Abstract
Evaluation of the emergence of influenza virus resistance to neuraminidase inhibitors (NAIs) is now demanded following experience with amantadinamines. Preliminary data have indicated that NAI-resistant virus is unlikely to emerge readily in the clinic and this is consistent with the difficulty experienced in selecting resistant virus in vitro. Resistance mutations can occur in both neuraminidase and haemagglutinin genes. The neuraminidase mutations are viral subtype specific and, therefore, clinically relevant subtypes must be employed for in vitro studies if pre-clinical data are to have predictive value. Haemagglutinin mutations generated in vitro are probably both subtype and cell culture system specific and, therefore, may not be predictive of clinical findings. Analysis of influenza-positive samples from NAI-treated patients in the clinical setting must include samples from late treatment time-points (day 4 and later) in order for resistant virus to be detected as in vitro studies and current clinical experience have indicated that resistant virus is slow to emerge and is transient.
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Selected References
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- Gubareva L. V., Matrosovich M. N., Brenner M. K., Bethell R. C., Webster R. G. Evidence for zanamivir resistance in an immunocompromised child infected with influenza B virus. J Infect Dis. 1998 Nov;178(5):1257–1262. doi: 10.1086/314440. [DOI] [PubMed] [Google Scholar]
- Gubareva L. V., Robinson M. J., Bethell R. C., Webster R. G. Catalytic and framework mutations in the neuraminidase active site of influenza viruses that are resistant to 4-guanidino-Neu5Ac2en. J Virol. 1997 May;71(5):3385–3390. doi: 10.1128/jvi.71.5.3385-3390.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hayden F. G., Hay A. J. Emergence and transmission of influenza A viruses resistant to amantadine and rimantadine. Curr Top Microbiol Immunol. 1992;176:119–130. doi: 10.1007/978-3-642-77011-1_8. [DOI] [PubMed] [Google Scholar]
- McKimm-Breschkin J. L. Resistance of influenza viruses to neuraminidase inhibitors--a review. Antiviral Res. 2000 Jul;47(1):1–17. doi: 10.1016/s0166-3542(00)00103-0. [DOI] [PubMed] [Google Scholar]
- Mendel D. B., Roberts N. A. In-vitro and in-vivo efficacy of influenza neuraminidase inhibitors. Curr Opin Infect Dis. 1998 Dec;11(6):727–732. doi: 10.1097/00001432-199812000-00013. [DOI] [PubMed] [Google Scholar]
- Mendel D. B., Sidwell R. W. Influenza virus resistance to neuraminidase inhibitors. Drug Resist Updat. 1998;1(3):184–189. doi: 10.1016/s1368-7646(98)80038-1. [DOI] [PubMed] [Google Scholar]
- Tai C. Y., Escarpe P. A., Sidwell R. W., Williams M. A., Lew W., Wu H., Kim C. U., Mendel D. B. Characterization of human influenza virus variants selected in vitro in the presence of the neuraminidase inhibitor GS 4071. Antimicrob Agents Chemother. 1998 Dec;42(12):3234–3241. doi: 10.1128/aac.42.12.3234. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tisdale M. Monitoring of viral susceptibility: new challenges with the development of influenza NA inhibitors. Rev Med Virol. 2000 Jan-Feb;10(1):45–55. doi: 10.1002/(sici)1099-1654(200001/02)10:1<45::aid-rmv265>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
- Zambon M., Hayden F. G., Global Neuraminidase Inhibitor Susceptibility Network Position statement: global neuraminidase inhibitor susceptibility network. Antiviral Res. 2001 Mar;49(3):147–156. doi: 10.1016/s0166-3542(01)00124-3. [DOI] [PubMed] [Google Scholar]