The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness

Retrovirology

Volumn 11, Issue 1, 2014, Pages

  Wares, Melissa ^a,b   Mesplède, Thibault ^a   Quashie, Peter K ^a,c   Osman, Nathan ^a,b   Han, Yingshan ^a   Wainberg, Mark A ^a,b,c  

^a MCGILL UNIVERSITY   (Canada)

^b MCGILL UNIVERSITY   (Canada)

^c MCGILL UNIVERSITY   (Canada)

Author keywords

Antiretrovirals; HIV integrase; INSTI na ve; M50I; Polymorphism; R263K; Resistance mutation; Subtype B

Indexed keywords

ANTIRETROVIRUS AGENT; DOLUTEGRAVIR; EFAVIRENZ; ELVITEGRAVIR; INTEGRASE; RALTEGRAVIR;

ARTICLE; CELL CULTURE; CROSS RESISTANCE; GENE MUTATION; GENETIC POLYMORPHISM; GENOTYPE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IC 50; IN VIVO STUDY; PROTEIN EXPRESSION; PROTEIN PURIFICATION; TISSUE CULTURE; VIRUS INFECTIVITY; VIRUS REPLICATION; WILD TYPE;

HUMAN IMMUNODEFICIENCY VIRUS 1;

AMINO ACID SUBSTITUTION; ANTI-HIV AGENTS; DRUG RESISTANCE, VIRAL; HETEROCYCLIC COMPOUNDS, 3-RING; HIV INFECTIONS; HIV INTEGRASE; HIV-1; HUMANS; MUTATION, MISSENSE; VIRUS REPLICATION;

EID: 84892453291     PISSN: None     EISSN: 17424690     Source Type: Journal    
DOI: 10.1186/1742-4690-11-7     Document Type: Article

References (31)

