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J Acquir Immune Defic Syndr. 2016 Oct 1;73(2):138-48. doi: 10.1097/QAI.0000000000001080.

Plasma IP-10 Is Increased in Immunological NonResponders and Associated With Activated Regulatory T Cells and Persisting Low CD4 Counts.

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*Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway;†Department of Infectious Diseases, Institute of Clinical Medicine, University of Oslo, Oslo, Norway;‡Centre for Molecular Medicine Norway, Nordic EMBL Partnership, Oslo University Hospital, University of Oslo, Oslo, Norway;§Biotechnology Centre, University of Oslo, Oslo, Norway;‖K.G. Jebsen Centre for Inflammation Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway;¶Department of Immunology, Oslo University Hospital, Oslo, Norway;#Research Laboratory, Nordland Hospital, Bodø, Norway;**Faculty of Health Sciences, K.G. Jebsen TREC, University of Tromsø, Norway;††Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway;‡‡Department of Clinical Science, University of Bergen, Bergen, Norway;§§Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway;‖‖Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Oslo, Norway; and¶¶Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Oslo, Norway.



To explore immune mechanisms and identify biomarkers associated with an inadequate immune recovery in patients with HIV with efficient antiretroviral therapy.


A cross-sectional study of 67 HIV-infected patients on antiretroviral therapy for ≥24 months with HIV RNA ≤20 copies per milliliter; 41 were defined as immunological nonresponders (INR) (CD4 < 400 cells per microliter) and 26 as immunological responders (CD4 > 600 cells per microliter). CD4 counts were also registered 2 years after inclusion.


Cytokines, soluble markers of microbial translocation, and tryptophan catabolites were measured in plasma by multiplex assay, ELISA, or mass spectrometry. T-cell activation, differentiation, and regulatory T cells (Tregs) were analyzed by flow cytometry in 2 subgroups with comparable nadir CD4 counts.


Plasma interferon-inducible protein-10 (IP-10) levels were higher (P < 0.05), the T cells were more activated (CD38HLA-DR) (P < 0.05), the naive/effector memory T-cell ratio was lower (P < 0.01) and the proportion of resting Tregs (CD4CD45RAFoxP3) was reduced (P < 0.001) in INR patients compared with immunological responders. INR patients with CD4 counts ≤300 cells per microliter also demonstrated a higher fraction of activated Tregs (aTreg) (CD4CD147CD25) (P < 0.05). In the INR group, the aTreg percentages correlated with plasma IP-10 levels and inversely with CD4 counts (both P < 0.01). IP-10 levels (P < 0.05) and kynurenine/tryptophan ratio (P < 0.01) were negatively associated with the CD4 count 2 years after inclusion.


Patients with HIV with inadequate CD4 responses had higher levels of IP-10, more activated and differentiated T-cell phenotypes, as well as aTreg, compared with patients with satisfactory CD4 gain. High IP-10 levels were also associated with lower CD4 counts after 2 years.

[Indexed for MEDLINE]

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