Might the M184V substitution in HIV-1 RT confer clinical benefit?

AIDS Reviews

Volumn 4, Issue 4, 2002, Pages 224-232

  Petrella, Marco ^a   Wainberg, Mark A ^a  

^a MCGILL UNIVERSITY   (Canada)

Author keywords

3TC; Benefit; Fidelity; Fitness; HIV 1; M184V; Processivity; Resistance; Reverse transcriptase

Indexed keywords

ABACAVIR; ADEFOVIR; AMPRENAVIR; ANTIRETROVIRUS AGENT; DELAVIRDINE; DEOXYRIBONUCLEOSIDE TRIPHOSPHATE; DIDANOSINE; INDINAVIR; LAMIVUDINE; LOVIRIDE; NELFINAVIR; NEVIRAPINE; NUCLEOSIDE ANALOG; NUCLEOTIDE; PLACEBO; PROTEINASE INHIBITOR; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; STAVUDINE; TENOFOVIR; THYMIDINE DERIVATIVE; VIRUS DNA; ZALCITABINE; ZIDOVUDINE; ZIDOVUDINE 5' PHOSPHATE;

AMINO ACID SUBSTITUTION; ANTIBIOTIC SENSITIVITY; ANTIVIRAL ACTIVITY; CLINICAL STUDY; CLINICAL TRIAL; COMPARATIVE STUDY; CROSS RESISTANCE; DRUG EFFECT; DRUG EFFICACY; DRUG POTENTIATION; DRUG USE; DRUG WITHDRAWAL; ENZYME ACTIVITY; FACTORIAL ANALYSIS; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPOTHESIS; IC 50; IN VITRO STUDY; IN VIVO STUDY; LOW DRUG DOSE; MAINTENANCE THERAPY; MONOTHERAPY; NONHUMAN; PHENOTYPE; PROSPECTIVE STUDY; REVIEW; SIMIAN IMMUNODEFICIENCY VIRUS; STATISTICAL ANALYSIS; SUPERSENSITIVITY; TREATMENT OUTCOME; VALIDATION PROCESS; VIRUS LOAD; VIRUS MUTATION;

AMINO ACID SUBSTITUTION; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; CLINICAL TRIALS; DRUG RESISTANCE, MICROBIAL; HIV-1 REVERSE TRANSCRIPTASE; HUMANS; METHIONINE; MUTATION; REVERSE TRANSCRIPTASE INHIBITORS; TREATMENT OUTCOME; VALINE;

EID: 0036822850     PISSN: 11396121     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (134)

1. Quirós-Roldán E, Signorini S, Castelli F, et al. Analysis of HIV-1 mutation patterns in patients failing antiretroviral therapy. J Clin Lab Anal 2001;15:43-6.
2. Rousseau M, Vergne L, Montes B, et al. Patterns of resistance mutations to antiretroviral drugs in extensively treated HIV-infected patients with failure of highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2001;26:36-43.
3. Winters M, Baxter J, Mayers D, et al. Frequency of antiretroviral drug resistance mutations in HIV-1 strains from patients failing triple drug regimens. The Terry Beirn Community Programs for Clinical Research on AIDS. Antiviral Ther 2000;1:57-63.
4. Lorenzi P, Opravil M, Hirschel B, et al. Impact of drug resistance mutations on virologic response to salvage therapy. Swiss HIV Cohort Study. AIDS 1999;13:17-21.
5. Yeni P, Hammer S, Carpenter C, et al. Antiretroviral treatment for adult HIV infection in 2002: Updated recommendations of the International AIDS Society - USA Panel. JAMA 2002;288:222-35.
6. De Jong M, Schuurman R, Lange J, et al. Replication of a pre-existing resistant HIV-1 subpopulation in vivo after introduction of a strong selective drug pressure. Antivir Ther 1996;1:33-41.
