Restoration of CD4 T-cell responses to cytomegalovirus is short-lived in severely immunodeficient HIV-infected patients responding to highly active antiretroviral therapy.
OBJECTIVE
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/microL.


METHODS
Cytomegalovirus (CMV)-specific T-cell responses were analysed in adult HIV-1-infected patients with nadir CD4 T-cell counts below 50 cells/microL before HAART. CMV-specific CD4 T-cell responses were measured by interferon-gamma enzyme-linked immunospot assay (ELISpot assay), lymphoproliferation and interferon-gamma 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-gamma 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.
Keane
N M
NM
Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Perth, WA, Australia.
Price
P
P
Lee
S
S
Almeida
C A
CA
Stone
S F
SF
James
I
I
French
M A
MA
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology; D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000276:immunology; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood
D000956:Antigens, Viral; D015848:Interleukin-5; D012367:RNA, Viral; D007371:Interferon-gamma