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Journal of Virology, November 1999, p. 9404-9412, Vol. 73, No. 11
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Evolution of Envelope Sequences of Human Immunodeficiency Virus Type 1 in Cellular Reservoirs in the Setting of Potent Antiviral Therapy

Huldrych F. Günthard,1,dagger Simon D. W. Frost,2 Andrew J. Leigh-Brown,2 Caroline C. Ignacio,1 Kristin Kee,1 Alan S. Perelson,3 Celsa A. Spina,1,4 Diane V. Havlir,1 Marjan Hezareh,1 David J. Looney,1,4 Douglas D. Richman,1,4 and Joseph K. Wong1,4,*

University of California, San Diego,1 and San Diego Veterans Affairs Healthcare System,4 San Diego, California; University of Edinburgh, Edinburgh, Scotland2; and the Los Alamos National Laboratory, Los Alamos, New Mexico3

Received 17 March 1999/Accepted 9 July 1999

In human immunodeficiency virus (HIV)-infected patients treated with potent antiretroviral therapy, the persistence of latently infected cells may reflect the long decay half-life of this cellular reservoir or ongoing viral replication at low levels with continuous replenishment of the population or both. To address these possibilities, sequences encompassing the C2 and V3 domains of HIV-1 env were analyzed from virus present in baseline plasma and from viral isolates obtained after 2 years of suppressive therapy in six patients. The presence of sequence changes consistent with evolution was demonstrated for three subjects and correlated with less complete suppression of viral replication, as indicated by the rapidity of the initial virus load decline or the intermittent reappearance of even low levels of detectable viremia. Together, these results provide evidence for ongoing replication. In the remaining three patients, virus recovered after 2 years of therapy was either genotypically contemporary with or ancestral to virus present in plasma 2 years before, indicating that virus recovery had indeed resulted from activation of latently infected cells.

* Corresponding author. Mailing address: Stein Clinical Research Building No. 326, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0679. Phone: (619) 552-8585, ext. 7193. Fax: (619) 552-7445. E-mail: j2wong{at}ucsd.edu.

dagger Present address: University of Zürich, Zürich, Switzerland.

Journal of Virology, November 1999, p. 9404-9412, Vol. 73, No. 11
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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