Nucleoside and nucleotide inhibitors of HIV-1 replication

Cellular and Molecular Life Sciences

Volumn 63, Issue 2, 2006, Pages 163-186

  Vivet Boudou, V ^a   Didierjean, J ^a   Isel, C ^a   Marquet, R ^a  

^a INST DE BIOL MOLEC ET CELLULAIRE   (France)

Author keywords

AIDS; Chain termination; DNA synthesis; Drug; HIV 1; NRTI; Resistance; Reverse transcriptase

Indexed keywords

1,3 DIOXOLANE DERIVATIVE; 2' DEOXY 3' OXA 4' THIOCYTIDINE; 2',3' DIDEOXY 3' FLUORO BETA GUANOSINE; 2',3' DIDEOXYNUCLEOSIDE DERIVATIVE; 3' FLUOROTHYMIDINE; 4 (THYMIDIN 1 YL) 1,3 DIOXOLANE 2 METHANOL; 5,6 DIHYDRO 5 AZA 2' DEOXYCYTIDINE; ABACAVIR; AMDOXOVIR; AVX 754; CYTIDINE DERIVATIVE; DIDANOSINE; EFAVIRENZ; ELVUCITABINE; EMTRICITABINE; GUANOSINE DERIVATIVE; INDINAVIR; KP 1461; LAMIVUDINE; LOPINAVIR; MIV 210; NELFINAVIR; NEVIRAPINE; NUCLEOSIDE; RITONAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; SAQUINAVIR; STAVUDINE; TENOFOVIR; TENOFOVIR DISOPROXIL; UNCLASSIFIED DRUG; ZALCITABINE; ZIDOVUDINE;

ABDOMINAL PAIN; ANEMIA; BONE MARROW SUPPRESSION; CLINICAL OBSERVATION; CLINICAL TRIAL; COMMON COLD SYMPTOM; DIARRHEA; DNA FOOTPRINTING; DRUG BIOAVAILABILITY; DRUG CONTRAINDICATION; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG ERUPTION; DRUG HALF LIFE; DRUG POTENCY; DRUG SENSITIVITY; DRUG TOLERABILITY; ENZYME ACTIVE SITE; EYE DISEASE; FATIGUE; GASTROINTESTINAL SYMPTOM; GENE INSERTION; GENE MUTATION; HEADACHE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HYPERLIPIDEMIA; LIVER TOXICITY; MALAISE; MEDICAL INFORMATION; MITOCHONDRIAL TOXICITY; NAUSEA; NEPHROTOXICITY; NEUTROPENIA; NONHUMAN; PAIN; PROTEIN DEGRADATION; PROTEIN PHOSPHORYLATION; REVIEW; STATISTICAL SIGNIFICANCE; TERATOGENICITY; TOOTH DISEASE; UNSPECIFIED SIDE EFFECT; VIRUS INFECTION; VIRUS ISOLATION; VIRUS LOAD; VIRUS REPLICATION; VIRUS STRAIN;

DRUG RESISTANCE, VIRAL; HIV INFECTIONS; HIV-1; HUMANS; MODELS, BIOLOGICAL; MUTATION; NUCLEOSIDES; NUCLEOTIDES; PROTEIN STRUCTURE, TERTIARY; REVERSE TRANSCRIPTASE INHIBITORS; VIRUS REPLICATION;

HUMAN IMMUNODEFICIENCY VIRUS 1; THIA;

EID: 30844469498     PISSN: 1420682X     EISSN: 15691632     Source Type: Journal    
DOI: 10.1007/s00018-005-5367-x     Document Type: Review

References (260)

1. Barré-Sinoussi F., Cherman J. C., Rey F., Nugeyre H. T., Charmet S., Gruest J. et al. (1983) Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220: 868-871
2. Gallo R. C., Sarin P. S., Gelmann E. P., Robert-Guroff M., Richardson E., Kalyanaraman V. S. et al. (1983) Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science 220: 865-867
3. Skalka A. M. and Goff S. P. (eds) (1993) Reverse Transcriptase. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York
4. Huang H., Chopra R., Verdine G. and Harrison S. (1998) Structure of covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance. Science 282: 1669-1675
5. Jacobo-Molina A., Ding J. P., Nanni R. G., Clark A. D., Lu X. D., Tantillo C. et al. (1993) Crystal structure of human immunodeficiency virus type-1 reverse transcriptase complexed with double-stranded DNA at 3.0 Angstrom resolution shows bent DNA. Proc. Natl. Acad. Sci. USA 90: 6320-6324
6. Kohlstaedt L. A., Wang J., Friedman J. M., Rice P. A. and Steitz T. A. (1992) Crystal structure at 3.5 Å resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 256: 1783-1790
7. Wild C., Greenwell T. and Matthews T. (1993) A synthetic peptide from HIV-1 gp41 is a potent inhibitor of virus-mediated cell-cell fusion. AIDS Res. Hum. Retroviruses 9: 1051-1053
8. Wild C. T., Shugars D. C., Greenwell T. K., McDanal C. B. and Matthews T. J. (1994) Peptides corresponding to a predictive alpha-helical domain of human immunodeficiency virus type 1 gp41 are potent inhibitors of virus infection. Proc. Natl. Acad. Sci. USA 91: 9770-9774
9. Spence R. A., Kati W. M. anderson K. S. and Johnson K. A. (1995) Mechanism of inhibition of HIV-1 reverse transcriptase by nonnucleoside inhibitors. Science 267: 988-993
10. Esnouf R., Ren J. S., Ross C., Jones Y., Stammers D. and Stuart D. (1995) Mechanism of inhibition of HIV-1 reverse transcriptase by non-nucleoside inhibitors. Nat. Struct. Biol. 2: 303-308
11. Mitsuya H., Weinhold K. J., Furman P. A., St Clair M. H., Lehrman S. N., Gallo R. C. et al. (1985) 3′-Azido-3′-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc. Natl. Acad. Sci. USA 82: 7096-7100
12. Dahlberg J. E., Mitsuya H., Blam S. B., Broder S. and Aaronson S. A. (1987) Broad spectrum antiretroviral activity of 2′,3′- dideoxynucleosides. Proc. Natl. Acad. Sci. USA 84: 2469-2473
13. Kim C. H., Marquez V. E., Broder S., Mitsuya H. and Driscoll J. S. (1987) Potential anti-AIDS drugs. 2′,3′-dideoxycytidine analogues. J. Med. Chem. 30: 862-866
14. Balzarini J., Herdewijn P. and De Clercq E. (1989) Differential patterns of intracellular metabolism of 2′,3′-didehydro-2′,3′- dideoxythymidine and 3′-azido-2′,3′-dideoxythymidine, two potent anti-human immunodeficiency virus compounds. J. Biol. Chem. 264: 6127-6133
15. Furman P. A., Fyfe J. A., St Clair M. H., Weinhold K., Rideout J. L., Freeman G. A. et al. (1986) Phosphorylation of 3′-azido-3′- deoxythymidine and selective interaction of the 5′-triphosphate with human immunodeficiency virus reverse transcriptase. Proc. Natl. Acad. Sci. USA 83: 8333-8337
16. Eisenberg E. J., He G. X. and Lee W. A. (2001) Metabolism of GS-7340, a novel phenyl monophosphoramidate intracellular prodrug of PMPA, in blood. Nucleosides Nucleotides Nucleic Acids 20: 1091-1098
17. Johnson M. A. and Fridland A. (1989) Phosphorylation of 2′,3′-dideoxyinosine by cytosolic 5′-nucleotidase of human lymphoid cells. Mol. Pharmacol. 36: 291-295
18. Ray A. S., Yang Z., Shi J., Hobbs A., Schinazi R. F., Chu C. K. et al. (2002) Insights into the molecular mechanism of inhibition and drug resistance for HIV-1 RT with carbovir triphosphate. Biochemistry 41: 5150-5162
19. Lavie A., Schlichting I., Vetter I. R., Konrad M., Reinstein J. and Goody R. S. (1997) The bottleneck in AZT activation. Nat. Med. 3: 922-924
20. Lavie A., Vetter I. R., Konrad M., Goody R. S., Reinstein J. and Schlichting I. (1997) Structure of thymidylate kinase reveals the cause behind the limiting step in AZT activation. Nat. Struct. Biol. 4: 601-604
21. Schneider B., Xu Y. W., Sellam O., Sarfati R., Janin J., Veron M. et al. (1998) Pre-steady state of reaction of nucleoside diphosphate kinase with anti-HIV nucleotides. J. Biol. Chem. 273: 11491-11497
22. Shafer R. W. (2002) Genotypic testing for human immunodeficiency virus type 1 drug resistance. Clin. MicroBiol. Rev. 15: 247-277
23. Leitner T., Foley B., Hahn B., Korber B., Marx P., McCutchan F. et al. (eds) (2003) HIV Sequence Compendium 2003, Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos
24. Roberts J. D., Bebenek K. and Kunkel T. A. (1988) The accuracy of reverse transcriptase from HIV-1. Science 242: 1171-1173
25. Preston B. D., Poiesz B. J. and Loeb L. A. (1988) Fidelity of HIV-1 reverse transcriptase. Science 242: 1168-1171
26. Rezende L. F. and Prasad V. R. (2004) Nucleoside-analog resistance mutations in HIV-1 reverse transcriptase and their influence on polymerase fidelity and viral mutation rates. Int. J. Biochem. Cell. Biol. 36: 1716-1734
27. Perelson A. S., Neumann A. U., Markowitz M., Leonard J. M. and Ho D. D. (1996) HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science 271: 1582-1586
28. Kellam P. and Larder B. A. (1995) Retroviral recombination can lead to linkage of reverse transcriptase mutations that confer increased zidovudine resistance. J. Virol. 69: 669-674
29. Moutouh L., Corbeil J. and Richman D. D. (1996) Recombination leads to the rapid emergence of HIV-1 dually resistant mutants under selective drug pressure. Proc. Natl. Acad. Sci. USA 93: 6106-6111
30. Coffin J. M. (1995) HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science 267: 483-489
31. Larder B. A., Darby G. and Richman D. D. (1989) HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science 243: 1731-1734
