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Session 10 Oral Abstract Session Late Breakers I Session Time: Monday, 2 pm - 4 pm Room 6E

3:00   LB5. Rapid Evolution of the Neutralizing Antibody Response following Primary HIV Infection D. D. Richman*1, T. Wrin2, S. Little1, and C. Petropoulos2 1VA San Diego Healthcare System and Univ. of California, San Diego and 2ViroLogic, Inc., South San Francisco, CA Background: The measurement of neutralizing antibody responses to autologous virus has been technically challenging. Using a novel HIV entry assay, we have evaluated the co-evolution of HIV envelope and neutralizing antibody from plasma following primary HIV-1 infection. Methods: Recombinant viruses pseudotyped with patient virus envelope proteins were produced by transfecting cells with an envelope expression vector plus an HIV genomic vector containing a firefly luciferase indicator gene. Viruses were incubated with serial 5-fold dilutions of antibody and used to infect target cells that express CD4 plus the CCR5 and CXCR4 co-receptors. Matrices of neutralizing antibody assays were performed by testing autologous virus and antibody from serial (2- to 4-month intervals) plasma specimens from treatment-naïve patients with primary HIV infection (n = 14; average follow-up 18 months; range 6-39 months). Results: Most patients (12/14) rapidly generated strong neutralizing antibody responses to autologous virus. However, each sequential virus consistently and rapidly escaped the concurrent neutralizing antibody response. Peak neutralization titers (average 1:1497 dilution, range 1:339-1:4627) developed several months after a virus emerged and the response remained elevated for many months, to years, thereafter. Neutralizing antibody titers were generally greater to early viruses than to later viruses from the same patient. Neutralization responses to a heterologous R5 primary virus (JR-CSF) were weak and delayed. Responses to an X4 lab strain (NL4-3) increased over time, but varied in intensity among patients. The magnitude of neutralizing antibody response to autologous virus did not correlate with mean plasma HIV RNA or duration of HIV infection. Conclusions: The rate of viral neutralization escape is remarkable and indicates that neutralizing antibody can exert a previously unappreciated level of selective pressure on viral evolution. These data have important implications for natural history and vaccine development.

©2002 9th Conference on Retroviruses and Opportunistic Infections