7. Mayers D. Prevalence and incidence of resistance to zidovudine and other antiretroviral drugs. Am J Med 1997;102:70-5.
8. Balotta C, Berlusconi A, Pan A, et al. Prevalence of transmitted nucleoside analogue-resistant HIV-1 strains and pre-existing mutations in pol reverse transcriptase and protease region: Outcome after treatment in recently infected individuals. Antivir Ther 2000;5:7-14.
9. Molla A, Korneyeva M, Gao Q, et al. Ordered accumulation of mutations in HIV protease confers resistance to ritonavir. Nat Med 1996;2:760-6.
10. Condra J. Virologic and clinical implications of resistance to HIV-1 protease inhibitors. Drug Resistance Updates 1998;1:292-9.
11. Deeks S. Failure of HIV-1 protease inhibitors to fully suppress viral replication. Implications for salvage therapy. Adv Exptl Med Biol 1999;458:175-82.
12. Frost S, Nijhuis M, Schuurman R, et al. Evolution of lamivudine resistance in HIV type 1-infected individuals: The relative roles of drift and selection. J Virol 2000;74:6262-8.
13. Gotte M, Wainberg M. Biochemical mechanisms involved in overcoming HIV resistance to nucleoside inhibitors of reverse transcriptase. Drug Resist Updat 2000;3:30-8.
14. Loveday C. International perspectives on antiretroviral resistance. Nucleoside reverse transcriptase inhibitor resistance. J Acquir Immune Defic Syndr 2001;26:10-24.
15. Deeks S. International perspectives on antiretroviral resistance. Non-nucleoside reverse transcriptase inhibitor resistance. J Acquir Immune Defic Syndr 2001;26:25-33.
16. Bacheler L, Jeffrey S, Hanna G, et al. Genotypic correlates of phenotypic resistance to efavirenz in virus isolates from patients failing nonnucleoside reverse transcriptase inhibitor therapy. J Virol 2001;75:4999-5008.
17. Tisdale M, Kemp S, Parry N, et al. Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3′-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase. Proc Natl Acad Sci USA 1993;90:5653-6.
18. Gao Q, Gu Z, Parniak M, et al. The same mutation that encodes low-level HIV type 1 resistance to 2′,3′-dideoxyinosine and 2′,3′-dideoxycytidine confers high-level resistance to the (-) enantiomer of 2′,3′-dideoxy-3′-thiacytidine. Antimicrob Agents Chemother 1993;37:1390-2.
19. Boucher C, Cammack N, Schipper P, et al. High-level resistance to (-) enantiomeric 2′-deoxy-3′-thiacytidine in vitro is due to one amino acid substitution in the catalytic site of HIV type 1 reverse transcriptase. Antimicrob Agents Chemother 1993;37:2231-4.
20. Quan Y, Gu Z, Li X, et al. Endogenous reverse transcription assays reveal high-level resistance to the triphosphate of (-) 2′-dideoxy-3′-thiacytidine by mutated M184V HIV type 1. J Virol 1996;70:5642-5.
21. Hertogs K, Bloor S, De Vroey V, et al. A novel HIV type 1 reverse transcriptase mutational pattern confers phenotypic lamivudine resistance in the absence of mutation 184V. Antimicrob Agents Chemother 2000;44:568-73.
22. Wainberg M, Hsu M, Gu Z, et al. Effectiveness of 3TC in HIV clinical trials may be due in part to the M184V substitution in 3TC-resistant HIV-1 reverse transcriptase. AIDS 1996;10:3-10.
23. Wainberg M, Parniak M. Is HIV resistance to 3TC of clinical benefit? International Antiviral News 1997;5:3-5.
24. Bean P. The multiple benefits associated with HIV drug-resistance mutation M184V. Am Clin Lab 2002;21:16-8.
25. Miller V, Strak T, Loeliger A, et al. The impact of the M184V substitution in HIV-1 reverse transcriptase on treatment response. HIV Med 2002;3:135-45.
