The Kynurenine Pathway of Tryptophan Catabolism, CD4+ T-Cell Recovery, and Mortality Among HIV-Infected Ugandans Initiating Antiretroviral Therapy

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dc.contributor.authorByakwaga, Helen
dc.contributor.authorBoum, Yap
dc.contributor.authorHuang, Yong
dc.contributor.authorMuzoora, Conrad
dc.contributor.authorKembabazi, Annet
dc.contributor.authorWeiser, Sheri D.
dc.contributor.authorBennett, John
dc.contributor.authorCao, Huyen
dc.contributor.authorHaberer, Jessica E.
dc.contributor.authorDeeks, Steven G.
dc.contributor.authorBangsberg, David R.
dc.contributor.authorMcCune, Joseph M.
dc.contributor.authorMartin, Jeffrey N.
dc.contributor.authorHunt, Peter W.
dc.date.accessioned2022-01-31T16:14:03Z
dc.date.available2022-01-31T16:14:03Z
dc.date.issued2014
dc.description.abstractHuman immunodeficiency virus (HIV) infection–induced indoleamine 2,3-dioxygenase-1 (IDO) expression in activated monocytes and dendritic cells catabolizes tryptophan to kynurenine and other downstream catabolites that inhibit T-cell proliferation and interleukin 17 (IL-17) production. The prognostic significance of this pathway in treated HIV disease is unknown. We measured systemic IDO activity (calculated as the ratio of plasma levels of kynurenine to tryptophan; hereafter, the “KT ratio”) in HIV-infected Ugandans before and during antiretroviral therapy (ART)–mediated viral suppression and its association with the rate of subsequent CD4+ T-cell count recovery and mortality. Among 435 participants, a higher pre-ART KT ratio was associated with a higher plasma virus load (P < .001) and lipopolysaccharide level (P = .018), a lower CD4+ T-cell count (P < .001), and female sex (P = .047). Through month 12 of ART-mediated viral suppression, the plasma KT ratio decreased by approximately 50% (P < .001). After adjustment for pre-ART CD4+ T-cell count, virus load, age, and sex, a higher month 12 KT ratio predicted a slower rate of subsequent CD4+ T-cell count recovery (P = .001). Thirty-nine participants died. After adjustment for pre-ART CD4+ T-cell count, virus load, body mass index, sex, and age, a higher pre-ART and month 6 KT ratio predicted increased mortality (P ≤ .016). The kynurenine pathway of tryptophan catabolism independently predicts poor CD4+ T-cell count recovery and increased mortality among HIV-infected Ugandans initiating ART and may be an important target for interventions.en_US
dc.identifier.citationByakwaga, H., Boum, Y., Huang, Y., Muzoora, C., Kembabazi, A., Weiser, S. D., ... & Hunt, P. W. (2014). The kynurenine pathway of tryptophan catabolism, CD4+ T-cell recovery, and mortality among HIV-infected Ugandans initiating antiretroviral therapy. The Journal of infectious diseases, 210(3), 383-391. DOI: 10.1093/infdis/jiu115en_US
dc.identifier.other10.1093/infdis/jiu115
dc.identifier.urihttps://nru.uncst.go.ug/xmlui/handle/123456789/1690
dc.language.isoenen_US
dc.publisherThe Journal of infectious diseasesen_US
dc.subjectTryptophanen_US
dc.subjectKynurenineen_US
dc.subjectIndoleamine 2en_US
dc.subject3-dioxygenase-1en_US
dc.subjectHIVen_US
dc.subjectMortalityen_US
dc.subjectAntiretroviral therapyen_US
dc.subjectUgandaen_US
dc.titleThe Kynurenine Pathway of Tryptophan Catabolism, CD4+ T-Cell Recovery, and Mortality Among HIV-Infected Ugandans Initiating Antiretroviral Therapyen_US
dc.typeArticleen_US
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