HIV-2 integrase polymorphisms and longitudinal genotypic analysis of HIV-2 infected patients failing a raltegravir-containing regimen

PLoS ONE

Volumn 9, Issue 3, 2014, Pages

  Cavaco Silva, Joana ^a   Abecasis, Ana ^a   Miranda, Ana Cláudia ^b   Poças, José ^c   Narciso, Jorge ^d   Águas, Maria João ^e   Maltez, Fernando ^f   Almeida, Isabel ^g   Germano, Isabel ^f   Diniz, António ^h   Gonçalves, Maria De Fátima ^b   Gomes, Perpétua ^a,b,i   Cunha, Celso ^a   Camacho, Ricardo Jorge ^a,j  

^a INSTITUTO DE HIGIENE E MEDICINA TROPICAL   (Portugal)

^b Centro Hospitalar de Lisboa Ocidental   (Portugal)

^c HOSPITAL DE SÃO BERNARDO   (Portugal)

^d Hospital Dos SAMS   (Portugal)

^e HOSPITAL GARCIA DE ORTA   (Portugal)

^f Hospital Garcia de Orta ^*  (Portugal)

^g HOSPITAL DE SANTO ANTÓNIO   (Portugal)

^h HOSPITAL PULIDO VALENTE   (Portugal)

ⁱ INSTITUTO SUPERIOR DE CIÊNCIAS DA SAÚDE EGAS MONIZ   (Portugal)

^j REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

more..

Author keywords

[No Author keywords available]

Indexed keywords

INTEGRASE; RALTEGRAVIR; 2 PYRROLIDONE DERIVATIVE; INTEGRASE INHIBITOR; P31 INTEGRASE PROTEIN, HUMAN IMMUNODEFICIENCY VIRUS 2;

AMINO ACID SUBSTITUTION; ANTIVIRAL RESISTANCE; ARTICLE; CONTROLLED STUDY; DNA POLYMORPHISM; GENE MUTATION; GENE SEQUENCE; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC RESISTANCE; HIV 2 INTEGRASE GENE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 2; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MAJOR CLINICAL STUDY; NUCLEOTIDE SEQUENCE; STRUCTURAL GENE; TREATMENT FAILURE; VIRUS LOAD; DRUG EFFECTS; GENETIC POLYMORPHISM; GENETICS; GENOTYPE; HIV INFECTIONS; HUMAN IMMUNODEFICIENCY VIRUS 1;

DRUG RESISTANCE, VIRAL; GENOTYPE; HIV INFECTIONS; HIV INTEGRASE; HIV INTEGRASE INHIBITORS; HIV-1; HIV-2; HUMANS; POLYMORPHISM, GENETIC; PYRROLIDINONES;

EID: 84899857420     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0092747     Document Type: Article

References (75)