32. Richman D. D. (1990) Susceptibility to nucleoside analogues of zidovudine-resistant isolates of human immunodeficiency virus. Am. J. Med. 88: 8S-10S
33. Kellam P., Boucher C. A. and Larder B. A. (1992) Fifth mutation in human immunodeficiency virus type 1 reverse transcriptase contributes to the development of high-level resistance to zidovudine. Proc. Natl. Acad. Sci. USA 89: 1934-1938
34. Hooker D. J., Tachedjian G., Solomon A. E., Gurusinghe A. D., Land S., Birch C. et al. (1996) An in vivo mutation from leucine to tryptophan at position 210 in human immunodeficiency virus type 1 reverse transcriptase contributes to high-level resistance to 3′-azido-3′-deoxythymidine. J. Virol. 70: 8010-8018
35. Larder B. A. and Kemp S. D. (1989) Multiple mutations in HIV-1 reverse transcriptase confer high-level resistance to zidovudine (AZT). Science 246: 1155-1158
36. Richman D. D., Guatelli J. C., Grimes J., Tsiatis A. and Gingeras T. (1991) Detection of mutations associated with zidovudine resistance in human immunodeficiency virus by use of the polymerase chain reaction. J. Infect. Dis. 164: 1075-1081
37. Boucher C. A., O'Sullivan E., Mulder J. W., Ramautarsing C., Kellam P., Darby G. et al. (1992) Ordered appearance of zidovudine resistance mutations during treatment of 18 human immunodeficiency virus-positive subjects. J. Infect. Dis. 165: 105-110
38. Larder B. A., Coates K. E. and Kemp S. D. (1991) Zidovudine-resistant human immunodeficiency virus selected by passage in cell culture. J. Virol. 65: 5232-5236
39. Gao Q., Gu Z. X., Parniak M. A., Li X. G. and Wainberg M. A. (1992) In vitro selection of variants of human immunodeficiency virus type 1 resistant to 3′-azido-3′-deoxythymidine and 2′,3′-dideoxyinosine. J. Virol. 66: 12-19
40. Pellegrin I., Izopet J., Reynes J., Denayrolles M., Montes B., Pellegrin J. L. et al. (1999) Emergence of zidovudine and multidrug-resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus didanosine combination therapy. STADI Group. Aids 13: 1705-1709
41. Izopet J., Bicart-See A., Pasquier C., SandRes. K., Bonnet E., Marchou B. et al. (1999) Mutations conferring resistance to zidovudine diminish the antiviral effect of stavudine plus didanosine. J. Med. Virol. 59: 507-511
42. Lin P. F., Samanta H., Rose R. E., Patick A. K., Trimble J., Bechtold C. M. et al. (1994) Genotypic and phenotypic analysis of human immunodeficiency virus type 1 isolates from patients on prolonged stavudine therapy. J. Infect. Dis. 170: 1157-1164
43. Ronde A. de, Dooren M. van, Rooij E. de, Gemen B. van, Lange J. and Goudsmit J. (2000). Infection by zidovudine-resistant HIV-1 compromises the virological response to stavudine in a drug-naive patient. Aids 14: 2632-2633
44. Coakley E. P., Gillis J. M. and Hammer S. M. (2000). Phenotypic and genotypic resistance patterns of HIV-1 isolates derived from individuals treated with didanosine and stavudine. Aids 14, F9-F15
45. Kozal M. J., Shafer R. W., Winters M. A., Katzenstein D. A. and Merigan T. C. (1993) A mutation in human immunodeficiency virus reverse transcriptase and decline in CD4 lymphocyte numbers in long-term zidovudine recipients. J. Infect. Dis. 167: 526-532
46. Shafer R. W., Iversen A. K., Winters M. A., Aguiniga E., Katzenstein D. A. and Merigan T. C. (1995) Drug resistance and heterogeneous long-term virologic responses of human immunodeficiency virus type 1-infected subjects to zidovudine and didanosine combination therapy. The AIDS Clinical Trials Group 143 Virology Team. J. Infect. Dis. 172: 70-78
47. Demeter L. M., Nawaz T., Morse G., Dolin R., Dexter A., Gerondelis P. et al. (1995) Development of zidovudine resistance mutations in patients receiving prolonged didanosine monotherapy. J. Infect. Dis. 172: 1480-1485
48. Winters M. A., Shafer R. W., Jellinger R. A., Mamtora G., Gingeras T. and Merigan T. C. (1997) Human immunodeficiency virus type 1 reverse transcriptase genotype and drug susceptibility changes in infected individuals receiving dideoxyinosine monotherapy for 1 to 2 years. Antimicrob. Agents. Chemother. 41: 757-762
49. Lacey S. F. and Larder B. A. (1994) Mutagenic study of codons 74 and 215 of the human immunodeficiency virus type 1 reverse transcriptase, which are significant in nucleoside analog resistance. J. Virol. 68: 3421-3424
50. Larder B. A. (1994) Interactions between drug resistance mutations in human immunodeficiency virus type 1 reverse transcriptase. J. Gen. Virol. 75: 951-957
51. Boucher C. A., Cammack N., Schipper P., Schuurman R., Rouse P., Wainberg M. A. et al. (1993) High-level resistance to (-) enantiomeric 2′-deoxy-3′-thiacytidine in vitro is due to one amino acid substitution in the catalytic site of human immunodeficiency virus type 1 reverse transcriptase. Antimicrob. Agents Chemother. 37: 2231-2234
52. Gonzales M. J., Wu T. D., Taylor J., Belitskaya I., Kantor R., Israelski D. et al. (2003) Extended spectrum of HIV-1 reverse transcriptase mutations in patients receiving multiple nucleoside analog inhibitors. Aids 17: 791-799
53. Miller V. and Larder B. A. (2001) Mutational patterns in the HIV genome and cross-resistance following nucleoside and nucleotide analogue drug exposure. Antivir. Ther. 6 (suppl 3), 25-44
54. Wainberg M. A. and White A. J. (2001) Current insights into reverse transcriptase inhibitor-associated resistance. Antivir. Ther. 6 (suppl 2), 11-19
55. Whitcomb J. M., Parkin N. T., Chappey C., Hellmann N. S. and Petropoulos C. J. (2003) Broad nucleoside reverse-transcriptase inhibitor cross-resistance in human immunodeficiency virus type 1 clinical isolates. J. Infect. Dis. 188: 992-1000
56. Harrigan P. R., Stone C., Griffin P., Najera I., Bloor S., Kemp S. et al. (2000). Resistance profile of the human immunodeficiency virus type 1 reverse transcriptase inhibitor abacavir (1592U89) after monotherapy and combination therapy. CNA2001 Investigative Group. J. Infect. Dis. 181: 912-920
57. Lennerstrand J., Stammers D. K. and Larder B. A. (2001) Biochemical mechanism of human immunodeficiency virus type 1 reverse transcriptase resistance to stavudine. Antimicrob. Agents. Chemother. 45: 2144-2146
58. Shulman N. S., Hughes M. D., Winters M. A., Shafer R. W., Zolopa A. R., Hellmann N. S. et al. (2002) Subtle decreases in stavudine phenotypic susceptibility predict poor virologic response to stavudine monotherapy in zidovudine-experienced patients. J. Acquir. Immune. Defic. Syndr. 31: 121-127
59. Larder B. A. and Bloor S. (2001) Analysis of clinical isolates and site-directed mutants reveal the genetic determinats of didanosine resistance. Antivir. Ther. 6 (suppl. 1): 38, abstract 47
60. Wainberg M. A., Miller M. D., Quan Y., Salomon H., Mulato A. S., Lamy P. D. et al. (1999) In vitro selection and characterization of HIV-1 with reduced susceptibility to PMPA. Antivir. Ther. 4: 87-94
61. Miller M. D., Margot N. A., Hertogs K., Larder B. and Miller V. (2001) Antiviral activity of tenofovir (PMPA) against nucleoside-resistant clinical HIV samples. Nucleosides Nucleotides Nucleic Acids 20: 1025-1028
62. Margot N. A., Isaacson E., McGowan I., Cheng A. K., Schooley R. T. and Miller M. D. (2002) Genotypic and phenotypic analyses of HIV-1 in antiretroviral-experienced patients treated with tenofovir DF. Aids 16: 1227-1235
63. Wolf K., Walter H., Beerenwinkel N., Keulen W., Kaiser R., Hoffmann D. et al. (2003) Tenofovir resistance and resensitization. Antimicrob. Agents Chemother. 47: 3478-3484
64. Hirsch M., Steigbigel R., Staszewski S., Mellors J., Scerpella E., Hirschel B. et al. (1999) A randomized, controlled trial of indinavir, zidovudine, and lamivudine in adults with advanced human immunodeficiency virus type 1 infection and prior antiretroviral therapy. J. Infect. Dis. 180: 659-665
65. Delfraissy P. J. F. (ed.) (2004) Prise en charge thérapeutique des personnes infectées par le VIH-1. Medecine-Sciences Flammarion, Ministère de la santé et de la protection sociale/ANRS