26. Schinazi R, Lloyd R Jr, Nguyen M, et al. Characterization of human immunodeficiency viruses resistant to oxathiolane-cytosine nucleosides. Antimicrob Agents Chemother 1993;37:875-81.
27. Pluda J, Cooley T, Montaner J, et al. A phase I/II study of 2′-deoxy-3′-thiacytidine (lamivudine) in patients with advanced HIV infection. J Infect Dis 1995;171:1438-47.
28. Perry C, Faulds D. Lamivudine. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in the management of HIV infection. Drugs 1997;53:657-80.
29. Anderson K. The molecular basis of inhibition and toxicity of modified cytosine analogues targeting HIV-1 reverse transcriptase. Antivir Chem Chemother 2001;12:13-7.
30. Mitsuya H, Jarrett R, Matsukura M, et al. Long-term inhibition of human T-lymphotropic virus type III/lymphadenopathy-associated virus (human immunodeficiency virus) DNA synthesis and RNA expression in T cells protected by 2′,3′-dideoxynucleosides in vitro. Proc Natl Acad Sci USA 1987;84:2033-7.
31. Furman P, Barry D. Spectrum of antiviral activity and mechanism of action of zidovudine. An overview. Am J Med 1988;85:176-81.
32. Goody R, Muller B, Restle T. Factors contributing to the inhibition of HIV reverse transcriptase by chain-terminating nucleotides in vitro and in vivo. FEBS Lett 1991;291:1-5.
33. Furman P, Painter G, Anderson K. An analysis of the catalytic cycle of HIV-1 reverse transcriptase: Opportunities for chemotherapeutic intervention based on enzyme inhibition. Curr Pharm Des 2000;6:547-67.
34. Anderson K. Perspectives on the molecular mechanism of inhibition and toxicity of nucleoside analogs that target HIV-1 reverse transcriptase. Biochim Biophys Acta 2002; 1587:296-9.
35. Larder B, Kemp S, Harrigan P. Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy. Science 1995;269:696-9.
36. Wainberg M, Salomon H, Gu Z, et al. Development of HIV-1 resistance to (-)2′-deoxy-3′-thiacytidine in patients with AIDS or advanced AIDS-related complex. AIDS 1995;9:351-7.
37. Schuurman R, Nijhuis M, Van Leeuwen R, et al. Rapid changes in HIV type 1 RNA load and appearance of drug-resistant virus populations in persons treated with lamivudine (3TC). J Infect Dis 1995;171:1411-9.
38. Keulen W, Back N, Van Wijk A, et al. Initial appearance of the 184Ile variant in lamivudine-treated patients is caused by the mutational bias of HIV type 1 reverse transcriptase. J Virol 1997;71:3346-50.
39. Rezende L, Drosopoulos W, Prasad V. The influence of 3TC resistance mutation M184I on the fidelity and error specificity of HIV type 1 reverse transcriptase. Nucleic Acids Res 1998;26:3066-72.
40. Back N, Nijhuis M, Keulen W, et al. Reduced replication of 3TC-resistant HIV-1 variants in primary cells due to a processivity defect of the reverse transcriptase enzyme. EMBO J 1996;15:4040-9.
41. Devereux H, Emery V, Johnson M, et al. Replicative fitness in vivo of HIV-1 variants with multiple drug resistance-associated mutations. J Med Virol 2001;65:218-24.
42. Kohlstaedt L, Wang J, Friedman J, et al. Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 1992;256:1783-90.
43. Huang H, Chopra R, Verdine G, et al. Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: Implications for drug resistance. Science 1998;282:1669-75.
44. Feng J, Anderson K. Mechanistic studies examining the efficiency and fidelity of DNA synthesis by the 3TC-resistant mutant (184V) of HIV-1 reverse transcriptase. Biochemistry 1999;38:9440-8.
