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Development of the antibody response in acute HIV-1 infection

Aasa-Chapman, Marlén MIa; Hayman, Annab; Newton, Philippac; Cornforth, Davidc; Williams, Ianc; Borrow, Persephoned; Balfe, Peterb; McKnight, Áinea

Basic Science

Background: Cytotoxic T lymphocytes have been shown to reduce viraemia during acute HIV-1 infection; however the role of neutralizing antibodies in this process is unclear. One confounding factor may be artefacts introduced by viral culture.

Objective: To assess the development of autologous neutralizing and non-neutralizing antibodies following acute HIV-1 infection using recombinant viruses with envelopes amplified directly from patient peripheral blood mononuclear cells, thereby avoiding in vitro selection.

Methods: Disease progression in four homosexual men was monitored from acute infection for up to 2.5 years, in the absence of antiretroviral therapy. Antibodies to viral envelope protein were quantified by enzyme-linked immunosorbent assay. Development of neutralizing antibodies was monitored using a quantitative infectivity reduction assay, sequential serum, recombinant viruses and target cells with defined receptor expression.

Results: The time to development of neutralizing antibodies after onset of symptoms was 3, 5, 7 and 16 months in the four patients. There was no correlation between development of neutralizing antibodies and the resolution of viraemia in any of the patients. However, antibodies to the envelope were detectable as early as 2 weeks after onset of symptoms.

Conclusions: Neutralizing antibodies do not contribute to the control of viraemia in acute HIV-1 infection. However, antibodies to the envelope could be detected at the time of reduction in plasma viraemia and so other effector functions of antibodies may play a role in viral clearance.

From the Departments of aImmunology and Molecular Pathology, bVirology, cSexually Transmitted Diseases, University College London and the dEdward Jenner Institute for Vaccine Research, Compton, UK. *Present address: The Aaron Diamond AIDS Research Center, New York, USA.

Requests for reprints to: Dr Á. McKnight, Windeyer Institute of Medical Sciences, Wohl Virion Centre, 46 Cleveland St, London W1T 4JF, UK.

Received: 15 May 2003; revised: 12 August 2003; accepted: 19 August 2003.

© 2004 Lippincott Williams & Wilkins, Inc.