The Kynurenine Pathway of Tryptophan Catabolism and AIDS-Associated Kaposi Sarcoma in Africa.

TitleThe Kynurenine Pathway of Tryptophan Catabolism and AIDS-Associated Kaposi Sarcoma in Africa.
Publication TypeJournal Article
Year of Publication2015
AuthorsByakwaga, H, Hunt, PW, Laker-Oketta, M, Glidden, DV, Huang, Y, Bwana, BM, A Mocello, R, Bennett, J, Walusansa, V, Dollard, SC, Bangsberg, DR, Mbidde, EK, Martin, JN
JournalJ Acquir Immune Defic Syndr
Volume70
Issue3
Pagination296-303
Date Published2015 Nov 1
ISSN1944-7884
Abstract

BACKGROUND: Other than Kaposi 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, interquartile range: 90 to 190 nM/μM) than KS cases (110, interquartile range: 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% confidence interval: 27% to 77%) in the odds of KS compared with 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.

DOI10.1097/QAI.0000000000000747
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID26181812
PubMed Central IDPMC4607630
Grant ListD43 CA153717 / CA / NCI NIH HHS / United States
R01 CA119903 / CA / NCI NIH HHS / United States
R21 AI078774 / AI / NIAID NIH HHS / United States
R56 AI100765 / AI / NIAID NIH HHS / United States