Resistance development is a major obstacle to antiviral therapy, and all active antiviral agents have shown to select for resistance mutations. Aspects of antiviral resistance development are discussed for specific compounds or drug classes in the previous chapters, while this chapter provides an overview regarding the evolution of different viruses (HIV, HBV, HCV, and Influenza) under pressure of antiviral therapy. Virus replication is an error prone process resulting in a large number of variants (quasispecies) in patients. Resistance evolution under suboptimal therapy can be schematically distinguished into three phases. (1) preexisting variants less sensitive to the respective drug are selected from the quasispecies population, (2) outgrowing variants acquire additional mutations increasing their resistance, and (3) compensatory mutations accumulate to overcome the generally reduced replica-tive capacity of resistant variants. Successful therapy should be aimed at suppression of all existing viral variants, thus preventing selection of minority species and their subsequent evolution. This implies that the amount of mutations required for first escape to the viral regimen (genetic barrier) should be larger than the expected number of mutations present in viruses in the quasispecies. Accordingly, combination therapy can achieve complete inhibition of replication for most HIV, HBV, and Influenza infected patients without resistance development. However, resistant viruses can become selected under circumstances of suboptimal antiviral therapy and these resistant viruses can be transmitted. Proper use of drugs and worldwide monitoring for the presence and spread of drug resistant viruses are therefore of utmost importance.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Abed Y, Goyette N, Boivin G (2005) Generation and characterization of recombinant influenza A (H1N1) viruses harboring amantadine resistance mutations. Antimicrob Agents Chemother 49:556–559
Abed Y, Baz M, Boivin G (2006) Impact of neuraminidase mutations conferring influenza resistance to neuraminidase inhibitors in the N1 and N2 genetic backgrounds. Antivir Ther 11:971–976
Aoki FY, Boivin G, Roberts N (2007) Influenza virus susceptibility and resistance to oseltamivir. Antivir Ther 12:603–616
Arion D, Kaushik N, McCormick S, Borkow G, Parniak MA (1998) Phenotypic mechanism of HIV-1 resistance to 3′-azido-3′-deoxythymidine (AZT): increased polymerization processivity and enhanced sensitivity to pyrophosphate of the mutant viral reverse transcriptase. Biochem 37:15908–15917
Bartholomeusz A, Locarnini S (2006) Hepatitis B virus mutations associated with antiviral therapy J Med Virol 78 Suppl 1:S52–S55
Borroto-Esoda K, Miller MD, Arterburn S (2007) Pooled analysis of amino acid changes in the HBV polymerase in patients from four major adefovir dipivoxil clinical trials. J Hepatol 47:492–498
Bright RA, Medina MJ, Xu X, Perez-Oronoz G, Wallis TR, Davis XM, Povinelli L, Cox NJ,Klimov AI (2005) Incidence of adamantane resistance among influenza A (H3N2) viruses isolated worldwide from 1994 to 2005: a cause for concern. Lancet 366:1175–1181
Bright RA, Shay DK, Shu B, Cox NJ, Klimov AI (2006) Adamantane resistance among influenza A viruses isolated early during the 2005–2006 influenza season in the United States. JAMA 295:891–894
Coffin JM (1995) HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science 267:483–489
