HIV-1 reverse transcriptase inhibitor resistance mutations and fitness: A view from the clinic and ex vivo

Virus Research

Volumn 134, Issue 1-2, 2008, Pages 104-123

  Martinez Picado, Javier ^a,b   Martínez, Miguel Angel ^a  

^a HOSPITAL UNIVERSITARI GERMANS TRIAS I PUJOL   (Spain)

^b INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS ICREA   (Spain)

Author keywords

AIDS; Antiretroviral therapy; Drug resistance; HIV 1; Human immunodeficiency virus; Nonnucleoside analogues; Nucleoside analogues; Replication capacity; Reverse transcriptase; Viral fitness

Indexed keywords

ANTIRETROVIRUS AGENT; NUCLEOSIDE ANALOG; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR;

ARTICLE; DISEASE COURSE; EVOLUTIONARY ADAPTATION; FITNESS; GENETIC VARIABILITY; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; IMMUNE RESPONSE; IMMUNITY; LONG TERM CARE; MORBIDITY; MORTALITY; MULTIDRUG RESISTANCE; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; VIRUS LOAD; VIRUS MUTATION; VIRUS REPLICATION; VIRUS RESISTANCE;

ANTI-RETROVIRAL AGENTS; DRUG RESISTANCE, MULTIPLE, VIRAL; HIV INFECTIONS; HIV REVERSE TRANSCRIPTASE; HIV-1; HUMANS; REVERSE TRANSCRIPTASE INHIBITORS; VIRUS REPLICATION;

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 43049095987     PISSN: 01681702     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.virusres.2007.12.021     Document Type: Article

References (190)

1. Ali A., and Yang O.O. A novel small reporter gene and HIV-1 fitness assay. J. Virol. Methods 133 (2006) 41-47
2. Antinori A., Liuzzi G., Cingolani A., Bertoli A., Di Giambenedetto S., Trotta M.P., Rizzo M.G., Girardi E., De Luca A., and Perno C.F. Drug-resistant mutants of HIV-1 in patients exhibiting increasing CD4 cell count despite virological failure of highly active antiretroviral therapy. AIDS 15 (2001) 2325-2327
3. Antinori A., Zaccarelli M., Cingolani A., Forbici F., Rizzo M.G., Trotta M.P., Di Giambenedetto S., Narciso P., Ammassari A., Girardi E., De Luca A., and Perno C.F. Cross-resistance among nonnucleoside reverse transcriptase inhibitors limits recycling efavirenz after nevirapine failure. AIDS Res. Hum. Retroviruses 18 (2002) 835-838
4. Archer R.H., Dykes C., Gerondelis P., Lloyd A., Fay P., Reichman R.C., Bambara R.A., and Demeter L.M. Mutants of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase resistant to nonnucleoside reverse transcriptase inhibitors demonstrate altered rates of RNase H cleavage that correlate with HIV-1 replication fitness in cell culture. J. Virol. 74 (2000) 8390-8401
5. Arts E.J., and Quiñones-Mateu M.E. Sorting out the complexities of HIV-1 fitness. AIDS 17 (2003) 780-781
6. Back N.K., Nijhuis M., Keulen W., Boucher C.A., Oude Essink B.O., van Kuilenburg A.B., van Gennip A.H., and Berkhout B. Reduced replication of 3TC-resistant HIV-1 variants in primary cells due to a processivity defect of the reverse transcriptase enzyme. EMBO J. 15 (1996) 4040-4049
7. Bangsberg D.R., Acosta E.P., Gupta R., Guzman D., Riley E.D., Harrigan P.R., Parkin N., and Deeks S.G. Adherence-resistance relationships for protease and non-nucleoside reverse transcriptase inhibitors explained by virological fitness. AIDS 20 (2006) 223-231
8. Barbour J.D., and Grant R.M. The role of viral fitness in HIV pathogenesis. Curr. HIV/AIDS Rep. 2 (2005) 29-34
9. Barbour J.D., Wrin T., Grant R.M., Martin J.N., Segal M.R., Petropoulos C.J., and Deeks S.G. Evolution of phenotypic drug susceptibility and viral replication capacity during long-term virologic failure of protease inhibitor therapy in human immunodeficiency virus-infected adults. J. Virol. 76 (2002) 11104-11112
10. Barbour J.D., Wrin T., Hecht F.M., Hellmann N.S., Petropoulos C.J., Segal M.R., and Grant R.M. Wide variation in pro/pol replication capacity in recently transmitted HIV-1 is conferred in part by protease inhibitor resistance mutations. Antivir. Ther. 7 (2003) S80
11. Barbour J.D., Hecht F.M., Wrin T., Liegler T.J., Ramstead C.A., Busch M.P., Segal M.R., Petropoulos C.J., and Grant R.M. Persistence of primary drug resistance among recently HIV-1 infected adults. AIDS 18 (2004) 1683-1689
12. Barbour J.D., Hecht F.M., Wrin T., Segal M.R., Ramstead C.A., Liegler T.J., Busch M.P., Petropoulos C.J., Hellmann N.S., Kahn J.O., and Grant R.M. Higher CD4+ T cell counts associated with low viral pol replication capacity among treatment-naive adults in early HIV-1 Infection. J. Infect. Dis. 190 (2004) 251-256
13. Belec L., Legoff J., Si-Mohamed A., Andreoletti L., Mbopi-Keou F.X., Kolberg J., Matta M., Detmer J., Piketty C., and Kazatchkine M.D. Sustained high proportion of zidovudine-resistant HIV variants despite prolonged substitution of zidovudine by other nucleoside reverse transcriptase inhibitors. J. Med. Virol. 68 (2002) 1-6
14. Bezemer D., de Ronde A., Prins M., Porter K., Gifford R., Pillay D., Masquelier B., Fleury H., Dabis F., Back N., Jurriaans S., and van der Hoek L. Evolution of transmitted HIV-1 with drug-resistance mutations in the absence of therapy: effects on CD4+ T-cell count and HIV-1 RNA load. Antivir. Ther. 11 (2006) 173-178
15. Bleiber G., Munoz M., Ciuffi A., Meylan P., and Telenti A. Individual contributions of mutant protease and reverse transcriptase to viral infectivity, replication, and protein maturation of antiretroviral drug-resistant human immunodeficiency virus type 1. J. Virol. 75 (2001) 3291-3300
16. Bonhoeffer S., Barbour A.D., and De Boer R.J. Procedures for reliable estimation of viral fitness from time-series data. Proc. Biol. Sci. 269 (2002) 1887-1893
17. Brenner B.G., Routy J.P., Petrella M., Moisi D., Oliveira M., Detorio M., Spira B., Essabag V., Conway B., Lalonde R., Sekaly R.P., and Wainberg M.A. Persistence and fitness of multidrug-resistant human immunodeficiency virus type 1 acquired in primary infection. J. Virol. 76 (2002) 1753-1761