66. Gao Q., Gu Z., Hiscott J., Dionne G. and Wainberg M. A. (1993) Generation of drug-resistant variants of human immunodeficiency virus type 1 by in vitro passage in increasing concentrations of 2′,3′-dideoxycytidine and 2′,3′-dideoxy-3′-thiacytidine. Antimicrob. Agents Chemother. 37: 130-133
67. Schinazi R. F., Lloyd R. M. Jr, Nguyen M. H., Cannon D. L., McMillan A., Ilksoy N. et al. (1993) Characterization of human immunodeficiency viruses resistant to oxathiolane-cytosine nucleosides. Antimicrob. Agents Chemother. 37: 875-881
68. Tisdale M., Kemp S. D., Parry N. R. and Larder B. A. (1993) 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 90: 5653-5656
69. Keulen W., Back N. K., Wijk A. van, Boucher C. A. and Berkhout B. (1997) Initial appearance of the 184Ile variant in lamivudine-treated patients is caused by the mutational bias of human immunodeficiency virus type 1 reverse transcriptase. J. Virol. 71: 3346-3350
70. Wainberg M. A., Salomon H., Gu Z., Montaner J. S., Cooley T. P., McCaffrey R. et al. (1995) Development of HIV-1 resistance to (-)2′-deoxy-3′-thiacytidine in patients with AIDS or advanced AIDS-related complex. Aids 9: 351-357
71. Schuurman R., Nijhuis M., Leeuwen R. van, Schipper P., Jong D. de, Collis P. et al. (1995) Rapid changes in human immunodeficiency virus type 1 RNA load and appearance of drug-resistant virus populations in persons treated with lamivudine (3TC). J. Infect. Dis. 171: 1411-1419
72. Kavlick M. F., Shirasaka T., Kojima E., Pluda J. M., Hui F., Jr., Yarchoan R. et al. (1995) Genotypic and phenotypic characterization of HIV-1 isolated from patients receiving (-)-2′,3′-dideoxy-3′- thiacytidine. Antivir. Res. 28: 133-146
73. Frost S. D., Nijhuis M., Schuurman R., Boucher C. A. and Brown A. J. (2000). Evolution of lamivudine resistance in human immunodeficiency virus type 1-infected individuals: the relative roles of drift and selection. J. Virol. 74: 6262-6268
74. Miller V., Ait-Khaled M., Stone C., Griffin P., Mesogiti D., Cutrell A. et al. (2000). HIV-1 reverse transcriptase (RT) genotype and susceptibility to RT inhibitors during abacavir monotherapy and combination therapy. Aids 14: 163-171
75. St Clair M. H., Martin J. L., Tudor-Williams G., Bach M. C., Vavro C. L., King D. M. et al. (1991) Resistance to ddI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase. Science 253: 1557-1559
76. Kozal M. J., Kroodsma K., Winters M. A., Shafer R. W., Efron B., Katzenstein D. A. et al. (1994) Didanosine resistance in HIV-infected patients switched from zidovudine to didanosine monotherapy. Ann. Intern. Med. 121: 263-268
77. Tisdale M., Alnadaf T. and Cousens D. (1997) Combination of mutations in human immunodeficiency virus type 1 reverse transcriptase required for resistance to the carbocyclic nucleoside 1592U89. Antimicrob. Agents Chemother. 41: 1094-1098
78. Martin J. L., Wilson J. E., Haynes R. L. and Furman P. A. (1993) Mechanism of resistance of human immunodeficiency virus type 1 to 2′,3′-dideoxyinosine. Proc. Natl. Acad. Sci. USA 90: 6135-6139
79. Molina J. M., Marcelin A. G., Pavie J. Merle C., Troccaz M., Lelen G. et al. (2003) Didanosine (ddI) in treatment experienced HIV-infected patients: results from a randomized double-blind study (AI454-176 Jaguar) (abstract H-447) 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago
80. Zhang D., Caliendo A. M., Eron J. J., DeVore K. M., Kaplan J. C., Hirsch M. S. et al. (1994) Resistance to 2′,3′-dideoxycytidine conferred by a mutation in codon 65 of the human immunodeficiency virus type 1 reverse transcriptase. Antimicrob. Agents Chemother. 38: 282-287
81. Gu Z., Fletcher R. S., Arts E. J., Wainberg M. A. and Parniak M. A. (1994) The K65R mutant reverse transcriptase of HIV-1 cross-resistant to 2′, 3′-dideoxycytidine, 2′,3′-dideoxy-3′- thiacytidine, and 2′,3′-dideoxyinosine shows reduced sensitivity to specific dideoxynucleoside triphosphate inhibitors in vitro. J. Biol. Chem. 269: 28118-28122
82. Garcia-Lerma J. G., MacInnes H., Bennett D., Reid P., Nidtha S., Weinstock H. et al. (2003) A novel genetic pathway of human immunodeficiency virus type 1 resistance to stavudine mediated by the K65R mutation. J. Virol. 77: 5685-5693
83. Roge B. T., Katzenstein T. L., Obel N., Nielsen H., Kirk O., Pedersen C. et al. (2003) K65R with and without S68: a new resistance profile in vivo detected in most patients failing abacavir, didanosine and stavudine. Antivir. Ther. 8: 173-182
84. Gu Z., Gao Q., Li X., Parniak M. A. and Wainberg M. A. (1992) Novel mutation in the human immunodeficiency virus type 1 reverse transcriptase gene that encodes cross-resistance to 2′,3′-dideoxyinosine and 2′,3′-dideoxycytidine. J. Virol. 66: 7128-7135
85. Gu Z., Gao Q., Fang H., Salomon H., Parniak M. A., Goldberg E. et al. (1994) Identification of a mutation at codon 65 in the IKKK motif of reverse transcriptase that encodes human immunodeficiency virus resistance to 2′,3′-dideoxycytidine and 2′,3′-dideoxy-3′- thiacytidine. Antimicrob. Agents Chemother. 38: 275-281
86. Bazmi H. Z., Hammond J. L., Cavalcanti S. C., Chu C. K., Schinazi R. F. and Mellors J. W. (2000). In vitro selection of mutations in the human immunodeficiency virus type 1 reverse transcriptase that decrease susceptibility to (-)-beta-D-dioxolane-guanosine and suppress resistance to 3′-azido-3′-deoxythymidine. Antimicrob. Agents Chemother. 44: 1783-1788
87. Srinivas R. V. and Fridland A. (1998) Antiviral activities of 9-R-2-phosphonomethoxypropyl adenine (PMPA) and bis(isopropyloxymethylcarbonyl) PMPA against various drug-resistant human immunodeficiency virus strains. Antimicrob. Agents Chemother. 42: 1484-1487
88. Fitzgibbon J. E., Howell R. M., Haberzettl C. A., Sperber S. J., Gocke D. J. and Dubin D. T. (1992) Human immunodeficiency virus type 1 pol gene mutations which cause decreased susceptibility to 2′,3′- dideoxycytidine. Antimicrob. Agents Chemother. 36: 153-157
89. Imamichi T., Sinha T., Imamichi H., Zhang Y. M., Metcalf J. A., Falloon J. et al. (2000). High-level resistance to 3′-azido-3′- deoxythimidine due to a deletion in the reverse transcriptase gene of human immunodeficiency virus type 1. J. Virol. 74: 1023-1028
90. Bloor S., Hertogs K., Larder B., Pauwels R. and Larder B. A. (1998) Virological basis for HIV-1 resistance to stavudine investigated by analysis of clinical samples. Antivir. Ther. 3 (suppl 1), 15-16
91. Hertogs K., Bethune M. P. de, Miller V., Ivens T., Schel P., Van Cauwenberge A. et al. (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
92. Miller M. D., Anton K. E., Mulato A. S., Lamy P. D. and Cherrington J. M. (1999) Human immunodeficiency virus 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. 179: 92-100
93. Winters M. A. and Merigan T. C. (2001) Variants other than aspartic acid at codon 69 of the human immunodeficiency virus type 1 reverse transcriptase gene affect susceptibility to nuleoside analogs. Antimicrob. Agents Chemother. 45: 2276-2279
94. Van Vaerenbergh K., Van Laethem K., Albert J., Boucher C. A., Clotet B., Floridia M. et al. (2000). Prevalence and characteristics of multinucleoside-resistant human immunodeficiency virus type 1 among European patients receiving combinations of nucleoside analogues. Antimicrob. Agents Chemother. 44: 2109-2117
95. Larder B. A., Bloor S., Kemp S. D., Hertogs K., Desmet R. L., Miller V. et al. (1999) A family of insertion mutations between codons 67 and 70 of human immunodeficiency virus type 1 reverse transcriptase confer multinucleoside analog resistance. Antimicrob. Agents Chemother. 43: 1961-1967
96. Winters M. A., Coolley K. L., Girard Y. A., Levee D. J., Hamdan H., Shafer R. W. et al. (1998) A 6-basepair insert in the reverse transcriptase gene of human immunodeficiency virus type 1 confers resistance to multiple nucleoside inhibitors. J. Clin. Invest. 102: 1769-1775
97. Jong J. J. de, Goudsmit J., Lukashov V. V., Hillebrand M. E., Baan E., Huismans R. et al. (1999) Insertion of two amino acids combined with changes in reverse transcriptase containing tyrosine-215 of HIV-1 resistant to multiple nucleoside analogs. Aids 13: 75-80
