The kynurenine pathway of tryptophan catabolism and AIDS-associated kaposi sarcoma in Africa

Helen Byakwaga, Peter W. Hunt, Miriam Laker-Oketta, David V. Glidden, Yong Huang, Bosco M. Bwana, A. Rain Mocello, John Bennett, Victoria Walusansa, Sheila C. Dollard, David R. Bangsberg, Edward K. Mbidde, Jeffrey N. Martin

Research output: Contribution to journalArticle

8 Scopus citations

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/mM) than KS cases (110, interquartile range: 90 to 150 nM/mM) (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.

Original languageEnglish (US)
Pages (from-to)296-303
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume70
Issue number3
DOIs
StatePublished - Jan 1 2015

Keywords

  • Africa
  • HIV
  • Indoleamine 2 3-dioxygenase-1
  • Kaposi sarcoma
  • Kynurenine
  • Plasma HIV RNA
  • Tryptophan

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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  • Cite this

    Byakwaga, H., Hunt, P. W., Laker-Oketta, M., Glidden, D. V., Huang, Y., Bwana, B. M., Mocello, A. R., Bennett, J., Walusansa, V., Dollard, S. C., Bangsberg, D. R., Mbidde, E. K., & Martin, J. N. (2015). The kynurenine pathway of tryptophan catabolism and AIDS-associated kaposi sarcoma in Africa. Journal of Acquired Immune Deficiency Syndromes, 70(3), 296-303. https://doi.org/10.1097/QAI.0000000000000747