Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors

Journal of Antimicrobial Chemotherapy

Volumn 71, Issue 7, 2016, Pages 1948-1953

  Brenner, Bluma G ^a   Thomas, Réjean ^b   Blanco, José Luis ^c   Ibanescu, Ruxandra Ilinca ^a   Oliveira, Maureen ^a   Mesplède, Thibault ^a   Golubkov, Olga ^a   Roger, Michel ^d   Garcia, Federico ^e,f   Martinez, Esteban ^c   Wainberg, Mark A ^a  

^a MCGILL UNIVERSITY   (Canada)

^b Clinique Medicale l'Actuel   (Canada)

^c UNIVERSITY OF BARCELONA   (Spain)

^d CENTRE HOSPITALIER DE L UNIVERSITÉ DE MONTRÉAL   (Canada)

^e UNIVERSITY OF GRANADA   (Spain)

^f HOSPITAL UNIVERSITARIO SAN CECILIO   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

COBICISTAT PLUS DARUNAVIR; COBICISTAT PLUS DARUNAVIR PLUS EMTRICITABINE PLUS TENOFOVIR; COBICISTAT PLUS ELVITEGRAVIR PLUS EMTRICITABINE PLUS TENOFOVIR DISOPROXIL; DARUNAVIR PLUS RITONAVIR; DOLUTEGRAVIR; ELVITEGRAVIR; GLYCINE; INTEGRASE; INTEGRASE INHIBITOR; LORAZEPAM; LOSARTAN; PITAVASTATIN; RALTEGRAVIR; TRAZODONE; UNCLASSIFIED DRUG; VIRUS RNA; FUSED HETEROCYCLIC RINGS; P31 INTEGRASE PROTEIN, HUMAN IMMUNODEFICIENCY VIRUS 1;

ADULT; ANTIVIRAL THERAPY; ARTICLE; B CELL CULTURE; CASE REPORT; CD4 LYMPHOCYTE COUNT; CELL CULTURE; CLINICAL ASSESSMENT; CODON; CROSS RESISTANCE; DRUG ABUSE; DRUG DOSE REGIMEN; DRUG SENSITIVITY; DRUG SUBSTITUTION; DRUG TREATMENT FAILURE; GENE MUTATION; GENETIC ANALYSIS; GENETIC POLYMORPHISM; GENOTYPE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IN VITRO SELECTION; IN VITRO STUDY; MALE; MEDICAL HISTORY; MIDDLE AGED; MONOTHERAPY; OUTCOME ASSESSMENT; PATIENT COMPLIANCE; PERIPHERAL BLOOD MONONUCLEAR CELL; PHENOTYPIC VARIATION; TREATMENT DURATION; UNSPECIFIED SIDE EFFECT; VIREMIA; VIROLOGY; VIRUS LOAD; VIRUS RESISTANCE; ANTIVIRAL RESISTANCE; DRUG EFFECTS; GENETICS; GENOTYPING TECHNIQUE; HIV INFECTIONS; ISOLATION AND PURIFICATION; MICROBIAL SENSITIVITY TEST; MISSENSE MUTATION; TREATMENT FAILURE;

ADULT; DRUG RESISTANCE, VIRAL; GENOTYPING TECHNIQUES; HETEROCYCLIC COMPOUNDS, 3-RING; HIV INFECTIONS; HIV INTEGRASE; HIV INTEGRASE INHIBITORS; HIV-1; HUMANS; MALE; MICROBIAL SENSITIVITY TESTS; MIDDLE AGED; MUTATION, MISSENSE; TREATMENT FAILURE;

EID: 84978961912     PISSN: 03057453     EISSN: 14602091     Source Type: Journal    
DOI: 10.1093/jac/dkw071     Document Type: Article

References (26)