98. Tamalet C., Yahi N., TourRes. C., Colson P., Quinson A. M., Poizot-Martin I. et al. (2000). Multidrug resistance genotypes (insertions in the beta3-beta4 finger subdomain and MDR mutations) of HIV-1 reverse transcriptase from extensively treated patients: incidence and association with other resistance mutations. Virology 270: 310-316
99. Masquelier B., Race E., Tamalet C., Descamps D., Izopet J., Buffet-Janvresse C. et al. (2001) Genotypic and phenotypic resistance patterns of human immunodeficiency virus type 1 variants with insertions or deletions in the reverse transcriptase (RT): multicenter study of patients treated with RT inhibitors. Antimicrob. Agents Chemother. 45: 1836-1842
100. Brun-Vezinet F., Descamps D., Ruffault A., Masquelier B., Calvez V., Peytavin G. et al. (2003) Clinically relevant interpretation of genotype for resistance to abacavir. Aids 17: 1795-1802
101. Ross L., Scarsella A., Raffanti S., Henry K., Becker S., Fisher R. et al. (2001) Thymidine analog and multinucleoside resistance mutations are associated with decreased phenotypic susceptibility to stavudine in HIV type 1 isolated from zidovudine-naive patients experiencing viremia on stavudine-containing regimens. AIDS Res. Hum. Retroviruses 17: 1107-1115
102. Goldschmidt V. and Marquet R. (2004) Primer unblocking by HIV-1 reverse transcriptase and resistance to nucleoside RT inhibitors (NRTIs). Int. J. Biochem. Cell. Biol. 36: 1687-1705
103. Deval J., Courcambeck J., Selmi B., Boretto J. and Canard B. (2004) Structural determinants and molecular mechanisms for the resistance of HIV-1 RT to nucleoside analogues. Curr. Drug Metab. 5: 305-316
104. Huang H., Chopra R., Verdine G. L. and Harrison S. C. (1998) Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance. Science 282: 1669-1675
105. Sarafianos S. G., Das K., Clark A. D. Jr, Ding J., Boyer P. L., Hughes S. H. et al. (1999) Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids. Proc. Natl. Acad. Sci. USA 96: 10027-10032
106. Feng J. Y. and Anderson K. S. (1999) Mechanistic studies examining the efficiency and fidelity of DNA synthesis by the 3TC-resistant mutant (184V) of HIV-1 reverse transcriptase. Biochemistry 38: 9440-9448
107. Krebs R., Immendorfer U., Thrall S. H., Wohrl B. M. and Goody R. S. (1997) Single-step kinetics of HIV-1 reverse transcriptase mutants responsible for virus resistance to nucleoside inhibitors zidovudine and 3-TC. Biochemistry 36: 10292-10300
108. Wilson J. E., Aulabaugh A., Caligan B., McPherson S., Wakefield J. K., Jablonski S. et al. (1996) Human immunodeficiency virus type-1 reverse transcriptase: contribution of Met-184 to binding of nucleoside 5′-triphosphate. J. Biol. Chem. 271: 13656-13662
109. Drosopoulos W. C. and Prasad V. R. (1996) Increased polymerase fidelity of E89G, a nucleoside analog-resistant variant of human immunodeficiency virus type 1 reverse transcriptase. J. Virol. 70: 4834-4838
110. Pandey V. N., Kaushik N., Rege N., Sarafianos S. G., Yadav P. N. and Modak M. J. (1996) Role of methionine 184 of human immunodeficiency virus type-1 reverse transcriptase in the polymerase function and fidelity of DNA synthesis. Biochemistry 35: 2168-2179
111. Wainberg M. A., Drosopoulos W. C., Salomon H., Hsu M., Borkow G., Parniak M. et al. (1996) Enhanced fidelity of 3TC-selected mutant HIV-1 reverse transcriptase. Science 271: 1282-1285
112. Oude Essink B. B., Back N. K. and Berkhout B. (1997) Increased polymerase fidelity of the 3TC-resistant variants of HIV-1 reverse transcriptase. Nucleic Acids. Res. 25: 3212-3217
113. Back N. K., Nijhuis M., Keulen W., Boucher C. A., Oude Essink B. O., Kuilenburg A. B. van et al. (1996) Reduced replication of 3TC-resistant HIV-1 variants in primary cells due to a processivity defect of the reverse transcriptase enzyme. EMBO J. 15: 4040-4049
114. Larder B. A., Kemp S. D. and Harrigan P. R. (1995) Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy. Science 269: 696-699
115. Brenner B. G., Routy J. P., Petrella M., Moisi D., Oliveira M., Detorio M. et al. (2002) Persistence and fitness of multidrug-resistant human immunodeficiency virus type 1 acquired in primary infection. J. Virol. 76: 1753-1761
116. Bouchonnet F., Dam E., Mammano F., Soultrait V. de, Hennere G., Benech H. et al. (2005) Quantification of the effects on viral DNA synthesis of reverse transcriptase mutations conferring human immunodeficiency virus type 1 resistance to nucleoside analogues. J. Virol. 79: 812-822
117. Wainberg M. A. (2004) The impact of the M184V substitution on drug resistance and viral fitness. Expert. Rev. Anti. Infect. Ther. 2: 147-151
118. Diallo K., Marchand B., Wei X., Cellai L., Gotte M. and Wainberg M. A. (2003) Diminished RNA primer usage associated with the L74V and M184V mutations in the reverse transcriptase of human immunodeficiency virus type 1 provides a possible mechanism for diminished viral replication capacity. J. Virol. 77: 8621-8632
119. Sharma P. L. and Crumpacker C. S. (1997) Attenuated replication of human immunodeficiency virus type 1 with a didanosine-selected reverse transcriptase mutation. J. Virol. 71: 8846-8851
120. Sharma P. L. and Crumpacker C. S. (1999) Decreased processivity of human immunodeficiency virus type 1 reverse transcriptase (RT) containing didanosine-selected mutation Leu74Val: a comparative analysis of RT variants Leu74Val and lamivudine-selected Met184Val. J. Virol. 73: 8448-8456
121. Rubinek T., Bakhanashvili M., Taube R., Avidan O. and Hizi A. (1997) The fidelity of 3′ misinsertion and mispair extension during DNA synthesis exhibited by two drug-resistant mutants of the reverse transcriptase of human immunodeficiency virus type 1 with Leu74→Val and Glu89→Gly. Eur. J. Biochem. 247: 238-247
122. Frankel F. A., Marchand B., Turner D., Gotte M. and Wainberg M. A. (2005) Impaired rescue of chain-terminated DNA synthesis associated with the L74V mutation in human immunodeficiency virus type 1 reverse transcriptase. Antimicrob. Agents Chemother. 49: 2657-2664
123. Miranda L. R., Gotte M. and Kuritzkes D. R. (2005) The L74V mutation in human immunodeficiency virus type 1 reverse transcriptase counteracts enhanced excision of zidovudine monophosphate associated with thymidine analog resistance mutations. Antimicrob. Agents Chemother. 49: 2648-2656
124. Arion D., Borkow G., Gu Z., Wainberg M. A. and Parniak M. A. (1996) The K65R mutation confers increased DNA polymerase processivity to HIV-1 reverse transcriptase. J. Biol. Chem. 271: 19860-19864
125. White K. L., Margot N. A., Wrin T., Petropoulos C. J., Miller M. D. and Naeger L. K. (2002) Molecular mechanisms of resistance to human immunodeficiency virus type 1 with reverse transcriptase mutations K65R and K65R+M184V and their effects on enzyme function and viral replication capacity. Antimicrob. Agents Chemother. 46: 3437-3446
126. Selmi B., Boretto J., Sarfati S. R., Guerreiro C. and Canard B. (2001) Mechanism-based suppression of dideoxynucleotide resistance by K65R human immunodeficiency virus reverse transcriptase using an alpha-boranophosphate nucleoside analogue. J. Biol. Chem. 276: 48466-48472
127. Shah F. S., Curr K. A., Hamburgh M. E., Parniak M., Mitsuya H., Arnez J. G. et al. (2000). Differential influence of nucleoside analog-resistance mutations K65R and L74V on the overall mutation rate and error specificity of human immunodeficiency virus type 1 reverse transcriptase. J. Biol. Chem. 275: 27037-27044
128. Deval J., White K. L., Miller M. D., Parkin N. T., Courcambeck J., Halfon P. et al. (2004) Mechanistic basis for reduced viral and enzymatic fitness of HIV-1 reverse transcriptase containing both K65R and M184V mutations. J. Biol. Chem. 279: 509-516
129. Deval J., Navarro J. M., Selmi B., Courcambeck J., Boretto J., Halfon P. et al. (2004) A loss of viral replicative capacity correlates with altered DNA polymerization kinetics by the human immunodeficiency virus reverse transcriptase bearing the K65R and L74V dideoxynucleoside resistance substitutions. J. Biol. Chem. 279: 25489-25496
