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Anti-Retroviral Therapy Decreases but Does Not Normalize Indoleamine 2,3-Dioxygenase Activity in HIV-Infected Patients
Authors:Jun Chen  Jiasheng Shao  Rentian Cai  Yinzhong Shen  Renfang Zhang  Li Liu  Tangkai Qi  Hongzhou Lu
Institution:1. Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.; 2. Department of Infectious Diseases, HuaShan Hospital, Fudan University, Shanghai, China.; 3. Department of Internal Medicine, Shanghai Medical College, Fudan University, Shanghai, China.; University Hospital of Heidelberg, Germany,
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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