HIV-1 antigen-specific and -nonspecific B cell responses are sensitive to combination antiretroviral therapy.
We studied how combination antiviral therapy affects B cell abnormalities associated with HIV-1 infection, namely elevated circulating immunoglobulin (Ig)G antibody-secreting cell (ASC) frequencies and hypergammaglobulinemia. Within a few weeks of starting antiviral therapy, there is a marked decline in IgG-ASC frequency in both acutely and chronically infected people, whereas the hypergammaglobulinemia often present during chronic infection is more gradually resolved. These reductions are sustained while HIV-1 replication is suppressed. HIV-1 antigen-specific B cell responses are also affected by therapy, manifested by a rapid decline in circulating gp120-specific ASCs. Anti-gp120 titers slowly decrease in chronically infected individuals and usually fail to mature in acutely infected individuals who were promptly treated with antiretroviral therapy. Long-term nonprogressors have high titer antibody responses to HIV-1 antigens, but no detectable gp120-specific IgG-ASC, and normal (or subnormal) levels of total circulating IgG-ASC. Overall, we conclude that HIV-1 infection drives B cell hyperactivity, and that this polyclonal activation is rapidly responsive to decreases in viral replication caused by combination antiviral therapy.
Aaron Diamond AIDS Research Center, The Rockefeller University, New York 10016, USA.
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Morris
J M
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Binley
B A
BA
Clas
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Bonhoeffer
T P
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Astill
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Kost
A
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Hurley
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Cao
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Markowitz
D D
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J P
JP
Moore
D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology*; D004359:Drug Therapy, Combination; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans
D000998:Antiviral Agents; D015483:HIV Antibodies; D015488:HIV Antigens