Abstract
The incidence of (EBV-related) malignancies in HIV-infected subjects has declined since the introduction of highly active antiretroviral therapy (HAART). To investigate the effect of HAART on EBV infection, we performed a longitudinal analysis of the T cell response to both a latent and a lytic Ag and EBV viral load in 10 subjects from early in HIV infection up to 5 years after HAART. All individuals responded to HAART by a decline in HIV viral load, a restoration of total CD4+ T cell numbers, and a decline in T cell immune activation. Despite this, EBV load remained unaltered, even after 5 years of therapy, although a decline in both CD4+ and CD8+ T cells specific for the lytic EBV protein BZLF1 suggested a decreased EBV reactivation rate. In contrast, latent EBV Ag EBNA1-specific CD4+ and CD8+ T cell responses were restored after 5 years of treatment to levels comparable to healthy individuals. In two individuals who were treated by HAART late during HIV progression, a lymphoma developed shortly after initiation of HAART, despite restoration of EBV-specific CD4+ and CD8+ T cells. In conclusion, long-term HAART does not alter the EBV DNA load, but does lead to a restoration of EBNA1-specific T cell responses, which might allow better control of EBV-infected cells when applied early enough during HIV infection.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Antiretroviral Therapy, Highly Active*
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / virology
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / virology
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Cytotoxicity, Immunologic / drug effects*
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Cytotoxicity, Immunologic / immunology
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DNA-Binding Proteins / immunology
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Disease Progression
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Epitopes, T-Lymphocyte / immunology
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Epstein-Barr Virus Nuclear Antigens / immunology
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HIV Infections / drug therapy*
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HIV Infections / immunology*
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HIV Infections / virology
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Herpesvirus 4, Human / drug effects
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Herpesvirus 4, Human / immunology*
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Humans
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Immunologic Memory / drug effects
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Longitudinal Studies
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology
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Lymphoma, Non-Hodgkin / drug therapy
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Lymphoma, Non-Hodgkin / immunology
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Lymphoma, Non-Hodgkin / virology
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Male
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Middle Aged
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Trans-Activators / immunology
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Viral Load
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Viral Proteins / immunology
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Virus Latency / drug effects
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Virus Latency / immunology*
Substances
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BZLF1 protein, Herpesvirus 4, Human
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DNA-Binding Proteins
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Epitopes, T-Lymphocyte
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Epstein-Barr Virus Nuclear Antigens
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Trans-Activators
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Viral Proteins
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EBV-encoded nuclear antigen 1