Immunosuppressive Tryptophan Catabolism and Gut Mucosal Dysfunction Following Early HIV Infection

J Infect Dis. 2015 Aug 1;212(3):355-66. doi: 10.1093/infdis/jiv037. Epub 2015 Jan 23.


Background: Tryptophan (Trp) catabolism into kynurenine (Kyn) contributes to immune dysfunction in chronic human immunodeficiency virus (HIV) infection. To better define the relationship between Trp catabolism, inflammation, gut mucosal dysfunction, and the role of early antiretroviral therapy (ART), we prospectively assessed patients early after they acquired HIV.

Methods: Forty patients in the early phase of infection were longitudinally followed for 12 months after receiving a diagnosis of HIV infection; 24 were untreated, and 16 were receiving ART. Kyn/Trp ratio, regulatory T-cells (Tregs) frequency, T-cell activation, dendritic cell counts, and plasma levels of gut mucosal dysfunction markers intestinal-type fatty acid-binding protein, soluble suppression of tumorigenicity 2, and lipopolysaccharide were assessed.

Results: Compared with healthy subjects, patients in the early phase of infection presented with elevated Kyn/Trp ratios, which further increased in untreated patients but normalized in ART recipients. Accordingly, in untreated subjects, the elevated Treg frequency observed at baseline continued to increase over time. The highest CD8(+) T-cell activation was observed during the early phase of infection and decreased in untreated patients, whereas activation normalized in ART recipients. The Kyn/Trp ratio was positively associated with CD8(+) T-cell activation and levels of inflammatory cytokines (interleukin 6, interferon γ-inducible protein 10, interleukin 18, and tumor necrosis factor α) and negatively associated with dendritic cell frequencies at baseline and in untreated patients. However, ART did not normalize plasma levels of gut mucosal dysfunction markers.

Conclusions: Early initiation of ART normalized enhanced Trp catabolism and immune activation but did not improve plasma levels of gut mucosal dysfunction markers.

Keywords: ART; HIV early infection; dendritic cells; gut mucosal dysfunction; indoleamine 2,3-dioxygenase-1 (IDO-1); inflammation; microbial translocation; regulatory T-cells (Tregs); sST2; tryptophan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Retroviral Agents / therapeutic use
  • Biomarkers / analysis
  • Dendritic Cells / immunology
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • Humans
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / metabolism
  • Kynurenine / immunology
  • Kynurenine / metabolism
  • Longitudinal Studies
  • Middle Aged
  • T-Lymphocytes, Regulatory / immunology
  • Tryptophan / immunology*
  • Tryptophan / metabolism


  • Anti-Retroviral Agents
  • Biomarkers
  • Kynurenine
  • Tryptophan