Chapter 110 : Susceptibility Test Methods: Viruses

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This chapter discusses the clinical situations in which antiviral resistance has emerged, thus necessitating in vitro susceptibility testing. It provides an overview of the phenotypic and genotypic susceptibility testing methods that have been employed to detect resistance. Persistent or worsening herpes simplex virus type 1 (HSV-1) or varicella zoster virus (VZV) infection while on acyclovir (ACV) may indicate drug resistance. Persistent or worsening human cytomegalovirus (HCMV) retinitis, pneumonitis, or colitis unresponsive to ganciclovir may also indicate drug-resistant virus. Monitoring for Human Immunodeficiency Virus type 1 (HIV-1) antiretroviral resistance is essential when beginning antiretroviral therapy (ART), for assessing failure of a particular regimen to suppress HIV replication and to test for cross-resistance to alternative antiretroviral drugs to aid in selection of appropriate salvage therapy. The plaque reduction assay (PRA) has been the "standard" method of antiviral susceptibility testing. A number of phenotypic assays are in use for testing of HIV-1 isolate susceptibility to nucleoside analog RT inhibitors. The major advantage of genotypic assays is the relatively rapid turnaround time compared to phenotypic assays. Multicenter studies were carried out to compare sequencing results among participating laboratories for detection of reverse transcriptase (RT) mutations. In this study, sequence concordance was high, even though different editing strategies were used by different labs, but 12% of the resistance mutations present in the 10 electronic files that were distributed and analyzed were not identified in some labs.

Citation: Arens M, Swierkosz E. 2011. Susceptibility Test Methods: Viruses , p 1729-1743. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch110
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1. Andersson, K. L.,, and R. T. Chung. 2009. Monitoring during and after antiviral therapy for hepatitis B. Hepatology 49: S166 S173.
2. Angus, P.,, R. Vaughan,, S. Xiong,, H. Yang,, W. Delaney,, C. Gibbs,, C. Brosgart,, D. Colledge,, R. Edwards,, A. Ayres,, A. Bartholomeusz,, and S. Locarnini. 2003. Resistance to adefovir dipivoxil therapy associated with the selection of a novel mutation in the HBV polymerase. Gastroenterology 125: 292 297.
3. Arens, M. 2001. Clinically relevant sequence-based genotyping of HBV, HCV, CMV, and HIV. J. Clin. Virol. 22: 11 29.
4. Baldanti, F.,, M. R. Underwood,, S. C. Stanat,, K. K. Biron,, S. Chou,, A. Sarasini,, E. Silini,, and G. Gerna. 1996. Single amino acid changes in the DNA polymerase confer foscarnet resistance and slow-growth phenotype, while mutations in the UL97-encoded phosphotransferase confer ganciclovir resistance in three double-resistant human cytomegalovirus strains recovered from patients with AIDS. J. Virol. 70: 1390 1395.
5. Baldanti, F.,, M. R. Underwood,, C. L. Talarico,, L. Simoncini,, A. Sarasini,, K. K. Biron,, and G. Gerna. 1998. The Cys 607→Tyr change in the UL97 phosphotransferase confers ganciclovir resistance to two human cytomegalovirus strains recovered from two immunocompromised patients. Antimicrob. Agents Chemother. 42: 444 446.
6. Bean, B.,, C. Fletcher,, J. Englund,, S. N. Lehrman,, and M. N. Ellis. 1987. Progressive mucocutaneous herpes simplex infection due to acyclovir-resistant virus in an immunocompromised patient: correlation of viral susceptibilities and plasma levels with response to therapy. Diagn. Microbiol. Infect. Dis. 7: 199 204.
7. Beddows, S.,, S. Galpin,, S. H. Kazmi,, A. Ashraf,, A. Johargy,, A. J. Frater,, N. White,, R. Braganza,, J. Clarke,, M. McClure,, and J. N. Weber. 2003. Performance of two commercially available sequence-based HIV-1 genotyping systems for the detection of drug resistance against HIV type 1 group M subtypes. J. Med. Virol. 70: 337 342.
8. Belshe, R. B.,, B. Burk,, F. Newman,, R. L. Cerruti,, and I. S. Sim. 1989. Resistance of influenza A virus to amantadine and rimantadine: results of one decade of surveillance. J. Infect. Dis. 159: 430 435.
9. Belshe, R. B.,, M. H. Smith,, C. B. Hall,, R. Betts,, and A. J. Hay. 1988. Genetic basis of resistance to rimantadine emerging during treatment of influenza virus infection. J. Virol. 62: 1508 1512.
10. Berkowitz, F. E.,, and M. J. Levin. 1985. Use of an enzymelinked immunosorbent assay performed directly on fixed infected cell monolayers for evaluating drugs against varicella-zoster virus. Antimicrob. Agents Chemother. 28: 207 210.
11. Beutner, K. R. 1995. Valacyclovir: a review of its antiviral activity, pharmacokinetic properties, and clinical efficacy. Antivir. Res. 28: 281 290.
12. Biron, K. K. 1991. Ganciclovir-resistant human cytomegalovirus isolates; resistance mechanisms and in vitro susceptibility to antiviral agents. Transplant. Proc. 23(Suppl. 3): 162 167.
13. Biron, K. K.,, and G. B. Elion. 1980. In vitro susceptibility of varicella-zoster virus to acyclovir. Antimicrob. Agents Chemother. 18: 443 447.
14. Biron, K. K.,, J. A. Fyfe,, S. C. Stanat,, L. K. Leslie,, J. B. Sorrell,, C. U. Lambe,, and D. M. Coen. 1986. A human cytomegalovirus mutant resistant to the nucleoside analog 9-{[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl}guanine (BW B759U) induces reduced levels of BW B759U triphosphate. Proc. Natl. Acad. Sci. USA 83: 8769 8773.