1. Wainberg MA, Zaharatos GJ, Brenner BG. Development of antiretroviral drug resistance. N Engl J Med 2011; 365: 637-46
2. Mesplede T, Quashie PK, Zanichelli V et al. Integrase strand transfer inhibitors in the management of HIV-positive individuals. Ann Med 2014; 46: 123-9
3. Osterholzer DA, Goldman M. Dolutegravir: a next-generation integrase inhibitor for treatment of HIV infection. Clin Infect Dis 2014; 59: 265-71
4. Walmsley S, Baumgarten A, Berenguer J et al. Brief Report: Dolutegravir plus abacavir/lamivudine for the treatment of HIV-1 infection in antiretroviral therapy-naive patients: Week 96 and Week 144 results from the SINGLE randomized clinical trial. J Acquir Immune Defic Syndr 2015; 70: 515-9
5. RaffiF, 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, noninferiority trial. Lancet Infect Dis 2013; 13: 927-35
6. Clotet B, Feinberg J, van Lunzen J 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
7. Quashie PK, Mesplede T, Han YS 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
8. Oliveira M, Mesplede T, Moisi D et al. The dolutegravir R263K resistance mutation in HIV-1 integrase is incompatible with the emergence of resistance against raltegravir. AIDS 2015; 29: 2255-60
9. Oliveira M, Mesplede T, Quashie PK et al. Resistance mutations against dolutegravir in HIV integrase impair the emergence of resistance against reverse transcriptase inhibitors. AIDS 2014; 28: 813-9
10. Mesplede T, Wainberg MA. Resistance against integrase strand transfer inhibitors and relevance to HIV persistence. Viruses 2015; 7: 3703-18
11. Quashie PK, Oliviera M, Veres T et al. Differential effects of the G118R, H51Y, and E138K resistance substitutions in different subtypes of HIV integrase. J Virol 2015; 89: 3163-75
12. Munir S, Thierry E, Malet I et al. G118R and F121Y mutations identified in patients failing raltegravir treatment confer dolutegravir resistance. J Antimicrob Chemother 2015; 70: 739-49
13. Katlama C, Soulié C, Blanc C et al. Dolutegravir monotherapy in HIV-infected patients with suppressed HIV viremia. In: Abstracts of the 15th European AIDS Conference Barcelona, Spain 2015, Abstract 714. European AIDS Clinical Society
14. Wainberg MA, Mesplede T, RaffiF. What if HIV were unable to develop resistance against a new therapeutic agent? BMC Med 2013; 11: 249
15. Figueroa MI, Sued O, Patterson P et al. Dolutegravir-Lamivudine as initial therapy in HIV-infected, ARV naive patients: First results of PADDLE. In: 15th European AIDS Conference Barcelona, October 21-24, 2015. Abstract 1066. European AIDS Clinical Society
16. Rojas J, Blanco JL, Martinez E et al. Dolutegravir monotherapy in HIV-infected patients with sustained viral suppression: a 24-week pilot study. In: 15th European AIDS Conference, Barcelona, Spain, 2015. Abstract 1108. European AIDS Clinical Society
17. Brenner BG, Lowe M, Moisi D et al. Subtype diversity associated with the development of HIV-1 resistance to integrase inhibitors. J Med Virol 2011; 83: 751-9
18. 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 2015; 70: 405-11
19. Quashie PK, Mesplede T, Han YS et al. Biochemical analysis of the role of G118R-linked dolutegravir drug resistance substitutions in HIV-1 integrase. Antimicrob Agents Chemother 2013; 57: 6223-35
20. Mesplede T, Wainberg MA. Is resistance to dolutegravir possible when this drug is used in first-line therapy? Viruses 2014; 6: 3377-85
21. Powdrill MH, Tchesnokov EP, Kozak RA et al. Contribution of a mutational bias in hepatitis C virus replication to the genetic barrier in the development of drug resistance. Proc Natl Acad Sci USA 2011; 108: 20509-13
22. Malet I, Fourati S, Charpentier C et al. The HIV-1 integrase G118R mutation confers raltegravir resistance to the CRF02_AG HIV-1 subtype. J Antimicrob Chemother 2011; 66: 2827-30
23. Malet I, Gimferrer Arriaga L, Artese A et al. New raltegravir resistance pathways induce broad cross-resistance to all currently used integrase inhibitors. J Antimicrob Chemother 2014; 69: 2118-22
24. Anstett K, Mesplede T, OliveiraMet al. Dolutegravir resistance mutation R263K cannot coexist in combination with many classical integrase inhibitor resistance substitutions. J Virol 2015; 89: 4681-4
25. Mesplede T, Moisi D, Oliveira M et al. Dolutegravir inhibits HIV-1 Env evolution in primary human cells. AIDS 2015; 29: 659-65
26. De Luca A, Wyen C. Should We Lower Drug Burden (Pro/Con Debate, Virological/Clinical Point of View). In: Abstracts of the 15th European AIDS Conference Barcelona, Spain, 2015. Session ML2. European AIDS Clinical Society