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Journal of Virology, February 2009, p. 2038-2043, Vol. 83, No. 4
0022-538X/09/$08.00+0     doi:10.1128/JVI.02154-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

In Vivo Fitness Cost of the M184V Mutation in Multidrug-Resistant Human Immunodeficiency Virus Type 1 in the Absence of Lamivudine{triangledown}

Roger Paredes,1,2 Manish Sagar,1 Vincent C. Marconi,1,3 Rebecca Hoh,4 Jeffrey N. Martin,4 Neil T. Parkin,5 Christos J. Petropoulos,5 Steven G. Deeks,4 and Daniel R. Kuritzkes1*

Section of Retroviral Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts,1 Fundacions irsiCaixa i Lluita contra la SIDA, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Catalonia, Spain,2 Infectious Disease Service, Brooke Army Medical Center, San Antonio Military Medical Center, San Antonio, Texas,3 University of California San Francisco and San Francisco General Hospital, San Francisco, California,4 Monogram Biosciences, Inc., South San Francisco, California5

Received 13 October 2008/ Accepted 7 November 2008

Lamivudine therapy selects for the M184V mutation. Although this mutation reduces the replicative capacity of human immunodeficiency virus in vitro, its impact on viral fitness in vivo has not been well defined. We used quantitative allele-specific PCR to precisely calculate the fitness differences between the mutated M184V virus and one that had reverted to the wild type in a cohort of patients by selectively interrupting reverse transcriptase inhibitor therapy, and we found that the M184V variants were consistently 4 to 8% less fit than the wild type in the absence of drug. After a lag phase of variable duration, wild-type variants emerged due to continued evolution of pol and back mutation rather than through emergence of an archived wild-type variant.

* Corresponding author. Mailing address: Section of Retroviral Therapeutics, Brigham and Women's Hospital, 65 Landsdowne St., Rm 449, Cambridge, MA 02139. Phone: (617) 768 8371. Fax: (617) 768 8738. E-mail: dkuritzkes{at}partners.org

{triangledown} Published ahead of print on 19 November 2008.

Journal of Virology, February 2009, p. 2038-2043, Vol. 83, No. 4
0022-538X/09/$08.00+0     doi:10.1128/JVI.02154-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Cherwa, J. E. Jr., Sanchez-Soria, P., Members of the University of Arizona Virology Labo, , Wichman, H. A., Fane, B. A. (2009). Viral Adaptation to an Antiviral Protein Enhances the Fitness Level to Above That of the Uninhibited Wild Type. J. Virol. 83: 11746-11750 [Abstract] [Full Text]  


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