15. Biron, K. K.,, S. C. Stanat,, J. B. Sorrell,, J. A. Fyfe,, P. M. Keller,, C. U. Lambe,, and D. J. Nelson. 1985. Metabolic activation of the nucleoside analog q-[2-hydroxy- 1-(hydroxymethyl)ethoxymethyl] guanine in human diploid fibroblasts infected with human cytomegalovirus. Proc. Natl. Acad. Sci. USA 82: 2473 2477.
16. Boivin, G.,, S. Chou,, M. R. Quirk,, A. Erice,, and M. C. Jordon. 1996. Detection of ganciclovir resistance mutations and quantitation of cytomegalovirus (CMV) DNA in leukocytes of patients with fatal disseminated CMV disease. J. Infect. Dis. 173: 523 528.
17. Boyd, M. R.,, S. Safrin,, and E. R. Kern. 1993. Penciclovir: a review of its spectrum of activity, selectivity, and cross-resistance pattern. Antivir. Chem. Chemother. 4(Suppl.1): 3 11.
18. Boyer, P. L.,, H.-Q. Gao,, and S. H. Hughes. 1998. A mutation at position 190 of human immunodeficiency virus type 1 reverse transcriptase interacts with mutations at positions 74 and 75 via the template primer. Antimicrob. Agents Chemother. 42: 447 452.
19. Braun, P., and F. Wiesman. 2007. Phenotypic assays for the determination of coreceptor tropism in HIV-1 infected individuals. Eur. J. Med. Res. 12: 463 471.
20. Bright, R. A.,, M.-J. Medina,, X. Xu,, G. Perez-Oronoz,, T. R. Wallis,, X. M. Davis,, L. Povinelli,, N. J. Cox,, and A. I. Klimov. 2005. Incidence of adamantine resistance among influenza A (H3N2) viruses isolated worldwide from 1994-2005: a cause for concern. Lancet 366: 1175 1181.
21. Centers for Disease Control and Prevention. 1999. Neuraminidase inhibitors for treatment of influenza A and B infections. MMWR Morb. Mortal. Wkly. Rep. 48(RR14): 19.
22. Centers for Disease Control and Prevention. 2009. Update: drug susceptibility of swine-orgin influenza A (H1N1) viruses, April 2009. MMWR Morb. Mortal. Wkly Rep. 58: 433435.
23. Chatis, P. A.,, and C. S. Crumpacker. 1992. Resistance of herpesviruses to antiviral drugs. Antimicrob. Agents Chemother. 36: 1589 1595.
24. Chou, S.,, A. Erice,, M. C. Jordon,, G. M. Vercellotti,, K. R. Michels,, C. L. Talarico,, S. C. Stanat,, and K. K. Biron. 1995. Analysis of the UL97 phosphotransferase coding sequence in clinical cytomegalovirus isolates and identification of mutations conferring ganciclovir resistance. J. Infect. Dis. 171: 576 583.
25. Chou, S.,, S. Guentzel,, K. R. Michels,, R. C. Miner,, and W. L. Drew. 1995. Frequency of UL97 phosphotransferase mutations related to ganciclovir resistance in clinical cytomegalovirus isolates. J. Infect. Dis. 172: 239 242.
26. Chou, S.,, G. Marousek,, S. Guentzel,, S. E. Follansbee,, M. E. Poscher,, J. P. Lalezari,, R. C. Miner,, and W. L. Drew. 1997. Evolution of mutations conferring multidrug resistance during prophylaxis and therapy for cytomegalovirus disease. J. Infect. Dis. 176: 786 789.
27. Cingolani A.,, A. Antinori,, M. G. Rizzo,, R. Murri,, A. Ammassari,, F. Baldini,, S. Di Giambenedetto,, R. Cauda,, and A. De Luca. 2002. Usefulness of monitoring HIV drug resistance and adherence in individuals failing highly active antiretroviral therapy: a randomized study (ARGENTA). AIDS 16: 369 379.
28. Cirelli, R.,, K. Herne,, M. McCrary,, P. Lee,, and S. K. Tyring. 1996. Famciclovir: review of clinical efficacy and safety. Antivir. Res. 29: 141 151.
29. Coen, D. M., and D. D. Richman,. 2007. Antiviral agents, p. 447 485. In D. M. Knipe, and P. M. Howley (ed.), Fields Virology, 5th ed. Lippincott Williams & Wilkins, Philadelphia, PA.
30. Cole, N. L.,, and H. H. Balfour, Jr. 1987. In vitro susceptibility of cytomegalovirus isolates from immunocompromised patients to acyclovir and ganciclovir. Diagn. Microbiol. Infect. Dis. 6: 255 261.
31. Cunningham, S.,, B. Ank,, D. Lewis,, W. Lu,, M. Wantman,, J. Dileanis,, J. B. Jackson,, P. Palumbo,, P. Krogstad,, and S. H. Eshelman. 2001. Performance of the Applied Biosystems ViroSeq human immunodeficiency virus type 1 (HIV-1) genotyping system for sequence- based analysis of HIV-1 in pediatric plasma samples. J. Clin. Microbiol. 39: 1254 1257.
32. Dankner, W. M.,, D. Scholl,, S. C. Stanat,, M. Martin,, R. L. Sonke,, and S. A. Spector. 1990. Rapid antiviral DNADNA hybridization assay for human cytomegalovirus. J. Virol. Methods 28: 293 298.
33. De Clercq, E. 1982. Comparative efficacy of antiherpes drugs in different cell lines. Antimicrob. Agents Chemother. 21: 661 663.
34. DeGruttola, V.,, L. Dix,, R. D’Aquila,, D. Holder,, A. Phillips,, M. Ait-Kaled,, J. Baxter,, P. Clevenbergh,, S. Hammer,, R. Harrigan,, D. Katzenstein,, R. Lanier,, M. Miller,, M. Para,, S. Yerly,, A. Zolopa,, J. Murray,, A. Patick,, V. Miller,, S. Castillo,, L. Pedneault,, and J. Mellors. 2002. The relation between baseline HIV drug resistance and response to antiretroviral therapy: re-analysis of retrospective and prospective studies using a standardized data analysis plan. Antivir. Ther. 5: 41 48.
