Resistance mutations against dolutegravir in HIV integrase impair the emergence of resistance against reverse transcriptase inhibitors

AIDS

Volumn 28, Issue 6, 2014, Pages 813-819

  Oliveira, Maureen ^a   Mesplède, Thibault ^a   Quashie, Peter K ^a,b   Moïsi, Daniela ^a   Wainberg, Mark A ^a,b,c  

^a MCGILL UNIVERSITY   (Canada)

^b Faculties of Medicine of Canada   (Canada)

^c MCGILL UNIVERSITY   (Canada)

Author keywords

Dolutegravir; HIV 1; Lamivudine; Nevirapine; Resistance

Indexed keywords

DOLUTEGRAVIR; HUMAN IMMUNODEFICIENCY VIRUS INTEGRASE; INTEGRASE; LAMIVUDINE; NEVIRAPINE; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; CORD BLOOD MONONUCLEAR CELL; GENOTYPE; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; IN VITRO SELECTION; MAJOR CLINICAL STUDY; MONONUCLEAR CELL; NONHUMAN; PRIORITY JOURNAL; SITE DIRECTED MUTAGENESIS; VIRUS MUTATION; VIRUS RESISTANCE;

ANTI-HIV AGENTS; DRUG RESISTANCE, VIRAL; HETEROCYCLIC COMPOUNDS, 3-RING; HIV; HIV INFECTIONS; HIV INTEGRASE; HIV REVERSE TRANSCRIPTASE; HUMANS; MUTATION, MISSENSE; REVERSE TRANSCRIPTASE INHIBITORS; SELECTION, GENETIC; SERIAL PASSAGE; TREATMENT FAILURE;

EID: 84897975407     PISSN: 02699370     EISSN: 14735571     Source Type: Journal    
DOI: 10.1097/QAD.0000000000000199     Document Type: Article

References (32)