1. Hightower KE, Wang R, DeAnda F, Johns BA, Weaver K, Shen Y, Tomberlin GH, Carter HL, Broderick T, Sigethy S. Dolutegravir (S/GSK1349572) exhibits significantly slower dissociation than raltegravir and elvitegravir from wild-type and integrase inhibitor-resistant HIV-1 integrase-DNA complexes. Antimicrob Agents Chemother 2011, 55:4552-4559. 10.1128/AAC.00157-11, 3187001, 21807982.
2. Wainberg MA, Mesplède T, Quashie PK. The development of novel HIV integrase inhibitors and the problem of drug resistance. Current Opinion in Virology 2012, 2656:662.
3. Quashie PK, Mesplède T, Wainberg MA. HIV drug resistance and the advent of integrase inhibitors. Curr Infect Dis Rep 2013, 15:85-100. 10.1007/s11908-012-0305-1, 23180144.
4. Dyda F, Hickman AB, Jenkins TM, Engelman A, Craigie R, Davies DR. Crystal structure of the catalytic domain of HIV-1 integrase: similarity to other polynucleotidyl transferases. Science 1994, 266:1981-1986. 10.1126/science.7801124, 7801124.
5. Craigie R. HIV integrase, a brief overview from chemistry to therapeutics. J Biol Chem 2001, 276:23213-23216. 10.1074/jbc.R100027200, 11346660.
6. Lennox JL, DeJesus E, Lazzarin A, Pollard RB, Madruga JVR, Berger DS, Zhao J, Xu X, Williams-Diaz A, Rodgers AJ. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet 2009, 374:796-806. 10.1016/S0140-6736(09)60918-1, 19647866.
7. Lennox JL, DeJesus E, Berger DS, Lazzarin A, Pollard RB, Madruga JVR, Zhao J, Wan H, Gilbert CL, Teppler H. Raltegravir versus efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses. JAIDS Journal of Acquired Immune Deficiency Syndromes 2010, 55:39-48.
8. Sax PE, DeJesus E, Mills A, Zolopa A, Cohen C, Wohl D, Gallant JE, Liu HC, Zhong L, Yale K. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet 2012, 379:2439-2448. 10.1016/S0140-6736(12)60917-9, 22748591.
9. Zolopa A, Sax PE, DeJesus E, Mills A, Cohen C, Wohl D, Gallant JE, Liu HC, Plummer A, White KL. A randomized double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: analysis of week 96 results. JAIDS Journal of Acquired Immune Deficiency Syndromes 2013, 63:96-100.
10. van Lunzen J, Maggiolo F, Arribas JR, Rakhmanova A, Yeni P, Young B, Rockstroh JK, Almond S, Song I, Brothers C. Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial. The Lancet infectious diseases 2012, 12:111-118. 10.1016/S1473-3099(11)70290-0, 22018760.
11. Marcelin A-G, Delaugerre C, Beaudoux C, Descamps D, Morand-Joubert L, Amiel C, Schneider V, Ferre V, Izopet J, Si-Mohamed A. A cohort study of treatment-experienced HIV-1-infected patients treated with raltegravir: factors associated with virological response and mutations selected at failure. Int J Antimicrob Agents 2013, 42:42-47. 10.1016/j.ijantimicag.2013.02.016, 23562640.
12. Mouscadet J-F, Delelis O, Marcelin A-G, Tchertanov L. Resistance to HIV-1 integrase inhibitors: a structural perspective. Drug Resist Updat 2010, 13:139-150. 10.1016/j.drup.2010.05.001, 20570551.
13. Huang W, Frantzell A, Fransen S, Petropoulos CJ. Multiple genetic pathways involving amino acid position 143 of HIV-1 integrase are preferentially associated with specific secondary amino acid substitutions and confer resistance to raltegravir and cross-resistance to elvitegravir. Antimicrob Agents Chemother 2013, 57:4105-4113. 10.1128/AAC.00204-13, 23733474.
14. Kobayashi M, Yoshinaga T, Seki T, Wakasa-Morimoto C, Brown KW, Ferris R, Foster SA, Hazen RJ, Miki S, Suyama-Kagitani A. In vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob Agents Chemother 2011, 55:813-821. 10.1128/AAC.01209-10, 3028777, 21115794.
15. Mesplède T, Quashie PK, Wainberg MA. Resistance to HIV integrase inhibitors. Curr Opin HIV AIDS 2012, 7:401-408. 10.1097/COH.0b013e328356db89, 22789986.
16. Ballantyne AD, Perry CM. Dolutegravir: first global approval. Drugs 2013, 73:1627-1637. 10.1007/s40265-013-0121-4, 24052331.
17. Katlama C, Murphy R. Dolutegravir for the treatment of HIV. Expert Opin Investig Drugs 2012, 21:523-530. 10.1517/13543784.2012.661713, 22380682.
18. Cahn P, Pozniak AL, Mingrone H, Shuldyakov A, Brites C, Andrade-Villanueva JF, Richmond G, Buendia CB, Fourie J, Ramgopal M. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet 2013, 382:700-708. 10.1016/S0140-6736(13)61221-0, 23830355.
19. Quashie PK, Mesplède T, Han Y-S, Oliveira M, Singhroy DN, Fujiwara T, Underwood MR, Wainberg MA. Characterization of the R263K mutation in HIV-1 integrase that confers low-level resistance to the second-generation integrase strand transfer inhibitor dolutegravir. J Virol 2012, 86:2696-2705. 10.1128/JVI.06591-11, 3302270, 22205735.
20. 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, 11:17-29.
21. Garrido C, Villacian J, Zahonero N, Pattery T, Garcia F, Gutierrez F, Caballero E, Van Houtte M, Soriano V, de Mendoza C. Broad phenotypic cross-resistance to elvitegravir in HIV-infected patients failing on raltegravir-containing regimens. Antimicrob Agents Chemother 2012, 56:2873-2878. 10.1128/AAC.06170-11, 3370736, 22450969.
22. Low A, Prada N, Topper M, Vaida F, Castor D, Mohri H, Hazuda D, Muesing M, Markowitz M. Natural polymorphisms of human immunodeficiency virus type 1 integrase and inherent susceptibilities to a panel of integrase inhibitors. Antimicrob Agents Chemother 2009, 53:4275-4282. 10.1128/AAC.00397-09, 2764199, 19651917.
23. Mesplède T, Quashie PK, Osman N, Han Y, Singhroy DN, Lie Y, Petropoulos CJ, Huang W, Wainberg MA. Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Retrovirology 2013, 10:22. 10.1186/1742-4690-10-22, 3598531, 23432922.
24. Mbisa JL, Martin SA, Cane PA. Patterns of resistance development with integrase inhibitors in HIV. Infection and Drug Resistance 2011, 4:65. 3108751, 21694910.
25. Ceccherini-Silberstein F, Van Baelen K, Armenia D, Trignetti M, Rondelez E, Fabeni L, Scopelliti F, Pollicita M, Van Wesenbeeck L, Van Eygen V. Secondary integrase resistance mutations found in HIV-1 minority quasispecies in integrase therapy-naive patients have little or no effect on susceptibility to integrase inhibitors. Antimicrob Agents Chemother 2010, 54:3938-3948. 10.1128/AAC.01720-09, 2935022, 20479206.
26. Rockstroh JK, DeJesus E, Lennox JL, Yazdanpanah Y, Saag MS, Wan H, Rodgers AJ, Walker ML, Miller M, DiNubile MJ. Durable efficacy and safety of raltegravir versus efavirenz when combined with tenofovir/emtricitabine in treatment-naive HIV-1-infected patients: final 5-year results from STARTMRK. JAIDS Journal of Acquired Immune Deficiency Syndromes 2013, 63:77-85.
27. Molina J-M, LaMarca A, Andrade-Villanueva J, Clotet B, Clumeck N, Liu Y-P, Zhong L, Margot N, Cheng AK, Chuck SL. Efficacy and safety of once daily elvitegravir versus twice daily raltegravir in treatment-experienced patients with HIV-1 receiving a ritonavir-boosted protease inhibitor: randomised, double-blind, phase 3, non-inferiority study. The Lancet infectious diseases 2012, 12:27-35. 10.1016/S1473-3099(11)70249-3, 22015077.
28. DeJesus E, Rockstroh JK, Henry K, Molina J-M, Gathe J, Ramanathan S, Wei X, Yale K, Szwarcberg J, White K. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet 2012, 379:2429-2438. 10.1016/S0140-6736(12)60918-0, 22748590.
29. Bar-Magen T, Donahue DA, McDonough EI, Kuhl BD, Faltenbacher VH, Xu H, Michaud V, Sloan RD, Wainberg MA. HIV-1 subtype B and C integrase enzymes exhibit differential patterns of resistance to integrase inhibitors in biochemical assays. AIDS 2010, 24:2171-2179. 10.1097/QAD.0b013e32833cf265, 20647908.
30. Xu H-T, Asahchop EL, Oliveira M, Quashie PK, Quan Y, Brenner BG, Wainberg MA. Compensation by the E138K mutation in HIV-1 reverse transcriptase for deficits in viral replication capacity and enzyme processivity associated with the M184I/V mutations. J Virol 2011, 85:11300-11308. 10.1128/JVI.05584-11, 3194954, 21849444.
31. Quashie PK, Mesplède T, Han Y-S, Veres T, Osman N, Hassounah S, Sloan RD, Xu H-T, Wainberg MA. Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase. Antimicrob Agents Chemother 2013, 57:6223-6235. 10.1128/AAC.01835-13, 24080645.