35. Dekker, C.,, M. N. Ellis,, C. McLaren,, G. Hunter,, J. Rogers,, and D. W. Barry. 1983. Virus resistance in clinical practice. J. Antimicrob. Chemother. 12: 137 152.
36. Delwart, E. L.,, H. Pan,, H. W. Sheppard,, D. Wolpert,, A. U. Neumann,, B. Korber,, and J. L. Mullins. 1998. Slower evolution of human immunodeficiency virus type 1 quasispecies during progression to AIDS. J. Virol. 71: 7498 7508.
37. Demeter, L. M.,, R. D’Aquila,, O. Weislow,, E. Lorenzo,, A. Erice,. J. Fitzgibbon,, R. Shaker,, D. Richman,, T. M. Howard,, Y. Zhao,, E. Fisher,, D. Huang,, D. Mayers,, S. Sylvester,, M. Arens,, K. Sannerud,, S. Rasheed,, V. Johnson,, D. Kiritzkes,, P. Reichelderfer,, and A. Japour for the ACTG Sequencing Working Group. 1998. Interlaboratory concordance of DNA sequence analysis to detect reverse transcriptase mutations in HIV-1 proviral DNA. J. Virol. Methods 75: 93 104.
38. Deyde, V. M.,, M. Okomo-Adhiambo,, T. G. Sheu,, T. R. Wallis,, A. Fry,, N. Dharan,, A. I. Klimov,, and L. V. Gubareva. 2009. Pyrosequencing as a tool to detect molecular markers of resistance to neuraminidase inhibitors in seasonal influenza A viruses. Antivir. Res. 81: 16 24.
39. Deyde, V. M.,, X. Xu,, R. A. Bright,, M. Shaw,, C. B. Smith,, Y. Zhang,, Y. Shu,, L. V. Gubareva,, N. J. Cox,, and A. I. Klimov. 2007. Surveillance of resistance to adamantanes among influenza A(H3N2) and A(H1N1) viruses isolated worldwide. J. Infect. Dis. 196: 249 257.
40. Drew, W. L.,, R. C. Miner,, D. F. Busch,, S. E. Follansbee,, J. Gullett,, S. G. Mehalko,, S. M. Gordon,, W. F. Owen, Jr.,, T. R. Matthews,, W. C. Buhles,, and B. DeArmond. 1991. Prevalence of resistance in patients receiving ganciclovir for serious cytomegalovirus infection. J. Infect. Dis. 163: 716 719.
41. Durant, J.,, P. Clevenbergh,, P. Halfon,, P. Delgiudice,. S. Porsin,, P. Simonet,, N. Montagne,, C. A. B. Boucher,, J. M. Schapiro,, and P. Dellamonica. 1999. Drug-resistance genotyping in HIV-1 therapy: the VIRADAPT randomized controlled trial. Lancet 353: 2196 2199.
42. Englund, J. A.,, M. E. Zimmerman,, E. M. Swierkosz,, J. L. Goodman,, D. R. Scholl,, and H. H. Balfour, Jr. 1990. Herpes simplex virus resistant to acyclovir. A study in a tertiary care center. Ann. Intern. Med. 112: 416 422.
43. Erali, M.,, S. Page,, L. G. Reimer,, and D. R. Hillyard. 2001. Human immunodeficiency virus type 1 drug resistance test: a comparison of three sequence-based methods. J. Clin. Microbiol. 39: 2157 2165.
44. Erice, A. 1999. Resistance of human cytomegalovirus to antiviral drugs. Clin. Microbiol. Rev. 12: 286 297.
45. Erice, A., 2000. Antiviral susceptibility testing, p. 271 289. In G. A. Storch (ed.), Essentials of Diagnostic Virology. Churchill Livingstone, New York, NY.
46. Erice, A.,, S. Chou,, K. K. Biron,, S. C. Stanat,, H. H. Balfour, Jr.,, and M. C. Jordan. 1989. Progressive disease due to ganciclovir-resistant cytomegalovirus in immunocompromised patients. N. Engl. J. Med. 320: 289 293.
47. Erice, A.,, C. Gil-Roda,, J.-L. Perez,, H. H. Balfour, Jr.,, K. J. Sannerud,, M. N. Hanson,, G. Boivin,, and S. Chou. 1997. Antiviral susceptibilities and analysis of UL97 and DNA polymerase sequences of clinical cytomegalovirus isolates from immunocompromised patients. J. Infect. Dis. 175: 1087 1092.
48. Eshelman, S. H.,, J. Hackett, Jr.,, P. Swanson,, S. P. Cunningham,, B. Drews,, C. Brennan,, S. G. Devare,, L. Zekeng,, L. Kaptue,, and N. Marlowe. 2004. Performance of the Celera Diagnostics ViroSeq HIV-1 genotyping system for sequence-based analysis of diverse human immunodeficiency virus type 1 strains. J. Clin. Microbiol. 42: 2711 2717.
49. Fattovich, G.,, G. McIntyre,, M. Thursz,, K. Coleman,, G. Giuliano,, A. Alberti,, H. C. Thomas,, and W. F. Carman. 1995. Hepatitis B virus precore/core variation and interferon therapy. Hepatology 22: 1355 1362.
50. Fung, S. K., and A. S. F. Lok. 2004. Hepatitis B virus genotypes: do they play a role in the outcome of HBV infection? Hepatology 40: 790 792.
51. Gadler, H. 1983. Nucleic acid hybridization for measurement of effects of antiviral compounds on human cytomegalovirus DNA replication. Antimicrob. Agents Chemother. 24: 370 374.
52. Ghany, M. G.,, and E. C. Doo. 2009. Antiviral resistance and hepatitis B therapy. Hepatology 49: S174 S184.
53. Gilbert, C.,, and G. Boivin. 2005. Human cytomegalovirus resistance to antiviral drugs. Antimicrob. Agents Chemother. 49: 873 883.
