Antiviral activity of the neutralizing antibodies 2F5 and 2612 in asymptomatic HIV-1-infected humans:: a phase I evaluation

Background: The human monoclonal antibodies (MAbs) 2F5 and 2612 were identified to be two of the most potent neutralizing antibodies against HIV-1. In a first human study they have been shown to be safe after repeated intravenous infusions to 'symptomatic HIV-1-infected individuals. However, the antiviral effects of antibody treatment have not been fully analyzed in this first clinical trial. Methods: The aim of the present study was to gain a preliminary insight into the antiviral effects of 2F5 and 2612 in humans. For this purpose, plasma samples obtained from the previous phase I study were studied for RNA copy numbers by reverse transcriptase-polymerase chain reaction. As a measure for activation of complement levels of the major complement factor C3 were measured by enzyme-linked immunosorbent assay. Flow cytometry was used to study T-lymphocyte counts and the amount of infected peripheral blood mononuclear cells (PBMC) was determined by co-culture with uninfected donor PBMC. Virus escape from antibody neutralization was determined in vitro in a PBMC neutralization assay. Results: Transient reduction in viral loads was observed in five of seven patients. Vigorous complement activation was observed directly after HIV-specific antibody infusions. The number of infective peripheral blood mononuclear cells was reduced in some patients whereas CD4+ T-lymphocyte counts and CD4+/CD8+ ratios were transiently increased in all patients. Virus escape occurred only against 2G12. Conclusions: Analysis of disease progression markers indicate that antibody therapy may have antiviral effects. These findings suggest that neutralizing antibodies should be further evaluated as an alternative therapeutic approach in HIV-1 disease. (C) 2002 Lippincott Williams Wilkins.