1. UNAIDS (2006) AIDS epidemic update: December 2006. Available: http://data.unaids.org/pub/epireport/2006/2006-epiupdate-en.pdf. Accessed 18 November 2013.
2. Departamento de Doenças Infecciosas do INSA. Unidade de Referência e Vigilância Laboratorial Epidemiológica. Núcleo de Vigilância Laboratorial de Doenças Infecciosas (2013) Infeção VIH/SIDA: a situação em Portugal a 31 de Dezembro de 2012. Documento SIDA 144. Available: http://repositorio.insa.pt/ bitstream/10400.18/1622/3/Relatorio-SIDA-2012-WEB.pdf. Accessed 18 November 2013.
3. Hansmann A, Schim van der Loeff MF, Kaye S, Awasana AA, Sarge-Njie R, et al. (2005) Baseline plasma viral load and CD4 cell percentage predict survival in HIV-1- and HIV-2-infected women in a community-based cohort in The Gambia. J Acquir Immune Defic Syndr 38: 335-341. (Pubitemid 40333501)
4. de Silva TI, Cotten M, Rowland-Jones SL (2008) HIV-2: the forgotten AIDS virus. Trends Microbiol 16: 588-595.
5. Tuaillon E, Gueudin M, Lemee V, Gueit I, Roques P, et al. (2004) Phenotypic susceptibility to nonnucleoside inhibitors of virion-associated reverse transcriptase from different HIV types and groups. J Acquir Immune Defic Syndr 37: 1543-1549. (Pubitemid 39658189)
6. Witvrouw M, Pannecouque C, Switzer WM, Folks TM, De Clercq E, et al. (2004) Susceptibility of HIV-2, SIV and SHIV to various anti-HIV-1 compounds: implications for treatment and postexposure prophylaxis. Antivir Ther 9: 57-65. (Pubitemid 38313948)
7. Poveda E, Rodes B, Toro C, Soriano V (2004) Are fusion inhibitors active against all HIV variants? AIDS Res Hum Retroviruses 20: 347-348. (Pubitemid 38429408)
8. Borrego P, Calado R, Marcelino JM, Bartolo I, Rocha C, et al. (2012) Baseline susceptibility of primary HIV-2 to entry inhibitors. Antivir Ther 17: 565-570.
9. Desbois D, Roquebert B, Peytavin G, Damond F, Collin G, et al. (2008) In vitro phenotypic susceptibility of human immunodeficiency virus type 2 clinical isolates to protease inhibitors. Antimicrob Agents Chemother 52: 1545-1548. (Pubitemid 351522031)
10. Rodes B, Sheldon J, Toro C, Jimenez V, Alvarez MA, et al. (2006) Susceptibility to protease inhibitors in HIV-2 primary isolates from patients failing antiretroviral therapy. J Antimicrob Chemother 57: 709-713.
11. Smith RA, Anderson DJ, Pyrak CL, Preston BD, Gottlieb GS (2009) Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. J Infect Dis 199: 1323-1326.
12. Ntemgwa M, Brenner BG, Oliveira M, Moisi D, Wainberg MA (2007) Natural polymorphisms in the human immunodeficiency virus type 2 protease can accelerate time to development of resistance to protease inhibitors. Antimicrob Agents Chemother 51: 604-610. (Pubitemid 46185279)
13. Rodes B, Toro C, Sheldon JA, Jimenez V, Mansinho K, et al. (2006) High rate of proV47A selection in HIV-2 patients failing lopinavir-based HAART. AIDS 20: 127-129. (Pubitemid 41818127)
14. Lee SP, Xiao J, Knutson JR, Lewis MS, Han MK (1997) Zn2+ promotes the self-association of human immunodeficiency virus type-1 integrase in vitro. Biochemistry 36: 173-180. (Pubitemid 27024690)
15. Zheng R, Jenkins TM, Craigie R (1996) Zinc folds the N-terminal domain of HIV-1 integrase, promotes multimerization, and enhances catalytic activity. Proc Natl Acad Sci U S A 93: 13659-13664. (Pubitemid 26424175)
16. Drelich M, Wilhelm R, Mous J (1992) Identification of amino acid residues critical for endonuclease and integration activities of HIV-1 IN protein in vitro. Virology 188: 459-468.
17. Engelman A, Craigie R (1992) Identification of conserved amino acid residues critical for human immunodeficiency virus type 1 integrase function in vitro. J Virol 66: 6361-6369.
18. Kulkosky J, Jones KS, Katz RA, Mack JP, Skalka AM (1992) Residues critical for retroviral integrative recombination in a region that is highly conserved among retroviral/retrotransposon integrases and bacterial insertion sequence transposases. Mol Cell Biol 12: 2331-2338.