54. Gintowt, A. A.,, J. J. Germer,, P. S. Mitchell,, and J. D. C. Yao. 2005. Evaluation of the MagNA Pure LC used with the TRUGENE ™ HBV Genotyping Kit. J. Clin. Virol. 34: 155 157.
55. Gubareva, L. V.,, L. Kaiser,, M. N. Matrosovich,, Y. Soo-Hoo,, and F. G. Hayden. 2001. Selection of influenza virus mutants in experimentally infected volunteers treated with oseltamivir. J. Infect. Dis. 183: 523 531.
56. Gubareva, L. V.,, M. N. Mastrosovich,, M. K. Brenner,, R. C. Bethell,, and R. G. Webster. 1998. Evidence for zanamivir resistance in an immunocompromised child infected with influenza B virus. J. Infect. Dis. 179: 1257 1262.
57. Hanna, G. J., and R. T. D’Aquila. 2001. Clinical use of genotypic and phenotypic drug resistance testing to monitor antiretroviral chemotherapy. Clin. Infect. Dis. 32: 774 782.
58. Hantz, S.,, D. Michel,, A.-M. Fillet,, V. Guigonis,, G. Champier,, M.-C. Mazeron,, A. Bensman,, F. Denis,, T. Mertens,, A. Dehee,, and S. Alain. 2005. Early selection of a new UL97 mutant with a severe defect of ganciclovir phosphorylation after valaciclovir prophylaxis and short-term ganciclovir therapy in a renal transplant recipient. Antimicrob. Agents Chemother. 49: 1580 1583.
59. Harmenberg, J.,, B. Wahren,, and B. Oberg. 1980. Influence of cells and virus multiplicity on the inhibition of herpesviruses with acycloguanosine. Intervirology 14: 239 244.
60. Hassain, M.,, S. Fung,, E. Libbrecht,, E. Sablon,, C. Cursaro,, P. Andreone,, and A. S. F. Lok. 2006. Sensitive line probe assay that simultaneously detects mutations conveying resistance to lamivudine and adefovir. J. Clin. Microbiol. 44: 1094 1097.
61. Hayden, F. 2009. Developing new antiviral agents for influenza treatment; what does the future hold? Clin. Infect. Dis. 48( Suppl. 1): S3 S13.
62. Hayden, F. G.,, K. M. Cote,, and G. D. Douglas, Jr. 1980. Plaque inhibition assay for drug susceptibility testing of influenza viruses. Antimicrob. Agents Chemother. 17: 865 870.
63. Hertogs, K.,, M.-P. De Bethune,, V. Miller,, T. Ivens,, P. Schel,, A. Van Cauwenberge,, C. Van Den Eynde,, V. Van Gerwen,, H. Azijn,, M. Van Houtte,, F. Peeters,, S. Staszewski,, M. Conant,, S. Bloor,, S. Kemp,, B. Larder,, and R. Pauwels. 1998. A rapid method for simultaneous detection of phenotypic resistance to inhibitors of protease and reverse transcriptase in recombinant human immunodeficiency virus type 1 isolates from patients treated with antiretroviral drugs. Antimicrob. Agents Chemother. 42: 269 276.
64. Hill, E. L.,, M. N. Ellis,, and P. Nguyen-Dinh,. 1991. Antiviral and antiparasitic susceptibility testing, p. 1184 1188. In A. Balows,, W. J. Hausler, Jr.,, K. L. Hermann,, H. D. Isenberg,, and H. J. Shadomy (ed.), Manual of Clinical Microbiology, 5th ed. American Society for Microbiology, Washington, DC.
65. Hill, E. L.,, G. A. Hunter,, and M. N. Ellis. 1991. In vitro and in vivo characterization of herpes simplex virus clinical isolates recovered from patients infected with human immunodeficiency virus. Antimicrob. Agents Chemother. 35: 2322 2328.
66. Hirsch, M. S.,, F. Brun-Vezinet,, R. T. D’Aquila,, S. M. Hammer,, V. A. Johnson,, D. R. Kiritzkes,, C. Loveday,, J. W. Mellors,, B. Clotet,, B. Conway,, L. M. Demeter,, S. Vella,, D. M. Jacobsen,, and D. D. Richman. 2000. Antiretroviral drug resistance testing in adult HIV-1 infection: recommendations of an International AIDS Society—USA Panel. JAMA 283: 2417 2426.
67. Hirsch, M. S.,, B. Conway,, R. T. D’Aquila,, V. A. Johnson,, F. Brun-Vezinet,, B. Clotet,, L. M. Demeter,, S. M. Hammer,, D. M. Jacobsen,, D. R. Kuritzkes,, C. Loveday,, M. W. Mellors,, S. Vella,, and D. D. Richman. 1998. Antiretroviral drug resistance testing in adults with HIV infection: implications for clinical management. International AIDS Society—USA Panel. JAMA 279: 1984 1991.
68. Huang, D. D.,, S. H. Eshelman,, D. J. Brambilla,, P. E. Palumbo,, and J. W. Bremer. 2003. Evaluation of the editing process in human immunodeficiency virus type 1 genotyping. J. Clin. Microbiol. 41: 3265 3272.
69. Iversen, A. K.,, R. W. Shafer,, K. Wehrly,, M. A. Winters,, J. I. Mullins,, B. Chesebro,, and T. C. Merigan. 1996. Multidrug- resistant human immunodeficiency virus type 1 strains resulting from combination antiretroviral therapy. J. Virol. 70: 1086 1090.
70. Jacobson, M. A.,, T. G. Berger,, S. Fikrig,, P. Cecherer,, J. W. Moohr,, S. C. Stanat,, and K. K. Biron. 1990. Acyclovirresistant varicella zoster virus infection after chronic oral acyclovir therapy in patients with the acquired immunodeficiency syndrome (AIDS). Ann. Intern. Med. 112: 187 191.
71. Janssen, H. L. A.,, M. vanZonneveld,, H. Senturk,, S. Zeuzem,, U. S. Akarca,, Y. Cakaloglu,, C. Simon,, T. M. K. So,, G. Gerken,, R. A. deMan,, H. G. M. Niesters,, P. Zondervan,, B. Hansen, and S. W. Schalm. 2005. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomized trial. Lancet 365: 123 129.
