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

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/mu l, HIV-RNA 50 copies/ml or less, as compared to 20 full responders (CD4(+) >500 cells/mu l, 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. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins