Specific HIV-1 integrase polymorphisms change their prevalence in untreated versus antiretroviral-treated HIV-1-infected patients, all naive to integrase inhibitors

Journal of Antimicrobial Chemotherapy

Volumn 65, Issue 11, 2010, Pages 2305-2318

  Ceccherini Silberstein, Francesca ^a   Malet, Isabelle ^b   Fabeni, Lavinia ^a,c   Dimonte, Salvatore ^a   Svicher, Valentina ^a   D'Arrigo, Roberta ^c   Artese, Anna ^d   Costa, Giosuè ^d   Bono, Sara ^a   Alcaro, Stefano ^d   d'Arminio Monforte, Antonella ^e   Katlama, Christine ^b   Calvez, Vincent ^b   Antinori, Andrea ^c   Marcelin, Anne Genevieve ^b   Perno, Carlo Federico ^a,c  

^a UNIVERSITY OF ROME TOR VERGATA   (Italy)

^b PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

^c NATIONAL INSTITUTE FOR INFECTIOUS DISEASES L SPALLANZANI   (Italy)

^d UNIVERSITY MAGNA GRAECIA OF CATANZARO   (Italy)

^e UNIVERSITY OF MILAN   (Italy)

Author keywords

Antiretroviral therapy; Co evolution; HIV drug resistance; Integrase; Molecular docking; Polymorphisms; Reverse transcriptase

Indexed keywords

ABACAVIR; AMPRENAVIR; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; ATAZANAVIR; DIDANOSINE; EFAVIRENZ; ELVITEGRAVIR; EMTRICITABINE; INDINAVIR; INTEGRASE; INTEGRASE INHIBITOR; LAMIVUDINE; LOPINAVIR PLUS RITONAVIR; NELFINAVIR; NEVIRAPINE; RALTEGRAVIR; RNA DIRECTED DNA POLYMERASE; SAQUINAVIR; STAVUDINE; TENOFOVIR; TIPRANAVIR; ZALCITABINE; ZIDOVUDINE;

ANTIVIRAL RESISTANCE; ARTICLE; DNA POLYMORPHISM; GENE MUTATION; GENE SEQUENCE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; MAJOR CLINICAL STUDY; PREVALENCE;

AMINO ACID SUBSTITUTION; ANTI-RETROVIRAL AGENTS; HIV INFECTIONS; HIV INTEGRASE; HIV INTEGRASE INHIBITORS; HIV-1; HUMANS; MUTATION, MISSENSE; POLYMORPHISM, GENETIC; PREVALENCE; SEQUENCE ANALYSIS, DNA;

EID: 77957875432     PISSN: 03057453     EISSN: 14602091     Source Type: Journal    
DOI: 10.1093/jac/dkq326     Document Type: Article

References (80)

1. Lataillade M, Kozal MJ. The hunt for HIV-1 integrase inhibitors. AIDS Patient Care STDS 2006; 20: 489-501.
2. Pommier Y, Johnson AA, Marchand C. Integrase inhibitors to treat HIV/AIDS. Nat Rev Drug Discov 2005; 4: 236-48.
3. Semenova EA, Marchand C, Pommier Y. HIV-1 integrase inhibitors: update and perspectives. Adv Pharmacol 2008; 56: 199-228.
4. Grinsztejn B, Nguyen BY, Katlama C et al. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment experienced patients with multidrug resistant virus: a phase II randomised controlled trial. Lancet 2007; 369: 1261-9.
5. Cooper DA, Steigbigel RT, Gatell JM et al. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med 2008; 359: 355-65.
6. McColl DJ, Fransen S, Gupta S et al. Resistance and cross-resistance to first generation integrase inhibitors: insights from a phase 2 study of elvitegravir (GS-9137). In: Abstracts of the Sixteenth International HIV Drug Resistance Workshop, Barbados, West Indies, 2007. Abstract 9. Antivir Ther 2007; 12 Suppl 1: S11.
7. Steigbigel RT, Cooper DA, Kumar PN et al. Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med 2008; 359: 339-54.
8. Coffin JM, Hughes SH, Varmus HE. Retroviruses. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1997.
9. Rice P, Craigie R, Davies DR. Retroviral integrases and their cousins. Curr Opin Struct Biol 1996; 6: 76-83.
10. Engelman A, Mizuuchi K, Craigie R. HIV-1 DNA integration: mechanism of viral DNA cleavage and DNA strand transfer. Cell 1991; 67: 1211-21.
11. Swanstrom R, Wills JW. Synthesis, assembly, and processing of viral proteins. In: Coffin JM, Hughes SH, Varmus HE, eds. Retroviruses. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1997; 263-334.
12. Polard P, Chandler M. Bacterial transposases and retroviral integrases. Mol Microbiol 1995; 15: 13-23.
13. Zheng R, Jenkins TM, Craigie R. Zinc folds the N-terminal domain of HIV-1 integrase, promotes multimerization, and enhances catalytic activity. Proc Natl Acad Sci USA 1996; 93: 13659-64.
14. Engelman A, Cherepanov P. The lentiviral integrase binding protein LEDGF/p75 and HIV-1 replication. PLoS Pathog 2008; 4: e1000046.
15. Lutzke RA, Plasterk RH. Structure-based mutational analysis of the C-terminal DNA-binding domain of human immunodeficiency virus type 1 integrase: critical residues for protein oligomerization and DNA binding. J Virol 1998; 72: 4841-8.
16. Vink C, Oude Groeneger AM, Plasterk RH. Identification of the catalytic and DNA-binding region of the human immunodeficiency virus type I integrase protein. Nucleic Acids Res 1993; 21: 1419-25.
17. Wu X, Liu H, Xiao H et al. Human immunodeficiency virus type 1 integrase protein promotes reverse transcription through specific interactions with the nucleoprotein reverse transcription complex. J Virol 1999; 73: 2126-35.
18. Zhu K, Dobard C, Chow SA. Requirement for integrase during reverse transcription of human immunodeficiency virus type 1 and the effect of cysteine mutations of integrase on its interactions with reverse transcriptase. J Virol 2004; 78: 5045-55.
19. Dobard CW, Briones MS, Chow SA. Molecular mechanisms by which human immunodeficiency virus type 1 integrase stimulates the early steps of reverse transcription. J Virol 2007; 81: 10037-46.
20. Nymark-McMahon MH, Beliakova-Bethell NS, Darlix JL et al. Ty3 integrase is required for initiation of reverse transcription. J Virol 2002; 76: 2804-16.
21. Hehl EA, Joshi P, Kalpana GV et al. Interaction between human immunodeficiency virus type 1 reverse transcriptase and integrase proteins. J Virol 2004; 78: 5056-67.
22. Wilkinson TA, Januszyk K, Phillips ML et al. Identifying and characterizing a functional HIV-1 reverse transcriptase-binding site on integrase. J Biol Chem 2009; 284: 7931-9.
23. Bukrinsky MI, Sharova N, McDonald TL et al. Association of integrase, matrix, and reverse transcriptase antigens of human immunodeficiency virus type 1 with viral nucleic acids following acute infection. Proc Natl Acad Sci USA 1993; 90: 6125-9.
24. Bukovsky A, Göttlinger H. Lack of integrase can markedly affect human immunodeficiency virus type 1 particle production in the presence of an active viral protease. J Virol 1996; 70: 6820-5.
25. Engelman A, Englund G, Orenstein JM et al. Multiple effects of mutations in human immunodeficiency virus type 1 integrase on viral replication. J Virol 1995; 69: 2729-36.
26. Quillent C, Borman AM, Paulous S et al. Extensive regions of pol are required for efficient human immunodeficiency virus polyprotein processing and particle maturation. Virology 1996; 219: 29-36.
27. Mandal D, Feng Z, Stoltzfus CM. Gag-processing defect of human immunodeficiency virus type 1 integrase E246 and G247 mutants is caused by activation of an overlapping 5′ splice site. J Virol 2008; 82: 1600-4.
28. Sander O, Altmann A, Lenguauer T. Computational analysis of covariation and interactions between HIV-1 reverse transcriptase and integrase. In: Abstracts of the Sixth European HIV Drug Resistance Workshop, Budapest, Hungary, 2008. Abstract 108.
29. Van Eygen V, Van Marck H, Smits V et al. Identification of residues in HIV-1 integrase, RNAseH and the RT connection domain associated with the presence of thymidine analogue-associated resistance. In: Abstracts of the Sixth European HIV Drug Resistance Workshop, Budapest, Hungary, 2008. Abstract 53.
30. Low A, Prada N, Topper M et al. Natural polymorphisms of human immunodeficiency virus type 1 integrase and inherent susceptibilities to a panel of integrase inhibitors. Antimicrob Agents Chemother 2009; 53: 4275-82.
31. Buzón MJ, Marfil S, Puertas MC et al. Raltegravir susceptibility and fitness progression of HIV type-1 integrase in patients on long-term antiretroviral therapy. Antivir Ther 2008; 13: 881-93.
32. Johnson VA, Brun-Vézinet F, Clotet B et al.; Update of the drug resistance mutations in HIV-1: December 2009. Top HIV Med 2009; 17: 138-45.
33. Shafer RW, Schapiro JM. HIV-1 drug resistance mutations: an updated framework for the second decade of HAART. AIDS Rev 2008; 10: 67-84.
34. Fikkert V, Hombrouck A, Van Remoortel B et al. Multiple mutations in HIV-1 integrase confer resistance to the clinical trial drug S-1360. AIDS 2004; 18: 2019-28.
35. Hazuda D, Anthony N, Gomez R et al. A naphthyridine carboxamide provides evidence for discordant resistance between mechanistically identical inhibitors of HIV-1 integrase. Proc Natl Acad Sci USA 2004; 101: 11233-8.
36. Ceccherini-Silberstein F, Van Baelen K, Armenia D et al. Novel HIV-1 integrase mutations, found as minority quasispecies in patients naïve to integrase inhibitors, are associated with decreased susceptibility to integrase inhibitors in vitro. In: Abstracts of the Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston, MA, 2008. Poster Abstract 876, p. 394. Foundation for Retrovirology and Human Health, Alexandria, VA, USA. http://www.retroconference.org/2008/Abstracts/32950.htm.
37. Lataillade M, Chiarella J, Kozal MJ. Natural polymorphism of the HIV-1 integrase gene and mutations associated with integrase inhibitor resistance. Antivir Ther 2007; 12: 563-70.
38. Shimura K, Kodama E, Sakagami Y et al. Broad antiretroviral activity and resistance profile of the novel human immunodeficiency virus integrase inhibitor elvitegravir (JTK-303/GS-9137). J Virol 2008; 82: 764-74.
39. Ren C, May S, Miletti T et al. In vitro cross-resistance studies of five different classes of integrase inhibitors in recombinant HIV-1. In: Abstracts of the Sixteenth International HIV Drug Resistance Workshop, Barbados, West Indies, 2007. Abstract 1. Antivir Ther 2007; 12 Suppl 1: S3.
40. Wai J, Fisher T, Embrey M et al. Next generation of inhibitors of HIV-1 integrase strand transfer inhibitor: structural diversity and resistance profiles. In: Abstracts of the Fourteenth Conference on Retroviruses and Opportunistic Infections, Los Angeles, CA, 2007. Oral Abstract 87, p. 96. Foundation for Retrovirology and Human Health, Alexandria, VA, USA. http://www.retroconference.org/2007/Abstracts/29783.htm.
41. Goethals O, Clayton R, Van Ginderen M et al. Resistance mutations in HIV-1 integrase selected with Elvitegravir confer reduced susceptibility to a wide range of integrase inhibitors. J Virol 2008; 82: 10366-74.
