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Research Article

Minority HIV-1 Drug Resistance Mutations Are Present in Antiretroviral Treatment–Naïve Populations and Associate with Reduced Treatment Efficacy

  • Jeffrey A Johnson mail,

    To whom correspondence should be addressed. E-mail: JJohnson1@cdc.gov

    Affiliation: Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America

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  • Jin-Fen Li,

    Affiliation: Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America

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  • Xierong Wei,

    Affiliation: Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America

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  • Jonathan Lipscomb,

    Affiliation: Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America

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  • David Irlbeck,

    Affiliation: GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America

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  • Charles Craig,

    Affiliation: GlaxoSmithKline, Stevenage, United Kingdom

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  • Amanda Smith,

    Affiliation: Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America

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  • Diane E Bennett,

    Affiliation: Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America

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  • Michael Monsour,

    Affiliation: Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America

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  • Paul Sandstrom,

    Affiliation: National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, Ontario, Canada

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  • E. Randall Lanier,

    Affiliation: GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America

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  • Walid Heneine

    Affiliation: Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America

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  • Published: July 29, 2008
  • DOI: 10.1371/journal.pmed.0050158

About the Authors

Jeffrey A Johnson, Jin-Fen Li, Xierong Wei, Jonathan Lipscomb, Amanda Smith, Diane E Bennett, Michael Monsour, Walid Heneine
Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
David Irlbeck, E. Randall Lanier
GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America
Charles Craig
GlaxoSmithKline, Stevenage, United Kingdom
Paul Sandstrom
National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, Ontario, Canada

Corresponding Author

Email: JJohnson1@cdc.gov

Competing Interests

JAJ and WH are named on a CDC patent application on the use of the real-time polymerase chain reaction assays presented in this article. CC and ERL were employees and stockholders in GlaxoSmithKline during the period of this study. The other authors declare no competing interests.

Author Contributions

JAJ, ERL, and WH designed the experiments/the study. JAJ, JFL, XW, JL, DI, AS, DEB, PS, and ERL collected data or did experiments for the study. JAJ, JFL, JL, AS, MM, ERL, and WH analyzed the data. JFL, JL, and XW participated in testing, validating the samples, and modification of the method. AS participated in the description of project methods by which the specimens were collected; collection/analysis of conventional sequencing data and behavioral data; and tracking and deleting specimens that were subsequently determined to be ineligible for the study. JAJ wrote the first draft of the paper. JAJ, DI, CC, DEB, MM, PS, ERL, and WH contributed to writing the paper. DI participated in the generation and communication to the primary author of a subset of the data used for the analysis; in the identification, preparation, and shipment of samples used by the laboratory of the primary author (JAJ) for the case-control study; and in the review of the manuscript summarizing the analysis of the results. CC provided characterized samples for the study in addition to intellectual input and approval of the final version of the document. DEB and AS contributed many of the sequences used in the cross-sectional study. DEB contributed to the cross-sectional study design. PS enrolled patients and was responsible for the collection and initial drug resistance analysis of diagnostic specimens from a subset of drug-naïve individuals used in the cross-sectional study. ERL played a significant role in the design of the analysis of clinical samples/data from the efavirenz trials used for this study; provided samples and data; and assisted in the analysis and interpretation of the case-control data.