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AIDS. 2010 Jun 19;24(10):1455-60. doi: 10.1097/QAD.0b013e328339cf40.

Skewed T-cell maturation and function in HIV-infected patients failing CD4+ recovery upon long-term virologically suppressive HAART.

Author information

1
Department of Medicine, Surgery and Dentistry, Clinic of Infectious Diseases, San Paolo Hospital, University of Milan, Milan, Italy. giulia.marchetti@unimi.it

Abstract

OBJECTIVE:

Analysis of functionally defined T-cell differentiation in HIV-infected patients with low CD4(+) on virologically suppressive HAART is crucial to design clinically efficacious treatments.

METHODS:

We cross-sectionally investigated the maturation (CD45RA/CCR7, CD7) and function [antigen-specific enzyme-linked immunosorbent spot assay (ELISPOT), interleukin-2 (IL-2)/interferon-gamma-producing cells] of CD4(+) and CD8(+) T cells in 34 HIV-infected immunological nonresponders (INRs): CD4(+) cell count less than or equal to 200 cells/microl, HIV-RNA 50 copies/ml or less, as compared to 20 full responders (CD4(+) > 500 cells/microl, HIV-RNA < 50 copies/ml).

RESULTS:

We describe skewed T-cell maturation in INRs with outgrowth of effector memory CD45RA(-)CCR7(-) CD4(+)/CD8(+) and Th2-committed CD7(-)CD4(+), and reduced unprimed-naive T cells (P = 0.001). Functionally, INRs display reduced Gag-specific ELISPOT (P = 0.04) and IL-2-secreting CD8(+) (P = 0.08) while showing CMV-specific responses comparable to full responders.

CONCLUSION:

CD4 lymphopenia on HAART results in skewed, senescent T-cell maturation profile, inefficient T-helper function and poor HIV-specific CD8(+) response. This delineates a functional/phenotypic T-cell pattern that correlates to unfavourable clinical outcome.

PMID:
20539090
DOI:
10.1097/QAD.0b013e328339cf40
[Indexed for MEDLINE]

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