45. Soriano V, De Mendoza C. Genetic mechanisms of resistance to NRTI and NNRTI. HIV Clin Trials 2002;3:237-48.
46. De Mendoza C, Gallego O, Soriano V. Mechanisms of resistance to antiretroviral drugs - Clinical implications. AIDS Rev 2002;4:64-82.
47. Gao H, Boyer P, Serafianos S, et al. The role of steric hindrance in 3TC resistance of HIV type-1 reverse transcriptase. J Mol Biol 2000;300:403-18.
48. Kavlick M, Shirasaka T, Kojima E, et al. Genotypic and phenotypic characterization of HIV-1 isolated from patients receiving (-)-2′,3′-dideoxy-3′-thiacytidine. Antiviral Res 1995;28:133-46.
49. Wainberg M, Lewis L, Salomon H, et al. Resistance to (-)-2′,3′-dideoxy-3′-thiacytidine (3TC) in HIV-1 isolated from paediatric patients. Antivir Ther 1996;1:98-104.
50. Harrigan P, Stone C, Griffin P, et al. Resistance profile of the HIV type 1 reverse transcriptase inhibitor abacavir (1592U89) after monotherapy and combination therapy. CNA2001 Investigative Group. J Infect Dis 2000;181:912-20.
51. Miller V, Ait-Khaled M, Stone C, et al. HIV-1 reverse transcriptase (RT) genotype and susceptibility to RT inhibitors during abacavir monotherapy and combination therapy. AIDS 2000;14:163-71.
52. Walter H, Schmidt B, Werwein M, et al. Prediction of abacavir resistance from genotypic data: Impact of zidovudine and lamivudine resistance in vitro and in vivo. Antimicrob Agents Chemother 2002;46:89-94.
53. Gu Z, Gao Q, Li X, et al. Novel mutation in the HIV type 1 reverse transcriptase gene that encodes cross-resistance to 2′,3′-dideoxyinosine and 2′,3′-dideoxycytidine. J Virol 1992;66:7128-35.
54. Winters M, Shafer R, Jellinger R, et al. HIV type 1 reverse transcriptase genotype and drug susceptibility changes in infected individuals receiving dideoxyinosine monotherapy for 1 to 2 years. Antimicrob Agents Chemother 1997;41:757-62.
55. Tisdale M, Alnadaf T, Cousens D. Combination of mutations in HIV type 1 reverse transcriptase required for resistance to the carbocyclic nucleoside 1592U89. Antimicrob Agents Chemother 1997;41:1094-8.
56. Ray A, Yang Z, Shi J, et al. Insights into the molecular mechanism of inhibition and drug resistance for HIV-1 RT with carbovir triphosphate. Biochemistry 2002;41:5150-62.
57. Miller V, Sturmer M, Staszewski S, et al. The M184V mutation in HIV-1 reverse transcriptase (RT) conferring lamivudine resistance does not result in broad cross-resistance to nucleoside analogue RT inhibitors. AIDS 1998;12:705-12.
58. Miller V, Larder B. Mutational patterns in the HIV genome and cross-resistance following nucleoside and nucleotide analogue drug exposure. Antivir Ther 2001;6:25-44.
59. Ai-Khaled M, Rakik A, Griffin P, et al. Mutations in HIV-1 reverse transcriptase during therapy with abacavir, lamivudine and zidovudine in HIV-1-infected adults with no prior antiretroviral therapy. Antivir Ther 2002;7:43-51.
60. Mouroux M, Descamps D, Izopet J, et al. Low-rate emergence of thymidine analogue mutations and multi-drug resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naïve patients receiving stavudine plus lamivudine combination therapy. Antivir Ther 2001;6:179-83.
61. Larder B. Viral resistance and the selection of antiretroviral combinations. J Acquir Immune Defic Syndr Hum Retrovirol 1995;10:28-33.
62. Steszewski S. Zidovudine and lamivudine: Results of phase III studies. J Acquir Immune Defic Syndr Hum Retrovirol 1995;10:57.
