Antiviral drugs resistance

Acknowledgments This is part of the activities of the VIRGIL European Network of ExceUence on Antiviral Drug Resistance supported by a grant (LSHM-CT-2004-503359) from the Priority 1 Life Sciences, Genomics and Biotechnology for Health and is supported by a grant from the FWO (no. G.0267.04). 

Hirsch MS Antiviral drug resistance testing in adult HIV-1 infection 2008 recommendations of an international AIDS society-USA panel. Clin Infect Dis 2008 47 266. [PMID 18549313]... 

Richnian D.D. Antiviral Drug Resistance, John Wiley Sons. Inc., New York. NY, 1996. 

Safrin, S. (1995) Nucleosides and foscarnet—clinical aspects, in Antiviral Drug Resistance (Richman, D. D., ed.), Wiley, Chichester, pp. 103-122. 

Hayden FG. Amantidine and rimantidine—clinical aspects. In Richman DD, ed. Antiviral Drug Resistance. Chichester Wiley, 1996 59-77. 

Which one of the following statements about the mechanisms of antiviral drug resistance is false ... 

Gammon, D. B., Snoeck, R., Fiten, P, Krecmerova, M., Holy, A., De Cleicq, E., Opdenakker, G., Evans, D. H., Andrei, G. (2008). Mechanism of antiviral drug resistance of Vaccinia virus identification of residues in the viral DNA polymerase conferring differential resistance to Antipoxvirus drugs. J. Virol. 82,12520-12534. 

Fig. 3 Stepwise development of antiviral resistance. Because of the rapid mutation rate of viruses, the virus population before treatment (a) contains variants, which display by chance a low level of resistance to the drug (indicated by the darker hue). Treatment with suboptimal levels of an antiviral drug (b) creates a bottleneck, which selects for these variants (c). These can further replicate in the presence of the drug and thereby acquire additional mutations, leading to resistant variants with enhanced replicative fitness (d)...

Deval J, D Abramo CM, GOtte M (2006) Selective excision of non-obUgate chain-terminators by the hepatitis C virus NS5B polymerase. In 16th international HIV Drug Resistance workshop, Sitges, Spain, June 13-17, 2006. Antivir Ther 11 Suppl 1 S3 (abstract no 1)... 

Wang J, Jin Y, Rapp KL, Bennett M, Schinazi RF, Chu CK (2005) Synthesis, antiviral activity, and mechanism of drug resistance of d- and L-2, 3 -didehydro-2, 3 -dideoxy-2 -fluorocarbocycUc nucleosides, J Med Chem 48 3736-3748... 

Abstract This review provides an overview of the development of viral protease inhibitors as antiviral drugs. We concentrate on HlV-1 protease inhibitors, as these have made the most significant advances in the recent past. Thus, we discuss the biochemistry of HlV-1 protease, inhibitor development, clinical use of inhibitors, and evolution of resistance. Since many different viruses encode essential proteases, it is possible to envision the development of a potent protease inhibitor for other viruses if the processing site sequence and the catalytic mechanism are known. At this time, interest in developing inhibitors is Umited to viruses that cause chronic disease, viruses that have the potential to cause large-scale epidemics, or viruses that are sufQciently ubiquitous that treating an acute infection would be... 

Ilyushina NA, Bovin NV, Webster RG, Govorkova EA (2006) Combination chemotherapy, a potential strategy for reducing the emergence of drug-resistant influenza A variants. Antiviral Res 70 121-131... 

Hepatitis C Support project. Hepatitis C Basics (2006) New HCV antivirals and drug resistance. www.hcvadvocate.org... 

Melby T, DeMasi R, MiraUes G, HeUek-Snyder G, Greenberg M (2005) Evolution of enfuvirtide resistance in longitudinal samples obtained after continued enfuvirtide dosing post-virological failure. In 14th international drug resistance workshop, QC, Canada. Antiviral therapy, Suppl 1... 

Like HIV and other RNA viruses, HCV replicates as a quasispecies due to a high level of viral replication in combination with an error-prone replication strategy. Therefore, the issue of drug-resistance is expected to be a major challenge in this case as well. Indeed, resistance to HCV antiviral agents has already been... 

The cost-effectiveness analysis of antiviral therapy has to be seen under the precondition that no long-term effects, such as drug resistance, occnr. Future analysis might show that we strongly underestimated the long-term costs of HIV/AIDS. 

A crucial issue for antiviral therapy is the fact that all antiviral substances rapidly select for resistance thus, monitoring and overcoming resistance has become a most important clinical paradigm of antiviral therapy. This calls for cautious use of antiviral drugs and implementation of combination therapies. In parallel, efforts in drug discovery have to be continued to develop compounds with novel mode-of-action and activity against resistant strains. This book reviews the current status of antiviral therapy, from the roads to development of new compounds to their clinical use and cost effectiveness. Individual chapters address in more detail all available drug classes and outline new approaches currently under development. 

Schuetz JD, Connelly MC, Sun D, Pai-bir SG, Flynn PM, Srinivas RV et al. MRP4 A previously unidentified factor in resistance to nucleoside-based antiviral drugs. Nature Med 1999 5(9) 1048—1051. 

Invent and learn to manufacture effective antiviral agents and antibiotics to fight all serious diseases, including those caused by drug-resistant pathogens. 

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