42. Fransen S, Gupta S, Danovich R et al. Loss of raltegravir susceptibility in treated patients is conferred by multiple non-overlapping genetic pathways. In: Abstracts of the Seventeenth international HIV Drug Resistance Workshop, Sitges, Spain, 2008. Abstract 7. Antivir Ther 2008; 13 Suppl 3: A9.
43. Malet I, Delelis O, Valantin MA et al. Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro. Antimicrob Agents Chemother 2008; 52: 1351-8.
44. Miller MD, Danovich RM, Ke Y et al. Longitudinal analysis of resistance to the HIV-1 integrase inhibitor raltegravir: results from P005, a Phase 2 study in treatment experienced patients. In: Abstracts of the Seventeenth international HIV Drug Resistance Workshop, Sitges, Spain, 2008. Abstract 6. Antivir Ther 2008; 13 Suppl 3: A8.
45. Goodman D, Hluhanich R, Waters J et al. Integrase inhibitor resistance involves complex interactions among primary and secondary resistance mutations: a novel mutation L68V/I associates with E92Q and increases resistance. In: Abstracts of the Seventeenth international HIV Drug Resistance Workshop, Sitges, Spain, 2008. Abstract 13. Antivir Ther 2008; 13 Suppl 3: A15.
46. da Silva D, Van Wesenbeeck L, Breilh D et al. HIV-1 resistance patterns to integrase inhibitors in antiretroviral-experienced patients with virological failure on raltegravir-containing regimens. J Antimicrob Chemother 2010; 65: 1262-9.
47. Baldanti F, Paolucci S, Gulminetti R et al. Early emergence of raltegravir resistance mutations in patients receiving HAART salvage regimens. J Med Virol 2010; 82: 116-22.
48. Canducci F, Sampaolo M, Marinozzi MC et al. Dynamic patterns of human immunodeficiency virus type 1 integrase gene evolution in patients failing raltegravir-based salvage therapies. AIDS 2009; 23: 455-60.
49. Canducci F, Marinozzi MC, Sampaolo M et al. Genotypic/phenotypic patterns of HIV-1 integrase resistance to raltegravir. J Antimicrob Chemother 2010; 65: 425-33.
50. Van Baelen K, Rondelez E, Van Eygen V et al. A combined genotypic and phenotypic human immunodeficiency virus type 1 recombinant virus assay for the reverse transcriptase and integrase genes. J Virol Methods 2009; 161: 231-9.
51. Seki T, Kobayashi M, Wakasa-Morimoto C et al. S/GSK1349572 is a potent next generation HIV integrase inhibitor and demonstrates a superior resistance profile substantiated with 60 integrase mutant molecular clones. In: Abstracts of the Seventeenth Conference on Retroviruses and Opportunistic Infections, San Francisco, CA, 2010. Poster Abstract 555, p. 265. Foundation for Retrovirology and Human Health, Alexandria, VA, USA. http://www.retroconference.org/2010/PDFs/555.pdf.
52. Van Baelen K, Van Eygen V, Rondelez E et al. Clade-specific HIV-1 integrase polymorphisms do not reduce raltegravir and elvitegravir phenotypic susceptibility. AIDS 2008; 22: 1877-80.
53. Ceccherini-Silberstein F, Malet I, D'Arrigo R et al. Characterization and structural analysis of HIV-1 integrase conservation. AIDS Rev 2009; 1: 17-29.
54. Passaes CB, Guimarães ML, Fernandez SL et al. Lack of primary mutations associated with integrase inhibitors among HIV-1 subtypes B, C, and F circulating in Brazil. J Acquir Immune Defic Syndr 2009; 51: 7-12.
55. Sichtig N, Sierra S, Kaiser R et al. Evolution of raltegravir resistance during therapy. J Antimicrob Chemother 2009; 64: 25-32.
56. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B 1995; 57: 289-300.
57. Svicher V, Sing T, Santoro MM et al. Involvement of novel human immunodeficiency virus type 1 reverse transcriptase mutations in the regulation of resistance to nucleoside inhibitors. J Virol 2006; 80: 7186-98.
58. Ceccherini-Silberstein F, Svicher V, Sing T et al. Characterization and structural analysis of novel mutations in human immunodeficiency virus type 1 reverse transcriptase involved in the regulation of resistance to non-nucleoside inhibitors. J Virol 2007; 81: 11507-19.
59. + cell count, despite virological failure. J Infect Dis 2008; 10: 1408-18.
60. Chen JC, Krucinski J, Miercke LJ et al. Crystal structure of the HIV-1 integrase catalytic core and C-terminal domains: a model for viral DNA binding. Proc Natl Acad Sci USA 2000; 97: 8233-8.
