Publication Title

Journal of Acquired Immune Deficiency Syndromes

Document Type

Post-Print

Publication Date

7-7-2015

Subjects

Kaposi's sarcoma, Amino acids -- Metabolism, Kynurenine -- Metabolism, AIDS (Disease) -- Treatment -- Uganda

Physical Description

17 pages

Abstract

Background—Other than Kaposi's sarcoma (KS)-associated herpesvirus and CD4+ T cell lymphopenia, the mechanisms responsible for KS in the context of HIV are poorly understood. One recently explored pathway of HIV pathogenesis involves induction of the enzyme indoleamine 2,3 dioxygenase-1 (IDO), which catabolizes tryptophan into kynurenine and several other immunologically active metabolites that suppress T cell proliferation. We investigated the role of IDO in the development of KS in HIV disease.

Methods—In a case-control study among untreated HIV-infected Ugandans, cases were adults with KS and controls were without KS. IDO activity was assessed by the ratio of plasma kynurenine to tryptophan levels (KT ratio), measured by liquid chromatography tandem mass spectrometry.

Results—We studied 631 HIV-infected subjects: 222 KS cases and 409 controls. Non-KS controls had a higher median plasma KT ratio (130, IQR: 90 to190 nM/μM) than cases (110, IQR: 90 to 150 nM/μM) (p = 0.004). After adjustment for age, sex, CD4 count and plasma HIV RNA level, subjects with the highest (fourth quartile) plasma KT ratios had a 59% reduction (95% CI: 27% to 77%) in the odds of KS compared to those with the lowest (first quartile) levels. KS was also independently associated with lower CD4+ count, higher plasma HIV RNA, and men.

Conclusions—Among HIV-infected individuals, greater activity of the kynurenine pathway of tryptophan catabolism, as evidenced by higher levels of plasma KT ratio, was associated with lower occurrence of KS. Some consequences of immune activation in HIV infection might actually suppress certain cancers.

Description

This is the author's version of an article published in final edited form as: J Acquir Immune Defic Syndr. 2015 November 1; 70(3): 296–303. doi:10.1097/QAI.0000000000000747.

Copyright © 2015 Wolters Kluwer Health, Inc.

This work was previously presented in part at the 14th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies in Bethesda, Maryland, on November 12-13, 2013 and at the 21st Conference on Retroviruses and Opportunistic Infections in Boston, Massachusetts, on March 3-6, 2014.

Note: At the time of writing, David Bangsberg was affiliated with Massachusetts General Hospital, Center for Global Health, Harvard Medical School, Boston, Massachusetts.

DOI

10.1097/QAI.0000000000000747

Persistent Identifier

http://archives.pdx.edu/ds/psu/19046

Publisher

Wolters Kluwer Health, Inc.

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