HIV-1 Antigen-specific and -nonspecific B Cell Responses Are Sensitive to Combination Antiretroviral Therapy

doi:10.1084/jem.188.2.233

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J. Exp. Med., Volume 188, Number 2, July 20, 1998 233-245

HIV-1 Antigen-specific and -nonspecific B Cell Responses Are Sensitive to Combination Antiretroviral Therapy

By Lynn Morris, James M. Binley, Brian A. Clas, Sebastian Bonhoeffer, Thomas P. Astill, Rhonda Kost, Arlene Hurley, Yunzhen Cao, Martin Markowitz, David D. Ho, and John P. Moore

From the Aaron Diamond AIDS Research Center, The Rockefeller University, New York 10016

We studied how combination antiviral therapy affects B cell abnormalities associated with HIV-1 infection, namely elevatedcirculating immunoglobulin (Ig)G antibody-secreting cell (ASC)frequencies and hypergammaglobulinemia. Within a few weeks ofstarting antiviral therapy, there is a marked decline in IgG-ASCfrequency in both acutely and chronically infected people, whereasthe hypergammaglobulinemia often present during chronic infectionis more gradually resolved. These reductions are sustained whileHIV-1 replication is suppressed. HIV-1 antigen-specific B cellresponses are also affected by therapy, manifested by a rapiddecline in circulating gp120-specific ASCs. Anti-gp120 titersslowly decrease in chronically infected individuals and usuallyfail to mature in acutely infected individuals who were promptlytreated with antiretroviral therapy. Long-term nonprogressorshave high titer antibody responses to HIV-1 antigens, but no detectablegp120-specific IgG-ASC, and normal (or subnormal) levels of totalcirculating IgG-ASC. Overall, we conclude that HIV-1 infectiondrives B cell hyperactivity, and that this polyclonal activationis rapidly responsive to decreases in viral replication causedby combination antiviral therapy.

Key words: hypergammaglobulinemia; human immunodeficiency virus 1; B cells; antiretroviral therapy; antibody

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