title: Long-term highly active antiretroviral therapy in chronic HIV-1 infection: evidence for reconstitution of antiviral immunity.
abstract: In this study we investigated the long-term effect of highly active antiretroviral therapy (HAART) on HIV-specific CD4+ T-cell responses in comparison with virus-specific CD4+ T-cell responses against the persistent herpes viruses cytomegalovirus (CMV) and Epstein-Barr virus (EBV). To this end, HIV- and herpes virus-specific cellular immune responses were measured longitudinally in 10 seroconverters with long-term follow-up including 55 months of successful suppression of viral load by HAART. HIV- and CMV-specific CD4+ T cells producing interferon-gamma (IFNgamma) or interleukin-2 (IL-2) were analysed as well as proliferative capacity. EBV-specific CD4+ T cells were determined using a 12-day ex vivo assay. Initiation of HAART resulted in a transient increase of HIV-specific IL-2(+)IFNgamma(+)CD4(+) T cells and, to a lesser extent, IL-2(+)CD4(+) T cells. Long-term HAART resulted in an increase in HIV-, CMV- and EBV-specific CD4+ T-cell proliferative capacity. The increase in HIV- and herpes-virus-specific CD4+ T-cell proliferative capacity after 55 months of HAART suggests that the improved proliferative response is not specific for HIV, but reflects a more general improvement of antiviral immune responses, which is induced by HAART.
authors.affiliation: Department of Clinical Viro-Immunology, Sanquin Research at CLB and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, the Netherlands.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Jansen
authors.forename: Erwan
authors.initials: E
authors.lastname: Piriou
authors.forename: Iris M
authors.initials: IM
authors.lastname: De Cuyper
authors.forename: Karel
authors.initials: K
authors.lastname: van Dort
authors.forename: Joep M A
authors.initials: JM
authors.lastname: Lange
authors.forename: Frank
authors.initials: F
authors.lastname: Miedema
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D003587:Cytomegalovirus / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D013997:Time Factors; D016896:Treatment Outcome