18. Brenner B., Routy J.P., Quan Y., Moisi D., Oliveira M., Turner D., and Wainberg M.A. Persistence of multidrug-resistant HIV-1 in primary infection leading to superinfection. AIDS 18 (2004) 1653-1660
19. Briones C., and Soriano V. Different outcome in the first two patients with an HIV-1 multinucleoside drug-resistant T69SSS insertion in Spain. Antivir. Ther. 4 (1999) 125-127
20. Briones C., Mas A., Gómez-Mariano G., Altisent C., Menéndez-Arias L., Soriano V., and Domingo E. Dynamics of dominance of a dipeptide insertion in reverse transcriptase of HIV-1 from patients subjected to prolonged therapy. Virus Res. 66 (2000) 13-26
21. Cabana M., Fernández G., Parera M., Clotet B., and Martínez M.A. Catalytic efficiency and phenotype of HIV-1 proteases encoding single critical resistance substitutions. Virology 300 (2002) 71-78
22. Campbell T.B., Schneider K., Wrin T., Petropoulos C.J., and Connick E. Relationship between in vitro human immunodeficiency virus type 1 replication rate and virus load in plasma. J. Virol. 77 (2003) 12105-12112
23. Capetti A.F., Gabris A.I., Drago L., and Vigevani G.M. Can a K103N HIV strain stably overcome the wild type in the absence of non-nucleoside reverse transcriptase inhibitor selective pressure?. AIDS 19 (2005) 633-634
24. Coffin J.M. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science 267 (1995) 483-489
25. Collins J.A., Thompson M.G., Paintsil E., Ricketts M., Gedzior J., and Alexander L. Competitive fitness of nevirapine-resistant human immunodeficiency virus type 1 mutants. J. Virol. 78 (2004) 603-611
26. Cong M.E., Heneine W., and García-Lerma J.G. The fitness cost of mutations associated with human immunodeficiency virus type 1 drug resistance is modulated by mutational interactions. J. Virol. 81 (2007) 3037-3041
27. Daar, E.S., Frost, S.D.W., Wong, J.K., Hellmann, N.S., Wrin, T., Petropoulos, C.J., Richman, D.D., Pitt, J.A., Little, S.J., Leigh Brown, A.J., 2002. Mixed infection with multidrug resistant (MDR) and wild type HIV strains in primary HIV infection (PHI): early viral rebound suggests loss of immune control (Abstract 96). In: Proceedings of the 9th Conference on Retroviruses and Opportunistic Infections, February 24-28, 2002. Seattle, WA, USA, http://www.retroconference.org/2002/Abstract/13158.htm.
28. De Antoni A., Foli A., Lisziewicz J., and Lori F. Mutations in the pol gene of human immunodeficiency virus type 1 in infected patients receiving didanosine and hydroxyurea combination therapy. J. Infect. Dis. 176 (1997) 899-903
29. de Jong J.J., Goudsmit J., Lukashov V.V., Hillebrand M.E., Baan E., Huismans R., Danner S.A., ten Veen J.H., de Wolf F., and Jurriaans S. Insertion of two amino acids combined with changes in reverse transcriptase containing tyrosine-215 of HIV-1 resistant to multiple nucleoside analogs. AIDS 13 (1999) 75-80
30. de Ronde A., van Dooren M., van Der Hoek L., Bouwhuis D., de Rooij E., van Gemen B., de Boer R., and Goudsmit J. Establishment of new transmissible and drug-sensitive human immunodeficiency virus type 1 wild types due to transmission of nucleoside analogue-resistant virus. J. Virol. 75 (2001) 595-602
31. Deeks S.G., Barbour J.D., Martin J.N., Swanson M.S., and Grant R.M. Sustained CD4+ T cell response after virologic failure of protease inhibitor-based regimens in patients with human immunodeficiency virus infection. J. Infect. Dis. 181 (2000) 946-953
32. Deeks S.G., Wrin T., Liegler T., Hoh R., Hayden M., Barbour J.D., Hellmann N.S., Petropoulos C.J., McCune J.M., Hellerstein M.K., and Grant R.M. Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia. N. Engl. J. Med. 344 (2001) 472-480
33. Deeks S.G., Martin J.N., Sinclair E., Harris J., Neilands T.B., Maecker H.T., Hagos E., Wrin T., Petropoulos C.J., Bredt B., and McCune J.M. Strong cell-mediated immune responses are associated with the maintenance of low-level viremia in antiretroviral-treated individuals with drug-resistant human immunodeficiency virus type 1. J. Infect. Dis. 189 (2004) 312-321
34. Deeks S.G., Hoh R., Neilands T.B., Liegler T., Aweeka F., Petropoulos C.J., Grant R.M., and Martin J.N. Interruption of treatment with individual therapeutic drug classes in adults with multidrug-resistant HIV-1 infection. J. Infect. Dis. 192 (2005) 1537-1544
35. Deval J., Navarro J.M., Selmi B., Courcambeck J., Boretto J., Halfon P., Garrido-Urbani S., Sire J., and Canard B. 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 (2004) 25489-25496
36. Deval J., White K.L., Miller M.D., Parkin N.T., Courcambeck J., Halfon P., Selmi B., Boretto J., and Canard B. Mechanistic basis for reduced viral and enzymatic fitness of HIV-1 reverse transcriptase containing both K65R and M184V mutations. J. Biol. Chem. 279 (2004) 509-516
37. Devereux H.L., Emery V.C., Johnson M.A., and Loveday C. Replicative fitness in vivo of HIV-1 variants with multiple drug resistance-associated mutations. J. Med. Virol. 65 (2001) 218-224
38. Diallo K., Oliveira M., Moisi D., Brenner B., Wainberg M.A., and Götte M. Pressure of zidovudine accelerates the reversion of lamivudine resistance-conferring M184V mutation in the reverse transcriptase of human immunodeficiency virus type 1. Antimicrob. Agents Chemother. 46 (2002) 2254-2256
39. Diallo K., Marchand B., Wei X., Cellai L., Götte M., and Wainberg M.A. 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 (2003) 8621-8632
40. Domingo E., and Holland J.J. RNA virus mutations and fitness for survival. Annu. Rev. Microbiol. 51 (1997) 151-178
41. Domingo E., Escarmís C., Menéndez-Arias L., and Holland J.J. Viral quasispecies and fitness variations. In: Domingo E., Webster R., and Holland J.J. (Eds). Origin and Evolution of Viruses (1999), Academic Press, San Diego, CA, USA 141-161
42. Domingo E., Martín V., Perales C., Grande-Pérez A., García-Arriaza J., and Arias A. Viruses as quasispecies: biological implications. Curr. Top. Microbiol. Immunol. 299 (2006) 51-82
