Indoleamine 2,3 dioxygenase, age, and immune activation in people living with HIV

Stephanie L. Baer, Rhonda E. Colombo, Maribeth H. Johnson, Sushama Wakade, Gabriela Pacholczyk, Cheryl Newman-Whitlow, Stuart A. Thompson, Michael S. Saag, Jeffrey N. Martin, Michelle Floris-Moore, Lei Huang, Andrew L. Mellor

Research output: Contribution to journalArticlepeer-review

Abstract

Immune activation complicates HIV despite antiretroviral therapy (ART). Indoleamine 2,3 dioxygenase (IDO) catabolizes tryptophan (T) to kynurenine (K), regulating immune activity, and IDO activity increases with age. This study examines the relationship of IDO activity, bacterial translocation, and aging in people living with HIV (PLWH) on ART. Samples and data from PLWH on ART from the Centers for AIDS Research Network of Integrated Clinical Systems and from matched HIV-uninfected patients (controls) from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study were analyzed. The ratio of K to T (K:T) and neopterin were indicators of inflammation; 16S ribosomal DNA (16S rDNA) and lipopolysaccharide (LPS) were markers of bacterial translocation. Samples and data from 205 PLWH and 99 controls were analyzed. PLWH had higher K:T values across all ages, with a significant relationship between age and K:T for both groups. CD4 count or CD4 nadir had no association with K:T. There was no positive association between level of 16S rDNA or LPS detection and K:T. K:T and neopterin were associated. PLWH had elevated IDO activity, at younger ages, despite ART. This study suggests K:T ratio increases with age in both groups and is elevated in PLWH at all ages compared with age-matched controls.

Original languageEnglish (US)
Pages (from-to)1238-1244
Number of pages7
JournalJournal of Investigative Medicine
Volume69
Issue number6
DOIs
StatePublished - Aug 1 2021

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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