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Journal of Virology, August 2004, p. 8927-8930, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8927-8930.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Immune Escape Precedes Breakthrough Human Immunodeficiency Virus Type 1 Viremia and Broadening of the Cytotoxic T-Lymphocyte Response in an HLA-B27-Positive Long-Term-Nonprogressing Child

M. E. Feeney,1,2* Y. Tang,1 K. A. Roosevelt,1 A. J. Leslie,3 K. McIntosh,2 N. Karthas,2 B. D. Walker,1,4 and P. J. R. Goulder1,3

Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School,1 Children's Hospital, Boston, Massachusetts,2 Department of Paediatrics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom,3 Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts4

Received 21 January 2004/ Accepted 1 April 2004

The emergence of cytotoxic T-lymphocyte (CTL) escape mutations in human immunodeficiency virus type 1 (HIV-1) proteins has been anecdotally associated with progression to AIDS, but it has been difficult to determine whether viral mutation is the cause or the result of increased viral replication. Here we describe a perinatally HIV-infected child who maintained a plasma viral load of <400 copies/ml for almost a decade until a nonbinding escape mutation emerged within the immunodominant CTL epitope. The child subsequently experienced a reemergence of HIV-1 viremia accompanied by a marked increase in the number of CTL epitopes targeted. This temporal pattern suggests that CD8 escape can play a causal role in the loss of immune control.

* Corresponding author. Mailing address: Partners AIDS Research Center, 5th Floor, 149 13th St., Charlestown, MA 02129. Phone: (617) 726-6126. Fax: (617) 726-5411. E-mail: mfeeney{at}partners.org.

Journal of Virology, August 2004, p. 8927-8930, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8927-8930.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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