130. Lanier E., Irlbeck D., Ross L., Gerondelis P., Underwood M., Parkin N. et al. (2003) Multivariate analysis of predictors of response to abacavir: comparison of prior antiretroviral therapy, baseline HIV RNA, CDA count and viral resistance (abstract 82)10th Conference on Retroviruses and Opportunistic Infections, Boston
131. Rhee S. Y., Gonzales M. J., Kantor R., Betts B. J., Ravela J. and Shafer R. W. (2003) Human immunodeficiency virus reverse transcriptase and protease sequence database. Nucleic Acids Res. 31: 298-303
132. McColl D. J., Margot N. A., Wulfsohn M., Coakley D. F., Cheng A. K. and Miller M. D. (2004) Patterns of resistance emerging in HIV-1 from antiretroviral-experienced patients undergoing intensification therapy with tenofovir disoproxil fumarate. J. Acquir. Immune Defic. Syndr. 37: 1340-1350
133. Miller M. D. (2004) K65R, TAMs and tenofovir. AIDS Rev 6: 22-33
134. Wirden M., Marcelin A. G., Simon A., Kirstetter M., Tubiana R., Valantin M. A. et al. (2005) Resistance mutations before and after tenofovir regimen failure in HIV-1 infected patients. J. Med. Virol. 76: 297-301
135. Kerr S. G. and Anderson K. S. (1997) Pre-steady-state kinetic characterization of wild type and 3′-azido-3′-deoxythymidine (AZT) resistant human immunodeficiency virus type 1 reverse transcriptase: implication of RNA directed DNA polymerization in the mechanism of AZT resistance. Biochemistry 36: 14064-14070
136. Lacey S. F., Reardon J. E., Furfine E. S., Kunkel T. A., Bebenek K., Eckert K. A. et al. (1992) Biochemical studies on the reverse transcriptase and RNase H activities from human immunodeficiency virus strains resistant to 3′-azido-3′-deoxythymidine. J. Biol. Chem. 267: 15789-15794
137. Kim B. and Loeb L. A. (1995) A screen in Escherichia coli for nucleoside analogs that target human immunodeficiency virus (HIV) reverse transcriptase: coexpression of HIV reverse transcriptase and herpes simplex virus thymidine kinase. J. Virol. 69: 6563-6566
138. Hsieh J. C., Zinnen S. and Modrich P. (1993) Kinetic mechanism of the DNA-dependent DNA polymerase activity of human immunodeficiency virus reverse transcriptase. J. Biol. Chem. 268: 24607-24613
139. Reardon J. E. (1993) Human immunodeficiency virus reverse transcriptase: a kinetic analysis of RNA-dependent and DNA-dependent DNApolymerization. J. Biol. Chem. 268: 8743-8751
140. Canard B., Sarfati S. R. and Richardson C. C. (1998) Enhanced binding of azidothymidine-resistant human immunodeficiency virus 1 reverse transcriptase to the 3′-azido-3′-deoxythymidine 5′-monophosphate-terminated primer. J. Biol. Chem. 273: 14596-14604
141. Arion D., Kaushik N., McCormick S., Borkow G. and Parniak M. A. (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. Biochemistry 37: 15908-15917
142. Arion D., Sluis-Cremer N. and Parniak M. A. (2000). Mechanism by which phosphonoformic acid resistance mutations restore 3′-azido-3′- deoxythymidine (AZT) sensitivity to AZT-resistant HIV-1 reverse transcriptase. J. Biol. Chem. 275: 9251-9255
143. Gotte M., Arion D., Parniak M. A. and Wainberg M. A. (2000). The M184V mutation in the reverse transcriptase of human immunodeficiency virus type 1 impairs rescue of chain-terminated DNA synthesis. J. Virol. 74: 3579-3585
144. Carroll S. S., Geib J., Olsen D. B., Stahlhut M., Shafer J. A. and Kuo L. C. (1994) Sensitivity of HIV-1 reverse transcriptase and its mutants to inhibition by azidothymidine triphosphate. Biochemistry 33: 2113-2120
145. Meyer P. R., Matsuura S. E., Mian A. M., So A. G. and Scott W. A. (1999) A mechanism of AZT resistance: an increase in nucleotide-dependent primer unblocking by mutant HIV-1 reverse transcriptase. Mol. Cell. 4: 35-43
146. Lennerstrand J., Hertogs K., Stammers D. K. and Larder B. A. (2001) Correlation between viral resistance to zidovudine and resistance at the reverse transcriptase level for a panel of human immunodeficiency virus type 1 mutants. J. Virol. 75: 7202-7205
147. Meyer P. R., Matsuura S. E., Tolun A. A., Pfeifer I., So A. G., Mellors J. W. et al. (2002) Effects of specific zidovudine resistance mutations and substrate structure on nucleotide-dependent primer unblocking by human immunodeficiency virus type 1 reverse transcriptase. Antimicrob. Agents Chemother. 46: 1540-1545
148. Smith A. J., Meyer P. R., Asthana D., Ashman M. R. and Scott W. A. (2005) Intracellular substrates for the primer-unblocking reaction by human immunodeficiency virus type 1 reverse transcriptase: detection and quantitation in extracts from quiescent- and activated-lymphocyte subpopulations. Antimicrob. Agents Chemother. 49: 1761-1769
149. Meyer P. R., Matsuura S. E., So A. G. and Scott W. A. (1998) Unblocking of chain-terminated primer by HIV-1 reverse transcriptase through a nucleotide-dependent mechanism. Proc. Natl. Acad. Sci. USA 95: 13471-13476
150. Meyer P. R., Matsuura S. E., Schinazi R. F., So A. G. and Scott W. A. (2000). Differential removal of thymidine nucleotide analogues from blocked DNA chains by human immunodeficiency virus reverse transcriptase in the presence of physiological concentrations of 2′-deoxynucleoside triphosphates. Antimicrob. Agents Chemother. 44: 3465-3472
151. Ray A. S., Murakami E., Basavapathruni A., Vaccaro J. A., Ulrich D., Chu C. K. et al. (2003) Probing the molecular mechanisms of AZT drug resistance mediated by HIV-1 reverse transcriptase using a transient kinetic analysis. Biochemistry 42: 8831-8841
152. Naeger L. K., Margot N. A. and Miller M. D. (2002) ATP-dependent removal of nucleoside reverse transcriptase inhibitors by human immunodeficiency virus type 1 reverse transcriptase. Antimicrob. Agents Chemother. 46: 2179-2184
153. Isel C., Ehresmann C., Walter P., Ehresmann B. and Marquet R. (2001) 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. 276: 48725-48732
154. Boyer P. L., Sarafianos S. G., Arnold E. and Hughes S. H. (2001) Selective excision of AZTMP by drug-resistant human immunodeficiency virus reverse transcriptase. J. Virol. 75: 4832-4842
155. Ding J., Hughes S. H. and Arnold E. (1997) Protein-nucleic acid interactions and DNA conformation in a complex of human immunodeficiency virus type 1 reverse transcriptase with a double-stranded DNA template-primer. Biopolymers 44: 125-138
156. Marchand B. and Gotte M. (2003) Site-specific footprinting reveals differences in the translocation status of HIV-1 reverse transcriptase: implications for polymerase translocation and drug resistance. J. Biol. Chem. 278: 33362-33372
157. Sarafianos S. G., Clark A. D. Jr, Das K., Tuske S., Birktoft J. J., Ilankumaran P. et al. (2002) StructuRes. of HIV-1 reverse transcriptase with pre- and post-translocation AZTMP-terminated DNA. EMBO J. 21: 6614-6624
158. Sarafianos S. G., Clark A. D. Jr, Tuske S., Squire C. J., Das K., Sheng D. et al. (2003) Trapping HIV-1 reverse transcriptase before and after translocation on DNA. J. Biol. Chem. 278: 16280-16288
159. Sluis-Cremer N., Arion D., Parikh U., Koontz D., Schinazi R. F., Mellors J. W. et al. (2005) The 3′-azido group is not the primary determinant of 3′-azido-3′-deoxythymidine (AZT) responsible for the excision phenotype of AZT-resistant HIV-1. J. Biol. Chem. 280: 29047-29052
160. Boyer P. L., Sarafianos S. G., Arnold E. and Hughes S. H. (2002) The M184V mutation reduces the selective excision of zidovudine 5′- monophosphate (AZTMP) by the reverse transcriptase of human immunodeficiency virus type 1. J. Virol. 76: 3248-3256
161. Matamoros T., Franco S., Vazquez-Alvarez B. M., Mas A., Martinez M. A. and Menendez-Arias L. (2004) Molecular determinants of multi-nucleoside analogue resistance in HIV-1 reverse transcriptases containing a dipeptide insertion in the fingers subdomain: effect of mutations D67N and T215Y on removal of thymidine nucleotide analogues from blocked DNA primers. J. Biol. Chem. 279: 24569-24577