19. Hickman AB, Palmer I, Engelman A, Craigie R, Wingfield P (1994) Biophysical and enzymatic properties of the catalytic domain of HIV-1 integrase. J Biol Chem 269: 29279-29287. (Pubitemid 24366786)
20. Esposito D, Craigie R (1998) Sequence specificity of viral end DNA binding by HIV-1 integrase reveals critical regions for protein-DNA interaction. EMBO J 17: 5832-5843. (Pubitemid 28445994)
21. Gerton JL, Brown PO (1997) The core domain of HIV-1 integrase recognizes key features of its DNA substrates. J Biol Chem 272: 25809-25815. (Pubitemid 27438903)
22. Jenkins TM, Esposito D, Engelman A, Craigie R (1997) Critical contacts between HIV-1 integrase and viral DNA identified by structure-based analysis and photo-crosslinking. EMBO J 16: 6849-6859. (Pubitemid 27503496)
23. Appa RS, Shin CG, Lee P, Chow SA (2001) Role of the nonspecific DNAbinding region and alpha helices within the core domain of retroviral integrase in selecting target DNA sites for integration. J Biol Chem 276: 45848-45855.
24. Harper AL, Skinner LM, Sudol M, Katzman M (2001) Use of patient-derived human immunodeficiency virus type 1 integrases to identify a protein residue that affects target site selection. J Virol 75: 7756-7762. (Pubitemid 32738037)
25. Esposito D, Craigie R (1999) HIV integrase structure and function. Adv Virus Res 52: 319-333.
26. Gao K, Butler SL, Bushman F (2001) Human immunodeficiency virus type 1 integrase: arrangement of protein domains in active cDNA complexes. EMBO J 20: 3565-3576. (Pubitemid 32634363)
27. Engelman A, Hickman AB, Craigie R (1994) The core and carboxyl-terminal domains of the integrase protein of human immunodeficiency virus type 1 each contribute to nonspecific DNA binding. J Virol 68: 5911-5917. (Pubitemid 24258608)
28. Vink C, Oude Groeneger AM, Plasterk RH (1993) Identification of the catalytic and DNA-binding region of the human immunodeficiency virus type I integrase protein. Nucleic Acids Res 21: 1419-1425. (Pubitemid 23154373)
29. Woerner AM, Marcus-Sekura CJ (1993) Characterization of a DNA binding domain in the C-terminus of HIV-1 integrase by deletion mutagenesis. Nucleic Acids Res 21: 3507-3511. (Pubitemid 23241486)
30. Jenkins TM, Engelman A, Ghirlando R, Craigie R (1996) A soluble active mutant of HIV-1 integrase: involvement of both the core and carboxyl-terminal domains in multimerization. J Biol Chem 271: 7712-7718.
31. Xu L, Anderson J, Ferns B, Cook P, Wildfire A, et al. (2008) Genetic diversity of integrase (IN) sequences in antiretroviral treatment-naive and treatmentexperienced HIV type 2 patients. AIDS Res Hum Retroviruses 24: 1003-1007.
32. Smith RA, Raugi DN, Kiviat NB, Hawes SE, Mullins JI, et al. (2011) Phenotypic Susceptibility of HIV-2 to Raltegravir: Integrase Mutations Q148R and N155H Confer Raltegravir Resistance. AIDS 25: 2235-2241.
33. Roquebert B, Damond F, Collin G, Matheron S, Peytavin G, et al. (2008) HIV-2 integrase gene polymorphism and phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitors raltegravir and elvitegravir in vitro. J Antimicrob Chemother 62: 914-920.
34. Damond F, Lariven S, Roquebert B, Males S, Peytavin G, et al. (2008) Virological and immunological response to HAART regimen containing integrase inhibitors in HIV-2-infected patients. AIDS 22: 665-666. (Pubitemid 351640604)
35. Lataillade M, Chiarella J, Kozal MJ (2007) Natural polymorphism of the HIV-1 integrase gene and mutations associated with integrase inhibitor resistance. Antivir Ther 12: 563-570. (Pubitemid 47041156)
36. Bercoff DP, Triqueneaux P, Lambert C, Oumar AA, Ternes AM, et al. (2010) Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. Retrovirology 7: 98.
37. Charpentier C, Larrouy L, Collin G, Damond F, Matheron S, et al. (2010) Invitro phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitor S/GSK1349572. AIDS 24: 2753-2755.
