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

Marcus Altfeld, Todd M. Allen, Xu G. Yu, Mary N. Johnston, Deepak Agrawal, Bette T. Korber, David C. Montefiori, David H. O'Connor, Ben T. Davis, Paul K. Lee, Erica L. Maier, Jason Harlow, Philip J. R. Goulder, Christian Brander, Eric S. Rosenberg and Bruce D. Walker ()
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Marcus Altfeld: Harvard Medical School
Todd M. Allen: Harvard Medical School
Xu G. Yu: Harvard Medical School
Mary N. Johnston: Harvard Medical School
Deepak Agrawal: Harvard Medical School
Bette T. Korber: Los Alamos National Laboratory
David C. Montefiori: Duke University Medical Center
David H. O'Connor: University of Wisconsin
Ben T. Davis: Harvard Medical School
Paul K. Lee: Harvard Medical School
Erica L. Maier: Harvard Medical School
Jason Harlow: Harvard Medical School
Philip J. R. Goulder: Harvard Medical School
Christian Brander: Harvard Medical School
Eric S. Rosenberg: Harvard Medical School
Bruce D. Walker: Harvard Medical School

Nature, 2002, vol. 420, issue 6914, 434-439

Abstract: Abstract Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection1,2,3. 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.

Date: 2002
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DOI: 10.1038/nature01200

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