43. Dykes C., Fox K., Lloyd A., Chiulli M., Morse E., and Demeter L.M. Impact of clinical reverse transcriptase sequences on the replication capacity of HIV-1 drug-resistant mutants. Virology 285 (2001) 193-203
44. Dykes C., Wang J., Jin X., Planelles V., An D.S., Tallo A., Huang Y., Wu H., and Demeter L.M. Evaluation of a multiple-cycle, recombinant virus, growth competition assay that uses flow cytometry to measure replication efficiency of human immunodeficiency virus type 1 in cell culture. J. Clin. Microbiol. 44 (2006) 1930-1943
45. Eigen M. Selforganization of matter and the evolution of biological macromolecules. Naturwissenschaften 58 (1971) 465-523
46. Eigen M., and Schuster P. The Hypercycle: A Principle of Natural Self-Organization (1979), Springer, Berlin
47. Fan N., Rank K.B., Slade D.E., Poppe S.M., Evans D.B., Kopta L.A., Olmsted R.A., Thomas R.C., Tarpley W.G., and Sharma S.K. A drug resistance mutation in the inhibitor binding pocket of human immunodeficiency virus type 1 reverse transcriptase impairs DNA synthesis and RNA degradation. Biochemistry 35 (1996) 9737-9745
48. Fellay J., Shianna K.V., Ge D., Colombo S., Ledergerber B., Weale M., Zhang K., Gumbs C., Castagna A., Cossarizza A., Cozzi-Lepri A., De Luca A., Easterbrook P., Francioli P., Mallal S., Martinez-Picado J., Miro J.M., Obel N., Smith J.P., Wyniger J., Descombes P., Antonarakis S.E., Letvin N.L., McMichael A.J., Haynes B.F., Telenti A., and Goldstein D.B. A whole-genome association study of major determinants for host control of HIV-1. Science 317 (2007) 944-947
49. Fernández G., Clotet B., and Martínez M.A. Fitness landscape of human immunodeficiency virus type 1 protease quasispecies. J. Virol. 81 (2007) 2485-2496
50. Frankel F.A., Invernizzi C.F., Oliveira M., and Wainberg M.A. Diminished efficiency of HIV-1 reverse transcriptase containing the K65R and M184V drug resistance mutations. AIDS 21 (2007) 665-675
51. Frost S.D., Nijhuis M., Schuurman R., Boucher C.A., and Brown A.J. Evolution of lamivudine resistance in human immunodeficiency virus type 1-infected individuals: the relative roles of drift and selection. J. Virol. 74 (2000) 6262-6268
52. Gallant J.E. Antiretroviral drug resistance and resistance testing. Top. HIV Med. 13 (2005) 138-142
53. Gallant J.E. The M184V mutation: what it does, how to prevent it, and what to do with it when it's there. AIDS Read 16 (2006) 556-559
54. Gamarnik A., Wrin T., Ziermann R., Huang W., Whitehurst N., Whitcomb J.M., and Petropoulos C.J. Drug resistance is associated with impaired protease and reverse transcriptase function and reduced replication capacity: characterization of recombinant viruses derived from 200 HIV-1 infected patients. Antivir. Ther. 5 (2000) 92
55. García-Lerma J.G., Gerrish P.J., Wright A.C., Qari S.H., and Heneine W. 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 (2000) 9339-9346
56. García-Lerma J.G., Nidtha S., Blumoff K., Weinstock H., and Heneine W. Increased ability for selection of zidovudine resistance in a distinct class of wild-type HIV-1 from drug-naive persons. Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 13907-13912
57. García-Lerma J.G., MacInnes H., Bennett D., Weinstock H., and Heneine W. Transmitted human immunodeficiency virus type 1 carrying the D67N or K219Q/E mutation evolves rapidly to zidovudine resistance in vitro and shows a high replicative fitness in the presence of zidovudine. J. Virol. 78 (2004) 7545-7552
58. Gatanaga H., Hachiya A., Kimura S., and Oka S. Mutations other than 103N in human immunodeficiency virus type 1 reverse transcriptase (RT) emerge from K103R polymorphism under non-nucleoside RT inhibitor pressure. Virology 344 (2006) 354-362
59. Gerondelis P., Archer R.H., Palaniappan C., Reichman R.C., Fay P.J., Bambara R.A., and Demeter L.M. The P236L delavirdine-resistant human immunodeficiency virus type 1 mutant is replication defective and demonstrates alterations in both RNA 5'-end- and DNA 3'-end-directed RNase H activities. J. Virol. 73 (1999) 5803-5813
60. Gianotti N., Galli L., Boeri E., Maillard M., Serra G., Ratti D., Gallotta G., Vacchini D., Tremolada Y., Lazzarin A., Clementi M., and Castagna A. In vivo dynamics of the K103N mutation following the withdrawal of non-nucleoside reverse transcriptase inhibitors in human immunodeficiency virus-infected patients. New Microbiol. 28 (2005) 319-326
61. Goudsmit J. Viral Fitness: The Next SARS and West Nile in the Making (2004), Oxford University Press, Oxford
62. Goudsmit J., De Ronde A., Ho D.D., and Perelson A.S. Human immunodeficiency virus fitness in vivo: calculations based on a single zidovudine resistance mutation at codon 215 of reverse transcriptase. J. Virol. 70 (1996) 5662-5664
63. Goudsmit J., de Ronde A., de Rooij E., and de Boer R. Broad spectrum of in vivo fitness of human immunodeficiency virus type 1 subpopulations differing at reverse transcriptase codons 41 and 215. J. Virol. 71 (1997) 4479-4484
64. Grant R.M., Barbour J.D., Wrin T., Warmerdam M., Hellmann N.S., Kahn J.O., Petropoulos C.J., and Hecht F.R. Transmission of drug resistant HIV-1 exhibiting lower replication capacity is associated with higher CD4 cell counts. Antivir. Ther. 7 (2002) S41
65. Gu Z., Gao Q., Li X., Parniak M.A., and Wainberg M.A. 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 (1992) 7128-7135
66. Harrigan P.R., Kinghorn I., Bloor S., Kemp S.D., Nájera I., Kohli A., and Larder B.A. Significance of amino acid variation at human immunodeficiency virus type 1 reverse transcriptase residue 210 for zidovudine susceptibility. J. Virol. 70 (1996) 5930-5934
67. Harrigan P.R., Bloor S., and Larder B.A. Relative replicative fitness of zidovudine-resistant human immunodeficiency virus type 1 isolates in vitro. J. Virol. 72 (1998) 3773-3778
68. Harrigan P.R., Stone C., Griffin P., Nájera I., Bloor S., Kemp S., Tisdale M., Larder B., and CNA2001 Investigative Group. Resistance profile of the human immunodeficiency virus type 1 reverse transcriptase inhibitor abacavir (1592U89) after monotherapy and combination therapy. J. Infect. Dis. 181 (2000) 912-920