1. Wainberg MA, Zaharatos GJ, Brenner BG. Development of antiretroviral drug resistance. N Engl J Med 2011; 365:637-646.
2. Deeks SG, Autran B, Berkhout B, Benkirane M, Cairns S, Chomont N, et al. Towards an HIV cure: a global scientific strategy. Nat Rev Immunol 2012; 12:607-614.
3. Raffi F, Rachlis A, Stellbrink HJ, Hardy WD, Torti C, Orkin C, et al. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, noninferiority SPRING-2 study. Lancet 2013; 381:735-743.
4. Mesplede T, Quashie P, Oliveira M, Wainberg M. HIV resistance to dolutegravir (DTG) simultaneously diminishes viral DNA integration into host cells and viral replication fitness: implications for HIV reservoirs. 7th IAS Conference on HIV Pathogenesis Treatment and Prevention. Kuala Lumpur, Malaysia; 2013.
5. Quashie PK, Mesplede T, Han YS, Oliveira M, Singhroy DN, Fujiwara T, et al. Characterization of the R263K mutation in HIV-1 integrase that confers low-level resistance to the secondgeneration integrase strand transfer inhibitor dolutegravir. J Virol 2012; 86:2696-2705.
6. Kobayashi M, Yoshinaga T, Seki T, Wakasa-Morimoto C, Brown KW, Ferris R, et al. In vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob Agents Chemother 2011; 55:813-821.
7. Mesplede T, Quashie PK, Osman N, Han Y, Singhroy DN, Lie Y, et al. Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Retrovirology 2013; 10:22.
8. Underwood M, Dudas K, Horton J, Wang R, Deanda F, Griffith S, et al. Analysis and characterization of treatment-emergent resistance in ART-experienced, integrase inhibitor-naive subjects with dolutegravir (DTG) versus raltegravir (RAL) in SAILING (ING111762). International Workshop on HIV and Hepatitis Virus Drug Resistance and Curative Strategies. Toronto, Canada; 2013.
9. Cahn P, Pozniak AL, Mingrone H, Shuldyakov A, Brites C, Andrade-Villanueva JF, et al. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, noninferiority SAILING study. Lancet 2013; 382:700-708.
10. Messiaen P, Wensing AM, Fun A, Nijhuis M, Brusselaers N, Vandekerckhove L. Clinical use of HIV integrase inhibitors: a systematic review and meta-analysis. PLoS One 2013; 8:e52562.
11. Oliveira M, Brenner BG, Wainberg MA. Isolation of drugresistant mutant HIV variants using tissue culture drug selection. Methods Mol Biol 2009; 485:427-433.
12. Asahchop EL, Oliveira M, Wainberg MA, Brenner BG, Moisi D, Toni T, et al. Characterization of the E138K resistance mutation in HIV-1 reverse transcriptase conferring susceptibility to etravirine in B and non-B HIV-1 subtypes. Antimicrob Agents Chemother 2011; 55:600-607.
13. Brenner BG, Lowe M, Moisi D, Hardy I, Gagnon S, Charest H, et al. Subtype diversity associated with the development of HIV-1 resistance to integrase inhibitors. J Med Virol 2011; 83:751-759.
14. Tasara T, Maga G, Hottiger MO, Hubscher U. HIV-1 reverse transcriptase and integrase enzymes physically interact and inhibit each other. FEBS Lett 2001; 507:39-44.
15. Oz I, Avidan O, Hizi A. Inhibition of the integrases of human immunodeficiency viruses type 1 and type 2 by reverse transcriptases. Biochem J 2002; 361:557-566.
16. Bar-Magen T, Sloan RD, Donahue DA, Kuhl BD, Zabeida A, Xu H, et al. Identification of novel mutations responsible for resistance to MK-2048, a second-generation HIV-1 integrase inhibitor. J Virol 2010; 84:9210-9216.
17. Quashie PK, Mesplede T, Han YS, Veres T, Osman N, Hassounah S, et al. Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase. Antimicrob Agents Chemother 2013; 57:6223-6235.
18. McColl D, Fransen S, Gupta SS, Parkin N, Margot N, Ledford R, et al. Resistance and cross-resistance to first generation integrase inhibitors: insights from a phase 2 study of elvitegravir (GS-9137). 16th International HIV Drug Resistance Workshop, Barbados, West Indies; 2007.
19. Shimura K, Kodama E, Sakagami Y, Matsuzaki Y, Watanabe W, Yamataka K, et al. Broad antiretroviral activity and resistance profile of the novel human immunodeficiency virus integrase inhibitor elvitegravir (JTK-303/GS-9137). J Virol 2008; 82:764-774.
20. Kobayashi M, Nakahara K, Seki T, Miki S, Kawauchi S, Suyama A, et al. Selection of diverse and clinically relevant integrase inhibitor-resistant human immunodeficiency virus type 1 mutants. Antiviral Res 2008; 80:213-222.
21. Seki T, Kobayashi H, Miki S, Akihisa E, Suyama-Kagitani A, Kawauchi-Miki S, et al. High barrier to resistance for dolutegravir (DTG, S/GSK1349572) against raltegravir-resistant Y143 mutants: an in vitro passage study. International Workshop on HIV & Hepatitis Virus Drug Resistance, Sitges, Spain; 2012.
22. Fransen S, Gupta S, Frantzell A, Petropoulos CJ, Huang W. Substitutions at amino acid positions 143, 148, and 155 of HIV-1 integrase define distinct genetic barriers to raltegravir resistance in vivo. J Virol 2012; 86:7249-7255.
23. Winters B, Lloyd RJ, Miller M, Holodniy M. Evolution of IN inhibitor resistance mutations in patients failing elvitegravircontaining regimens. 19th CROI, Conference on retroviruses and opportunistic infections, Seattle, WA 2012, Abstract:701.
24. Underwood MR, Johns BA, Sato A, Martin JN, Deeks SG, Fujiwara T. The activity of the integrase inhibitor dolutegravir against HIV-1 variants isolated from raltegravir-treated adults. J Acquir Immune Defic Syndr 2012; 61:297-301.
25. Fransen S, Gupta S, Danovich R, Hazuda D, Miller M, Witmer M, et al. Loss of raltegravir susceptibility by human immunodeficiency virus type 1 is conferred via multiple nonoverlapping genetic pathways. J Virol 2009; 83:11440-11446.
26. Canducci F, Sampaolo M, Marinozzi MC, Boeri E, Spagnuolo V, Galli A, et al. Dynamic patterns of human immunodeficiency virus type 1 integrase gene evolution in patients failing raltegravir-based salvage therapies. AIDS 2009; 23:455-460.
27. Goethals O, Clayton R, Van Ginderen M, Vereycken I, Wagemans E, Geluykens P, et al. 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; 82:10366-10374.
28. Goethals O, Vos A, Van Ginderen M, Geluykens P, Smits V, Schols D, et al. Primary mutations selected in vitro with raltegravir confer large fold changes in susceptibility to firstgeneration integrase inhibitors, but minor fold changes to inhibitors with second-generation resistance profiles. Virology 2010; 402:338-346.
29. Canducci F, Marinozzi MC, Sampaolo M, Boeri E, Spagnuolo V, Gianotti N, et al. Genotypic/phenotypic patterns of HIV-1 integrase resistance to raltegravir. J Antimicrob Chemother 2010; 65:425-433.
30. Sato A, Seki T, Kobayashi M, Yoshinaga T, Fujiwara T, Underwood M, et al. In vitro passage of drug resistant HIV-1 against a next generation integrase inhibitor (INI), S/GSK1349572. 49th ICAAC, San Francisco, CA; 2009.
31. Mesplede T, Wares M, Osman N, Quashie P, Han Y, Singhroy DN, et al. Secondary resistance mutations in the R263K integrase inhibitor resistance pathway. 7th IAS Conference on HIV Pathogenesis Treatment and Prevention. Kuala Lumpur, Malaysia; 2013.
32. Blanco JL, Varghese V, Rhee SY, Gatell JM, Shafer RW. HIV-1 integrase inhibitor resistance and its clinical implications. J Infect Dis 2011; 203:1204-1214.