title: Potent antiretroviral therapy initiates normalization of hypergammaglobulinemia and a decline in HIV type 1-specific antibody responses.
abstract: Next to a profound T cell immunodeficiency, HIV-1 infection induces activation and dysfunction of B cells, resulting in hypergammaglobulinemia. Whereas T cell immune reconstitution with potent antiretroviral therapy has been extensively documented, limited data are available on B cell immune reconstitution. We studied the effect of potent antiretroviral therapy on antibody titers to the viral proteins gp120 and p24 and on total IgG concentrations. Three retrospectively chosen groups were studied: a successfully treated group, untreated controls, and subjects with virological failure after several months of successful therapy. In the successfully treated group, the median total IgG concentrations normalized, whereas they remained elevated in the untreated group and rebounded after an initial decline in the therapy failure group. The HIV-1-specific antibody titers declined in the successfully treated group and followed the rebound of the HIV RNA levels in the therapy failure group. With potent antiretroviral therapy the hypergammaglobulinemia normalized whereas HIV-1-specific immune responses were weakened. The weakening of antiviral immunity with therapy may be relevant for current attempts to gain immunological control over the virus through structured treatment interruptions or therapeutic vaccinations.
authors.affiliation: Division of Infectious Diseases, Tropical Medicine, and AIDS, AMC, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: D W
authors.initials: DW
authors.lastname: Notermans
authors.forename: J J
authors.initials: JJ
authors.lastname: de Jong
authors.forename: J
authors.initials: J
authors.lastname: Goudsmit
authors.forename: M
authors.initials: M
authors.lastname: Bakker
authors.forename: M T
authors.initials: MT
authors.lastname: Roos
authors.forename: L
authors.initials: L
authors.lastname: Nijholt
authors.forename: J
authors.initials: J
authors.lastname: Cremers
authors.forename: J A
authors.initials: JA
authors.lastname: Hellings
authors.forename: S A
authors.initials: SA
authors.lastname: Danner
authors.forename: A
authors.initials: A
authors.lastname: de Ronde
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D015483:HIV Antibodies / Q000187:drug effects*; D016655:HIV Core Protein p24 / Q000187:drug effects / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000187:drug effects / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D006801:Humans; D006942:Hypergammaglobulinemia / Q000188:drug therapy*; D007074:Immunoglobulin G / Q000276:immunology; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D019438:Ritonavir / Q000627:therapeutic use; D017211:Treatment Failure; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D012367:RNA, Viral; D019259:Lamivudine; D015215:Zidovudine; D019438:Ritonavir