69. Haubrich R., Wrin T., Hellmann N., McCutchan J.A., Keiser P., Kemper C., Witt M., Leedom J., Forthal D., Richman D., and TheCCTG. Replication Capacity as a predictor of immunological and virological benefit despite virologic failure of an antiretroviral regimen. Antivir. Ther. 7 (2002) S101
70. Havlir D.V., Eastman S., Gamst A., and Richman D.D. Nevirapine-resistant human immunodeficiency virus: kinetics of replication and estimated prevalence in untreated patients. J. Virol. 70 (1996) 7894-7899
71. Hogan C.M., and Hammer S.M. Host determinants in HIV infection and disease. Part 1. Cellular and humoral immune responses. Ann. Intern. Med. 134 (2001) 761-776
72. Hogan C.M., and Hammer S.M. Host determinants in HIV infection and disease. Part 2. Genetic factors and implications for antiretroviral therapeutics. Ann. Intern. Med. 134 (2001) 978-996
73. Holland J.J., de la Torre J.C., Clarke D.K., and Duarte E. Quantitation of relative fitness and great adaptability of clonal populations of RNA viruses. J. Virol. 65 (1991) 2960-2967
74. Hoogewerf M., Regez R.M., Schouten W.E., Weigel H.M., Frissen P.H., and Brinkman K. Change to abacavir-lamivudine-tenofovir combination treatment in patients with HIV-1 who had complete virological suppression. Lancet 362 (2003) 1979-1980
75. Hu Z., Giguel F., Hatano H., Reid P., Lu J., and Kuritzkes D.R. Fitness comparison of thymidine analog resistance pathways in human immunodeficiency virus type 1. J. Virol. 80 (2006) 7020-7027
76. Hu Z., Hatano H., Hammond S.P., Smith D., Wild M., Gupta S., Whitcomb J., Kalayjian R.C., Gripshover B., and Kuritzkes D.R. Virologic characterization of HIV type 1 with a codon 70 deletion in reverse transcriptase. J. Acquir. Immune Defic. Syndr. 45 (2007) 494-500
77. Huang W., Wrin T., Gamarnik A., Beauchaine J., Whitcomb J.M., and Petropoulos C.J. Reverse transcriptase mutations that confer non-nucleoside reverse transcriptase inhibitor resistance may also impair replication capacity. Antivir. Ther. 7 (2002) S60
78. Huang W., Gamarnik A., Limoli K., Petropoulos C.J., and Whitcomb J.M. Amino acid substitutions at position 190 of human immunodeficiency virus type 1 reverse transcriptase increase susceptibility to delavirdine and impair virus replication. J. Virol. 77 (2003) 1512-1523
79. Huigen M.C.D.G., Albert J., Lindström A., Ohlis A., Bratt G., de Graaf L., Nijhuis M., and Boucher C.A.B. Compensatory fixation explains long term persistence of the M41L in HIV-1 reverse transcriptase in a large transmission cluster. Antivir. Ther. 11 (2006) S113
80. Huigen M.C., de Graaf L., Eggink D., Schuurman R., Muller V., Stamp A., Stammers D.K., Boucher C.A., and Nijhuis M. Evolution of a novel 5-amino-acid insertion in the β3-β4 loop of HIV-1 reverse transcriptase. Virology 364 (2007) 395-406
81. Iglesias-Ussel M.D., Casado C., Yuste E., Olivares I., and López-Galíndez C. In vitro analysis of human immunodeficiency virus type 1 resistance to nevirapine and fitness determination of resistant variants. J. Gen. Virol. 83 (2002) 93-101
82. Imamichi T., Berg S.C., Imamichi H., Lopez J.C., Metcalf J.A., Falloon J., and Lane H.C. Relative replication fitness of a high-level 3′-azido-3′-deoxythymidine-resistant variant of human immunodeficiency virus type 1 possessing an amino acid deletion at codon 67 and a novel substitution (Thr → Gly) at codon 69. J. Virol. 74 (2000) 10958-10964
83. Imamichi T., Murphy M.A., Imamichi H., and Lane H.C. Amino acid deletion at codon 67 and Thr-to-Gly change at codon 69 of human immunodeficiency virus type 1 reverse transcriptase confer novel drug resistance profiles. J. Virol. 75 (2001) 3988-3992
84. Iversen A.K., Shafer R.W., Wehrly K., Winters M.A., Mullins J.I., Chesebro B., and Merigan T.C. Multidrug-resistant human immunodeficiency virus type 1 strains resulting from combination antiretroviral therapy. J. Virol. 70 (1996) 1086-1090
85. Jeeninga R.E., Keulen W., Boucher C., Sanders R.W., and Berkhout B. Evolution of AZT resistance in HIV-1: the 41-70 intermediate that is not observed in vivo has a replication defect. Virology 283 (2001) 294-305
86. Johnson V.A., Brun-Vézinet F., Clotet B., Gunthard H.F., Kuritzkes D.R., Pillay D., Schapiro J.M., and Richman D.D. Update of the drug resistance mutations in HIV-1: 2007. Top. HIV Med. 15 (2007) 119-125
87. Joly V., Descamps D., Peytavin G., Touati F., Mentre F., Duval X., Delarue S., Yeni P., and Brun-Vézinet F. Evolution of human immunodeficiency virus type 1 (HIV-1) resistance mutations in nonnucleoside reverse transcriptase inhibitors (NNRTIs) in HIV-1-infected patients switched to antiretroviral therapy without NNRTIs. Antimicrob. Agents Chemother. 48 (2004) 172-175
88. Joos B., Trkola A., Fischer M., Kuster H., Rusert P., Leemann C., Boni J., Oxenius A., Price D.A., Phillips R.E., Wong J.K., Hirschel B., Weber R., and Gunthard H.F. Low human immunodeficiency virus envelope diversity correlates with low in vitro replication capacity and predicts spontaneous control of plasma viremia after treatment interruptions. J. Virol. 79 (2005) 9026-9037
89. Julias J.G., Boyer P.L., McWilliams M.J., Alvord W.G., and Hughes S.H. Mutations at position 184 of human immunodeficiency virus type-1 reverse transcriptase affect virus titer and viral DNA synthesis. Virology 322 (2004) 13-21
90. Karlsson A.C., Deeks S.G., Barbour J.D., Heiken B.D., Younger S.R., Hoh R., Lane M., Sallberg M., Ortiz G.M., Demarest J.F., Liegler T., Grant R.M., Martin J.N., and Nixon D.F. Dual pressure from antiretroviral therapy and cell-mediated immune response on the human immunodeficiency virus type 1 protease gene. J. Virol. 77 (2003) 6743-6752
91. Kellam P., Boucher C.A., and Larder B.A. Fifth mutation in human immunodeficiency virus type 1 reverse transcriptase contributes to the development of high-level resistance to zidovudine. Proc. Natl. Acad. Sci. U.S.A. 89 (1992) 1934-1938
