Genetic barrier to resistance for dolutegravir

AIDS Reviews

Volumn 17, Issue 1, 2014, Pages 59-68

  Llibre, Josep M ^a,b   Pulido, Federico ^c   García, Federico ^d   Deltoro, Miguel García ^e   Blanco, José L ^f   Delgado, Rafael ^c  

^a HOSPITAL UNIVERSITARI GERMANS TRIAS I PUJOL   (Spain)

^b UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^c HOSPITAL UNIVERSITARIO 12 DE OCTUBRE   (Spain)

^d Instituto de Investigación Biosanitaria ibs   (Spain)

^e HOSPITAL GENERAL UNIVERSITARIO DE VALENCIA   (Spain)

^f INSTITUT D INVESTIGACIONS BIOMÈDIQUES AUGUST PI I SUNYER IDIBAPS   (Spain)

Author keywords

Dolutegravir; Genetic barrier; HIV 1 resistance; Integrase inhibitor; Raltegravir

Indexed keywords

DOLUTEGRAVIR; INTEGRASE INHIBITOR;

ANTIVIRAL RESISTANCE; ANTIVIRAL THERAPY; CROSS RESISTANCE; DRUG EFFICACY; DRUG MECHANISM; DRUG TREATMENT FAILURE; GENOTYPE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IN VITRO STUDY; IN VIVO STUDY; MULTICENTER STUDY (TOPIC); MULTIDRUG RESISTANCE; NONHUMAN; NUCLEOPHILICITY; PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; VIRUS LOAD;

EID: 84928199537     PISSN: 11396121     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (65)

