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Restoration of CD4 T‐cell responses to cytomegalovirus is short‐lived in severely immunodeficient HIV‐infected patients responding to highly active antiretroviral therapy
Author(s) -
Keane NM,
Price P,
Lee S,
Almeida CA,
Stone SF,
James I,
French MA
Publication year - 2004
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/j.1468-1293.2004.00245.x
Subject(s) - elispot , medicine , immunology , cd8 , cytomegalovirus , interferon gamma , t cell , immune system , immunopathology , lentivirus , cd4 t cell , human cytomegalovirus , interleukin 2 , antiretroviral therapy , viral load , virology , viral disease , virus , herpesviridae
Objectives To define the level of pathogen‐specific immune reconstitution persisting over 3 to 5 years of highly active antiretroviral therapy (HAART) in HIV‐infected patients who began therapy with CD4 T‐cell counts below 50 cells/μL. Methods Cytomegalovirus (CMV)‐specific T‐cell responses were analysed in adult HIV‐1‐infected patients with nadir CD4 T‐cell counts below 50 cells/μL before HAART. CMV‐specific CD4 T‐cell responses were measured by interferon‐γ enzyme‐linked immunospot assay (ELISpot assay), lymphoproliferation and interferon‐γ levels in cell culture supernatants. Results CD4 T‐cell responses to CMV were low in untreated patients and remained low during the first year on HAART, but increased progressively to levels similar to those found in HIV‐seronegative CMV‐seropositive controls at 3 years. Responses then declined markedly and at 5 years were lower than controls. This could not be explained by changes in CD4 or CD8 T‐cell counts or plasma HIV RNA levels. Interferon‐γ and interleukin‐5 responses to a mitogen were maintained or elevated. Conclusions CMV‐specific CD4 T‐cell responses were found to decline after 3–5 years on HAART and may provide inadequate long‐term protection against CMV disease in patients who are severely immunodeficient prior to treatment.