92. Keulen W., Back N.K., van Wijk A., Boucher C.A., and Berkhout B. 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 (1997) 3346-3350
93. Kosalaraksa P., Kavlick M.F., Maroun V., Le R., and Mitsuya H. 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 (1999) 5356-5363
94. Koval C.E., Dykes C., Wang J., and Demeter L.M. Relative replication fitness of efavirenz-resistant mutants of HIV-1: correlation with frequency during clinical therapy and evidence of compensation for the reduced fitness of K103N + L100I by the nucleoside resistance mutation L74V. Virology 353 (2006) 184-192
95. Kuritzkes D.R. A fossil record of zidovudine resistance in transmitted isolates of HIV-1. Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 13485-13487
96. Larder B.A. Interactions between drug resistance mutations in human immunodeficiency virus type 1 reverse transcriptase. J. Gen. Virol. 75 (1994) 951-957
97. Larder B.A., Bloor S., Kemp S.D., Hertogs K., Desmet R.L., Miller V., Sturmer M., Staszewski S., Ren J., Stammers D.K., Stuart D.I., and Pauwels R. 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 (1999) 1961-1967
98. Lecossier D., Shulman N.S., Morand-Joubert L., Shafer R.W., Joly V., Zolopa A.R., Clavel F., and Hance A.J. Detection of minority populations of HIV-1 expressing the K103N resistance mutation in patients failing nevirapine. J. Acquir. Immune Defic. Syndr. 38 (2005) 37-42
99. Leigh Brown A.J., Frost S.D.W., Mathews W.C., Dawson K., Hellmann N.S., Daar E.S., Richman D.D., and Little S.J. Transmission fitness of drug-resistant human immunodeficiency virus and the prevalence of resistance in the antiretroviral-treated population. J. Infect. Dis. 187 (2003) 683-686
100. Lennerstrand J., Stammers D.K., and Larder B.A. Biochemical mechanism of human immunodeficiency virus type 1 reverse transcriptase resistance to stavudine. Antimicrob. Agents Chemother. 45 (2001) 2144-2146
101. Liegler T.J., Hayden M.S., Lee K.H., Hoh R., Deeks S.G., and Grant R.M. Protease inhibitor-resistant HIV-1 from patients with preserved CD4 cell counts is cytopathic in activated CD4 T lymphocytes. AIDS 15 (2001) 179-184
102. Little S.J., Holte S., Routy J.P., Daar E.S., Markowitz M., Collier A.C., Koup R.A., Mellors J.W., Connick E., Conway B., Kilby M., Wang L., Whitcomb J.M., Hellmann N.S., and Richman D.D. Antiretroviral-drug resistance among patients recently infected with HIV. N. Engl. J. Med. 347 (2002) 385-394
103. Little S.J., Dawson K., Hellmann N.S., Richman D.D., and Frost S.D.W. Persistence of transmitted drug-resistant virus among subjects with primary HIV infection deferring antiretroviral therapy. Antivir. Ther. 7 (2003) S129
104. Little, S., Frost, S., Smith, D., May, S., Parkin, N., Richman, D., 2007. Transmission of HIV drug resistance and treatment response (Abstract 60). In: Proceedings of the 14th Conference on Retroviruses and Opportunistic Infections, February 25-28, 2007. Los Angeles, CA, USA, http://www.retroconference.org/2007/Abstracts/30598.htm.
105. Lockman S., Shapiro R.L., Smeaton L.M., Wester C., Thior I., Stevens L., Chand F., Makhema J., Moffat C., Asmelash A., Ndase P., Arimi P., van Widenfelt E., Mazhani L., Novitsky V., Lagakos S., and Essex M. Response to antiretroviral therapy after a single, peripartum dose of nevirapine. N. Engl. J. Med. 356 (2007) 135-147
106. Lu J., and Kuritzkes D.R. A novel recombinant marker virus assay for comparing the relative fitness of HIV-1 reverse transcriptase variants. J. Acquir. Immune Defic. Syndr. 27 (2001) 7-13
107. Lu J., Whitcomb J., and Kuritzkes D.R. Effect of the Q207D mutation in HIV type 1 reverse transcriptase on zidovudine susceptibility and replicative fitness. J. Acquir. Immune Defic. Syndr. 40 (2005) 20-23
108. Lukashov V.V., Huismans R., Jebbink M.F., Danner S.A., de Boer R.J., and Goudsmit J. Selection by AZT and rapid replacement in the absence of drugs of HIV type 1 resistant to multiple nucleoside analogs. AIDS Res. Hum. Retroviruses 17 (2001) 807-818
109. Maeda Y., Venzon D.J., and Mitsuya H. Altered drug sensitivity, fitness, and evolution of human immunodeficiency virus type 1 with pol gene mutations conferring multi-dideoxynucleoside resistance. J. Infect. Dis. 177 (1998) 1207-1213
110. Mammano F., Trouplin V., Zennou V., and Clavel F. Retracing the evolutionary pathways of human immunodeficiency virus type 1 resistance to protease inhibitors: virus fitness in the absence and in the presence of drug. J. Virol. 74 (2000) 8524-8531
111. Maree A.F., Keulen W., Boucher C.A., and De Boer R.J. Estimating relative fitness in viral competition experiments. J. Virol. 74 (2000) 11067-11072
112. Margot N.A., Waters J.M., and Miller M.D. In vitro human immunodeficiency virus type 1 resistance selections with combinations of tenofovir and emtricitabine or abacavir and lamivudine. Antimicrob. Agents Chemother. 50 (2006) 4087-4095
113. Marozsan A.J., Moore D.M., Lobritz M.A., Fraundorf E., Abraha A., Reeves J.D., and Arts E.J. Differences in the fitness of two diverse wild-type human immunodeficiency virus type 1 isolates are related to the efficiency of cell binding and entry. J. Virol. 79 (2005) 7121-7134
114. Martinez-Picado J., and Tam L.W.Y. Risk of selecting resistance mutations during treatment interruption. Curr. Opin. HIV AIDS 2 (2007) 6-13
115. Martinez-Picado J., Sutton L., De Pasquale M.P., Savara A.V., and D'Aquila R.T. Human immunodeficiency virus type 1 cloning vectors for antiretroviral resistance testing. J. Clin. Microbiol. 37 (1999) 2943-2951
116. Martinez-Picado J., Morales-Lopetegi K., Wrin T., Prado J.G., Frost S.D., Petropoulos C.J., Clotet B., and Ruiz L. Selection of drug-resistant HIV-1 mutants in response to repeated structured treatment interruptions. AIDS 16 (2002) 895-899
