Primary mutations selected in vitro with raltegravir confer large fold changes in susceptibility to first-generation integrase inhibitors, but minor fold changes to inhibitors with second-generation resistance profiles

Virology

Volumn 402, Issue 2, 2010, Pages 338-346

  Goethals, Olivia ^a   Vos, Ann ^a   Van Ginderen, Marcia ^a   Geluykens, Peggy ^a   Smits, Veerle ^a   Schols, Dominique ^b   Hertogs, Kurt ^a   Clayton, Reginald ^a  

^a Virco BVBA   (Belgium)

^b REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

HIV; Integrase; MK 2048; Raltegravir; Resistance

Indexed keywords

INTEGRASE INHIBITOR; MK 2048; RALTEGRAVIR; UNCLASSIFIED DRUG;

ANTIVIRAL RESISTANCE; ANTIVIRAL SUSCEPTIBILITY; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; CROSS RESISTANCE; GENOTYPE; HUMAN IMMUNODEFICIENCY VIRUS 1; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; SITE DIRECTED MUTAGENESIS; VIRUS MUTATION; VIRUS REPLICATION; VIRUS STRAIN;

AMINO ACID SUBSTITUTION; ANTI-HIV AGENTS; DNA MUTATIONAL ANALYSIS; DRUG RESISTANCE, VIRAL; HIV INTEGRASE; HIV INTEGRASE INHIBITORS; HIV-1; HUMANS; MODELS, MOLECULAR; MUTATION, MISSENSE; PROTEIN STRUCTURE, TERTIARY; PYRROLIDINONES;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 77953022020     PISSN: 00426822     EISSN: 10960341     Source Type: Journal    
DOI: 10.1016/j.virol.2010.03.034     Document Type: Article

References (51)

