HIV-1 evolution following transmission to an HLA-B*5801-positive patient

Abstract

The human immunodeficiency virus type 1 (HIV-1)-specific immune responses of patients with the HLA-B*57/5801 alleles who spontaneously control viral replication serve as an important model for T cell-based HIV-1 vaccines. Determining the breadth of this response and the extent of virologie escape in primary infection in these patients is therefore critical. Here we document the development of mutations in 3 HLA-B*5801 -restricted epitopes in gag, nef, and pol in an HLA-B*5801 -positive patient who had a viral load of only 1159 copies/mL at day 167 after infection. A full genome sequence analysis was performed to determine the extent of mutations in HLA-B*5801-restricted epitopes, and longitudinal sequence data of specific genes were combined with enzyme-linked immunospot assay analysis of critical epitopes to determine the importance of escape mutations. Thus, relative control of viral replication can be maintained in spite of the rapid development of multiple escape mutations within cytotoxic T lymphocyte epitopes. © 2009 by the Infectious Diseases Society of America. All rights reserved.