63. Catucci M, Venturi G, Romano L, et al. Development and significance of the HIV-1 reverse transcriptase M184V mutation during combination therapy with lamivudine, zidovudine, and protease inhibitors. J Acquir Immune Defic Syndr 1999;21:203-8.
64. Masquelier B, Descamps D, Carriere I, et al. Zidovudine resensitization and dual HIV-1 resistance to zidovudine and lamivudine in the delta lamivudine roll-over study. Antivir Ther 1999;4:69-77.
65. Gotte M, Arion D, Parniak M, et al. The M184V mutation in the reverse transcriptase of HIV type 1 impairs rescue of chain-terminated DNA synthesis. J Virol 2000;74:3579-85.
66. Isel C, Ehresmann C, Walter P, et al. The emergence of different resistance mechanisms toward nucleoside inhibitors is explained by the properties of the wild type HIV-1 reverse transcriptase. J Biol Chem 2001;276:48725-32.
67. Boyer P, Sarafianos S, Arnold E, et al. Selective excision of AZTMP by drug-resistant HIV reverse transcriptase. J Virol 2001;75:4832-42.
68. Meyer P, Matsuura S, Mian A, et al. A mechanism of AZT resistance: An increase in nucleotide-dependent primer unblocking by mutant HIV-1 reverse transcriptase. Mol Cell 1999;4:35-43.
69. Meyer P, Pfeifer I, Matsuura S, et al. Effects of M41L and T215Y mutations in HIV-1 reverse transcriptase on removal of chain-terminators from blocked primer/templates. Antivir Ther 2000;5:14.
70. Meyer P, Matsuura S, Tolun A, et al. Effects of specific zidovudine resistance mutations and substrate structure on nucleotide-dependent primer unblocking by HIV type 1 reverse transcriptase. Antimicrob Agents Chemother 2002;46:1540-5.
71. Quan Y, Gu Z, Li X, et al. Endogenous reverse transcriptase assays reveal synergy between combinations of the M184V and other drug resistance-conferring mutations in interactions with nucleoside analog triphosphates. J Mol Biol 1998;277:237-47.
72. Boyer P, Sarafianos S, Arnold E, et al. The M184V mutation reduces the selective excision of zidovudine 5′-monophosphate (AZTMP) by the reverse transcriptase of HIV type 1. J Virol 2002;76:3248-56.
73. Miller M, Anton K, Mulato A, et al. HIV type 1 expressing the lamivudine-associated M184V mutation in reverse transcriptase shows increased susceptibility to adefovir and decreased replication capability in vitro. J Infect Dis 1999;179:92-100.
74. Wainberg M, Miller M, Quan Y, et al. In vitro selection and characterization of HIV-1 with reduced susceptibility to PMPA. Antivir Ther 1999;4:87-94.
75. Naeger L, Margot N, Miller M. Tenofovir (PMPA) is less susceptible to pyrophosphorolysis and nucleotide-dependent chain-terminator removal than zidovudine or stavudine. Nucleosides Nucleotides Nucleic Acids 2001;20:635-9.
76. Miller M, Margot N, Hertogs K, et al. Antiviral activity of tenofovir (PMPA) against nucleoside-resistant clinical HIV samples. Nucleosides Nucleotides Nucleic Acids 2001;20:1025-8.
77. Delaugerre C, Mouroux M, Yvon-Groussin A, et al. Prevalence and conditions of selection of E44D/A and V118I HIV type 1 reverse transcriptase mutations in clinical practice. Antimicrob Agents Chemother 2001;45:946-8.
78. Romano L, Venturi G, Bloor S, et al. Broad nucleoside-analogue resistance implications for HIV type 1 reverse transcriptase mutations at codons 44 and 118. J Infect Dis 2002;185:898-904.
79. Naeger L, Margot N, Miller M. Increased drug susceptibility of HIV-1 reverse transcriptase mutants containing M184V and zidovudine-associated mutations: Analysis of enzyme processivity, chain-terminator removal and viral replication. Antivir Ther 2001;6:115-26.