1. Anker M., Corales R.B. Raltegravir (MK-0518): a novel integrase inhibitor for the treatment of HIV infection. Expert. Opin. Investig. Drugs 2008, 17(1):97-103.
2. Asante-Appiah E., Skalka A.M. Molecular mechanisms in retrovirus DNA integration. Antiviral Res. 1997, 36(3):139-156.
3. Belyk, K.M., Morisson, H.G., Jones, P., and Summa, V., 2006. Potassium salt of an HIV integrase inhibitor (Merck, and I. d. r. d. b. m. P. A. S. P. A., Eds.).
4. Cahn P., Sued O. Raltegravir: a new antiretroviral class for salvage therapy. Lancet 2007, 369(9569):1235-1236.
5. Cannon P.M., Wilson W., Byles E., Kingsman S.M., Kingsman A.J. Human immunodeficiency virus type 1 integrase: effect on viral replication of mutations at highly conserved residues. J. Virol. 1994, 68(8):4768-4775.
6. Ceccherini-Silberstein F., Malet I., D'Arrigo R., Antinori A., Marcelin A.G., Perno C.F. Characterization and structural analysis of HIV-1 integrase conservation. AIDS Rev. 2009, 11(1):17-29.
7. Charpentier C., Karmochkine M., Laureillard D., Tisserand P., Belec L., Weiss L., Si-Mohamed A., Piketty C. Drug resistance profiles for the HIV integrase gene in patients failing raltegravir salvage therapy. HIV Med. 2008, 9(9):765-770.
8. Chen X., Tsiang M., Yu F., Hung M., Jones G.S., Zeynalzadegan A., Qi X., Jin H., Kim C.U., Swaminathan S., Chen J.M. Modeling, analysis, and validation of a novel HIV integrase structure provide insights into the binding modes of potent integrase inhibitors. J. Mol. Biol. 2008, 380(3):504-519.
9. Clavel F., Hance A.J. HIV drug resistance. N. Engl. J. Med. 2004, 350(10):1023-1035.
10. Cooper D.A., Steigbigel R.T., Gatell J.M., Rockstroh J.K., Katlama C., Yeni P., Lazzarin A., Clotet B., Kumar P.N., Eron J.E., Schechter M., Markowitz M., Loutfy M.R., Lennox J.L., Zhao J., Chen J., Ryan D.M., Rhodes R.R., Killar J.A., Gilde L.R., Strohmaier K.M., Meibohm A.R., Miller M.D., Hazuda D.J., Nessly M.L., DiNubile M.J., Isaacs R.D., Teppler H., Nguyen B.Y. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N. Engl. J. Med. 2008, 359(4):355-365.
11. DeGruttola V., Dix L., D'Aquila R., Holder D., Phillips A., Ait-Khaled M., Baxter J., Clevenbergh P., Hammer S., Harrigan R., Katzenstein D., Lanier R., Miller M., Para M., Yerly S., Zolopa A., Murray J., Patick A., Miller V., Castillo S., Pedneault L., Mellors J. The relation between baseline HIV drug resistance and response to antiretroviral therapy: re-analysis of retrospective and prospective studies using a standardized data analysis plan. Antivir. Ther. 2000, 5(1):41-48.
12. DeJesus E., Berger D., Markowitz M., Cohen C., Hawkins T., Ruane P., Elion R., Farthing C., Zhong L., Cheng A.K., McColl D., Kearney B.P. Antiviral activity, pharmacokinetics, and dose response of the HIV-1 integrase inhibitor GS-9137 (JTK-303) in treatment-naive and treatment-experienced patients. J. Acquir. Immune Defic. Syndr. 2006, 43(1):1-5.
13. Delelis O., Malet I., Na L., Tchertanov L., Calvez V., Marcelin A.G., Subra F., Deprez E., Mouscadet J.F. The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. Nucleic Acids Res. 2009, 37(4):1193-1201.
14. Engelman A., Mizuuchi K., Craigie R. HIV-1 DNA integration: mechanism of viral DNA cleavage and DNA strand transfer. Cell 1991, 67(6):1211-1221.
15. Esposito D., Craigie R. HIV integrase structure and function. Adv. Virus Res. 1999, 52:319-333.
16. Fikkert V., Hombrouck A., Van Remoortel B., De Maeyer M., Pannecouque C., De Clercq E., Debyser Z., Witvrouw M. Multiple mutations in human immunodeficiency virus-1 integrase confer resistance to the clinical trial drug S-1360. Aids 2004, 18:2019-2028.
17. Fikkert V., Van Maele B., Vercammen J., Hantson A., Van Remoortel B., Michiels M., Gurnari C., Pannecouque C., De Maeyer M., Engelborghs Y., De Clercq E., Debyser Z., Witvrouw M. Development of resistance against diketo derivatives of human immunodeficiency virus type 1 by progressive accumulation of integrase mutations. J. Virol. 2003, 77:11459-11470.
18. Fransen S., Gupta S., Danovich R., D.F., H., Miller M.D., Witmer M.V., Petropoulos C.J., Parkin N.T., Huang W. 17th International HIV Drug Resistance Workshop, Sitges, Spain 2008.