72. Japour, A. J.,, D. L. Mayers,, V. A. Johnson,, D. R. Kuritzkes,, L. A. Beckett,, J.-M. Arduino,, J. Lane,, R. J. Black,, P. S. Reichelderfer,, R. T. D’Aquila,, C. S. Crumpacker, the RV-43 Study Group, and the AIDS Clinical Trials Group Virology Committee Resistance Working Group. 1993. Standardized peripheral blood mononuclear cell culture assay for determination of drug susceptibilities of clinical human immunodeficiency virus type 1 isolates. Antimicrob. Agents Chemother. 37: 1095 1101.
73. Johnson, V.,, F. Brun-Vezinet,, B. Clotet,, H. F. Gunthard,, D. R. Kuritzkes,, D. Pillay,, J. M. Schapiro,, and D. D. Richman. 2008. Update of the drug resistance mutations in HIV-1: December 2008. Top. HIV Med. 16: 138 145.
74. Kantor, R.,, D. A. Katzenstein,, B. Efron,, A. P. Carvalho,, B. Wynhoven,, P. Cane,, J. Clarke,, S. Sirivichayakul,, M. A. Soares,, J. Snoeck,, C. Pillay,, H. Rudich,, R. Rodrigues,, A. Holguin,, K. Ariyoshi,, M. B. Bouzas,, P. Cahn,, W. Sugiura,, V. Soriano,, L. F. Brigido,, Z. Grossman,, L. Morris,, A.-M. Vandamme,, A. Tanuri,, P. Rhanuphak,, J. N. Weber,, D. Pillay,, P. R. Harrigan,, R. Camacho,, J. M. Schapiro,, and R. W. Shafer. 2005. Impact of HIV-1 subtype and antiviral therapy on protease and reverse transcriptase genotype: results of a global collaboration. PLoS Med. 2: 325 337.
75. Kellam, P.,, and B. A. Larder. 1994. A recombinant virus assay: a rapid, phenotypic assay for assessment of drug susceptibility of human immunodeficiency virus type 1 isolates. Antimicrob. Agents. Chemother. 38: 23 30.
76. Kusumi, K.,, B. Conway,, S. Cunningham,, A. Berson,, C. Evans,, A. K. N. Iversen,, D. Colvin,, M. V. Gallo,, S. Coutre,, E. G. Shpaer,, D. V. Faulkner,, A. DeRonde,, S. Volkman,, C. Williams,, M. S. Hirsch,, and J. I. Mullins. 1992. Human immunodeficiency virus type 1 envelope gene structure and diversity in vivo and after cocultivation in vitro. J. Virol. 66: 875 885.
77. Lai, C.-L.,, N. Leung,, E.-K. Teo,, M. Tong,, F. Wong,, H.-W. Hann,, S. Han,, T. Poynard,, M. Myers,, G. Chao,, D. Lloyd,, N. A. Brown, and the Telbivudine Phase II Investigator Group. 2005. A 1-year trial of telbivudine, lamivudine, and the combination in patients with hepatitis B e antigen-positive chronic hepatitis B. Gastroenterology 129: 528 536.
78. Landry, M. L.,, S. Stanat,, K. Biron,, D. Brambilla,, W. Britt,, J. Jokela,, S. Chou,. W. L. Drew,, A. Erice,, B. Gilliam,, N. Lurain,, J. Manischewitz,, R. Miner,, M. Nokta,, P. Reichelderfer,, S. Spector,, A. Weinberg,, B. Yen-Lieberman,, C. Crumpacker, and the AIDS Clinical Trials Group CMV Resistance Working Group. 2000. A standardized plaque reduction assay for determination of drug susceptibilities of cytomegalovirus clinical isolates. J. Clin. Microbiol. 44: 688 692.
79. Larder, B. A.,, G. Darby,, and D. D. Richman. 1989. HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science 243: 1731 1734.
80. Leary, J. J.,, R. Wittrock,, R. T. Sarisky,, A. Weinberg,, and M. J. Levin. 2002. Susceptibilities of herpes simplex viruses to penciclovir and acyclovir in eight cell lines. Antimicrob. Agents Chemother. 46: 762 768.
81. Lehrman, S. N.,, J. M. Douglas,, L. Corey,, and D. W. Barry. 1986. Recurrent genital herpes and suppressive oral acyclovir therapy. Relation between clinical outcome and in-vitro drug sensitivity. Ann. Intern. Med. 104: 786 790.
82. Little, S. J.,, S. Holte,, J. Routy,, E. S. Daar,, M. Markowitz,, A. C. Collier,, R. A. Koup,, J. W. Mellors,, E. Connick,, B. Conway,, M. Kilby,, L. Wang,, J. M. Whitcomb,, N. S. Hellmann,, and D. D. Richman. 2002. Antiretroviral-drug resistance among patients recently infected with HIV. N. Engl. J. Med. 347: 385 394.
83. Lok, A. S. F. 2007. Navigating the maze of hepatitis B treatments. Gastroenterology 132: 1586 1594.
84. Lok, A. S. F.,, and B. J. McMahon. 2007. Chronic hepatitis B: AASLD practice guidelines. Hepatology 45: 507 539.
85. Lu, J.,, S. G. Deeks,, R. Hoh,, G. Beatty,, B. A. Kuritzkes,, J. N. Martin,, and D. R. Kuritzkes. 2006. Rapid emergence of enfuvirtide resistance in HIV-1-infected patients. J. Acquir. Immune Defic. Syndr. 43: 60 64.
86. Lurain, N. S.,, K. D. Thompson,, E. W. Holmes,, and G. S. Read. 1992. Point mutations in the DNA polymerase gene of human cytomegalovirus that results in resistance to antiviral agents. J. Virol. 66: 7146 7152.