162. Chamberlain P. P., Ren J., Nichols C. E., Douglas L., Lennerstrand J., Larder B. A. et al. (2002) Crystal structuRes. of zidovudine- or lamivudine-resistant human immunodeficiency virus type 1 reverse transcriptases containing mutations at codons 41: 184, and 215. J. Virol. 76: 10015-10019
163. Rigourd M., Lanchy J. M., Le Grice S. F., Ehresmann B., Ehresmann C. and Marquet R. (2000). Inhibition of the initiation of HIV-1 reverse transcription by 3′-azido-3′-deoxythymidine: comparison with elongation. J. Biol. Chem. 275: 26944-26951
164. Rigourd M., Ehresmann C., Parniak M. A., Ehresmann B. and Marquet R. (2002) Primer unblocking and rescue of DNA synthesis by azidothymidine (AZT)-resistant HIV-1 reverse transcriptase: comparison between initiation and elongation of reverse transcription and between (-) and (+) strand DNA synthesis. J. Biol. Chem. 277: 18611-18618
165. Meyer P. R., Smith A. J., Matsuura S. E. and Scott W. A. (2004) Effects of primer-template sequence on ATP-dependent removal of chain-terminating nucleotide analogues by HIV-1 reverse transcriptase. J. Biol. Chem. 279: 45389-45398
166. Meyer P. R., Matsuura S. E., Zonarich D., Chopra R. R., Pendarvis E., Bazmi H. Z. et al. (2003) Relationship between 3′-azido-3′- deoxythymidine resistance and primer unblocking activity in foscarnet-resistant mutants of human immunodeficiency virus type 1 reverse transcriptase. J. Virol. 77: 6127-6137
167. Meyer P. R., Lennerstrand J., Matsuura S. E., Larder B. A. and Scott W. A. (2003) Effects of dipeptide insertions between codons 69 and 70 of human immunodeficiency virus type 1 reverse transcriptase on primer unblocking, deoxynucleoside triphosphate inhibition, and DNA chain elongation. J. Virol. 77: 3871-3877
168. Nikolenko G. N., Palmer S., Maldarelli F., Mellors J. W., Coffin J. M. and Pathak V. K. (2005) Mechanism for nucleoside analog-mediated abrogation of HIV-1 replication: balance between RNase H activity and nucleotide excision. Proc. Natl. Acad. Sci. USA 102: 2093-2098
169. Borkow G., Arion D., Wainberg M. A. and Parniak M. A. (1999) The thiocarboxanilide nonnucleoside inhibitor UC781 restoRes. antiviral activity of 3′-azido-3′-deoxythymidine (AZT) against AZT-resistant human immunodeficiency virus type 1. Antimicrob. Agents Chemother. 43: 259-263
170. Odriozola L., Cruchaga C. andreola M., Dolle V., Nguyen C. H., Tarrago-Litvak L. et al. (2003) Nonnucleoside inhibitors of HIV-1 reverse transcriptase inhibit phosphorolysis and resensitize the 3′-azido- 3′-deoxythymidine (AZT)-resistant polymerase to AZTTP. J Biol. Chem. 278: 1163-1172
171. Basavapathruni A., Bailey C. M. and Anderson K. S. (2004) Defining a molecular mechanism of synergy between nucleoside and nonnucleoside AIDS drugs. J. Biol. Chem. 279: 6221-6224
172. Cruchaga C., Odriozola L. andreola M., Tarrago-Litvak L. and Martinez-Irujo J. J. (2005) Inhibition of phosphorolysis catalyzed by HIV-1 reverse transcriptase is responsible for the synergy found in combinations of 3′-azido-3′-deoxythymidine with nonnucleoside inhibitors. Biochemistry 44: 3535-3546
173. Richman D., Shih C. K., Lowy I., Rose J., Prodanovich P., Goff S. et al. (1991) Human immunodeficiency virus type 1 mutants resistant to nonnucleoside inhibitors of reverse transcriptase arise in tissue culture. Proc. Natl. Acad. Sci. USA 88: 11241-11245
174. Larder B. A. (1992) 3′-Azido-3′-deoxythymidine resistance suppressed by a mutation conferring human immunodeficiency virus type 1 resistance to nonnucleoside reverse transcriptase inhibitors. Antimicrob. Agents Chemother. 36: 2664-2669
175. Selmi B., Deval J., Alvarez K., Boretto J., Sarfati S., Guerreiro C. et al. (2003) The Y181C substitution in AZT-resistant human immunodeficiency virus type 1 reverse transcriptase suppresses the ATP-mediated repair of the AZTMP-terminated primer. J. Biol. Chem. 278: 40464-40470
176. Blanca G., Baldanti F., Paolucci S., Skoblov A. Y., Victorova L., Hubscher U. et al. (2003) Nevirapine resistance mutation at codon 181 of the HIV-1 reverse transcriptase confers stavudine resistance by increasing nucleotide substrate discrimination and phosphorolytic activity. J. Biol. Chem. 278: 15469-15472
177. Boyer P. L., Imamichi T., Sarafianos S. G., Arnold E. and Hughes S. H. (2004) Effects of the Delta67 complex of mutations in human immunodeficiency virus type 1 reverse transcriptase on nucleoside analog excision. J. Virol. 78: 9987-9997
178. Palmer S., Shafer R. W. and Merigan T. C. (1999) Highly drug-resistant HIV-1 clinical isolates are cross-resistant to many antiretroviral compounds in current clinical development. Aids 13: 661-667
179. Naeger L. K., Margot N. A. and Miller M. D. (2001) 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 6: 115-126
180. Shulman N., Bosch R., Wang J., Albrecht M., Hellmann N. S. and Katzenstein D. A. (2001) Impact of M184V/I mutation on HIV phenotypic resistance to nucleoside analogs (NRTIS) in NRTI-experienced patients (abstract 1759). 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago
181. Parkin N., Chappey C., Petropoulos C. J. and Hellmann N. S. (2003) HIV-1 reverse transcriptase mutations that suppress zidovudine resistance also increase in vitro susceptibility to tenofovir, but not stavudine. Antivir. Ther. 8: 34
182. Picard V., Angelini E., Maillard A., Race E., Clavel F., Chene G. et al. (2001) Comparison of genotypic and phenotypic resistance patterns of human immunodeficiency virus type 1 isolates from patients treated with stavudine and didanosine or zidovudine and lamivudine. J. Infect. Dis. 184: 781-784
183. Back N. K. and Berkhout B. (1997) Limiting deoxynucleoside triphosphate concentrations emphasize the processivity defect of lamivudine-resistant variants of human immunodeficiency virus type 1 reverse transcriptase. Antimicrob. Agents Chemother. 41: 2484-2491
184. Selmi B., Boretto J., Navarro J. M., Sire J., Longhi S., Guerreiro C. et al. (2001) The valine-to-threonine 75 substitution in human immunodeficiency virus type 1 reverse transcriptase and its relation with stavudine resistance. J. Biol. Chem. 276: 13965-13974
185. Maeda Y., Venzon D. J. and Mitsuya H. (1998) Altered drug sensitivity, fitness, and evolution of human immunodeficiency virus type 1 with pol gene mutations conferring multi-dideoxynucleoside resistance. J. Infect. Dis. 177: 1207-1213
186. Kosalaraksa P., Kavlick M. F., Maroun V., Le R. and Mitsuya H. (1999) Comparative fitness of multi-dideoxynucleoside-resistant human immunodeficiency virus type 1 (HIV-1) in an in vitro competitive HIV-1 replication assay. J. Virol. 73: 5356-5363
187. Sarafianos S. G., Pandey V. N., Kaushik N. and Modak M. J. (1995) Glutamine 151 participates in the substrate dNTP binding function of HIV-1 reverse transcriptase. Biochemistry 34: 7207-7216
188. Iversen A. K., Shafer R. W., Wehrly K., Winters M. A., Mullins J. I., Chesebro B. et al. (1996) Multidrug-resistant human immunodeficiency virus type 1 strains resulting from combination antiretroviral therapy. J. Virol. 70: 1086-1090
189. Garcia-Lerma J. G., Gerrish P. J., Wright A. C., Qari S. H. and Heneine W. (2000). Evidence of a role for the Q151L mutation and the viral background in development of multiple dideoxynucleoside-resistant human immunodeficiency virus type 1. J. Virol. 74: 9339-9346
190. Shafer R. W., Kozal M. J., Winters M. A., Iversen A. K., Katzenstein D. A., Ragni M. V. et al. (1994) Combination therapy with zidovudine and didanosine selects for drug-resistant human immunodeficiency virus type 1 strains with unique patterns of pol gene mutations. J. Infect. Dis. 169: 722-729
191. Kavlick M. F., Wyvill K., Yarchoan R. and Mitsuya H. (1998) Emergence of multi-dideoxynucleoside-resistant human immunodeficiency virus type 1 variants, viral sequence variation, and disease progression in patients receiving antiretroviral chemotherapy. J. Infect. Dis. 177: 1506-1513
