Resistance Mutations

The broadest spectrum of antiviral diugs is available against HIV. However, monotherapy with any of these diugs leads to rapid treatment failure due to selection and further evolution of resistant viruses. Since acquisition of resistance mutations requires vims replication,... 

Short replication cycles that may be completed within a few hours, a large amount of viral progeny from one infected host-cell, as well as the general inaccuracy of viral nucleic acid polymerases result in an evolution occurring in fast motion, allowing rapid adaptation of viruses to selective pressures (see chapter by Boucher and Nijhius, this volume). Generalizing, it can be stated that any effective antiviral therapy will lead to the occurrence of resistance mutations. A well studied example... 

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A general mechanism of resistance is reducing the affinity of the antiretroviral compound for its mutant target protein. Resistance mutations associated with reduced affinity are observed during treatment failure with a fusion inhibitor, nonnucleoside reverse transcriptase inhibitors (NNRTl), integrase inhibitor, and protease inhibitors as reviewed in Chaps. 3,4, 6, and 7 (Hazuda et al. 2007 Hsiou et al. 2001 King et al. 2002 Mink et al. 2005). 

Taken together, the genetic barrier cannot be simply defined by the sum of resistance mutations, but also the genetic background of the virus, the variation in the viral population, interaction of mutations, and their impact on viral replication play a role. 

Fig. 2 The HBV polymerase and envelope proteins, whose reading frames overlap each other, and position of the main HBV drug-resistant mutations...

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