117. Mas A., Parera M., Briones C., Soriano V., Martínez M.A., Domingo E., and Menéndez-Arias L. Role of a dipeptide insertion between codons 69 and 70 of HIV-1 reverse transcriptase in the mechanism of AZT resistance. EMBO J. 19 (2000) 5752-5761
118. Masquelier B., Race E., Tamalet C., Descamps D., Izopet J., Buffet-Janvresse C., Ruffault A., Mohammed A.S., Cottalorda J., Schmuck A., Calvez V., Dam E., Fleury H., and Brun-Vézinet F. 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 (2001) 1836-1842
119. Masquelier B., Bhaskaran K., Pillay D., Gifford R., Balestre E., Jorgensen L.B., Pedersen C., van der Hoek L., Prins M., Balotta C., Longo B., Kucherer C., Poggensee G., Ortiz M., de Mendoza C., Gill J., Fleury H., and Porter K. Prevalence of transmitted HIV-1 drug resistance and the role of resistance algorithms: data from seroconverters in the CASCADE collaboration from 1987 to 2003. J. Acquir. Immune Defic. Syndr. 40 (2005) 505-511
120. Matsumi S., Kosalaraksa P., Tsang H., Kavlick M.F., Harada S., and Mitsuya H. Pathways for the emergence of multi-dideoxynucleoside-resistant HIV-1 variants. AIDS 17 (2003) 1127-1137
121. Menéndez-Arias L. Targeting HIV: antiretroviral therapy and development of drug resistance. Trends Pharmacol. Sci. 23 (2002) 381-388
122. Menéndez-Arias L. Mechanisms of resistance to nucleoside analogue inhibitors of HIV-1 reverse transcriptase. Virus Res 134 (2008) 124-146
123. Menéndez-Arias L., Matamoros T., and Cases-Gonzalez C.E. Insertions and deletions in HIV-1 reverse transcriptase: consequences for drug resistance and viral fitness. Curr. Pharm. Des. 12 (2006) 1811-1825
124. Miller V. HIV-1 reverse transcriptase (RT) genotype and susceptibility to RT inhibitor during abacavir monotherapy and combination therapy. AIDS 14 (2000) 163-171
125. Miller M.D., Lamy P.D., Fuller M.D., Mulato A.S., Margot N.A., Cihlar T., and Cherrington J.M. Human immunodeficiency virus type 1 reverse transcriptase expressing the K70E mutation exhibits a decrease in specific activity and processivity. Mol. Pharmacol. 54 (1998) 291-297
126. Miller M.D., Anton K.E., Mulato A.S., Lamy P.D., and Cherrington J.M. 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 (1999) 92-100
127. Moore C.B., John M., James I.R., Christiansen F.T., Witt C.S., and Mallal S.A. Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level. Science 296 (2002) 1439-1443
128. Nagylaki T. Introduction to Theoretical Population Genetics (1992), Springer-Verlag KG, Berlin, Germany
129. Nicastri E., Sarmati L., d'Ettorre G., Palmisano L., Parisi S.G., Uccella I., Rianda A., Concia E., Vullo V., Vella S., and Andreoni M. Replication capacity, biological phenotype, and drug resistance of HIV strains isolated from patients failing antiretroviral therapy. J. Med. Virol. 69 (2003) 1-6
130. Nikolenko G.N., Delviks-Frankenberry K.A., Palmer S., Maldarelli F., Fivash Jr. M.J., Coffin J.M., and Pathak V.K. Mutations in the connection domain of HIV-1 reverse transcriptase increase 3′-azido-3′-deoxythymidine resistance. Proc. Natl. Acad. Sci. U.S.A. 104 (2007) 317-322
131. Nora T., Charpentier C., Tenaillon O., Hoede C., Clavel F., and Hance A.J. Contribution of recombination to the evolution of human immunodeficiency viruses expressing resistance to antiretroviral treatment. J. Virol. 81 (2007) 7620-7628
132. Olivares I., Gutiérrez-Rivas M., López-Galíndez C., and Menéndez-Arias L. Tryptophan scanning mutagenesis of aromatic residues within the polymerase domain of HIV-1 reverse transcriptase: critical role of Phe-130 for p51 function and second-site revertant restoring viral replication capacity. Virology 324 (2004) 400-411
133. Olivares I., Mulky A., Boross P.I., Tozser J., Kappes J.C., López-Galíndez C., and Menéndez-Arias L. HIV-1 protease dimer interface mutations that compensate for viral reverse transcriptase instability in infectious virions. J. Mol. Biol. 372 (2007) 369-381
134. Olmsted R.A., Slade D.E., Kopta L.A., Poppe S.M., Poel T.J., Newport S.W., Rank K.B., Biles C., Morge R.A., Dueweke T.J., Yagi Y., Romero D.L., Thomas R.C., Sharma S.K., and Tarpley W.G. (Alkylamino) piperidine bis(heteroaryl)piperizine analogs are potent, broad-spectrum nonnucleoside reverse transcriptase inhibitors of drug-resistant isolates of human immunodeficiency virus type 1 (HIV-1) and select for drug-resistant variants of HIV-1IIIB with reduced replication phenotypes. J. Virol. 70 (1996) 3698-3705
135. Paintsil E., Margolis A., Collins J.A., and Alexander L. The contribution of HIV fitness to the evolution pattern of reverse transcriptase inhibitor resistance. J. Med. Virol. 78 (2006) 425-430
136. Parera M., Fernández G., Clotet B., and Martínez M.A. HIV-1 protease catalytic efficiency effects caused by random single amino acid substitutions. Mol. Biol. Evol. 24 (2007) 382-387
137. Penn M.L., Myers M., Eckstein D.A., Liegler T.J., Hayden M., Mammano F., Clavel F., Deeks S.G., Grant R.M., and Goldsmith M.A. Primary and recombinant hiv type 1 strains resistant to protease inhibitors are pathogenic in mature human lymphoid tissues. AIDS Res. Hum. Retroviruses 17 (2001) 517-523
138. Perelson A.S., Neumann A.U., Markowitz M., Leonard J.M., and Ho D.D. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science 271 (1996) 1582-1586
139. Peters S., Munoz M., Yerly S., Sánchez-Merino V., López-Galíndez C., Perrin L., Larder B., Cmarko D., Fakan S., Meylan P., and Telenti A. Resistance to nucleoside analog reverse transcriptase inhibitors mediated by human immunodeficiency virus type 1 p6 protein. J. Virol. 75 (2001) 9644-9653
140. Petrella M., Oliveira M., Moisi D., Detorio M., Brenner B.G., and Wainberg M.A. Differential maintenance of the M184V substitution in the reverse transcriptase of human immunodeficiency virus type 1 by various nucleoside antiretroviral agents in tissue culture. Antimicrob. Agents Chemother. 48 (2004) 4189-4194