192. Shirasaka T., Kavlick M. F., Ueno T., Gao W. Y., Kojima E., Alcaide M. L. et al. (1995) Emergence of human immunodeficiency virus type 1 variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides. Proc. Natl. Acad. Sci. USA 92: 2398-2402
193. Shafer R. W., Winters M. A., Iversen A. K. and Merigan T. C. (1996) Genotypic and phenotypic changes during culture of a multinucleoside-resistant human immunodeficiency virus type 1 strain in the presence and absence of additional reverse transcriptase inhibitors. Antimicrob. Agents Chemother. 40: 2887-2890
194. Van Laethem K., Witvrouw M., Balzarini J., Schmit J. C., Sprecher S., Hermans P. et al. (2000). Patient HIV-1 strains carrying the multiple nucleoside resistance mutations are cross-resistant to abacavir. Aids 14: 469-471
195. Ueno T. and Mitsuya H. (1997) Comparative enzymatic study of HIV-1 reverse transcriptase resistant to 2′,3′-dideoxynucleotide analogs using the single-nucleotide incorporation assay. Biochemistry 36: 1092-1099
196. Deval J., Selmi B., Boretto J., Egloff M. P., Guerreiro C., Sarfati S. et al. (2002) The molecular mechanism of multidrug resistance by the Q151M human immunodeficiency virus type 1 reverse transcriptase and its suppression using alpha-boranophosphate nucleotide analogues. J. Biol. Chem. 277: 42097-42104
197. Kaushik N., Harris D., Rege N., Modak M. J., Yadav P. N. and Pandey V. N. (1997) Role of glutamine-151 of human immunodeficiency virus type-1 reverse transcriptase in RNA-directed DNA synthesis. Biochemistry 36: 14430-14438
198. Mas A., Parera M., Briones C., Soriano V., Martinez M. A., Domingo E. et al. (2000). Role of a dipeptide insertion between codons 69 and 70 of HIV-1 reverse transcriptase in the mechanism of AZT resistance. EMBO J. 19: 5752-5761
199. Boyer P. L., Sarafianos S. G., Arnold E. and Hughes S. H. (2002) Nucleoside analog resistance caused by insertions in the fingers of human immunodeficiency virus type 1 reverse transcriptase involves ATP-mediated excision. J. Virol. 76: 9143-9151
200. White K. L., Chen J. M., Margot N. A., Wrin T., Petropoulos C. J., Naeger L. K. et al. (2004) Molecular mechanisms of tenofovir resistance conferred by human immunodeficiency virus type 1 reverse transcriptase containing a diserine insertion after residue 69 and multiple thymidine analog-associated mutations. Antimicrob. Agents Chemother. 48: 992-1003
201. Hoek L. van der, Back N., Jebbink M. F., Ronde A. de, Bakker M., Jurriaans S. et al. (2005) Increased multinucleoside drug resistance and decreased replicative capacity of a human immunodeficiency virus type 1 variant with an 8-amino-acid insert in the reverse transcriptase. J. Virol. 79: 3536-3543
202. Tamalet C., Henry M., Colson P., Yahi N., Poggi C. and Lafeuillade A. (2004) Uncommon association of T69 3-base-pair insertion plus Q151M multidrug resistance mutations in human immunodeficiency virus type 1 reverse transcriptase. Antimicrob. Agents Chemother. 48: 4493-4494
203. Paolucci S., Baldanti F., Tinelli M., Maga G. and Gerna G. (2003) Detection of a new HIV-1 reverse transcriptase mutation (Q145M) conferring resistance to nucleoside and non-nucleoside inhibitors in a patient failing highly active antiretroviral therapy. Aids 17: 924-927
204. Paolucci S., Baldanti F., Maga G., Cancio R., Zazzi M., Zavattoni M. et al. (2004) Gln145Met/Leu changes in human immunodeficiency virus type 1 reverse transcriptase confer resistance to nucleoside and nonnucleoside analogs and impair virus replication. Antimicrob. Agents Chemother. 48: 4611-4617
205. De Clercq E. (2004) New anti-HIV agents in preclinical or clinical development. Front. Med. Chem. 1: 543-579
206. Otto M. (2004) New nucleoside reverse transcriptase inhibitors for the treatment of HIV infections. Curr. Opin. Pharmacol. 4: 431-436
207. Kim H. O., Schinazi R. F., Nampalli S., Shanmuganathan K., Cannon D. L., Alves A. J. et al. (1993) 1,3-Dioxolanylpurine nucleosides (2R, 4R) and (2R, 4S) with selective anti-HIV-1 activity in human lymphocytes. J. Med. Chem. 36: 30-37
208. Furman P. A., Jeffrey J., Kiefer L. L., Feng J. Y. anderson K. S., Borroto-Esoda K. et al. (2001) Mechanism of action of 1-β-D-2,6- diaminopurine dioxolane, a prodrug of the human immunodeficiency virus type 1 inhibitor 1-β-D-dioxolane guanosine. Antimicrob. Agents Chemother. 45: 158-165
209. Jeffrey J. L., Feng J. Y., Qi C. C. anderson K. S. and Furman P. A. (2003) Dioxolane guanosine 5′-triphosphate, an alternative substrate inhibitor of wild-type and mutant HIV-1 reverse transcriptase: steady state and pre-steady state kinetic analyses. J. Biol. Chem. 278: 18971-18979
210. Mewshaw J. P., Myrick F. T., Wakefield D. A. C. S., Hooper B. J., Harris J. L., McCreedy B. et al. (2002) Dioxolane guanosine, the active form of the prodrug diaminopurine dioxolane, is a potent inhibitor of drug-resistant HIV-1 isolates from patients for whom standard nucleoside therapy fails. J. Acquir. Immune Defic. Syn. 29: 11-20
211. Gu Z., Wainberg M. A., Nguyen-Ba N., L'Heureux L., De Muys J.-M., Bowlin T. L. et al. (1999) Mechanism of action and in vitro activity of 1′,3′-dioxolanylpurine nucleoside analogues against sensitive and drug-resistant human immunodeficiency virus type 1 variants. Antimicrob. Agents Chemother. 43: 2376-2382
212. Bazmi H. Z., Hammond J. L., Cavalcanti S. C. H., Chu C. K., Schinazi R. F. and Mellors J. W. (2000). In vitro selection of mutations in the human immunodeficiency virus type 1 reverse transcriptase that decrease susceptibility to (-)-β-D-dioxolane-guanosine and suppress resistance to 3′-azido-3′-deoxythymidine. Antimicrob. Agents Chemother. 44: 1783-1788
213. Chong Y., Borroto-Esoda K., Furman P. A., Schinazi R. F. and Chu C. K. (2002) Molecular mechanism of DAPD/DXG against zidovudine- and lamivudine-drug resistant mutants: a molecular modeling approach. Antivir. Chem. Chemother. 13: 115-128
214. Chong Y. and Chu C. (2004) Molecular mechanism of dioxolane nucleosides against 3TC resistant M184V mutant HIV. Antivir. Research 63: 7-13
215. Tremblay C., Poulin D., Hicks J., Selliah S., Chamberland A., Giguel F. et al. (2003) Favorable interactions between enfuvirtide and 1-β-D-2,6-diaminopurine dioxolane in vitro. Antimicrob. Agents Chemother. 47: 3644-3646
216. Borroto-Esoda K., Myrick F., Feng J., Jeffrey J. and Furman P. (2004) In vitro combination of amdoxovir and the inosine monophosphate dehydrogenase inhibitors mycophenolic acid and ribavirin demonstrates potent activity against wild-type and drug-resistant variants of human immunodeficiency virus type 1. Antimicrob. Agents Chemother. 48: 4387-4394
217. Stuyver L., McBrayer T., Schurmann D., Kravec I., Beard A., Cartee L. et al. (2004) Potent antiviral effect of reverset in HIV-1-infected adults following a single oral dose. Antivir. Ther. 9: 529-536
218. Schinazi R., Mellors J., Bazmi H., Diamond S., Garber S., Gallagher K. et al. (2002) DPC 817: a cytidine nucleoside analog with activity against zidovudine- and lamivudine-resistant viral variants. Antimicrob. Agents Chemother. 46: 1394-1401
219. Ray A., Schinazi R., Murakami E., Basavapathruni A., Shi J., Zorca S. et al. (2003) Probing the mechanistic consequences of 5-flurine substitution on cytidine nucleotide analogue incorporation by HIV-1 reverse transcriptase. Antivir. Chem. Chemother. 14: 115-125
220. Ma L., Hurwitz S. J., Shi J., McAtee J. J., Liotta D. C., McClure H. M. et al. (1999) Pharmacokinetics of the antiviral agent -D-2′,3′- didehydro-2′,3′-dideoxy-5-fluorocytidine in rhesus monkeys. Antimicrob. Agents Chemother. 43: 381-384
221. Erickson-Viitanen S., Wu J., Shi G., Unger S., King R., Fish B. et al. (2003) Cellular pharmacology of D-d4FC, a nucleoside analogue active against drug-resistant HIV Antivir. Chem. Chemother. 14: 39-47
222. Stoddart C., Bozeman C. and Schinazi R. (2002) Activity of the cytidine analog reverset (RVT) against 3TC-resistanct HIV-1 in SCID-hu Thy/Liv mice (abstract CR3). HIV DART 2002, Frontiers in Drug Development for Antiretroviral Therapies, Naples, Fla