61. Hsiou Y, Ding J, Das K et al. Structure of unliganded HIV-1 reverse transcriptase at 2.7 Å resolution: implications of conformational changes for polymerization and inhibition mechanisms. Structure 1996; 4: 853-60.
62. Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comput Chem 2010; 31: 455-61.
63. McDonald DQ, Still WC. AMBER torsional parameters for the peptide backbone. Tetrahedron Lett 1992; 33: 7743-6.
64. Ceccherini-Silberstein F, Gago F, Santoro M et al. High sequence conservation of human immunodeficiency virus type 1 reverse transcriptase under drug pressure despite the continuous appearance of mutations. J Virol 2005; 79: 10718-29.
65. Ceccherini-Silberstein F, Svicher V, Santoro MM et al. Impact of HIV-1 reverse transcriptase polymorphism R83K on virological response in drug-naïve patients starting thymidine analogue containing HAART. In: Abstracts of the Sixteenth International HIV Drug Resistance Workshop, Barbados, West Indies, 2007. Abstract 68. Antivir Ther 2007; 12 Suppl 1: S77.
66. Tasara T, Maga G, Hottiger MO et al. HIV-1 reverse transcriptase and integrase enzymes physically interact and inhibit each other. FEBS Lett 2001; 507: 39-44.
67. Zawahir Z, Neamati N. Inhibition of HIV-1 integrase activity by synthetic peptides derived from the HIV-1 HXB2 Pol region of the viral genome. Bioorg Med Chem Lett 2006; 16: 5199-202.
68. Oz Gleenberg I, Avidan O, Goldgur Y et al. Peptides derived from the reverse transcriptase of human immunodeficiency virus type 1 as novel inhibitors of the viral integrase. J Biol Chem 2005; 280: 21987-96.
69. Mellors JW, Bazmi HZ, Schinazi RF et al. Novel mutations in reverse transcriptase of human immunodeficiency virus type 1 reduce susceptibility to foscarnet in laboratory and clinical isolates. Antimicrob Agents Chemother 1995; 39: 1087-92.
70. Auwerx J, Van Nieuwenhove J, Rodríguez-Barrios F et al. The N137 and P140 amino acids in the p51 and the P95 amino acids in the p66 subunit of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase are instrumental to maintain catalytic activity and to design new classes of anti-HIV-1 drugs. FEBS Lett 2005; 579: 2294-300.
71. Ortuso F, Langer T, Alcaro S. GBPM: GRID-based pharmacophore model: concept and application studies to protein-protein recognition. Bioinformatics 2006; 22: 1449-55.
72. Alcaro S, Artese A, Ceccherini-Silberstein F et al. Computational analysis of human immunodeficiency virus (HIV) type-1 reverse transcriptase crystallographic models based on significant conserved residues found in highly active antiretroviral therapy (HAART)-treated patients. Curr Med Chem 2010; 17: 290-308.
73. Mulky A, Sarafianos SG, Jia Y et al. Identification of amino acid residues in the human immunodeficiency virus type-1 reverse transcriptase tryptophan-repeat motif that are required for subunit interaction using infectious virions. J Mol Biol 2005; 349: 673-84.
74. Ao Z, Fowke KR, Cohen EA et al. Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Retrovirology 2005; 2: 62.
75. Buzón MJ, Dalmau J, Puertas MC et al. The HIV-1 integrase genotype strongly predicts raltegravir susceptibility but not viral fitness of primary virus isolates. AIDS 2010; 24: 17-25.
76. van Hal SJ, Herring B, Deris Z et al. HIV-1 integrase polymorphisms are associated with prior antiretroviral drug exposure. Retrovirology 2009; 6: 12.
77. Garrido C, Geretti AM, Zahonero N et al. Integrase variability and susceptibility to HIV integrase inhibitors: impact of subtypes, antiretroviral experience and duration of HIV infection. J Antimicrob Chemother 2010; 65: 320-6.
78. Eshleman SH, Hudelson SE, Smith P et al. Analysis of pol integrase sequences in diverse HIV type 1 strains using a prototype genotyping assay. AIDS Res Hum Retroviruses 2009; 25: 343-5.
79. Myers RE, Pillay D. HIV analysis of natural sequence variation and covariation in human immunodeficiency virus type 1 integrase. J Virol 2008; 82: 9228-35.
80. Rhee SY, Liu TF, Kiuchi M et al. Natural variation of HIV-1 group M integrase: implications for a new class of antiretroviral inhibitors. Retrovirology 2008; 5: 74.