141. Petropoulos C.J., Parkin N.T., Limoli K.L., Lie Y.S., Wrin T., Huang W., Tian H., Smith D., Winslow G.A., Capon D.J., and Whitcomb J.M. A novel phenotypic drug susceptibility assay for human immunodeficiency virus type 1. Antimicrob. Agents Chemother. 44 (2000) 920-928
142. Prado J.G., Franco S., Matamoros T., Ruiz L., Clotet B., Menéndez-Arias L., Martínez M.A., and Martinez-Picado J. Relative replication fitness of multi-nucleoside analogue-resistant HIV-1 strains bearing a dipeptide insertion in the fingers subdomain of the reverse transcriptase and mutations at codons 67 and 215. Virology 326 (2004) 103-112
143. Prado J.G., Parkin N.T., Clotet B., Ruiz L., and Martinez-Picado J. HIV type 1 fitness evolution in antiretroviral-experienced patients with sustained CD4+ T cell counts but persistent virologic failure. Clin. Infect. Dis. 41 (2005) 729-737
144. Quiñones-Mateu M.E., and Arts E.J. Fitness of drug resistant HIV-1: methodology and clinical implications. Drug Resist. Updat. 5 (2002) 224-233
145. Quiñones-Mateu M.E., Ball S.C., Marozsan A.J., Torre V.S., Albright J.L., Vanham G., van Der Groen G., Colebunders R.L., and Arts E.J. A dual infection/competition assay shows a correlation between ex vivo human immunodeficiency virus type 1 fitness and disease progression. J. Virol. 74 (2000) 9222-9233
146. Quiñones-Mateu M.E., Tadele M., Parera M., Mas A., Weber J., Rangel H.R., Chakraborty B., Clotet B., Domingo E., Menéndez-Arias L., and Martínez M.A. Insertions in the reverse transcriptase increase both drug resistance and viral fitness in a human immunodeficiency virus type 1 isolate harboring the multi-nucleoside reverse transcriptase inhibitor resistance 69 insertion complex mutation. J. Virol. 76 (2002) 10546-10552
147. Rangel H.R., Weber J., Chakraborty B., Gutiérrez A., Marotta M.L., Mirza M., Kiser P., Martínez M.A., Esté J.A., and Quiñones-Mateu M.E. Role of the human immunodeficiency virus type 1 envelope gene in viral fitness. J. Virol. 77 (2003) 9069-9073
148. Rayner M.M., Cordova B., and Jackson D.A. Population dynamics studies of wild-type and drug-resistant mutant HIV in mixed infections. Virology 236 (1997) 85-94
149. Richman D.D., Wrin T., Little S.J., and Petropoulos C.J. Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proc. Natl. Acad. Sci. U.S.A. 100 (2003) 4144-4149
150. Roger M. Influence of host genes on HIV-1 disease progression. FASEB J. 12 (1998) 625-632
151. Ross L., Johnson M., Graham N., Shaefer M., and St. Clair M. The reverse transcriptase codon 69 insertion is observed in nucleoside reverse transcriptase inhibitor-experienced HIV-1-infected individuals, including those without prior or concurrent zidovudine therapy. J. Hum. Virol. 2 (1999) 290-295
152. Schuurman R., Nijhuis M., van Leeuwen R., Schipper P., de Jong D., Collis P., Danner S.A., Mulder J., Loveday C., Christopherson C., Kwok S., Sninsky J., and Boucher C.A.B. 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 (1995) 1411-1419
153. Selmi B., Deval J., Boretto J., and Canard B. Nucleotide analogue binding, catalysis and primer unblocking in the mechanisms of HIV-1 reverse transcriptase-mediated resistance to nucleoside analogues. Antivir. Ther. 8 (2003) 143-154
154. Shafer R.W., Winters M.A., Iversen A.K., and Merigan T.C. 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 (1996) 2887-2890
155. Sharma P.L., and Crumpacker C.S. Attenuated replication of human immunodeficiency virus type 1 with a didanosine-selected reverse transcriptase mutation. J. Virol. 71 (1997) 8846-8851
156. Sharma P.L., and Crumpacker C.S. 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 (1999) 8448-8456
157. Shirasaka T., Kavlick M.F., Ueno T., Gao W.Y., Kojima E., Alcaide M.L., Chokekijchai S., Roy B.M., Arnold E., Yarchoan R., and Mitsuya H. Emergence of human immunodeficiency virus type 1 variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides. Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 2398-2402
158. Simon V., Padte N., Murray D., Vanderhoeven J., Wrin T., Parkin N., Di Mascio M., and Markowitz M. Infectivity and replication capacity of drug-resistant human immunodeficiency virus type 1 variants isolated during primary infection. J. Virol. 77 (2003) 7736-7745
159. St. Clair M.H., Martin J.L., Tudor-Williams G., Bach M.C., Vavro C.L., King D.M., Kellam P., Kemp S.D., and Larder B.A. Resistance to ddI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase. Science 253 (1991) 1557-1559
160. Stoddart C.A., Liegler T.J., Mammano F., Linquist-Stepps V.D., Hayden M.S., Deeks S.G., Grant R.M., Clavel F., and McCune J.M. Impaired replication of protease inhibitor-resistant HIV-1 in human thymus. Nat. Med. 7 (2001) 712-718
161. Sugiura W., Matsuda M., Matsuda Z., Abumi H., Okano A., Oishi T., Moriya K., Yamamoto Y., Fukutake K., Mimaya J., Ajisawa A., Taki M., Yamada K., and Nagai Y. Identification of insertion mutations in HIV-1 reverse transcriptase causing multiple drug resistance to nucleoside analogue reverse transcriptase inhibitors. J. Hum. Virol. 2 (1999) 146-153
162. Suzuki K., Kaufmann G.R., Mukaide M., Cunningham P., Harris C., Leas L., Kondo M., Imai M., Pett S.L., Finlayson R., Zaunders J., Kelleher A., and Cooper D.A. Novel deletion of HIV type 1 reverse transcriptase residue 69 conferring selective high-level resistance to nevirapine. AIDS Res. Hum. Retroviruses 17 (2001) 1293-1296
163. Svarovskaia E.S., Cheslock S.R., Zhang W.H., Hu W.-S., and Pathak V.K. Retroviral mutation rates and reverse transcriptase fidelity. Front. Biosci. 8 (2003) D117-D134
164. Svarovskaia, E., Feng, J., Margot, N., Myrick, F., Goodman, D., Ly, J., White, K., Borroto-Esoda, K., Miller, M., 2007. The A62V and S68G mutations in HIV-1 reverse transcriptase partially restore the replication defect associated with the K65R mutation (Abstract 591). In: Proceedings of the 14th Conference on Retroviruses and Opportunistic Infections, February 25-28, 2007. Los Angeles, CA, USA, http://www.retroconference.org/2007/Abstracts/30039.htm.