223. Geleziunas R., Gallagher K., Zhang H., Bacheler L., Garber S., Wu J. T. et al. (2003) HIV-1 resistance profile of the novel nucleoside reverse transcriptase inhibitor beta-D-2′,3′-dideoxy-2′,3′- didehydro-5-fluorocytidine (reverset). Antivir. Chem. Chemother. 14: 49-59
224. Murphy R., Schurmann D., Kravec I., Beard A., Eron J., Cartee L. et al. (2003) Pharmacokinetics, safety and antiviral activity of the nucleoside reverset following single doses in HIV-1 infected patients. Antivir. Ther. 8, S330
225. Dutschman G., Bridges E., Liu S., Gullen E., Guo X., Kukhanova M. et al. (1998) Metabolism of 2′,3′-dideoxy-2′,3′-didehydro-beta- L(-)- 5-fluorocytidine and its activity in combination with clinically approved anti-human immunodeficiency virus beta-D(+) nucleoside analogs in vitro. Antimicrob. Agents Chemother. 42: 1799-1804
226. Chen S. (2002) Comparative evaluation of L-Fd4C and related nucleoside analogs as promising antiviral agents. Curr. Med. Chem. 9: 899-912
227. Dunkle L. M., Gathe J., Pedevillano D., Robison H., Rice W. and Pottage J. J. (2003) Elvucitabine: potent antiviral activity demonstrated in multidrug resistant HIV infection (abstract 2). 12th International HIV Drug Resistance Workshop, Los Cabos, Mexico
228. Schinazi R. F., MacMillan A., Cannon D., Mathis R., Lloyd R., Peck A. et al. (1992) Selective inhibition of human immunodeficiency viruses by racemates and enantiomers of cis-5-fluoro-1-(2(hydroxymethyl)-1,3-oxathiolan-5-yl) cytosine. Antimicrob. Agents Chemother. 36: 2423-2431
229. Black P., Ussery M., Otto M., Stuyver L., Hurwitz S., Barnett T. et al. Potent antiviral activity of racivit in the HUPBMC-SCID mouse model of HIV infection (abstract O17) (2000). Frontiers in Drug Development for Antiretroviral Therapies, HIV DART, San Juan, Puerto Rico
230. Otto M., Arasteh K., Kreckel P., Drauz D., Beard A., Cartee L. et al. (2003) Sustained anti-HIV-1 effect of racivit combined with d4T and Sustiva following a 14-day treatment of infected volunteers (abstract P552) 10th Conference on Retroviruses and Opportunistic Infections, Boston
231. De Muys J., Gourdeau H., Nguyen-Ba N., Taylor D., Ahmed P., Mansour T. et al. (1999) Anti-human immunodeficiency virus type 1 activity, intracellular metabolism, and pharmacokinetic evaluation of 2′-deoxy-3′-oxa- 4′-thiocytidine. Antimicrob. Agents Chemother. 43: 1835-1844
232. Richard N., Salomon H., Oliveira M., Rando R., Mansour T., Gu Z. et al. (2000). Selection of resistance-conferring mutations in HIV-1 by the nucleoside reverse transcriptase inhibitors (+/-)dOTC and (+/-)dOTFC. Antivir. Chem. Chemother. 11: 359-365
233. Taylor D., Ahmed P., Tyms A., Wood L., Kelly L., Chambers P. et al. (2000). Drug resistance and drug combination featuRes. of the human immunodeficiency virus inhibitor, BCH-10652 [(+/-)-2′-deoxy-3′-oxa- 4′-thiocytidine, dOTC]. Antivir. Chem. Chemother. 11: 291-301
234. Flexner C., Van der Horst C., Jacobson M., Powderly W., Duncanson F. and Ganes D. (1994) Relationship between plasma concentrations of 3′-deoxy-3′-fluorothymidine (alovudine) and antiretroviral activity in two concentration-controlled trials. J. Infect. Dis. 170: 1394-1403
235. Rusconi S. (2003) Alovudine medivir. Curr. Opin. Invest. Drugs 4: 219-223
236. Kim E., Vrang L., Oberg B. and Merigan T. (2001) Anti-HIV type 1 activity of 3′-fluoro-3′-deoxythymidine for several different multidrugresistant mutants. AIDS Res. Hum. Retrovir. 17: 401-407
237. Calvez V. (2002) MIV-310 reduces markedly viral load in patients with virological failure despite multiple-drug therapy: results from a 4-week phase II study. Antivir. Ther. 7, S3
238. Katlama C., Ghosn J., Tubiana R., Wirden M., Valantin M., Harmenberg J. et al. (2004) MIV-310 reduces HIV viral load in patients failing multiple antiretroviral therapy: results from a 4-week phase II study. Aids 18: 1299-1304
239. Sundseth R., Joyner S., Moore J., Dornsife R. and Dev I. (1996) The anti-human immunodeficiency virus agent 3′-fluorothymidine induces DNA damage and apoptosis in human lymphoblastoid cells. Antimicrob. Agents Chemother. 40: 331-335
240. Chu C., Yadav V., Chong Y. and Schinazi R. (2005) Anti-HIV activity of (-)-(2R,4R)-1(2-hydroxymethyl-1,3-dioxolan-4-yl)thymine against drug-resistant HIV-1 mutants and studies of its molecular mechanism. J. Med. Chem. 48: 3949-3952
241. Kim H. O., Ahn S. K., Alves A. J., Beach J. W., Jeong L. S., Choi B. G. et al. (1992) Asymmetric synthesis of 1,3-dioxolane pyrimidine nucleosides and their anti-HIV activity. J. Med. Chem. 35: 1987-1995
242. Chu C., Chong Y. and R. F., S. (2004) Dioxolane-thymidine nucleoside. (DOT) against drug-resistant HIV-1 mutants and its molecular mechanism. Antivir. Ther. 9: 21
243. Zhang H., Öberg B., Harmenberg J., Vrang L., Zhou X., Rydergard C. et al. (2002) Inhibition of multiple-drug resistant (MDR) HIV-1 by 3′-fluoro-2′,3′-dideoxyguanosine (FLG) (abstract 1853) 42nd Interscience Congress on Antimicrob. Agents Chemother., San Diego
244. Loeb L., Essigmann J., Kazazi F., Zhang J., Rose K. and Mullins J. (1999) Lethal mutagenesis of HIV with mutagenic nucleoside analogs. Proc. Nat. Acad. Sci. USA 96: 1492-1497
245. Harris K., Brabant W., Styrchak S., Gall A. and Daifuku R. (2005) KP-1212/1461, a nucleoside designed for the treatment of HIV by viral mutagenesis. Antivir. Res. 67: 1-9
246. Anderson J. P., Daifuku R. and Loeb L. A. (2004) Viral error catastrophe by mutagenic nucleosides. Ann. Rev. Microbiol. 58: 183-205
247. Murakami E., Basavapathruni A., Bradley W. and Anderson K. (2005) Mechanism of action of a novel viral mutagenic covert nucleotide: molecular interactions with HIV-1 reverse transcriptase and host cell DNA polymerases. Antivir. Res. 67: 10-17
248. Maag H., Rydzewski R., McRoberts M., Crawford-Ruth D., Verheyden J. and Prisbe E. (1992) Synthesis and anti-HIV activity of 4-azido- and 4-methoxynucleosides. J. Med. Chem. 35: 1440-1451
249. Sugimoto I., Shuto S., Mori S., Shigeta S. and Matsuda A. (1999) Synthesis of 4′ alpha-branched thymidines as a new type of antiviral agent. Bioorg. Med. Chem. Lett. 9: 385-388
250. Kodama E., Kohgo S., Kitano K., Machida H., Gatanaga H., Shigeta S. et al. (2001) 4′-Ethynyl nucleoside analogs: potent inhibitors of multidrug resistant human immunodeficiency virus variants in vitro. Antimicrob. Agents Chemother. 45: 1539-1546
251. Chen M. S., Suttmann R., Papp E., Cannon P., McRoberts M., Bach C. et al. (1993) Selective action of 4-azidothymidine triphosphate on reverse transcriptase of human immunodeficiency virus type 1 and human DNA polymerases alpha and beta. Biochemistry 32: 6002-6010
252. De Clercq E. (2004) Antiviral drugs in current clinical use. J. Clin. Virol. 30: 115-133
253. Tuske S., Sarafianos S. G., Clark A. D. Jr, Ding J., Naeger L. K., White K. L. et al. (2004) StructuRes. of HIV-1 RT-DNA complexes before and after incorporation of the anti-AIDS drug tenofovir. Nat. Struct. Mol. Biol. 11: 469-474
254. Boyer P. L., Julias J. G., Marquez V. E. and Hughes S. H. (2005) Fixed conformation nucleoside analogs effectively inhibit excision-proficient HIV-1 reverse transcriptases. J. Mol. Biol. 345: 441-450
255. Biebricher C. and Eigen M. (2005) The error threshold. Virus Res. 107: 117-127
256. Smith R. A., Loeb L. A. and Preston B. D. (2005) Lethal mutagenesis of HIV. Virus Res. 107: 215-228
257. Daifuku R. (2003) Stealth nucleosides : mode of action and potential use in the treatment of viral diseases. BioDrugs 17: 169-177
258. Crotty S., Maag D., Arnold J. J., Zhong W., Lau J. Y. N., Hong Z. et al. (2000). The broad-spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen. Nat. Med. 6: 1375-1379
259. Crotty S., Cameron C. E. and Andino R. (2001) RNA virus error catastrophe : direct molecular test by using ribavirin. Proc. Natl. Acad. Sci. USA 98: 6895-6900
260. Contreras A., Hiasa Y., He W., Terella A., Schmidt E. and Chung R. (2002) Viral RNA mutations are region specific and increased by ribavirin in a full-length hepatitis C virus replication system. J. Virol. 76: 8505-8517