Colonno RJ, Rose R, Baldick CJ, Levine S, Pokornowski K, Yu CF, Walsh A, Fang J, Hsu M, Mazzucco C, Eggers B, Zhang S, Plym M, Klesczewski K, Tenney DJ (2006) Entecavir resistance is rare in nucleoside naive patients with hepatitis B. Hepatology 44:1656–1665
Das K, Xiong X, Yang H, Westland CE, Gibbs CS, Sarafianos SG, Arnold E (2001) Molecular modeling and biochemical characterization reveal the mechanism of hepatitis B virus polymerase resistance to lamivudine (3TC) and emtricitabine (FTC). J Virol 75:4771–4779
De FR, Migliaccio G (2005) Challenges and successes in developing new therapies for hepatitis C. Nature 436:953–960
de Jong MD, Schuurman R, Lange JMA, Boucher CAB (1996) Replication of a pre-existing resistant HIV-1 subpopulation in vivo after introduction of a strong selective drug pressure. Antivir Ther 1:33–41
de Jong MD, Tran TT, Truong HK, Vo MH, Smith GJ, Nguyen VC, Bach VC, Phan TQ, Do QH, Guan Y, Peiris JS, Tran TH, Farrar J (2005) Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med 353:2667–2672
De Meyer S, Azijn H, Surleraux D, Jochmans D, Tahri A, Pauwels R, Wigerinck P, de Bethune MP (2005) TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. Antimicrob Agents Chemother 49:2314–2321
Delaney WE, Yang H, Westland CE, Das K, Arnold E, Gibbs CS, Miller MD, Xiong S (2003) The hepatitis B virus polymerase mutation rtV173L is selected during lamivudine therapy and enhances viral replication in vitro. J Virol 77:11833–11841
Delwart EL, Sheppard HW, Walker BD, Goudsmit J, Mullins JI (1994) Human immunodeficiency virus type 1 evolution in vivo tracked by DNA heteroduplex mobility assays. J Virol 68:6672–6683
Delwart EL, Pan H, Neumann A, Markowitz M (1998) Rapid, transient changes at the env locus of plasma Human Immunodeficiency Virus type 1 populations during the emergence fo protease inhibitor resistance. J Virol 72:2416–2421
Dierynck I, De WM, Gustin E, Keuleers I, Vandersmissen J, Hallenberger S, Hertogs K (2007) Binding kinetics of darunavir to human immunodeficiency virus type 1 protease explain the potent antiviral activity and high genetic barrier. J Virol 81:13845–13851
Domingo E, Menendez Arias L, Quinones-Mateu ME, Holguin A, Gutierrez-Rivas M, Martinez MA, Quer J, Novella IS, Holland JJ (1997) Viral quasispecies and the problem of vaccine-escape and drug-resistant mutants. Prog Drug Res 48:99–128
Doyon L, Croteau G, Thibeault D, Poulin F, Pilote L, Lamarre D (1996) Second locus involved in human immunodeficiency virus type 1 resistance to protease inhibitors. J Virol 70:3763–3769
Doyon L, Payant C, Brakier Gingras L, Lamarre D (1998) Novel Gag-Pol frameshift site in human immunodeficiency virus type 1 variants resistant to protease inhibitors. J Virol 72:6146–6150
Durantel D, Brunelle MN, Gros E, Carrouee-Durantel S, Pichoud C, Villet S, Trepo C, Zoulim F (2005) Resistance of human hepatitis B virus to reverse transcriptase inhibitors: from genotypic to phenotypic testing. J Clin Virol 34 Suppl 1:S34–S43
Ferraris O, Lina B (2008) Mutations of neuraminidase implicated in neuraminidase inhibitors resistance. J Clin Virol 41:13–19
Gallant JE, Rodriguez AE, Weinberg WG, Young B, Berger DS, Lim ML, Liao Q, Ross L, Johnson J, Shaefer MS (2005) Early virologic nonresponse to tenofovir, abacavir, and lamivu-dine in HIV-infected antiretroviral-naive subjects. J Infect Dis 192:1921–1930
