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Published online on March 18, 2003, 10.1073/pnas.0630530100

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Medical Sciences
Rapid evolution of the neutralizing antibody response to HIV type 1 infection

Douglas D. Richman *{dagger}, Terri Wrin {ddagger}, Susan J. Little *, and Christos J. Petropoulos {ddagger}

*Departments of Pathology and Medicine, Veterans Affairs San Diego Healthcare System and the University of California at San Diego, La Jolla, CA 92093-0679; and {ddagger}ViroLogic, Inc., 345 Oyster Point Boulevard, South San Francisco, CA 94080

Communicated by Robert M. Chanock, National Institutes of Health, Bethesda, MD, January 28, 2003 (received for review December 10, 2002)

A recombinant virus assay was used to characterize in detail neutralizing antibody responses directed at circulating autologous HIV in plasma. Examining serial plasma specimens in a matrix format, most patients with primary HIV infection rapidly generated significant neutralizing antibody responses to early (0-39 months) autologous viruses, whereas responses to laboratory and heterologous primary strains were often lower and delayed. Plasma virus continually and rapidly evolved to escape neutralization, indicating that neutralizing antibody exerts a level of selective pressure that has been underappreciated based on earlier, less comprehensive characterizations. These data argue that neutralizing antibody responses account for the extensive variation in the envelope gene that is observed in the early months after primary HIV infection.

{dagger}To whom correspondence should be addressed at: Departments of Pathology and Medicine, Veterans Affairs San Diego Healthcare System and University of California at San Diego, 0679, 9500 Gilman Drive, La Jolla, CA 92093-0679.

E-mail: drichman{at}ucsd.edu.

www.pnas.org/cgi/doi/10.1073/pnas.0630530100
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