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. 2014 Jul 1;9(7):e100446.
doi: 10.1371/journal.pone.0100446. eCollection 2014.

Anti-retroviral therapy decreases but does not normalize indoleamine 2,3-dioxygenase activity in HIV-infected patients

Jun Chen  1 , Jiasheng Shao  1 , Rentian Cai  1 , Yinzhong Shen  1 , Renfang Zhang  1 , Li Liu  1 , Tangkai Qi  1 , Hongzhou Lu  2
Affiliations

Anti-retroviral therapy decreases but does not normalize indoleamine 2,3-dioxygenase activity in HIV-infected patients

Jun Chen et al. PLoS One. .

Abstract

Background: Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, catabolizes tryptophan to kynurenine and other downstream catabolites. It is known to be an immune mediator in HIV pathogenesis. The impact of anti-retroviral therapy on its activity has not been well established.

Methods: We measured systemic IDO activity (the ratio of plasma kynurenine to tryptophan) in HIV-infected patients before and after highly active antiretroviral therapy (HAART) and its association with a microbial translocation marker, soluble CD14 (sCD14).

Results: Among 76 participants, higher baseline IDO activity was associated with lower CD4+ T cell counts (P<0.05) and higher plasma sCD14 levels (P<0.001). After 1 year of HAART, IDO activity decreased significantly (P<0.01), but was still higher than in healthy controls (P<0.05). The baseline IDO activity did not predict CD4+ T cell recovery after 1 year of therapy. The percentages of myeloid and plasmacytoid dendritic cells were not correlated with IDO activity.

Conclusions: IDO activity is elevated in HIV-infected patients, which is partially associated with microbial translocation. HAART reduced, but did not normalize the activity of IDO.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. The impact of HAART on plasma concentrations of tryptophan (A) and kynurenine (B) and the activity of IDO (C) in HIV-infected patients.
NS, not significant; *, P<0.05; **, P<0.01; ***, P<0.001; ****, P<0.0001.
Figure 2
Figure 2. The relationship between CD4+ T cell counts and plasma concentrations of tryptophan (A) and kynurenine (B), and the activity of IDO (C) in HIV-infected patients.
The relationship between baseline IDO activity and CD4+ T cell counts after one year of therapy (D).
Figure 3
Figure 3. The relationship between plasma sCD14 levels and the kynurenine pathway of tryptophan catabolism.
The impact of HAART on the plasma concentrations of sCD14, including the relationship with the following: CD4+ T cell counts (A), CD4 to CD8 ratio (B), and plasma levels of sCD14 (C). The relationship between plasma sCD14 levels with tryptophan (D) and kynurenine (E) levels and the activity of IDO (F) in HIV-infected patients naïve to therapy. The correlation of IDO activity with sCD14 levels in patients after therapy (G) and in healthy controls (H).
Figure 4
Figure 4. The relationship between the percentages of DCs in PBMC with IDO activity.
(A) A comparison of the percentage of DCs in HIV-infected patients and healthy controls. The relationship between the percentage of pDCs (B) and mDCs (C) in PBMC with IDO activity in healthy controls and in HIV-infected patients (D and E).
See this image and copyright information in PMC

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