Garcia-Lerma JG, MacInnes H, Bennett D, Weinstock H, Heneine W (2004) Transmitted human immunodeficiency virus type 1 carrying the D67N or K219Q/E mutation evolves rapidly to zidovudine resistance in vitro and shows a high replicative fitness in the presence of zidovudine. J Virol 78:7545–7552
Gubareva LV, Kaiser L, Matrosovich MN, Soo-Hoo Y, Hayden FG (2001) Selection of influenza virus mutants in experimentally infected volunteers treated with oseltamivir. J Infect Dis 183:523–531
Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Brosgart CL, Borroto-Esoda K, Arterburn S, Chuck SL (2006) Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years. Gastroenterology 131:1743–1751
Hayden FG (2006) Antivirals for influenza: historical perspectives and lessons learned. Antiviral Res 71:372–378
Hayden FG, Belshe RB, Clover RD, Hay AJ, Oakes MG, Soo W (1989) Emergence and apparent transmission of rimantadine-resistant influenza A virus in families. N Engl J Med 321:1696–1702
Hazuda DJ, Miller MD, Nguyen BN, Zhao J, for the P005 study team (2007) Resistance to HIV- integrase inhibitor raltegravir: analysis of protocol 005, a Phase II study in patients with triple-class resistant HIV-1 infection. Antivir Ther 12:S10
Herlocher ML, Truscon R, Elias S, Yen HL, Roberts NA, Ohmit SE, Monto AS (2004) Influenza viruses resistant to the antiviral drug oseltamivir: transmission studies in ferrets. J Infect Dis 190:1627–1630
Hertogs K, de Bethune MP, Miller V, Ivens T, Schel P, Van Cauwenberge A, Van Den Eynde C, Van Gerwen V, Azijn H, Van Houtte M, Peeters F, Staszewski S, Conant M, Bloor S, Kemp S, Larder B, Pauwels R (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
Howe AY, Cheng H, Thompson I, Chunduru SK, Herrmann S, O'Connell J, Agarwal A, Chopra R, Del Vecchio AM (2006) Molecular mechanism of a thumb domain hepatitis C virus nonnucleo-side RNA-dependent RNA polymerase inhibitor. Antimicrob Agents Chemother 50:4103–4113
Hsiou Y, Ding J, Das K, Clark AD Jr, Boyer PL, Lewi P, Janssen PA, Kleim JP, Rosner M, Hughes SH, Arnold E (2001) The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance. J Mol Biol 309:437–445
Huigen MC, van Ham PM, de GL, Kagan RM, Boucher CA, Nijhuis M (2008) Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase. Retrovirology 5:20
Ives JA, Carr JA, Mendel DB, Tai CY, Lambkin R, Kelly L, Oxford JS, Hayden FG, Roberts NA (2002) The H274Y mutation in the influenza A/H1N1 neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo. Antiviral Res 55:307–317
Jourdain G, Ngo-Giang-Huong N, Le CS, Bowonwatanuwong C, Kantipong P, Leechanachai P, Ariyadej S, Leenasirimakul P, Hammer S, Lallemant M (2004) Intrapartum exposure to nevi- rapine and subsequent maternal responses to nevirapine-based antiretroviral therapy. N Engl J Med 351:229–240
Kantor R (2006) Impact of HIV-1 pol diversity on drug resistance and its clinical implications. Curr Opin Infect Dis 19:594–606
King NM, Melnick L, Prabu-Jeyabalan M, Nalivaika EA, Yang SS, Gao Y, Nie X, Zepp C, Heefner DL, Schiffer CA (2002) Lack of synergy for inhibitors targeting a multi-drug-resistant HIV-1protease. Protein Sci 11:418–429
Kiso M, Mitamura K, Sakai-Tagawa Y, Shiraishi K, Kawakami C, Kimura K, Hayden FG, Sugaya N, Kawaoka Y (2004) Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet 364:759–765
