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Viral Phenotypic Resistance Assays

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Antimicrobial Drug Resistance

Abstract

The emergence of the human immunodeficiency virus (HIV) pandemic in the early 1980s led to a marked escalation in virology research. A rapidly expanding knowledge base percolated not only within the HIV field but also in that of other viral diseases. The identification of drug targets in these viruses led to the development and approval of antiviral agents. However, especially for HIV, it quickly became apparent that the use of these agents could select for drug-resistant viruses. The need for assays to identify resistant strains and to guide physicians in treatment decisions was urgent. Today, the availability of numerous antiretroviral agents for HIV therapy, combined with assays to guide their use, allows the selection of combination regimens that can effectively suppress HIV replication for many years. The vast amount of experience gained over many years of HIV drug development and clinical research notably hastened more recent hepatitis C virus (HCV) drug development efforts. Combination drug regimens for HCV that include one or more direct-acting antiviral agents to different targets have beenevaluated rapidly and optimized to minimize the emergence of resistance-associated variants and to promote viral clearance.

This chapter reviews the major phenotypic antiviral susceptibility assays, with a focus on HIV- and HCV-related assays. The use of intact virus assays, the development and clinical applications of recombinant virus assays for HIV drug resistance, replication capacity and coreceptor tropism determination, the use of HCV replicon assays for drug development, and the status of phenotypic assays for other viruses including HBV, CMV, HSV, and influenza virus are discussed.

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Authors and Affiliations

  1. Monogram Biosciences, Laboratory Corporation of America® Holdings, South San Francisco, CA, USA

    Jacqueline D. Reeves Ph.D.

  2. Data First Consulting, Inc., Belmont, CA, 94002, USA

    Neil T. Parkin Ph.D.

Authors
  1. Jacqueline D. Reeves Ph.D.
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  2. Neil T. Parkin Ph.D.
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Correspondence to Jacqueline D. Reeves Ph.D. .

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Editors and Affiliations

  1. Treiber Therapeutics, Cambridge, Massachusetts, USA

    Douglas L. Mayers

  2. Wayne State University School of Medicine, Detroit Medical Center, Detroit, Michigan, USA

    Jack D. Sobel

  3. Canada Research Chair in Antimicrobial Resistance, Centre de recherche en Infectiologie, University of Laval, Quebec City, Canada

    Marc Ouellette

  4. Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, Michigan, USA

    Keith S. Kaye

  5. Infection Control and Prevention Unit of Infectious Diseases, Assaf Harofeh Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel

    Dror Marchaim

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Reeves, J.D., Parkin, N.T. (2017). Viral Phenotypic Resistance Assays. In: Mayers, D., Sobel, J., Ouellette, M., Kaye, K., Marchaim, D. (eds) Antimicrobial Drug Resistance. Springer, Cham. https://doi.org/10.1007/978-3-319-47266-9_35

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