Blinded, Multicenter Comparison of Methods To Detect a Drug-Resistant Mutant of Human Immunodeficiency Virus Type 1 at Low Frequency

Author:

Halvas Elias K.1,Aldrovandi Grace M.2,Balfe Peter3,Beck Ingrid A.4,Boltz Valerie F.5,Coffin John M.5,Frenkel Lisa M.4,Hazelwood J. Darren6,Johnson Victoria A.6,Kearney Mary5,Kovacs Andrea7,Kuritzkes Daniel R.8,Metzner Karin J.9,Nissley Dwight V.10,Nowicki Marek7,Palmer Sarah5,Ziermann Rainer11,Zhao Richard Y.12,Jennings Cheryl L.13,Bremer James13,Brambilla Don14,Mellors John W.1

Affiliation:

1. University of Pittsburgh, Pittsburgh, Pennsylvania

2. Children's Hospital of Los Angeles, Keck School of Medicine, Los Angeles, California

3. Columbia University, New York, New York

4. University of Washington, Seattle, Washington

5. HIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland

6. Birmingham VA Medical Center and University of Alabama at Birmingham, Birmingham, Alabama

7. University of Southern California, Los Angeles, California

8. Section of Retroviral Therapeutics, Brigham and Women's Hospital and Division of AIDS, Harvard Medical School, Boston, Massachusetts

9. University of Erlangen- Nuremberg, Erlangen, Germany

10. Basic Research Program, SAIC-Frederick, National Cancer Institute, Frederick, Maryland

11. Bayer HealthCare-Diagnostics, Berkeley, California

12. University of Maryland School of Medicine, Baltimore, Maryland

13. Rush Medical College, Chicago, Illinois

14. New England Research Institute, Watertown, Massachusetts

Abstract

ABSTRACT We determined the abilities of 10 technologies to detect and quantify a common drug-resistant mutant of human immunodeficiency virus type 1 (lysine to asparagine at codon 103 of the reverse transcriptase) using a blinded test panel containing mutant-wild-type mixtures ranging from 0.01% to 100% mutant. Two technologies, allele-specific reverse transcriptase PCR and a Ty1HRT yeast system, could quantify the mutant down to 0.1 to 0.4%. These technologies should help define the impact of low-frequency drug-resistant mutants on response to antiretroviral therapy.

Publisher

American Society for Microbiology

Subject

Microbiology (medical)

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