11th Conference on Retroviruses and Opportunistic Infections San Francisco, California - February 8 - 11, 2004

Conf Retrovir Opportunistic Infect 2004 Feb 8-11; 11:(abstract no. 19)

S Deeks¹, T Wrin², J Galovich², J Martin¹, and C Petropoulos^2
1Univ. of California, San Francisco, USA and ²ViroLogic Inc., South San Francisco, CA, USA

BACKGROUND: Acutely HIV-infected individuals often generate potent neutralizing antibody responses to autologous virus. This response is typically followed by the rapid development of neutralization escape mutations. The role of neutralizing antibody responses in chronically HIV-infected adults experiencing with a variety of outcomes on antiretroviral treatment is not known.

METHODS: Neutralizing antibody responses were measured in a single cycle recombinant virus assay using a virus pseudotyped with patient-derived HIV envelope proteins. Virus was grown in CD4+ U87 cells co-expressing CCR5 and CXCR4. Neutralizing antibody responses to the initial autologous virus (study visit 1) and to NL43, JRCSF, and a negative control (aMVL) were tested using plasma collected every 4 months in an ongoing prospective cohort (Study of the Consequences of the Protease Inhibitor Era, SCOPE).

RESULTS: A total of 22 patients were studied longitudinally (8 untreated individuals beginning HAART and 14 antiretroviral treated with partial viral suppression and drug-resistant HIV). Neutralizing antibody response to autologous virus was uniformly low in all individuals and comparable to background neutralizing responses against aMLV. Neutralizing responses to autologous virus was very low among patients with stable low-level drug-resistant viremia and did not evolve over time; these low responses were observed even in a subset of well-characterized individuals with high levels of HIV-specific CD4+ and CD8+ T-cell responses. In contrast, neutralizing antibody responses were very high to a heterologous neutralization-sensitive lab strain (NL43) in most patients. These heterologous responses decreased dramatically after the introduction of HAART and increased during periods of intermittent viremia (blips).

CONCLUSIONS: Chronic HIV infection is associated with high levels of neutralizing antibody responses that appears not to be directed at autologous virus, and is therefore unlikely to be contributing to virologic control. In contrast to observations made during acute HIV infection, there was only limited evidence that HIV continued to develop novel escape mutations. These data indicate that HIV replication in chronic disease drives the production of high amounts of ineffective HIV-specific antibodies and that the capacity of the immune system to continuously generate antibodies directed at emerging epitopes within HIV envelope is eventually exhausted.

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Copyright © 2004 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.