38. Armstrong-James D, Stebbing J, Scourfield A, Smit E, Ferns B, et al. (2010) Clinical outcome in resistant HIV-2 infection treated with raltegravir and maraviroc. Antiviral Res 86: 224-226.
39. Garrett N, Xu L, Smit E, Ferns B, El Gadi S, et al. (2008) Raltegravir treatment response in an HIV-2 infected patient: a case report. AIDS 22: 1091-1092. (Pubitemid 351769751)
40. Wandeler G, Furrer H, Rauch A (2011) Sustained virological response to a raltegravir-containing salvage therapy in an HIV-2-infected patient. AIDS 25: 2306-2308.
41. Charpentier C, Roquebert B, Delelis O, Larrouy L, Matheron S, et al. (2010) Hot spots of integrase genotypic changes leading to HIV-2 resistance to raltegravir. Antimicrob Agents Chemother 55(3):1293-1295.
42. Ni XJ, Delelis O, Charpentier C, Storto A, Collin G, et al. (2011) G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to Raltegravir whereas Y143C does not. Retrovirology 8: 68.
43. Roquebert B, Blum L, Collin G, Damond F, Peytavin G, et al. (2008) Selection of the Q148R integrase inhibitor resistance mutation in a failing raltegravir containing regimen. AIDS 22: 2045-2046.
44. Salgado M, Toro C, Simon A, Garrido C, Blanco F, et al. (2009) Mutation N155H in HIV-2 integrase confers high phenotypic resistance to raltegravir and impairs replication capacity. J Clin Virol 46: 173-175.
45. Trevino A, de Mendoza C, Caballero E, Rodriguez C, Parra P, et al. (2011) Drug resistance mutations in patients infected with HIV-2 living in Spain. J Antimicrob Chemother 66: 1484-1488.
46. Xu L, Anderson J, Garrett N, Ferns B, Wildfire A, et al. (2009) Dynamics of raltegravir resistance profile in an HIV type 2-infected patient. AIDS Res Hum Retroviruses 25: 843-847.
47. Matheron S, Damond F, Benard A, Taieb A, Campa P, et al. (2006) CD4 cell recovery in treated HIV-2-infected adults is lower than expected: results from the French ANRS CO5 HIV-2 cohort. AIDS 20: 459-462.
48. Smith RA, Raugi DN, Pan C, Coyne M, Hernandez A, et al. (2012) Three main mutational pathways in HIV-2 lead to high-level raltegravir and elvitegravir resistance: implications for emerging HIV-2 treatment regimens. PLoS One 7: e45372.
49. McColl DJ, Fransen S, Gupta S, Parkin N, Margot N, et al. (2007) Resistance and cross-resistance to first generation integrase inhibitors: insights from a Phase II study of elvitegravir (GS-9137). Antivir Ther 12:S11.
50. Abram ME, Hluhanich RM, Goodman DD, Andreatta KN, Margot NA, et al. (2013) Impact of primary elvitegravir resistance-associated mutations in HIV-1 integrase on drug susceptibility and viral replication fitness. Antimicrob Agents Chemother 57: 2654-2663.
51. DeAnda F, Hightower KE, Nolte RT, Hattori K, Yoshinaga T, et al. (2013) Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. PLoS One 8: e77448.
52. Eron JJ, Clotet B, Durant J, Katlama C, Kumar P, et al. (2013) Safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravirresistant HIV type 1 infection: 24-week results of the VIKING Study. J Infect Dis 207: 740-748.
53. Kobayashi M, Yoshinaga T, Seki T, Wakasa-Morimoto C, Brown KW, et al. (2011) In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob Agents Chemother 55: 813-821.
54. Mesplede T, Quashie PK, Osman N, Han Y, Singhroy DN, et al. (2013) Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Retrovirology 10: 22.
55. Quashie PK, Mesplede T, Han YS, Oliveira M, Singhroy DN, et al. (2012) Characterization of the R263K mutation in HIV-1 integrase that confers lowlevel resistance to the second-generation integrase strand transfer inhibitor dolutegravir. J Virol 86: 2696-2705.
56. Colson P, Henry M, Tourres C, Lozachmeur D, Gallais H, et al. (2004) Polymorphism and drug-selected mutations in the protease gene of human immunodeficiency virus type 2 from patients living in Southern France. J Clin Microbiol 42: 570-577. (Pubitemid 38222630)
