HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus.

Published

Journal Article

Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8+ T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8+ T-cell responses. The declining CD8+ T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8+ T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development.

Full Text

Duke Authors

Cited Authors

  • Altfeld, M; Allen, TM; Yu, XG; Johnston, MN; Agrawal, D; Korber, BT; Montefiori, DC; O'Connor, DH; Davis, BT; Lee, PK; Maier, EL; Harlow, J; Goulder, PJR; Brander, C; Rosenberg, ES; Walker, BD

Published Date

  • November 28, 2002

Published In

Volume / Issue

  • 420 / 6914

Start / End Page

  • 434 - 439

PubMed ID

  • 12459786

Pubmed Central ID

  • 12459786

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/nature01200

Language

  • eng

Conference Location

  • England