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.
Morris
L
L
Aaron Diamond AIDS Research Center, The Rockefeller University, New York 10016, USA.
Binley
J M
JM
Clas
B A
BA
Bonhoeffer
S
S
Astill
T P
TP
Kost
R
R
Hurley
A
A
Cao
Y
Y
Markowitz
M
M
Ho
D D
DD
Moore
J P
JP
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