165. Svedhem V., Lindkvist A., Lidman K., and Sonnerborg A. Persistence of earlier HIV-1 drug resistance mutations at new treatment failure. J. Med. Virol. 68 (2002) 473-478
166. Svicher V., Sing T., Santoro M.M., Forbici F., Rodriguez-Barrios F., Bertoli A., Beerenwinkel N., Bellocchi M.C., Gago F., d'Arminio Monforte A., Antinori A., Lengauer T., Ceccherini-Silberstein F., and Perno C.F. Involvement of novel human immunodeficiency virus type 1 reverse transcriptase mutations in the regulation of resistance to nucleoside inhibitors. J. Virol. 80 (2006) 7186-7198
167. Tamalet C., Izopet J., Koch N., Fantini J., and Yahi N. Stable rearrangements of the β3-β4 hairpin loop of HIV-1 reverse transcriptase in plasma viruses from patients receiving combination therapy. AIDS 12 (1998) F161-F166
168. Tisdale M., Alnadaf T., and Cousens D. Combination of mutations in human immunodeficiency virus type 1 reverse transcriptase required for resistance to the carbocyclic nucleoside 1592U89. Antimicrob. Agents Chemother. 41 (1997) 1094-1098
169. Troyer R.M., Collins K.R., Abraha A., Fraundorf E., Moore D.M., Krizan R.W., Toossi Z., Colebunders R.L., Jensen M.A., Mullins J.I., Vanham G., and Arts E.J. Changes in human immunodeficiency virus type 1 fitness and genetic diversity during disease progression. J. Virol. 79 (2005) 9006-9018
170. Turner D., and Wainberg M.A. HIV transmission and primary drug resistance. AIDS Rev. 8 (2006) 17-23
171. Turner D., Brenner B.G., Routy J.-P., Moisi D., and Wainber M.A. Decreased rates of transmission of drug-resistant HIV-1 strains containing the M184V mutation in reverse transcriptase. Antivir. Ther. 7 (2003) S143
172. van der Hoek L., Back N., Jebbink M.F., de Ronde A., Bakker M., Jurriaans S., Reiss P., Parkin N., and Berkhout B. 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 (2005) 3536-3543
173. van Maarseveen N.M., Huigen M.C., de Jong D., Smits A.M., Boucher C.A., and Nijhuis M. A novel real-time PCR assay to determine relative replication capacity for HIV-1 protease variants and/or reverse transcriptase variants. J. Virol. Methods 133 (2006) 185-194
174. Van Vaerenbergh K., Van Laethem K., Albert J., Boucher C.A., Clotet B., Floridia M., Gerstoft J., Hejdeman B., Nielsen C., Pannecouque C., Perrin L., Pirillo M.F., Ruiz L., Schmit J.C., Schneider F., Schoolmeester A., Schuurman R., Stellbrink H.J., Stuyver L., Van Lunzen J., Van Remoortel B., Van Wijngaerden E., Vella S., Witvrouw M., Yerly S., De Clercq E., Destmyer J., and Vandamme A.M. Prevalence and characteristics of multinucleoside-resistant human immunodeficiency virus type 1 among European patients receiving combinations of nucleoside analogues. Antimicrob. Agents Chemother. 44 (2000) 2109-2117
175. Villena C., Prado J.G., Puertas M.C., Martínez M.A., Clotet B., Ruiz L., Parkin N.T., Menéndez-Arias L., and Martinez-Picado J. Relative fitness and replication capacity of a multinucleoside analogue-resistant clinical human immunodeficiency virus type 1 isolate with a deletion of codon 69 in the reverse transcriptase coding region. J. Virol. 81 (2007) 4713-4721
176. Wang J., Dykes C., Domaoal R.A., Koval C.E., Bambara R.A., and Demeter L.M. The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNA(Lys, 3) that correlate with reductions in replication efficiency. Virology 348 (2006) 462-474
177. Weber J., Rangel H.R., Chakraborty B., Tadele M., Martínez M.A., Martinez-Picado J., Marotta M.L., Mirza M., Ruiz L., Clotet B., Wrin T., Petropoulos C.J., and Quiñones-Mateu M.E. A novel TaqMan real-time PCR assay to estimate ex vivo human immunodeficiency virus type 1 fitness in the era of multi-target (pol and env) antiretroviral therapy. J. Gen. Virol. 84 (2003) 2217-2228
178. Weber J., Chakraborty B., Weberova J., Miller M.D., and Quiñones-Mateu M.E. Diminished replicative fitness of primary human immunodeficiency virus type 1 isolates harboring the K65R mutation. J. Clin. Microbiol. 43 (2005) 1395-1400
179. Weber J., Weberova J., Carobene M., Mirza M., Martinez-Picado J., Kazanjian P., and Quiñones-Mateu M.E. Use of a novel assay based on intact recombinant viruses expressing green (EGFP) or red (DsRed2) fluorescent proteins to examine the contribution of pol and env genes to overall HIV-1 replicative fitness. J. Virol. Methods 136 (2006) 102-117
180. Wei X., Liang C., Götte M., and Wainberg M.A. The M184V mutation in HIV-1 reverse transcriptase reduces the restoration of wild-type replication by attenuated viruses. AIDS 16 (2002) 2391-2398
181. Wei X., Decker J.M., Wang S., Hui H., Kappes J.C., Wu X., Salazar-Gonzalez J.F., Salazar M.G., Kilby J.M., Saag M.S., Komarova N.L., Nowak M.A., Hahn B.H., Kwong P.D., and Shaw G.M. Antibody neutralization and escape by HIV-1. Nature 422 (2003) 307-312
182. Wei X., Liang C., Götte M., and Wainberg M.A. Negative effect of the M184V mutation in HIV-1 reverse transcriptase on initiation of viral DNA synthesis. Virology 311 (2003) 202-212
183. White K.L., Margot N.A., Wrin T., Petropoulos C.J., Miller M.D., and Naeger L.K. 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 (2002) 3437-3446
184. Whitney J.B., Oliveira M., Detorio M., Guan Y., and Wainberg M.A. The M184V mutation in reverse transcriptase can delay reversion of attenuated variants of simian immunodeficiency virus. J. Virol. 76 (2002) 8958-8962
185. Winters M.A., Coolley K.L., Girard Y.A., Levee D.J., Hamdan H., Shafer R.W., Katzenstein D.A., and Merigan T.C. 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 (1998) 1769-1775
186. Winters M.A., Coolley K.L., Cheng P., Girard Y.A., Hamdan H., Kovari L.C., and Merigan T.C. Genotypic, phenotypic, and modeling studies of a deletion in the β3-β4 region of the human immunodeficiency virus type 1 reverse transcriptase gene that is associated with resistance to nucleoside reverse transcriptase inhibitors. J. Virol. 74 (2000) 10707-10713
187. Wu H., Huang Y., Dykes C., Liu D., Ma J., Perelson A.S., and Demeter L.M. Modeling and estimation of replication fitness of human immunodeficiency virus type 1 in vitro experiments by using a growth competition assay. J. Virol. 80 (2006) 2380-2389
188. Yerly S., Rakik A., De Loes S.K., Hirschel B., Descamps D., Brun-Vézinet F., and Perrin L. Switch to unusual amino acids at codon 215 of the human immunodeficiency virus type 1 reverse transcriptase gene in seroconvertors infected with zidovudine-resistant variants. J. Virol. 72 (1998) 3520-3523
189. Yerly S., Jost S., Telenti A., Flepp M., Kaiser L., Chave J.P., Vernazza P., Battegay M., Furrer H., Chanzy B., Burgisser P., Rickenbach M., Gebhardt M., Bernard M.C., Perneger T., Hirschel B., and Perrin L. Infrequent transmission of HIV-1 drug-resistant variants. Antivir. Ther. 9 (2004) 375-384
190. Yoshimura K., Feldman R., Kodama E., Kavlick M.F., Qiu Y.L., Zemlicka J., and Mitsuya H. In vitro induction of human immunodeficiency virus type 1 variants resistant to phosphoralaninate prodrugs of Z-methylenecyclopropane nucleoside analogues. Antimicrob. Agents Chemother. 43 (1999) 2479-2483