Kleim JP, Rösner M, Winkler I, Paessens A, Kirsch R, Hsiou Y, Arnolds E, Riess G (1996) Selective pressure of a quinoxaline nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1 replication results in the emergence of nucleoside RT-inhibitor-specific (RT Leu-74 -> Val or Ile and Val-75 - > Leu or Ile) HIV-1 mutants. Proc Natl Acad Sci USA 93:34–38
Kukolj G, McGibbon GA, McKercher G, Marquis M, Lefebvre S, Thauvette L, Gauthier J, Goulet S, Poupart MA, Beaulieu PL (2005) Binding site characterization and resistance to a class of non-nucleoside inhibitors of the hepatitis C virus NS5B polymerase. J Biol Chem 280:39260–39267
Labrosse B, Morand-Joubert L, Goubard A, Rochas S, Labernardiere JL, Pacanowski J, Meynard JL, Hance AJ, Clavel F, Mammano F (2006) Role of the envelope genetic context in the development of enfuvirtide resistance in human immunodeficiency virus type 1-infected patients. J Virol 80:8807–8819
Lai CL, Gane E, Liaw YF, Hsu CW, Thongsawat S, Wang Y, Chen Y, Heathcote EJ, Rasenack J, Bzowej N, Naoumov NV, di Bisceglie AM, Zeuzem S, Moon YM, Goodman Z, Chao G, Constance BF, Brown NA (2007) Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med 357:2576–2588
Landman R, Descamps D, Peytavin G, Trylesinski A, Katlama C, Girard PM, Bonnet B, Yeni P, Bentata M, Michelet C, Benalycherif A, Brun VF, Miller MD, Flandre P (2005) Early virologic failure and rescue therapy of tenofovir, abacavir, and lamivudine for initial treatment of HIV-1 infection: TONUS study. HIV Clin Trials 6:291–301
Lanier ER, Hazen R, Ross L, Freeman A, Harvey R (2005) Lack of antagonism between abacavir, lamivudine, and tenofovir against wild-type and drug-resistant HIV-1. J Acquir Immune Defic Syndr 39:519–522
Le PS, Jiang WR, Leveque V, Rajyaguru S, Ma H, Kang H, Jiang S, Singer M, Ali S, Klumpp K, Smith D, Symons J, Cammack N, Najera I (2006a) In vitro selected Con1 subgenomic replicons resistant to 2′-C-methyl-cytidine or to R1479 show lack of cross resistance. Virol 351:349–359
Le PS, Kang H, Harris SF, Leveque V, Giannetti AM, Ali S, Jiang WR, Rajyaguru S, Tavares G, Oshiro C, Hendricks T, Klumpp K, Symons J, Browner MF, Cammack N, Najera I (2006b) Selection and characterization of replicon variants dually resistant to thumb- and palm-binding nonnucleoside polymerase inhibitors of the hepatitis C virus. J Virol 80:6146–6154
Lecossier D, Shulman NS, Morand-Joubert L, Shafer RW, Joly V, Zolopa AR, Clavel F, Hance AJ (2005) Detection of minority populations of HIV-1 expressing the K103N resistance mutation in patients failing nevirapine. J Acquir Immune Defic Syndr 38:37–42
Leigh Brown AJ (1997) Analysis of HIV-1 env gene sequences reveals evidence for a low effective number in the viral population. Proc Natl Acad Sci USA 94:1862–1865
Leigh Brown AJ, Richman DD (1997) HIV-1: gambling on the evolution of drug resistance? Nat Med 3:268–271
Lin K, Hazuda D, Otto M, Boucher C, Schooley R, O'Rear J, Kempf D, Kwong A, Parkin N, for the HCV Drug Resistance Advisory Group (2007) Initial recommendations for HCV drug resistance analysis: a consensus statement from the HCV Drug Resistance Advisory Group. Glob Antivir J 3:29
Lindenbach BD, Rice CM (2005) Unravelling hepatitis C virus replication from genome to function. Nature 436:933–938
Locarnini S, Mason WS (2006) Cellular and virological mechanisms of HBV drug resistance. J Hepatol 44:422–431
Lockman S, Shapiro RL, Smeaton LM, Wester C, Thior I, Stevens L, Chand F, Makhema J, Moffat C, Asmelash A, Ndase P, Arimi P, van WE, Mazhani L, Novitsky V, Lagakos S, Essex M (2007) Response to antiretroviral therapy after a single, peripartum dose of nevirapine. N Engl J Med 356:135–147