19. Goethals O., Clayton R., Van Ginderen M., Vereycken I., Wagemans E., Geluykens P., Dockx K., Strijbos R., Smits V., Vos A., Meersseman G., Jochmans D., Vermeire K., Schols D., Hallenberger S., Hertogs K. Resistance mutations in human immunodeficiency virus type 1 integrase selected with elvitegravir confer reduced susceptibility to a wide range of integrase inhibitors. J. Virol. 2008, 82(21):10366-10374.
20. Grinsztejn B., Nguyen B.Y., Katlama C., Gatell J.M., Lazzarin A., Vittecoq D., Gonzalez C.J., Chen J., Harvey C.M., Isaacs R.D. 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, 369:1261-1269.
21. Hazuda D.J., Anthony N.J., Gomez R.P., Jolly S.M., Wai J.S., Zhuang L., Fisher T.E., Embrey M., Guare J.P., Egbertson M.S., Vacca J.P., Huff J.R., Felock P.J., Witmer M.V., Stillmock K.A., Danovich R., Grobler J., Miller M.D., Espeseth A.S., Jin L., Chen I.W., Lin J.H., Kassahun K., Ellis J.D., Wong B.K., Xu W., Pearson P.G., Schleif W.A., Cortese R., Emini E., Summa V., Holloway M.K., Young S.D. A naphthyridine carboxamide provides evidence for discordant resistance between mechanistically identical inhibitors of HIV-1 integrase. Proc. Natl. Acad. Sci. U. S. A. 2004, 101:11233-11238.
22. Hazuda D.J., Felock P., Witmer M., Wolfe A., Stillmock K., Grobler J.A., Espeseth A., Gabryelski L., Schleif W., Blau C., Miller M.D. Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science 2000, 287(5453):646-650.
23. Hombrouck A., Voet A., Van Remoortel B., Desadeleer C., De Maeyer M., Debyser Z., Witvrouw M. Mutations in human immunodeficiency virus type 1 integrase confer resistance to the naphthyridine L-870, 810 and cross-resistance to the clinical trial drug GS-9137. Antimicrob. Agents Chemother. 2008, 52(6):2069-2078.
24. Horwitz J., Chua J., Noel M. Nucleosides: V. The monomesylates of 1-(2'-deoxy-bèta-D-lyxofuranosyl)thymidine. J. Org. Chem. 1964, 29:2076-2078.
25. Johnson V.A., Brun-Vezinet F., Clotet B., Gunthard H.F., Kuritzkes D.R., Pillay D., Schapiro J.M., Richman D.D. Update of the drug resistance mutations in HIV-1. Top HIV Med. 2008, 16(5):138-145.
26. Klein, R., and Struble, K. (2009). Isentress (raltegravir) indication extended for the treatment of HIV-1 infection in treatment-naïve patients. (U. S. F. a. D. Administration, Ed.). HIV AIDS Update.
27. Kobayashi M., Nakahara K., Seki T., Miki S., Kawauchi S., Suyama A., Wakasa-Morimoto C., Kodama M., Endoh T., Oosugi E., Matsushita Y., Murai H., Fujishita T., Yoshinaga T., Garvey E., Foster S., Underwood M., Johns B., Sato A., Fujiwara T. Selection of diverse and clinically relevant integrase inhibitor-resistant human immunodeficiency virus type 1 mutants. Antiviral Res. 2008, 80(2):213-222.
28. Kuki, A., Li, X., Plewe, M. B., Wang, H., and Zhang, J. (2005). HIV-integrase inhibitors, pharmaceutical compositions, and methods for their use (I. Agouron Pharmaceuticals, Ed.) Patent US2005165040.
29. LaFemina R.L., Schneider C.L., Robbins H.L., Callahan P.L., LeGrow K., Roth E., Schleif W.A., Emini E.A. Requirement of active human immunodeficiency virus type 1 integrase enzyme for productive infection of human T-lymphoid cells. J. Virol. 1992, 66(12):7414-7419.
30. Lataillade M., Chiarella J., Kozal M.J. Natural polymorphism of the HIV-1 integrase gene and mutations associated with integrase inhibitor resistance. Antivir Ther 2007, 12:563-570.
31. Ledergerber B., Egger M., Erard V., Weber R., Hirschel B., Furrer H., Battegay M., Vernazza P., Bernasconi E., Opravil M., Kaufmann D., Sudre P., Francioli P., Telenti A. AIDS-related opportunistic illnesses occurring after initiation of potent antiretroviral therapy: the Swiss HIV Cohort Study. Jama 1999, 282(23):2220-2226.
32. Malet I., Delelis O., Valantin M.A., Montes B., Soulie C., Wirden M., Tchertanov L., Peytavin G., Reynes J., Mouscadet J.F., Katlama C., Calvez V., Marcelin A.G. Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro. Antimicrob. Agents Chemother. 2008, 52(4):1351-1358.
