| Drug General Information |
| Drug ID |
D0QD1G
|
| Drug Name |
Elvitegravir |
|
| Synonyms |
EVG |
| Drug Type |
Small molecular drug |
| Structure |
|
| Drug Resistance Mutations |
| Target Name |
HIV Integrase |
Target Info |
| Uniprot ID |
POL_HV1B1(1160-1447) |
| Species |
Human immunodeficiency virus type 1 (HIV-1) |
| Reference Sequence |
FLDGIDKAQDEHEKYHSNWRAMASDFNLPPVVAKEIVASCDKCQLKGEAMHGQVDCSPGI
WQLDCTHLEGKVILVAVHVASGYIEAEVIPAETGQETAYFLLKLAGRWPVKTIHTDNGSN
FTSATVKAACWWAGIKQEFGIPYNPQSQGVVESMNKELKKIIGQVRDQAEHLKTAVQMAV
FIHNFKRKGGIGGYSAGERIVDIIATDIQTKELQKQITKIQNFRVYYRDSRNPLWKGPAK
LLWKGEGAVVIQDNSDIKVVPRRKAKIIRDYGKQMAGDDCVASRQDED [Human immu
nodeficiency virus type 1 (HIV-1)]
|
| Targeted Disease |
HIV infection |
| Drug Resistance Mutations |
| Mutation info |
Missense: N155H |
[1], [2], [3] |
| Level of Resistance |
Reduce EVG susceptibility >30 fold |
|
| Mutation info |
Missense: Q148H |
[4] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: Q148K |
[4] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: Q148R |
[4] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: H51Y |
[5], [6], [7] |
| Level of Resistance |
Reduce EVG susceptibility 2-3 fold |
|
| Mutation info |
Missense: E92Q |
[1], [2], [3] |
| Level of Resistance |
Reduce EVG susceptibility >30 fold |
|
| Mutation info |
Missense: S153Y |
[5], [7] |
| Level of Resistance |
Reduce DTG susceptibility about 2 fold |
|
| Mutation info |
Missense: T66K |
[7], [1] |
| Level of Resistance |
Reduce EVG susceptibility 40-80 fold |
|
| Mutation info |
Missense: S147G |
[8], [1] |
| Level of Resistance |
Reduce EVG susceptibility 5-10 fold |
|
| Mutation info |
Missense: T66A |
[8], [1] |
| Level of Resistance |
Reduce EVG susceptibility 5 fold |
|
| Mutation info |
Missense: E138A/K/T + G140A/C/S |
[9], [10] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: E138A |
[9], [10] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: E138K |
[9], [10] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: E138T |
[9], [10] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: E92V |
[9], [10] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: G118R |
[9], [10] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: G140A |
[9], [10] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: G140C |
[9], [10] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: G140S |
[9], [10] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: G163K |
[9], [10] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: G163R |
[9], [10] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: H51Y + R263K |
[9], [10] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: N155S |
[9], [10] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: N155T |
[9], [10] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: P145S |
[9], [10] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: Q148N |
[9], [10] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: R263K |
[9], [10] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: S153F |
[9], [10] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: S230R |
[9], [10] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: T66I |
[9], [10] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: V151A |
[9], [10] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: V151L |
[9], [10] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: E157Q |
[5] |
| Level of Resistance |
Reduce EVG susceptibility 2-3 fold |
|
| Mutation info |
Missense: F121Y |
[5] |
| Level of Resistance |
Reduce EVG susceptibility about 30 fold |
|
| Mutation info |
Missense: Q146P |
[5] |
| Level of Resistance |
Reduce EVG susceptibility about 10 fold |
|
| Mutation info |
Missense: E92G |
[8] |
| Level of Resistance |
Reduce EVG susceptibility 10 fold |
|
| Mutation info |
Missense: T97A |
[8] |
| Level of Resistance |
Reduce EVG susceptibility 5-10 fold |
|
| References |
| REF 1 |
Development of elvitegravir resistance and linkage of integrase inhibitor mutations with protease and reverse transcriptase resistance mutations. PLoS One. 2012;7(7):e40514.
|
| REF 2 |
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 Jun 30;379(9835):2429-38.
|
| REF 3 |
Infrequent development of drug resistance in HIV-1-infected treatment-naive subjects after 96 weeks of treatment with elvitegravir/cobicistat/emtri... Antivir Ther. 2017;22(5):443-446.
|
| REF 4 |
Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med. 2008 Jul 24;359(4):355-65.
|
| REF 5 |
Broad antiretroviral activity and resistance profile of the novel human immunodeficiency virus integrase inhibitor elvitegravir (JTK-303/GS-9137). J Virol. 2008 Jan;82(2):764-74.
|
| REF 6 |
Strand transfer inhibitors of HIV-1 integrase: bringing IN a new era of antiretroviral therapy. Antiviral Res. 2010 Jan;85(1):101-18.
|
| REF 7 |
In vitro resistance selections using elvitegravir, raltegravir, and two metabolites of elvitegravir M1 and M4. Antiviral Res. 2012 Feb;93(2):288-96.
|
| REF 8 |
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 Jan;12(1):27-35.
|
| REF 9 |
The HIVdb system for HIV-1 genotypic resistance interpretation. Intervirology. 2012;55(2):98-101.
|
| REF 10 |
Evolutionary consequences of drug resistance: shared principles across diverse targets and organisms. Nat Rev Genet. 2015 Aug;16(8):459-71.
|
