title: The Kynurenine Pathway of Tryptophan Catabolism and AIDS-Associated Kaposi Sarcoma in Africa.
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.
authors.affiliation: *Mbarara University of Science and Technology, Mbarara, Uganda; †University of California, San Francisco, CA; ‡Infectious Diseases Institute, Kampala, Uganda; §Uganda Cancer Institute, Kampala, Uganda; ‖Centers for Disease Control and Prevention, Atlanta, GA; ¶Massachusetts General Hospital, Center for Global Health, Harvard Medical School, Boston, MA; and #Uganda Virus Research Institute, Entebbe, Uganda.
authors.forename: Helen
authors.initials: H
authors.lastname: Byakwaga
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hunt
authors.forename: Miriam
authors.initials: M
authors.lastname: Laker-Oketta
authors.forename: David V
authors.initials: DV
authors.lastname: Glidden
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Bosco M
authors.initials: BM
authors.lastname: Bwana
authors.forename: A Rain
authors.initials: AR
authors.lastname: Mocello
authors.forename: John
authors.initials: J
authors.lastname: Bennett
authors.forename: Victoria
authors.initials: V
authors.lastname: Walusansa
authors.forename: Sheila C
authors.initials: SC
authors.lastname: Dollard
authors.forename: David R
authors.initials: DR
authors.lastname: Bangsberg
authors.forename: Edward K
authors.initials: EK
authors.lastname: Mbidde
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000453:epidemiology* / Q000378:metabolism*; D000328:Adult; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism; D007737:Kynurenine / Q000378:metabolism*; D008288:Malaria / Q000150:complications; D008297:Male; D012367:RNA, Viral; D012514:Sarcoma, Kaposi / Q000453:epidemiology* / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism*; D014376:Tuberculosis / Q000150:complications; D019562:Viral Load
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012367:RNA, Viral; D007737:Kynurenine; D014364:Tryptophan