Potent antiretroviral therapy initiates normalization of hypergammaglobulinemia and a decline in HIV type 1-specific antibody responses

Next to a profound T cell immunodeficiency, HIV-1 infection induces activat ion and dysfunction of B cells, resulting in hypergammaglobulinemia. Wherea s T cell immune reconstitution with potent antiretroviral therapy has been extensively documented, limited data are available on B cell immune reconst itution. 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 seve ral months of successful therapy. In the successfully treated group, the me dian 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 successfu lly treated group and followed the rebound of the HIV RNA levels in the the rapy failure group. With potent antiretroviral therapy the hypergammaglobul inemia normalized whereas HIV-1-specific immune responses were weakened. Th e weakening of antiviral immunity with therapy may be relevant for current attempts to gain immunological control over the virus through structured tr eatment interruptions or therapeutic vaccinations.