1. Min S, Sloan L, DeJesus E, et al. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1-infected adults. AIDS. 2011;25:1737-45.
2. Blanco J, Varghese V, Rhee S, et al. HIV-1 integrase inhibitor resistance and its clinical implications. J Infect Dis. 2011;203:1204-14.
3. Stellbrink H, Reynes J, Lazzarin A, et al. Dolutegravir in antiretroviralnaive adults with HIV-1: 96-week results from a randomized dose-ranging study. AIDS. 2013;27:1771-8.
4. Walmsley S, Antela A, Clumeck N, et al. Dolutegravir plus abacavir-la-mivudine for the treatment of HIV-1 infection. N Engl J Med. 2013;369: 1807-18.
5. Clotet B, Feinberg J, van L, et al. Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study. Lancet. 2014;383:2222-31.
6. Raffi F, Jaeger H, Quiros-Roldan E, et al. Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. Lancet Infect Dis. 2013;13:927-35.
7. Cahn P, Pozniak AL, Mingrone H, et al. 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;382:700-8.
8. Canducci F, Ceresola E, Boeri E, et al. Cross-resistance profile of the novel integrase inhibitor Dolutegravir (S/GSK1349572) using clonal viral variants selected in patients failing raltegravir. J Infect Dis. 2011; 204:1811-5.
9. Kobayashi M, Yoshinaga T, Seki T, et al. In vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob Agents Chemother. 2011;55:813-21.
10. th European AIDS Conference Oct 2013 Brussels, Belgium. [PE7/3].
11. Castagna A, Maggiolo F, Penco G, et al. Dolutegravir in antiretroviral-experienced patients with raltegravir- and/or elvitegravir-resistant HIV-1: 24-week results of the Phase III VIKING-3 Study. J Infect Dis. 2014; 210:354-62.
12. Llibre J. First-line boosted protease inhibitor-based regimens in treatment-naive HIV-1-infected patients-making a good thing better. AIDS Rev. 2009;11:215-22.
13. van L, Maggiolo F, Arribas J, et al. 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. Lancet Infect Dis. 2012;12:111-8.
14. Hightower K, Wang R, DeAnda F, et al. 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;55:4552-9.
15. Llibre J, Schapiro J, Clotet B. Clinical implications of genotypic resistance to the newer antiretroviral drugs in HIV-1-infected patients with virological failure. Clin Infect Dis. 2010;50:872-81.
16. Hare S, Gupta S, Valkov E, et al. Retroviral intasome assembly and inhibition of DNA strand transfer. Nature. 2010;464:232-6.
17. Hare S, Smith S, Metifiot M, et al. Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572). Mol Pharmacol. 2011;80:565-72.
18. Cherepanov P. Integrase illuminated. EMBO Rep. 2010;11:328.
19. DeAnda F, Hightower K, Nolte R, et al. Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. PLoS One. 2013;8:e77448.
20. Raffi F, Rachlis A, Stellbrink H, et al. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet. 2013;381:735-43.
21. Quashie P, Mesplede T, Han Y, et al. 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;86:2696-705.
22. Mesplede T, Quashie P, Osman N, et al. Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Retrovirology. 2013;10:22.
23. Oliveira M, Mesplede T, Quashie P, et al. Resistance mutations against dolutegravir in HIV integrase impair the emergence of resistance against reverse transcriptase inhibitors. AIDS. 2014;28:813-9.
24. Wainberg M, Mesplede T, Raffi F. What if HIV were unable to develop resistance against a new therapeutic agent? BMC Med. 2013; 11:249.
25. Johnson V, Calvez V, Gunthard H, et al. Update of the drug resistance mutations in HIV-1: March 2013. Top Antivir Med. 2013;21:6-14.
26. Hazuda D. HIV integrase as a target for antiretroviral therapy. Curr Opin HIV AIDS. 2012;7:383-9.
27. Gatell J, Katlama C, Grinsztejn B, et al. Long-term efficacy and safety of the HIV integrase inhibitor raltegravir in patients with limited treatment options in a Phase II study. J Acquir Immune Defic Syndr. 2010;53:456-63.
28. Eron J, Clotet B, Durant J, et al. Safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING Study. J Infect Dis. 2013; 207:740-8.
29. Casadellà M, van Ham P, Noguera-Julian M, et al. Primary resistance to integrase strand-transfer inhibitors in Europe. CROI, 2014. Boston, MA. [Abstract 580].
30. Margot N, Martin R, Miller M, et al. Drug resistance mutations in treatment-naïve HIV-infected patients 2000-2013. CROI, 2014. Boston, MA. [Abstract 578].
31. Martin L, Guillot V, Chueca N, et al. Baseline resistance to integrase strand inhibitors in newly diagnosed patients in Spain. 11th European Meeting on HIV & Hepatitis, Rome, 2013. [Abstract p-15].
32. Ceccherini-Silberstein F, Van B, Armenia D, et al. 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; 54:3938-48.
33. Garrido C, Geretti A, 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.
34. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at: http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. In. [Accessed November 22, 2014].
35. Alvarez M, Guillot V, Chueca N, et al. Predicted efficacy of Dolutegravir in an HIV cohort of patients failing a Raltegravir based regimen. 12th European Workshop on HIV & Hepatitis Treatment Strategies & Antiviral Drug Resistance, March 2014. Barcelona, Spain. [P-45].
36. Anta L, Barreiro P, Sierra-Enguita R, et al. Dolutegravir and Elvitegravir resistance mutations in HIV-infected patients failing Raltegravir. 12th European Workshop on HIV & Hepatitis Treatment Strategies & Antiviral Drug Resistance. March 2014. Barcelona, Spain. [P-39].
37. Santos J, Blanco J, Masià M, et al. Clinical consequences of Raltegravir failure in Spain. 12th European Workshop on HIV & Hepatitis Treatment Strategies & Antiviral Drug Resistance, March 2014. Barcelona, Spain. [O-11].
38. Santoro M, Fabeni L, Armenia D, et al. Reliability of HIV-1 Integrase genotyping in patients with low viremia levels. 12th European Workshop on HIV & Hepatitis Treatment Strategies & Antiviral Drug Resistance, March 2014. Barcelona, Spain. [O-9].
