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Chapter 16 : Phenotypic and Genotypic Antiviral Susceptibility Testing

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Phenotypic and Genotypic Antiviral Susceptibility Testing, Page 1 of 2

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Abstract:

Where the use of antibiotics goes back to the discovery of penicillin by Alexander Fleming in 1928, application of antiviral treatment was not achieved until the early 1960s with the use of the nucleoside analogue idoxuridine for treatment of herpetic keratitis (1) and methisazone for treatment of smallpox, variola, and cowpox. The first major advances in antiviral treatment were obtained for herpes viruses with the discovery of another nucleoside analogue, acyclovir, by the Burroughs Wellcome Company in the early 1980s. Despite these advances, the real wave of antiviral drug discovery was the result of the HIV epidemic, and started with the development of azidothymidine (AZT) as the first antiretroviral for AIDS patients (2). Nowadays a wide spectrum of antiviral agents are used for a variety of infections. However, similarly to bacteria, development of resistance is an important complication when using antiviral agents. In addition, many viral pathogens have an RNA genome and use RNA polymerases that lack proofread activity for their replication. Therefore, mutations will be introduced into the viral genome in every replication cycle and as a consequence an altered susceptibility or even resistance to an antiviral agent may develop. These resistant variants are easily selected under pressure of an antiviral treatment as shown by the rapid development of resistance when using AZT (3, 4). The viral reverse transcriptase incorporates this thymidine analogue into the viral genome, inhibiting proper replication. Resistant viruses rapidly evolve by acquiring resistance-associated mutations (RAM) in the gene encoding for the enzyme. With HIV being a retrovirus, these mutations are also incorporated in the host DNA and therefore the resistant viral genome is stored in the DNA of the patient and will emerge upon reintroducing the drug.

Citation: van der Beek M, Claas E. 2016. Phenotypic and Genotypic Antiviral Susceptibility Testing, p 201-227. In Loeffelholz M, Hodinka R, Young S, Pinsky B (ed), Clinical Virology Manual, Fifth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819156.ch16
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FIGURE 1

Flow chart for diagnosis and treatment in case of failure of antiviral therapy of DNA virus infections in immunocompromised patients. Global approach to diagnosis and treatment in case of persistent DNA virus infections in immunosuppressed patients.Assessment of viral response may include the viral load after treatment and the decrease in viral load in response to the given treatment.In case of severe symptomatic disease.Assessment of immunological recovery may include total and virus-specific T-cell counts and the possibility to decrease the use of immunosuppressive medication. Details may differ per virus ( ).

Citation: van der Beek M, Claas E. 2016. Phenotypic and Genotypic Antiviral Susceptibility Testing, p 201-227. In Loeffelholz M, Hodinka R, Young S, Pinsky B (ed), Clinical Virology Manual, Fifth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819156.ch16
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