87. Lurain, N. S.,, A. Weinberg,, C. S. Crumpacker,, and S. Chou. 2001. Sequencing of cytomegalovirus UL97 gene for genotypic antiviral resistance testing. Antimicrob. Agents Chemother. 45: 2775 2780.
88. MacArthur, R. D., and R. M. Novak. 2008. Maraviroc: the first of a new class of antiretroviral agents. Clin. Infect. Dis. 47: 236 241.
89. Marschner, I. C.,, A. C. Collier,, R. W. Combs,, R. T. D’Aquila,, V. DeGruttola,, M. A. Fischl,, S. M. Hammer,, M. D. Hughes,, V. A. Johnson,, D. A. Katzenstein,. D. D. Richman,, L. M. Smeaton,, S. A. Spector,, and M. S. Saag. 1998. Uses of changes in plasma levels of human immunodeficiency virus type 1 RNA to assess the clinical benefit of antiretroviral therapy. J. Infect. Dis. 177: 40 47.
90. Martin, J. L.,, M. N. Ellis,, P. M. Keller,, K. K. Biron,, S. N. Lehrman,, D. W. Barry,, and P. A. Furman. 1985. Plaque autoradiography assay for the detection and quantitation of thymidine kinase-deficient and thymidine kinase-altered mutants of herpes simplex virus in clinical isolates. Antimicrob. Agents Chemother. 28: 181 187.
91. Martinez-Picado, J.,, A. V. Savara,, L. Sutton,, and R. T. D’Aquila. 1999. Replicative fitness of protease inhibitorresistant mutants of human immunodeficiency virus type 1. J. Virol. 73: 3744 3752.
92. Martinez-Picado, J.,, L. Sutton,, M. P. De Pasquale,, A. V. Savara,, and R. T. D’Aquila. 1999. Human immunodeficiency virus type 1 cloning vectors for antiviral resistance testing. J. Clin. Microbiol. 37: 2943 2951.
93. McLaren, C.,, M. N. Ellis,, and G. A. Hunter. 1983. A colorimetric assay for the measurement of the sensitivity of herpes simplex viruses to antiviral agents. Antiviral Res. 3: 223 224.
94. Moore, J. P.,, and D. R. Kuritzkes. 2009. A pièce de resistance: how HIV-1 escapes small molecular CCR5 inhibitors. Curr. Opin. HIV AIDS 4: 118 124.
95. Moscona, A. 2009. Global transmission of oseltamivir-resistant influenza. N. Engl. J. Med. 360: 953 956.
96. Mracna, M.,, G. Becker-Pergola,, J. Dileanis,, L. A. Guay,, S. Cunningham,, J. B. Jackson,, and S. H. Eshleman. 2001. Performance of Applied Biosystems ViroSeq HIV-1 genotyping system for sequence-based analysis of non-subtype B human immunodeficiency virus type 1 from Uganda. J. Clin. Microbiol. 39: 4323 4327.
97.NCCLS. 2004. Antiviral Susceptibility Testing: Herpes Simplex Virus by Plaque Reduction Assay; Approved standard. NCCLS M33-A. NCCLS, Wayne, PA.
98. Olivero, A.,, A. Ciancio,, M. L. Abate,, S. Gaia,, A. Smedile,, and M. Rizzetto. 2006. Performance of sequence analysis, INNO-LiPA line probe assays and AFFIGENE assays in the detection of hepatitis B virus polymerase and precore/core promoter mutations. J. Viral Hepat. 13: 355 362.
99. Orito, E.,, M. Mizokami,, H. Sakugawa,, K. Michitaka,, K. Ishikawa,, and T. Ichida. 2001. A case-controlled study for clinical and molecular biological differences between hepatitis B viruses of genotypes B and C. Hepatology 33: 218 223.
100. Osiowy, C.,, and E. Giles. 2003. Evaluation of the INNOLiPA HBV Genotyping assay for determination of hepatitis B virus genotype. J. Clin. Microbiol. 41: 5473 5477.
101. Osiowy, C.,, J.-P. Villeneuve,, E. J. Heathcote,, E. Giles,, and J. Borlang. 2006. Detection of the rtN236T and rt181V/T mutations associated with resistance to adefovir dipivoxil in samples from patients with chronic hepatitis B virus infection by the INNO-LiPA HBV DR line probe assay (version 2). J. Clin. Microbiol. 44: 1994 1997.
102. Pahwa, S.,, K. Biron,, W. Lim,, P. Swenson,, M. H. Kaplan,, N. Sadick,, and R. Pahwa. 1988. Continuous varicella-zoster infection associated with acyclovir resistance in a child with AIDS. JAMA 260: 2879 2882.
103. Pepin, J.-M.,, F. Simon,, M. C. Dazza,, and F. Brun-Vezinet. 1992. The clinical significance of in vitro cytomegalovirus susceptibility to antiviral drugs. Res. Virol. 143: 126 128.
104. Perez, E. E.,, S. L. Rose,, B. Peyser,, S. L. Lamers,. B. Burkhardt,, B. M. Dunn,, A. D. Hutson,, J. W. Sleasman,, and M. M. Goodenow. 2001. Human immuno-deficiency virus type 1 protease genotype predicts immune and viral responses to combination therapy with protease inhibitors (PIs) in PI-naive patients. J. Infect. Dis. 183: 579 588.
105. Petropoulos, C. J.,, N. T. Parkin,, K. L. Limoli,, Y. S. Lie,, T. Wrin,, W. Huang,, H. Tian,, D. Smith,, G. A. Winslow,, D. J. Capon,, and J. M. Whitcomb. 2000. A novel phenotypic drug susceptibility assay for human immunodeficiency virus type 1. Antimicrob. Agents Chemother. 42: 920 928.
106. Rabalaiss, G. P.,, M. J. Levin,, and F. E. Berkowitz. 1987. Rapid herpes simplex virus susceptibility testing using an enzyme-linked immunosorbent assay performed in situ on fixed virus-infected monolayers. Antimicrob. Agents Chemother. 31: 946 948.