39. Hurt C, Sebastian J, Hicks C, et al. Resistance to HIV integrase strand transfer inhibitors among clinical specimens in the United States, 2009-2012. Clin Infect Dis. 2014;58:423-31.
40. Delgado M, Lopez-Hernandez I, Fernandez-Cuenca F, et al. Prevalencia de mutaciones de resistencia a inhibidores de la integrasa en pacientes VIH-1 atendidos en un área occidental de Andalucía (2011-2013). In. XVIII Congreso SEIMC (Spanish Infectious Diseases and MIcrobiology Society), Valencia May 2014. [Abstract 251].
41. Charpentier C, Laureillard D, Piketty C, et al. High frequency of integrase Q148R minority variants in HIV-infected patients naive of integrase inhibitors. AIDS. 2010;24:867-73.
42. Gibson R, Meyer A, Winner D, et al. Sensitive deep-sequencing-based HIV-1 genotyping assay to simultaneously determine susceptibility to protease, reverse transcriptase, integrase, and maturation inhibitors, as well as HIV-1 coreceptor tropism. Antimicrob Agents Chemother. 2014; 58:2167-85.
43. Pappa K, Baumgarten A, Felizarta F, et al. Abacavir/lamivudine is superior to efavirenz/tenofovir/emtricitabine in treatment-naive HIV subjects: 144-week results-SINGLE (ING114467). 54th ICAAC, September 2014; Washington DC. [Abstract H647a].
44. Lathouwers E, De M, Dierynck I, et al. Virological characterization of patients failing darunavir/ritonavir or lopinavir/ritonavir treatment in the ARTEMIS study: 96-week analysis. Antivir Ther. 2011;16:99-108.
45. Raffi F, Babiker A, Richert L, et al. First-line Raltegravir + Darunavir/Ritonavir is non-inferior to tenofovir/emtricitabine + DRV/r: The NEAT 001/ANRS 143 randomised trial. CROI 2014. Boston, MA. [Abstract 84LB].
46. Landovitz, R, Ribaudo H, et al. Efficacy and Tolerability of Atazanavir, Raltegravir, or Darunavir with FTC/TDF: ACTG A5257. CROI 2014. Boston, MA. [Abstarct 85].
47. Molina J, Andrade-Villanueva J, Echevarria J, et al. Once-daily atazanavir/ritonavir compared with twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 96-week efficacy and safety results of the CASTLE study. J Acquir Immune Defic Syndr. 2010; 53:323-32.
48. Daar E, Tierney C, Fischl M, et al. Atazanavir plus ritonavir or efavirenz as part of a 3-drug regimen for initial treatment of HIV-1. Ann Intern Med. 2011;154:445-56.
49. Rockstroh J, DeJesus E, Henry K, et al. A randomized, double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir DF vs ritonavir-boosted atazanavir plus coformulated emtricitabine and tenofovir DF for initial treatment of HIV-1 infection: analysis of week 96 results. J Acquir Immune Defic Syndr. 2013;62:483-6.
50. Zolopa A, Sax P, DeJesus E, et al. 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. J Acquir Immune Defic Syndr. 2013;63:96-100.
51. Lennox J, DeJesus E, Berger D, et al. Raltegravir versus Efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses. J Acquir Immune Defic Syndr. 2010;55:39-48.
52. Cohen C, Wohl D, Arribas J, et al. Week 48 results from a randomized clinical trial of rilpivirine/emtricitabine/tenofovir disoproxil fumarate vs. efavirenz/emtricitabine/tenofovir disoproxil fumarate in treatment-naive HIV-1-infected adults. AIDS. 2014;28:989-97.
53. Cohen C, Molina J, Cassetti I, et al. Week 96 efficacy and safety of rilpivirine in treatment-naive, HIV-1 patients in two Phase III randomized trials. AIDS. 2013;27:939-50.
54. Elion R, Molina J, Ramon Arribas L, et al. A randomized phase 3 study comparing once-daily elvitegravir with twice-daily raltegravir in treatment-experienced subjects with HIV-1 infection: 96-week results. J Acquir Immune Defic Syndr. 2013;63:494-7.
55. Molina J, Lamarca A, Andrade-Villanueva J, et al. 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. Lancet Infect Dis. 2012;12:27-35.
56. Banhegyi D, Katlama C, da Cunha C, et al. Week 96 efficacy, virology and safety of darunavir/r versus lopinavir/r in treatment-experienced patients in TITAN. Curr HIV Res. 2012;10:171-81.
57. Madruga J, Berger D, McMurchie M, et al. Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial. Lancet. 2007;370:49-58.
58. Garrido C, Villacian J, Zahonero N, et al. Broad phenotypic cross-resistance to elvitegravir in HIV-infected patients failing on raltegravir-containing regimens. Antimicrob Agents Chemother. 2012;56:2873-8.
59. Underwood M, Johns B, Sato A, et al. 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.
60. Vavro C, Huang J, Underwood M, et al. Integrase genotypic and phenotypic predictors of antiviral response to dolutegravir in subjects with resistance to integrase inhibitors. Intl Workshop on HIV & Hepatitis Virus Drug Res and Curative Strategies. June 2013. Toronto, Canada. [Abstract 29].
61. Vavro C, Huang J, Avatapally C, et al. Durable efficacy and limited Integrase resistance in subjects receiving Dolutegravir after failing a prior INI regimen: Week 48 results from VIKING-3. 12th European Workshop on HIV & Hepatitis Treatment Strategies & Antiviral Drug Resistance. March 2014. Barcelona, Spain. [O-10].
62. Underwood M, Dudas K, Horton J, et al. Analysis and characterization of treatment-emergent resistance in ART-experienced, integrase inhibitor-naive subjects with dolutegravir versus raltegravir in SAILING (ING111762). Intl Workshop on HIV & Hepatitis Virus Drug Res and Curative Strategies. June 2013. Toronto, Canada. [Abstract 21].
63. Hardy I, Brenner B, Quashie P, et al. Evolution of a novel pathway leading to dolutegravir resistance in a patient harbouring N155H and multiclass drug resistance. J Antimicrob Chemother. 2014. [Epub ahead of print].
64. de Souza C, Ferreira J, Guimaraes P, et al. High frequency of dolutegravir resistance in patients failing a raltegravir-containing salvage regimen. J Antimicrob Chemother. 2014;43:287-91.
65. Garrido C, De M, Alvarez E, et al. Plasma raltegravir exposure influences the antiviral activity and selection of resistance mutations. AIDS Res Hum Retroviruses. 2012;28:156-64.