Reconstitution of EBV latent but not lytic antigen-specific CD4+ and CD8+ T cells after HIV treatment with highly active antiretroviral therapy.
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.
Piriou
Erwan
E
Department of Clinical Viro-Immunology, Sanquin Research at CLB and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Jansen
Christine A
CA
van Dort
Karel
K
De Cuyper
Iris
I
Nanlohy
Nening M
NM
Lange
Joep M A
JM
van Oers
Marinus H J
MH
Miedema
Frank
F
van Baarle
Debbie
D
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects* / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D008137:Longitudinal Studies; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D015534:Trans-Activators / Q000276:immunology; D019562:Viral Load; D014764:Viral Proteins / Q000276:immunology; D017735:Virus Latency / Q000187:drug effects / Q000276:immunology*
C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte; D019309:Epstein-Barr Virus Nuclear Antigens; D015534:Trans-Activators; D014764:Viral Proteins; C417029:EBV-encoded nuclear antigen 1