80. Roberts J, Bebenek K, Kunkel T. The accuracy of reverse transcriptase from HIV-1. Science 1988;242:1171-3.
81. Preston B, Dougherty J. Mechanisms of retroviral mutation. Trends Microbiol 1996;4:16-21.
82. Menéndez-Arias L. Molecular basis of fidelity of DNA synthesis and nucleotide specificity of retroviral reverse transcriptases. Prog Nucleic Acid Res Mol Biol 2002;71:91-147.
83. Coffin J. HIV population dynamics in vivo: Implication for genetic variation, pathogenesis, and therapy. Science 1995;267:483-9.
84. Drosopoulos W, Rezende L, Wainberg M, et al. Virtues of being faithful: Can we limit the genetic variation in HIV? J Mol Med 1998;76:604-12.
85. Colgrove R, Japour A. A combinatorial ledge: Reverse transcriptase fidelity, total body viral burden, and the implications of multiple-drug HIV therapy for the evolution of antiviral resistance. Antiviral Res 1999;41:45-56.
86. Overbaugh J, Bangham C. Selection forces and constraints on retroviral sequence variation. Science 2001;292:1106-9.
87. Wainberg M, Drosopoulos W, Salomon H, et al. Enhanced fidelity of 3TC-selected mutant HIV-1 reverse transcriptase. Science 1996;271:1282-5.
88. Wainberg M. Increased fidelity of drug-selected M184V mutated HIV-1 reverse transcriptase as the basis for the effectiveness of 3TC in HIV clinical trials. Leukemia 1997;11:85-8.
89. Feng J, Anderson K. Mechanistic studies examining the efficiency and fidelity of DNA synthesis by the 3TC-resistant mutant (184V) of HIV-1 reverse transcriptase. Biochemistry 1999;38:9440-8.
90. Whitney J, Oliveira M, Detorio M, et al. The M184V mutation in reverse transcriptase can delay reversion of attenuated variants of simian immunodeficiency virus. J Virol 2002;76:8958-62.
91. Jonckheere H, Witvrouw M, De Clercq E, et al. Lamivudine resistance of HIV type 1 does not delay development of resistance to nonnucleoside HIV type 1-specific reverse transcriptase inhibitors as compared with wild-type HIV type 1. AIDS Res Hum Retroviruses 1998;14:249-53.
92. Keulen W, Van Wijk A, Schuurman R, et al. Increased polymerase fidelity of lamivudine-resistant HIV-1 variants does not limit their evolutionary potential. AIDS 1999;13:1343-9.
93. Molina J, Chene G, Ferchal F, et al. The ALBI trial: A randomized controlled trial comparing stavudine plus didanosine with zidovudine plus lamivudine and a regimen alternating both combinations in previously untreated patients infected with HIV. J Infect Dis 1999;180:351-8.
94. Picard V, Angelini E, Maillard A, et al. Comparison of genotypic and phenotypic resistance patterns of HIV type 1 isolates from patients treated with stavudine and didanosine or zidovudine and lamivudine. J Infect Dis 2001;184:781-4.
95. Ait-Khaled M, Stone C, Amphlett G, et al. M184 is associated with a low incidence of thymidine analogue and low phenotypic resistance to zidovudine and stavudine. AIDS 2002;1686-9.
96. The AVANTI Study Group. AVANTI 2: Randomized, double-blind trial to evaluate the efficacy and safety of zidovudine plus lamivudine versus zidovudine plus lamivudine plus indinavir in HIV-infected antiretroviral-naïve patients. AIDS 2000;14:367-74.
97. Gartland M, AVANTI Study Group. AVANTI 3: A randomized, double-blind trial to compare the efficacy and safety of lamivudine plus zidovudine versus lamivudine plus zidovudine plus nelfinavir in HIV-1-infected antiretroviral-naïve patients. Antivir Ther 2001;6:127-34.