107. Reeves, J. D.,, E. Coakley,, C. J. Petropoulos,, and J. M. Whitcomb. 2009. An enhanced sensitivity Trofile™ HIV coreceptor tropisms assay for selecting patients for therapy with entry inhibitors targeting CCR5: a review of analytical and clinical studies. J. Viral Entry 3: 94 102.
108. Richman, D. D. 1995. Clinical significance of drug resistance in human immunodeficiency virus. Clin. Infect. Dis. 21( Suppl. 2): S166 S169.
109. Richman, D. D.,, J. C. Guatelli,, J. Grimes,, A. Tsiatis,, and T. R. Gingeras. 1991. Detection of mutations associated with zidovudine resistance in human immunodeficiency virus utilizing the polymerase chain reaction. J. Infect. Dis. 164: 1075 1081.
110. Safrin, S.,, T. Assaykeen,, S. Follansbee,, and J. Mills. 1990. Foscarnet therapy for acyclovir-resistant mucocutaneous herpes simplex virus infection in 26 AIDS patients: preliminary data. J. Infect. Dis. 161: 1078 1084.
111. Safrin, S.,, T. G. Berger,, I. Gilson,, P. R. Wolfe,, C. B. Wofsy,, J. Mills,, and K. K. Biron. 1991. Foscarnet therapy in five patients with AIDS and acyclovir-resistant varicellazoster virus infection. Ann. Intern. Med. 115: 19 21.
112. Safrin, S.,, C. Crumpacker,, P. Chatis,, R. Davis,, R. Hafner,, J. Rush,, H. A. Kessler,, B. Landry,, J. Mills, and the AIDS Clinical Trials Group. 1991. A controlled trial comparing foscarnet with vidarabine for acyclovir-resistant mucocutaneous herpes simplex in the acquired immunodeficiency syndrome. N. Engl. J. Med. 325: 551 555.
113. Safrin, S.,, E. Palacios,, and B. J. Leahy. 1996. Comparative evaluation of microplate enzyme-linked immunosorbent assay versus plaque reduction assay for antiviral susceptibility testing of herpes simplex virus isolates. Antimicrob. Agents Chemother. 40: 1017 1019.
114. Schinazi, R. F.,, B. A. Larder,, and J. W. Mellors. 1997. Mutations in HIV-1 reverse transcriptase and protease associated with drug resistance. Int. Antiviral News 5: 129 134.
115. Schuurman, R.,, D. Brambilia,, T. de Groot,, D. Huang,, S. Land,, J. Bremer,, I. Benders,, and C. A. Boucher. 2002. Underestimation of HIV type 1 drug resistance mutations: results from the ENVA-2 genotyping proficiency program. AIDS Res. Hum. Retrovir. 18: 243 248.
116. Schuurman, R.,, L. Demeter,, P. Reichelderfer,, J. Tijnagel,, T. DeGroot,, and C. Boucher. 1999. Worldwide evaluation of DNA sequencing approaches for identification of drug resistance mutations in the human immunodeficiency virus type 1 reverse transcriptase. J. Clin. Microbiol. 37: 2291 2296.
117. Shafer, R. W. 2002. Genotypic testing for human immunodeficiency virus type 1 drug resistance. Clin. Microbiol. Rev. 15: 247 277.
118. Shafer, R. W.,, D. R. Jung,, and B. J. Betts. 2000. Human immunodeficiency virus type 1 reverse transcriptase and protease mutation search engine for queries. Nat. Med. 6: 1290 1292.
119. Shamliyan, T. A.,, R. MacDonald,, A. Shaukat,, B. C. Tayor,, J.-M. Yuan,, J. R. Johnson,, J. Tacklind,. I. Rutks,, R. Kane,, and T. J. Wilt. 2009. Antiviral therapy for adults with chronic hepatitis B: a systematic review for a National Institutes of Health Consensus Development Conference. Ann. Intern. Med. 150: 111 124.
120. Shaw, T.,, A. Bartholomeusz,, and S. Locarnini. 2006. HBV drug resistance: mechanisms, detection and interpretation. J. Hepatol. 44: 593 606.
121. Shaw, T.,, and S. Locarnini. 2004. Entecavir for the treatment of chronic hepatitis B. Expert Rev. Anti-infect. Ther. 2: 853 871.
122. Shi, C.,, and J. W. Mellors. 1997. A recombinant retroviral system for rapid in vivo analysis of human immunodeficiency virus type 1 susceptibility to reverse transcriptase inhibitors. Antimicrob. Agents Chemother. 41: 2781 2785.
123. Sibrack, C. D.,, L. T. Gutman,, C. M. Wilfert,, C. McLaren,, M. H. St. Clair,, P. M. Keller,, and D. W. Barry. 1982. Pathogenicity of acyclovir-resistant herpes simplex virus type 1 from an immunodeficient child. J. Infect. Dis. 146: 673 682.
124. Smith, I. L.,, J. M. Cherrington,, R. E. Jiles,, M. D. Fuller,, W. R. Freeman,, and S. A. Spector. 1997. High-level resistance of cytomegalovirus to ganciclovir is associated with alterations in both the UL97 and DNA polymerase genes. J. Infect. Dis. 176: 69 77. (Erratum, 177: 1140 1441, 1998.)
125. Spector, S. A.,, K. Hsia,, D. Wolf,, M. Shinkai,, and I. Smith. 1995=. Molecular detection of human cytomegalovirus and determination of genotypic ganciclovir resistance in clinical specimens. Clin. Infect. Dis. 21( Suppl. 2): S170 S173.
126. Standring-Cox, R.,, T. H. Bacon,, and B. A. Howard. 1996. Comparison of a DNA probe assay with the plaque reduction assay for measuring the sensitivity of herpes simplex virus and varicella-zoster virus to penciclovir and acyclovir. J. Virol. Methods 56: 3 11.