33. Markowitz M., Morales-Ramirez J.O., Nguyen B.Y., Kovacs C.M., Steigbigel R.T., Cooper D.A., Liporace R., Schwartz R., Isaacs R., Gilde L.R., Wenning L., Zhao J., Teppler H. Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10days in treatment-naive HIV-1-infected individuals. J. Acquir. Immune Defic. Syndr. 2006, 43:509-515.
34. McColl D., Fransen S., Gupta S., Parkin N., Margot N., Chuck S., Cheng A., Miller M. 11th European Aids Conference 2007, Spain, Madrid.
35. Melek M., Jones J.M., O'Dea M.H., Pais G., Burke T.R., Pommier Y., Neamati N., Gellert M. Effect of HIV integrase inhibitors on the RAG1/2 recombinase. Proc. Natl. Acad. Sci. U. S. A. 2002, 99(1):134-137.
36. Miller M.D., Danovich R., Ke Y., Witmer M.V., Zhao J., Harvey C.M., Nguyen B.Y., DF H. XVVIIth International HIV Drug Resistance Workshop 2008, Sitges, Spain.
37. Nakahara K., Wakasa-Morimoto C., Kobayashi M., Miki S., Noshi T., Seki T., Kanamori-Koyama M., Kawauchi S., Suyama A., Fujishita T., Yoshinaga T., Garvey E.P., Johns B.A., Foster S.A., Underwood M.R., Sato A., Fujiwara T. Secondary mutations in viruses resistant to HIV-1 integrase inhibitors that restore viral infectivity and replication kinetics. Antiviral Res. 2009, 81(2):141-146.
38. Palella F.J., Delaney K.M., Moorman A.C., Loveless M.O., Fuhrer J., Satten G.A., Aschman D.J., Holmberg S.D. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N. Engl. J. Med. 1998, 338(13):853-860. HIV Outpatient Study Investigators.
39. Pommier Y., Johnson A.A., Marchand C. Integrase inhibitors to treat HIV/AIDS. Nat. Rev. Drug Discov. 2005, 4:236-248.
40. Reinke R., Steffen N.R., Robinson W.E. Natural selection results in conservation of HIV-1 integrase activity despite sequence variability. AIDS 2001, 15(7):823-830.
41. Richman D.D. HIV chemotherapy. Nature 2001, 410(6831):995-1001.
42. Richman D.D. Antiviral drug resistance. Antiviral Res. 2006, 71(2-3):117-121.
43. Sakai H., Kawamura M., Sakuragi J., Sakuragi S., Shibata R., Ishimoto A., Ono N., Ueda S., Adachi A. Integration is essential for efficient gene expression of human immunodeficiency virus type 1. J. Virol. 1993, 67(3):1169-1174.
44. Sato M., Motomura T., Aramaki H., Matsuda T., Yamashita M., Ito Y., Kawakami H., Matsuzaki Y., Watanabe W., Yamataka K., Ikeda S., Kodama E., Matsuoka M., Shinkai H. Novel HIV-1 integrase inhibitors derived from quinolone antibiotics. J. Med. Chem. 2006, 49(5):1506-1508.
45. Steigbigel R.T., Cooper D.A., Kumar P.N., Eron J.E., Schechter M., Markowitz M., Loutfy M.R., Lennox J.L., Gatell J.M., Rockstroh J.K., Katlama C., Yeni P., Lazzarin A., Clotet B., Zhao J., Chen J., Ryan D.M., Rhodes R.R., Killar J.A., Gilde L.R., Strohmaier K.M., Meibohm A.R., Miller M.D., Hazuda D.J., Nessly M.L., DiNubile M.J., Isaacs R.D., Nguyen B.Y., Teppler H. Raltegravir with optimized background therapy for resistant HIV-1 infection. N. Engl. J. Med. 2008, 359(4):339-354.
46. Vacca J.P., Wai J.S., Fisher T.E., Embrey M., Hazuda D.J., Miller M.D., Felock P.J., Witmer M.V., Gabryelski L., Lyle T. 4th International AIDS Society (IAS) Conference, Sydney, Australia 2007.
47. Wai J.S., Fisher T.E., Embrey M., Egbertson M.S., Vacca J.P., Hazuda D.J., Miller M.D., Witmer M.V., Gabryelski L., Lyle T. CROI, Los Angeles, California 2007.
48. Winslow D.L., Garber S., Reid C., Scarnati H., Baker D., Rayner M.M., Anton E.D. Selection conditions affect the evolution of specific mutations in the reverse transcriptase gene associated with resistance to DMP 266. AIDS 1996, 10(11):1205-1209.
49. Witvrouw M., Van Maele B., Vercammen J., Hantson A., Engelborghs Y., De Clercq E., Pannecouque C., Debyser Z. Novel inhibitors of HIV-1 integration. Curr. Drug Metab. 2004, 5:291-304.
50. Wu X., Liu H., Xiao H., Conway J.A., Hehl E., Kalpana G.V., Prasad V., Kappes J.C. Human immunodeficiency virus type 1 integrase protein promotes reverse transcription through specific interactions with the nucleoprotein reverse transcription complex. J. Virol. 1999, 73(3):2126-2135.
51. Zhu K., Dobard C., Chow S.A. 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, 78:5045-5055.