Cytomegalovirus-Specific T Cells Persist at Very High Levels during Long-Term Antiretroviral Treatment of HIV Disease

• Published in: PloS one Vol. 5; no. 1; p. e8886
• Main Authors: Naeger, David M., Martin, Jeffrey N., Sinclair, Elizabeth, Hunt, Peter W., Bangsberg, David R., Hecht, Frederick, Hsue, Priscilla, McCune, Joseph M., Deeks, Steven G.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.01.2010; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adult; Adults; Age; Aging; AIDS; Anti-HIV Agents - therapeutic use; Antiretroviral agents; Antiretroviral drugs; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; Chronic infection; Cohort Studies; Comparative analysis; Cytomegalovirus; Cytomegalovirus - immunology; Cytometry; Drug therapy; Effector cells; Female; Flow Cytometry; Geriatrics; Health aspects; Highly active antiretroviral therapy; HIV; HIV infections; HIV Infections - drug therapy; HIV Infections - immunology; HIV patients; Human immunodeficiency virus; Humans; Immunodeficiency; Immunology/Immune Response; Immunosenescence; Infection; Infectious Diseases/HIV Infection and AIDS; Infectious Diseases/Viral Infections; Inflammation; Inflammatory response; Interferon-gamma - immunology; Interleukin-2 - immunology; Lymphocytes; Lymphocytes T; Male; Medical treatment; Middle Aged; Morbidity; Mortality; Older people; Patients; Pp65 protein; Proteins; T cells; San Francisco California; California; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0008886

In healthy, HIV seronegative, CMV seropositive adults, a large proportion of T cells are CMV-specific. High-level CMV-specific T cell responses are associated with accelerated immunologic aging ("immunosenesence") in the elderly population. The impact of untreated and treated HIV infection on the frequency of these cells remains undefined. We measured the proportion of CD4+ and CD8+ T cells responding to CMV pp65 and IE proteins was measured using flow cytometry in 685 unique HIV seronegative and seropositive individuals. The proportion of CMV-specific CD8+ T cells was consistently higher in the HIV-seropositive subjects compared to the HIV-seronegative subjects. This HIV effect was observed even in patients who lacked measurable immunodeficiency. Among the HIV-seropositive subjects, CMV-specific CD8+ T cell responses were proportionately lower during recent infection, higher during chronic untreated infection and higher still during long-term antiretroviral treated infection. The CD8+ T cell response to just two CMV proteins (pp65 and IE) was approximately 6% during long-term therapy, which was over twice that seen in HIV-seronegative persons. CMV-specific CD4+ T cell responses followed the same trends, but the magnitude of the effect was smaller. Long-term successfully treated HIV infected patients have remarkably high levels of CMV-specific effector cells. These levels are similar to that observed in the elderly, but occur at much younger ages. Future studies should focus on defining the potential role of the CMV-specific inflammatory response in non-AIDS morbidity and mortality, including immunosenescence.