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HIV-patients discrimination according to phenotype and functional assay of T-cells subsets

Background

To distinguish HIV-1 patients with clinical diversity by using a simplified model of T-cell interactions

Methods

During 28 months, 1074 blood samples from 200 HIV-1 patients and 418 blood samples from healthy blood donors were prospectively collected. T lymphocyte subsets and activation markers expression (CD4, CD69, CD25, CD8, CD28, HLA-DR) were determined initially and after PHA stimulation in whole blood cultures.

Results

Two step Cluster Analysis followed by a discriminant function analysis of the lymphocyte activation assay from the first blood sample, allowed the separation of HIV-1 patients in two groups: Cluster1 (67%) and Cluster2 (33%). Clusters definition relied on the level of three T-cells subsets: a) stimulated CD4+CD69+CD25high, b) unstimulated CD4+CD69+CD25+ and c) unstimulated CD4+CD25high. PHA stimulated CD4+CD69+ CD25high subset level alone allowed to classify correctly patients with 92% sensitivity and 87% specificity. Cluster-2 expressed more CD69 and HLA-DR activation markers on CD4 and CD8 lymphocytes, less CD8+CD28+ and responded less to mitogen even if viral load undetectable. Cluster-2 presented poorly clinical profile in terms of previous AIDS events, current CD4+ count, viral load, length of treatment. Over the time most patients (64%) were keeping their cluster category.

Discussion

We propose an algorithm to identify a subset of HIV patients with an over-determined immunodeficiency status characterized by a lower ability to reverse inappropriate activation of CD4 and CD8 T-lymphocytes leading probably to earlier exhaustion of their immunological resources. This subgroup of patients could display a worst clinical evolution, lower control capacity of viral load, even under antiretroviral therapy-mediated viral suppression.

Author information

Correspondence to Marie-Paule Guillaume.

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Keywords

  • Viral Load
  • Discriminant Function Analysis
  • Healthy Blood Donor
  • Cluster Category
  • Cluster Definition