57. Johnson VA, Calvez V, Gunthard HF, Paredes R, Pillay D, et al. (2013) Update of the drug resistance mutations in HIV-1: March 2013. Top Antivir Med 21: 6-14.
58. Gomes P, Van Laethem K, Geretti AM, Camacho R, Vandamme AM (2009) Algorithm for the interpretation of genotypic HIV-2 resistance data - Rega v8.0.2. Available:http://rega.kuleuven.be/cev/avd/files/software/rega-algorithm/ Rega-HIV2-Rules-v8.0.2.pdf. Accessed 18 November 2013.
59. Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32: 1792-1797.
60. Waterhouse AM, Procter JB, Martin DM, Clamp M, Barton GJ (2009) Jalview Version 2-a multiple sequence alignment editor and analysis workbench. Bioinformatics 25: 1189-1191.
61. Guido van Rossum (2011) Python Language Website. Available: http://www.python.org/. Accessed 18 November 2013.
62. Ceccherini-Silberstein F, Malet I, D'Arrigo R, Antinori A, Marcelin AG, et al. (2009) Characterization and structural analysis of HIV-1 integrase conservation. AIDS Rev 11: 17-29.
63. Ceccherini-Silberstein F, Malet I, Fabeni L, Dimonte S, Svicher V, et al. (2010) Specific HIV-1 integrase polymorphisms change their prevalence in untreated versus antiretroviral-treated HIV-1-infected patients, all naive to integrase inhibitors. J Antimicrob Chemother 65: 2305-2318.
64. van Gent DC, Groeneger AA, Plasterk RH (1992) Mutational analysis of the integrase protein of human immunodeficiency virus type 2. Proc Natl Acad Sci U S A 89: 9598-9602.
65. Bushman FD, Engelman A, Palmer I, Wingfield P, Craigie R (1993) Domains of the integrase protein of human immunodeficiency virus type 1 responsible for polynucleotidyl transfer and zinc binding. Proc Natl Acad Sci U S A 90: 3428-3432. (Pubitemid 23111379)
66. Dar MJ, Monel B, Krishnan L, Shun MC, Di Nunzio F, et al. (2009) Biochemical and virological analysis of the 18-residue C-terminal tail of HIV-1 integrase. Retrovirology 6: 94.
67. Gottlieb GS, Smith RA, Dia Badiane NM, Ba S, Hawes SE, et al. (2011) HIV-2 integrase variation in integrase inhibitor-naive adults in Senegal, West Africa. PLoS One 6: e22204.
68. Low A, Prada N, Topper M, Vaida F, Castor D, et al. (2009) Natural polymorphisms of human immunodeficiency virus type 1 integrase and inherent susceptibilities to a panel of integrase inhibitors. Antimicrob Agents Chemother 53: 4275-4282.
69. Buzon MJ, Dalmau J, Puertas MC, Puig J, Clotet B, et al. (2010) The HIV-1 integrase genotype strongly predicts raltegravir susceptibility but not viral fitness of primary virus isolates. AIDS 24: 17-25.
70. Buzon MJ, Marfil S, Puertas MC, Garcia E, Clotet B, et al. (2008) Raltegravir susceptibility and fitness progression of HIV type-1 integrase in patients on longterm antiretroviral therapy. Antivir Ther 13: 881-893.
71. Hu Z, Kuritzkes DR (2010) Effect of raltegravir resistance mutations in HIV-1 integrase on viral fitness. J Acquir Immune Defic Syndr 55: 148-155.
72. Fransen S, Karmochkine M, Huang W, Weiss L, Petropoulos CJ, et al. (2009) Longitudinal analysis of raltegravir susceptibility and integrase replication capacity of human immunodeficiency virus type 1 during virologic failure. Antimicrob Agents Chemother 53: 4522-4524.
73. Malet I, Delelis O, Soulie C, Wirden M, Tchertanov L, et al. (2009) Quasispecies variant dynamics during emergence of resistance to raltegravir in HIV-1-infected patients. J Antimicrob Chemother 63: 795-804.
74. Charpentier C, Larrouy L, Matheron S, Damond F, Delelis O, et al. (2011) Long-lasting persistence of integrase resistance mutations in HIV-2-infected patients after raltegravir withdrawal. Antivir Ther 16: 937-940.
75. Malet I, Delelis O, Valantin MA, Montes B, Soulie C, et al. (2008) Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro. Antimicrob Agents Chemother 52: 1351-1358. (Pubitemid 351521998)