Lok AS, Zoulim F, Locarnini S, Bartholomeusz A, Ghany MG, Pawlotsky JM, Liaw YF, Mizokami M, Kuiken C (2007) Antiviral drug-resistant HBV: standardization of nomenclature and assays and recommendations for management. Hepatology 46:254–265
Lu L, Dekhtyar T, Masse S, Pithawalla R, Krishnan P, He W, Ng T, Koev G, Stewart K, Larson D, Bosse T, Wagner R, Pilot-Matias T, Mo H, Molla A (2007) Identification and characterization of mutations conferring resistance to an HCV RNA-dependent RNA polymerase inhibitor in vitro. Antiviral Res 76:93–97
Luber AD (2005) Genetic barriers to resistance and impact on clinical response. MedGenMed 7:69
Maguire MF, Guinea R, Griffin P, Macmanus S, Elston RC, Wolfram J, Richards N, Hanlon MH, Porter DJ, Wrin T, Parkin N, Tisdale M, Furfine E, Petropoulos C, Snowden BW, Kleim JP (2002)Changes in human immunodeficiency virus type 1 Gag at positions L449 and P453 are linked to I50V protease mutants in vivo and cause reduction of sensitivity to amprenavir and improved viral fitness in vitro. J Virol 76:7398–7406
Mammano F, Petit C, Clavel F (1998) Resistance-associated loss of viral fitness in human immunodeficiency virus type 1: phenotypic analysis of protease and gag coevolution in protease inhibitor-treated patients. J Virol 72:7632–7637
Manns MP, Foster GR, Rockstroh JK, Zeuzem S, Zoulim F, Houghton M (2007) The way forward in HCV treatment–finding the right path. Nat Rev Drug Discov 6:991–1000
Meyer PR, Matsuura SE, Mohsin Mian A, So AG, Scott WA (1999) A mechanism of AZT resistance: an increase in nucleotide-dependent primer unblocking by mutant HIV-1 reverse tran-scriptase. Mol Cell 4:35–43
Migliaccio G, Tomassini JE, Carroll SS, Tomei L, Altamura S, Bhat B, Bartholomew L, Bosserman MR, Ceccacci A, Colwell LF, Cortese R, De FR, Eldrup AB, Getty KL, Hou XS, LaFemina RL, Ludmerer SW, MacCoss M, McMasters DR, Stahlhut MW, Olsen DB, Hazuda DJ, Flores OA (2003)Characterization of resistance to non-obligate chain-terminating ribonucleoside analogs that inhibit hepatitis C virus replication in vitro. J Biol Chem 278:49164–49170
Mink M, Mosier SM, Janumpalli S, Davison D, Jin L, Melby T, Sista P, Erickson J, Lambert D, Stanfield-Oakley SA, Salgo M, Cammack N, Matthews T, Greenberg ML (2005) Impact of human immunodeficiency virus type 1 gp41 amino acid substitutions selected during enfuvirtide treatment on gp41 binding and antiviral potency of enfuvirtide in vitro. J Virol 79:12447–12454
Mo H, Lu L, Pilot-Matias T, Pithawalla R, Mondal R, Masse S, Dekhtyar T, Ng T, Koev G, Stoll V, Stewart KD, Pratt J, Donner P, Rockway T, Maring C, Molla A (2005) Mutations conferring resistance to a hepatitis C virus (HCV) RNA-dependent RNA polymerase inhibitor alone or in combination with an HCV serine protease inhibitor in vitro. Antimicrob Agents Chemother 49:4305–4314
Najera I, Richman DD, Olivares I, Rojas JM, Peinado MA, Perucho M, Najera R, Lopez Galindez C (1994) Natural occurrence of drug resistance mutations in the reverse transcriptase of human immunodeficiency virus type 1 isolates. AIDS Res Hum Retroviruses 10:1479–1488
Nijhuis M, Boucher CAB, Schipper P, Leitner T, Schuurman R, Albert J (1998) Stochastic processes strongly influence HIV-1 evolution during suboptimal protease inhibitor therapy. Proc Natl Acad Sci USA 95:14441–14446
