AEGiS-14IAC: Reconstitution of autologous isolate neutralizing antibodies under HAART and emergence of neutralization escape mutants in vivo.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Reconstitution of autologous isolate neutralizing antibodies under HAART and emergence of neutralization escape mutants in vivo.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. ThOrA1480)

Matsushita S, Kimura T, Wang F, Kim J, Koito A, Yoshimura K
Center for AIDS Research, Kumamoto University, Kumamoto, Japan

BACKGROUND: Effects of HAART in chronically infected patients, with regard to neutralizing antibody (NAb) responses against autologous isolates and a role of such NAbs in patients during viral rebound are poorly understood.

METHODS: We investigated the longitudinal change of NAb response against an autologous HIV-1 in 19 chronically infected patients on HAART. In the course of the study we experienced three patients who had NAbs to pre-existing autologous HIV-1 and an episode of viral rebound after a long-term viral suppression. Envelope genes of pre-existing and rebounded viruses were sequenced and examined by phylogenetic analysis. Neutralization-sensitivity was examined by using envelope-pseudotyping.

RESULTS: Reconstitution of neutralization activities was observed in 3 of 6 patients with no significant activities at the initiation of HAART. 13 out of 19 patients initially showed significant activities, but these were relatively weak in many subjects and most sustained the activities during HAART. For the patients with viral rebound, phylogenetic analysis of env (V1-V4) sequences indicated that rebounded viruses had evolved from or pre-existed in baseline populations. Rebounded viruses were found to be significantly resistant to neutralization by autologous antibody in patients, who experienced viral rebound thus indicating that rebounded viruses were selected by NAbs. The site responsible for conferring neutralization resistance against autologous antibody was identified in the up-stream C3 region in two out of three patients.

CONCLUSIONS: We obtained evidence for reconstitution of spontaneous neutralization activities in some chronically infected patients. The viral rebound in the presence of neutralization antibodies is associated with the emergence of the relatively resistant mutants to autologous antibodies. The neutralization resistance observed in vivo was conferred by C3 changes.

Keywords: AEGIS, Antiretroviral Therapy, Highly Active, HIV-1, Human, virology

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ThOrA1480