors, Tumor Necrosis Factor; 0/Receptors, Tumor Necrosis Factor, Type II; 0/Reverse Transcriptase Inhibitors; 343-65-7/Kynurenine; 73-22-3/Tryptophan; 89-00-9/Quinolinic Acid

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