127. St. Clair, M. H.,, P. M. Hartigan,, J. C. Andrews,, C. L. Vavro,, M. S. Simberkoff,, J. D. Hamilton, and the VA Cooperative Study Group. 1993. Zidovudine resistance, syncytium-inducing phenotype, and HIV disease progression in a case-control study. J. Acquir. Immune Defic. Syndr. 6: 891 897.
128. St. Clair, M. H.,, J. L. Martin,, G. Tudor-Williams,, M. C. Bach,, C. L. Vavro,, D. M. King,, P. Kellam,, S. D. Kemp,, and B. A. Larder. 1991. Resistance to ddI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase. Science 253: 1557 1559.
129. Swierkosz, E. M.,, and K. K. Biron,. 1994. Antiviral susceptibility testing, p. 8.26.2 8.26.21. In H. D. Isenberg (ed.). Clinical Microbiology Procedures Handbook, supplement 1. American Society for Microbiology, Washington, DC.
130. Swierkosz, E. M.,, and K. K. Biron,. 1995. Antiviral susceptibility testing, p. 139 154. In E. H. Lennette,, D. A. Lennette,, and E. T. Lennette (ed.), Diagnostic Procedures for Viral, Rickettsial and Chlamydial Infections, 7th ed. American Public Health Association, Washington, DC.
131. Swierkosz, E. M.,, D. R. Scholl,, J. L. Brown,, J. D. Jollick,, and C. A. Gleaves. 1987. Improved DNA hybridization method for detection of acyclovir-resistant herpes simplex virus. Antimicrob. Agents Chemother. 31: 1465 1469.
132. Tebas, P.,, D. Scholl,, J. Jollick,, K. McHarg,, M. Arens,, and P. D. Olivo. 1998. A rapid assay to screen for drug-resistant herpes simplex virus. J. Infect. Dis. 177: 217 220.
133. Tebas, P.,, E. C. Stabel,, and P. D. Olivo. 1995. Antiviral susceptibility testing with a cell line which expresses b-galactosidase after infection with herpes simplex virus. Antimicrob. Agents Chemother. 39: 1287 1291.
134. Tenney, D. J.,, S. M. Levine,, R. E. Rose,, A. W. Walsh,, S. P. Weinheimer,, L. Discotto,, M. Plym,, K. Pokornowski,, C. F. Yu,, P. Angus,, A. Ayres,, A. Bartholomeusz,, W. Sievert,, G. Thompson,, N. Warner,, S. Locarnini,, and R. J. Colonno. 2004. Clinical emergence of entecavir-resistant hepatitis B virus requires additional substitutions in virus already resistant to lamivudine. Antimicrob. Agents and Chemother. 48: 3498 3507.
135. Tural, C.,, L. Ruiz,, C. Holtzer,, J. Schapiro,, P. Viciana,, J. Gonzalez,, P. Domingo,, C. Boucher,, C. Rey-Joly,, and B. Clotet. 2002. Clinical utility of HIV-1 genotyping and expert advice: the Havana trial. AIDS 16: 209 218.
136. Valsamakis, A. 2007. Molecular testing in the diagnosis and management of chronic hepatitis B. Clin. Microbiol. Rev. 20: 426 439.
137. Van Laethem, K.,, and A.-M. Vandamme. 2006. Interpreting resistance data for HIV-1 therapy management-know the limitations. AIDS Rev. 8: 37 43.
138. Walter, H.,, B. Schmidt,, K. Korn,, A. M. Vandamme,, T. Harrer,, and K. Uberla. 1999. Rapid, phenotypic HIV-1 drug sensitivity assay for protease and reverse transcriptase inhibitors. J. Clin. Virol. 13: 71 80.
139. Wang, Y.,, L. Wei,, D. Jiang,, X. Cong,, R. Fei,, J. Xiao,, and Y. Wang. 2005. In vitro resistance to interferon of hepatitis B virus with precore mutation. World J. Gastroenterol. 11: 649 655.
140. Wilson, J. W.,, P. Bean,, T. Robins,, F. Graziano,, and D. H. Persing. 2000. Comparative evaluation of three human immunodeficiency virus genotyping systems: the HIV-GenotypR method, the HIV PRT GeneChip assay, and the HIV-1 RT line probe assay. J. Clin. Microbiol. 38: 3022 3028.
141. Wolf, D. G.,, I. L. Smith,, D. J. Lee,, W. R. Freeman,, M. Flores-Aguilar,, and S. A. Spector. 1995. Mutations in human cytomegalovirus UL97 gene confer clinical resistance to ganciclovir and can be detected directly in patient plasma. J. Clin. Investig. 95: 257 263.
142. Woo, H.-Y.,, H. Park,, B.-I. Kim,, W.-K. Jeon,, Y. K. Cho,, and Y. J. Kim. 2007. Comparison of mass spectrometric analysis and TRUGENE™ HBV genotyping for monitoring lamivudine resistance in chronic hepatitis B patients. Antivir. Ther. 12: 7 13.
143. Yuan, H.-J.,, and W. M. Lee. 2007. Molecular mechanisms of resistance to antiviral therapy in patients with chronic hepatitis B. Curr. Mol. Med. 7: 185 197.
144. Yuen, L. K. W.,, A. Ayres,, M. Littlejohn,, D. Colledge,, A. Edgely,, W. J. Maskill,, S. A. Locarnini,, and A. Bartholomeusz. 2007. SEQHEPB: a sequence analysis program and relational database for chronic hepatitis B. Antivir. Res. 75: 64 74.
145. Zhang, J.,, S.-Y. Rhee,, J. Taylor,, and R. Shafer. 2005. Comparison of the precision and sensitivity of the Antivirogram and PhenoSense HIV drug susceptibility assays. J. Acquir. Immune Defic. Syndr. 38: 439 444.


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Proposed guidelines for antiviral susceptibility results of herpes group and influenza A viruses

Citation: Arens M, Swierkosz E. 2011. Susceptibility Test Methods: Viruses , p 1729-1743. In Versalovic J, Carroll K, Funke G, Jorgensen J, Landry M, Warnock D (ed), Manual of Clinical Microbiology, 10th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816728.ch110

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