Nijhuis M, Schuurman R, de Jong D, Erickson J, Gustchina E, Albert J, Schipper P, Gulnik S, Boucher CAB (1999) Increased fitness of drug resistant HIV-1 protease as a result of acquisition of compensatory mutations during suboptimal therapy. AIDS 13:2349–2359
Nijhuis M, van Maarseveen NM, Lastere S, Schipper P, Coakley E, Glass B, Rovenska M, de JD, Chappey C, Goedegebuure IW, Heilek-Snyder G, Dulude D, Cammack N, Brakier-Gingras L, Konvalinka J, Parkin N, Krausslich HG, Brun-Vezinet F, Boucher CA (2007) A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism. PLoS Med 4:e36
Ono SK, Kato N, Shiratori Y, Kato J, Goto T, Schinazi RF, Carrilho FJ, Omata M (2001) The poly- merase L528M mutation cooperates with nucleotide binding-site mutations, increasing hepatitis B virus replication and drug resistance. J Clin Invest 107:449–455
Pawlotsky JM, Chevaliez S, McHutchison JG (2007) The hepatitis C virus life cycle as a target for new antiviral therapies. Gastroenterology 132:1979–1998
Petropoulos CJ, Parkin NT, Limoli KL, Lie YS, Wrin T, Huang W, Tian H, Smith D, Winslow GA, Capon DJ, Whitcomb JM (2000) A novel phenotypic drug susceptibility assay for HIV-1. Antim Ag Chemoth 44:920–928
Podzamczer D, Ferrer E, Gatell JM, Niubo J, Dalmau D, Leon A, Knobel H, Polo C, Iniguez D, Ruiz I (2005) Early virological failure with a combination of tenofovir, didanosine and efavirenz. Antivir Ther 10:171–177
Prado JG, Wrin T, Beauchaine J, Ruiz L, Petropoulos CJ, Frost SD, Clotet B, D'Aquila RT, Martinez-Picado J (2002) Amprenavir-resistant HIV-1 exhibits lopinavir cross-resistance and reduced replication capacity. AIDS 16:1009–1017
Quinones-Mateu ME, Arts EJ (2001) HIV-1 fitness: implications for drug resistance, disease progression an global epidemic evolution. In: Kuiken C, Foley B, Hahn B, Marx PA, McCutchan F, Mellors J (eds) HIV sequence compendium 2001. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM
Rameix-Welti MA, Agou F, Buchy P, Mardy S, Aubin JT, Veron M, van der WS, Naffakh N (2006) Natural variation can significantly alter the sensitivity of influenza A (H5N1) viruses to oseltamivir. Antimicrob Agents Chemother 50:3809–3815
Ruane PJ, DeJesus E (2004) New nucleoside/nucleotide backbone options: a review of recent studies. J Acquir Immune Defic Syndr 37 Suppl 1:S21–S29
Sarafianos SG, Das K, Clark AD Jr, Ding J, Boyer PL, Hughes SH, Arnold E (1999) Lamivu-dine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with β-branched amino acids. Proc Natl Acad Sci USA 96:10027–10032
Sarrazin C, Kieffer TL, Bartels D, Hanzelka B, Muh U, Welker M, Wincheringer D, Zhou Y, Chu HM, Lin C, Weegink C, Reesink H, Zeuzem S, Kwong AD (2007) Dynamic hepatitis C virus genotypic and phenotypic changes in patients treated with the protease inhibitor telaprevir. Gastroenterology 132:1767–1777
Shaw T, Bartholomeusz A, Locarnini S (2006) HBV drug resistance: mechanisms, detection and interpretation. J Hepatol 44:593–606
Sheldon J, Rodes B, Zoulim F, Bartholomeusz A, Soriano V (2006) Mutations affecting the replication capacity of the hepatitis B virus. J Viral Hepat 13:427–434
SPREAD Programme (2008) Transmission of drug-resistant HIV-1 in Europe remains limited to single classes. AIDS 22:625–635
Staschke KA, Colacino JM, Baxter AJ, Air GM, Bansal A, Hornback WJ, Munroe JE, Laver WG (1995) Molecular basis for the resistance of influenza viruses to 4-guanidino-Neu5Ac2en. Virol 214:642–646