98. Maguire M, Gartland M, Moore S, et al. Absence of zidovudine resistance in antiretroviral-naïve patients following zidovudine/lamivudine/protease inhibitor combination therapy: Virological evaluation of the AVANTI 2 and AVANTI 3 studies. AIDS 2000;4:1195-201.
99. Boyer P, Hughes S. Analysis of mutations at position 184 in reverse transcriptase of HIV type 1. Antimicrob Agents Chemother 1995;39:1624-8.
100. Oude Essink B, Back N, Berkhout B. Increased polymerase fidelity of the 3TC-resistant variants of HIV-1 reverse transcriptase. Nucleic Acids Res 1997;25:3212-7.
101. Sharma P, Crumpacker C. Decreased processivity of HIV type 1 reverse transcriptase (RT) containing didanosine-selected mutation Leu74Val: A comparative analysis of RT variants Leu74Val and lamivudine-selected Met184Val. J Virol 1999;73:8448-56.
102. Caliendo A, Savara A, An D, et al. Effects of zidovudine-selected HIV type 1 reverse transcriptase amino acid substitutions on processive DNA synthesis and viral replication. J Virol 1996;70:2146-53.
103. Arion D, Kaushik N, McCormick S, et al. 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. Biochemistry 1998;37:15908-17.
104. Back N, Berkhout B. Limiting deoxynucleoside triphosphate concentrations emphasize the processivity defect of lamivudine-resistant variants of HIV type 1 reverse transcriptase. Antimicrob Agents Chemother 1997;41:2484-91.
105. Miller M, Lamy P, Fuller M, et al. HIV type 1 reverse transcriptase expressing the K70E mutation exhibits a decrease in specific activity and processivity. Mol Pharmacol 1998;54:291-7.
106. Harrigan P, Bloor S, Larder B. Relative replicative fitness of zidovudine-resistant HIV type 1 isolates in vitro. J Virol 1998;72:3773-8.
107. Kosalaraksa P, Kavlick M, Maroun V, et al. Comparative fitness of multi-dideoxynucleoside-resistant HIV-1 in an in vitro competitive HIV-1 replication assay. J Virol 1999;73:5356-63.
108. Berkhout B. HIV-1 evolution under pressure of protease inhibitors: Climbing the stairs of viral fitness. J Biomed Sci 1999;6:298-305.
109. Quiñones-Mateu M, Ball S, Marozsan A, et al. A dual infection/competition assay shows a correlation between ex vivo HIV type 1 fitness and disease progression. J Virol 2000;74:9222-33.
110. Nijhuis M, Deeks S, Boucher C. Implications of antiretroviral resistance on viral fitness. Curr Opin Infect Dis 2001;14:23-8.
111. Dykes C, Fox K, Lloyd A, et al. Impact of clinical reverse transcriptase sequences on the replication capacity of HIV-1 drug-resistant mutants. Virology 2001;285:193-203.
112. Quiñones-Mateu M, Weber J, Rangel H, et al. HIV-1 fitness and antiretroviral drug resistance. AIDS Rev 2001;3:223-42.
113. Brenner B, Routy J, Petrella M, et al. Persistence and fitness of multidrug-resistant HIV type 1 acquired in primary infection. J Virol 2002;76:1753-61.
114. Van Rompay K, Matthews T, Higgins J, et al. Virulence and reduced fitness of simian immunodeficiency virus with the M184V mutation in reverse transcriptase. J Virol 2002;76:6083-92.
115. Inouye P, Cherry E, Hsu M, et al. Neutralizing antibodies directed against the V3 loop select for different escape variants in a virus with mutated reverse transcriptase (M184V) than in wild-type HIV type 1. AIDS Res Hum Retroviruses 1998;14:735-40.
116. Picchio G, Valdez H, Sabbe R, et al. Altered viral fitness of HIV-1 following failure of protease inhibitor-based therapy. J Acquir Immune Defic Syndr 2000;25:289-95.
