14th International AIDS Conference Barcelona, Spain — July 7-12, 2002

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. MoOrA1051

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 (2-4 mo intervals) plasma specimens from treatment-naïve patients with primary HIV infection (N=14; avg follow up 18 mo; range 6-39 mo).

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 (avg 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. 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.

Presenting author: Douglas Richman

1University of California San Diego, 9500 Gilman Drive (0679), La Jolla CA, 92093-0679, United States.

2ViroLogic, So. San Francisco, CA, United States.

3 University of California San Diego, San Diego, CA, United States.

4ViroLogic, So. San Francisco, CA, United States.

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Copyright © 2002 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.