Tai CY, Escarpe PA, Sidwell RW, Williams MA, Lew W, Wu H, Kim CU, Mendel DB (1998) Characterization of human influenza virus variants selected in vitro in the presence of the neu-raminidase inhibitor GS 4071. Antimicrob Agents Chemother 42:3234–3241
Thomson MM, Najera R (2005) Molecular epidemiology of HIV-1 variants in the global AIDS pandemic: an update. AIDS Rev 7:210–224
Tomei L, Altamura S, Bartholomew L, Biroccio A, Ceccacci A, Pacini L, Narjes F, Gennari N, Bisbocci M, Incitti I, Orsatti L, Harper S, Stansfield I, Rowley M, De FR, Migliaccio G (2003) Mechanism of action and antiviral activity of benzimidazole-based allosteric inhibitors of the hepatitis C virus RNA-dependent RNA polymerase. J Virol 77:13225–13231
Tomei L, Altamura S, Bartholomew L, Bisbocci M, Bailey C, Bosserman M, Cellucci A, Forte E, Incitti I, Orsatti L, Koch U, De FR, Olsen DB, Carroll SS, Migliaccio G (2004) Characterization of the inhibition of hepatitis C virus RNA replication by nonnucleosides. J Virol 78:938–946
Tong X, Chase R, Skelton A, Chen T, Wright-Minogue J, Malcolm BA (2006) Identification and analysis of fitness of resistance mutations against the HCV protease inhibitor SCH 503034. Antiviral Res 70:28–38
Warner N, Locarnini S, Kuiper M, Bartholomeusz A, Ayres A, Yuen L, Shaw T (2007) The L80I substitution in the reverse transcriptase domain of the hepatitis B virus polymerase is associated with lamivudine resistance and enhanced viral replication in vitro. Antimicrob Agents Chemother 51:2285–2292
Weinstock HS, Zaidi I, Heneine W, Bennett D, Garcia-Lerma JG, Douglas JM Jr, LaLota M, Dickinson G, Schwarcz S, Torian L, Wendell D, Paul S, Goza GA, Ruiz J, Boyett B, Kaplan JE (2004) The epidemiology of antiretroviral drug resistance among drug-naive HIV-1-infected persons in 10 US cities. J Infect Dis 189:2174–2180
Wensing AM, Boucher CA (2003) Worldwide transmission of drug-resistant HIV. AIDS Rev 5:140–155
Whitley RJ, Hayden FG, Reisinger KS, Young N, Dutkowski R, Ipe D, Mills RG, Ward P (2001) Oral oseltamivir treatment of influenza in children. Pediatr Infect Dis J 20:127–133
Wolfs TF, Zwart G, Bakker M, Goudsmit J (1992) HIV-1 genomic RNA diversification following sexual and parenteral virus transmission. Virol 189:103–110
Yi M, Tong X, Skelton A, Chase R, Chen T, Prongay A, Bogen SL, Saksena AK, Njoroge FG, Veselenak RL, Pyles RB, Bourne N, Malcolm BA, Lemon SM (2006) Mutations conferring resistance to SCH6, a novel hepatitis C virus NS3/4A protease inhibitor. Reduced RNA replication fitness and partial rescue by second-site mutations. J Biol Chem 281:8205–8215
Zhang Y-M, Imamichi H, Imamichi T, Lane HC, Falloon J, Vasudevachari MB, Salzman NP (1997) Drug resistance during indinavir therapy is caused by mutations in the protease gene and in its gag substrate cleavage sites. J Virol 71:6662–6670
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Nijhuis, M., van Maarseveen, N., Boucher, C. (2009). Antiviral Resistance and Impact on Viral Replication Capacity: Evolution of Viruses Under Antiviral Pressure Occurs in Three Phases. In: Kräusslich, HG., Bartenschlager, R. (eds) Antiviral Strategies. Handbook of Experimental Pharmacology, vol 189. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-79086-0_11
Download citation
DOI: https://doi.org/10.1007/978-3-540-79086-0_11
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-79085-3
Online ISBN: 978-3-540-79086-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)