117. Liegler T, Hayden M, Lee K, et al. Protease inhibitor-resistant HIV-1 from patients with preserved CD4 cell counts is cytopathic in activated CD4 T lymphocytes. AIDS 2001;15:179-84.
118. Antinori A, Liuzzi G, Cingolani A, et al. Drug-resistant mutants of HIV-1 in patients exhibiting increasing CD4 cell count despite virological failure of highly active antiretroviral therapy. AIDS 2001;15:2325-7.
119. Stoddart C, Liegler T, Mammano F, et al. Impaired replication of protease inhibitor-resistant HIV-1 in human thymus. Nat Med 2001;7:712-8.
120. Eron J, Benoit S, Jemsek J, et al. Treatment with lamivudine, zidovudine, or both in HIV-positive patients with 200 to 500 CD4+ cells per cubic millimeter. North American HIV Working Party. N Engl J Med 1995;333:1662-9.
121. Eron J Jr. The treatment of antiretroviral-naïve subjects with the 3TC/zidovudine combination: A review of North American (NUCA 3001) and European (NUCB 3001) trials. AIDS 1996;10:11-9.
122. Kuritzkes D, Quinn J, Benoit S, et al. Drug resistance and virologic response in NUCA 3001, a randomized trial of lamivudine (3TC) versus zidovudine (ZDV) versus ZDV plus 3TC in previously untreated patients. AIDS 1996;10:975-81.
123. Fischer K, Gutfreund K, Tyrrell D. Lamivudine resistance in hepatitis B: Mechanisms and clinical implications. Drug Resist Updat 2001;4:118-28.
124. Rizzetto M. Efficacy of lamivudine in HBeAg-negative chronic hepatitis B. J Med Virol 2002;66:435-51.
125. Liaw Y. Impact of YMDD mutations during lamivudine therapy in patients with chronic hepatitis B. Antivir Chem Chemother 2001;12:67-71.
126. Papatheodoridis G, Dimou E, Papadimitropoulos V. Nucleoside analogues for chronic hepatitis B: Antiviral efficacy and viral resistance. Am J Gastroenterol 2002;97:1618-28.
127. Melegari M, Scaglioni P, Wands J. Hepatitis B virus mutants associated with 3TC and famciclovir administration are replication defective. Hepatology 1998;27:628-33.
128. Pialoux G, Raffi F, Brun-Vezinet F, et al. A randomized trial of three maintenance regimens given after three months of induction therapy with zidovudine, lamivudine, and indinavir in previously untreated HIV-1-infected patients. N Engl J Med 1998;339:1269-76.
129. Flandre P, Raffi F, Descamps D, et al. Final analysis of the Trilege induction-maintenance trial: Results at 18 months. AIDS 2002;16:561-8.
130. Descamps D, Flandre P, Calvez V, et al. Mechanisms of virologic failure in previously untreated HIV-infected patients from a trial of induction-maintenance therapy. JAMA 2000;283:205-11.
131. Press N, Woods R, Raboud J, et al. The effect of different HAART regimens on slope of viral rebound in HIV-infected patients failing therapy. 9th CROI. Seattle, Washington. February 2002. [abstract 419-W].
132. CAESAR Coordinating Committee. Randomised trial of addition of lamivudine or lamivudine plus loviride to zidovudine-containing regimens for patients with HIV-1 infection: The CAESAR trial. Lancet 1997;349:1413-21.
133. Montaner J, DeMasi R, Hill A. The effects of lamivudine treatment on HIV-1 disease progression are highly correlated with plasma HIV-1 RNA and CD4 cell count. AIDS 1998;12:23-8.
134. Kuritzkes D, Bassett R, Johnson V, et al. Continued lamivudine versus delavirdine in combination with indinavir and zidovudine or stavudine in lamivudine-experienced patients: Results of ACTG protocol 370. AIDS 2000;14:1553-61.