| Drug General Information |
| Drug ID |
D0I1FQ
|
| Drug Name |
Raltegravir |
|
| Synonyms |
RGV; MK 0518; Isentress(TM); K-0518; MK-0518; Raltegravir (INN); N-(2-(4-(4-fluorobenzylcarbamoyl); N-((4-Fluorophenyl)methyl)-1,6-dihydro-5-hydroxy-1-methyl-2-(1-methyl-1-(((5-methyl-1,3,4-oxadiazol-2-yl)carbonyl)amino)ethyl)-6-oxo-4-pyrimidinecarboxamide; RAL |
| Drug Type |
Small molecular drug |
| Company |
Merck |
| 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] |
| Level of Resistance |
Reduce RAL susceptibility >10 fold |
|
| Mutation info |
Missense: Q148H |
[1] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: Q148K |
[1] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: Q148R |
[1] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: Y143C |
[2], [3], [4] |
| Level of Resistance |
Reduce RAL susceptibility 5 fold |
|
| Mutation info |
Missense: Y143R |
[2], [3], [4] |
| Level of Resistance |
Reduce RAL susceptibility 20 fold |
|
| Mutation info |
Missense: T97A |
[2], [5], [6] |
| Level of Resistance |
Reduce susceptibility to RAL |
|
| Mutation info |
Missense: E92Q |
[3], [6], [7] |
| Level of Resistance |
Reduce RAL susceptibility >5 fold |
|
| Mutation info |
Missense: T66A |
[8], [9] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: E138A/K/T + G140A/C/S |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: E138A |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: E138K |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: E138T |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: E92G |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: E92V |
[10], [11] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: F121Y |
[10], [11] |
| Level of Resistance |
Reduce RAL susceptibility 10 fold |
|
| Mutation info |
Missense: G118R |
[10], [11] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: G140A |
[10], [11] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: G140C |
[10], [11] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: G140S |
[10], [11] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: G163K |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: G163R |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: H51Y |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: N155S |
[10], [11] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: N155T |
[10], [11] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: R263K |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: T66I |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: T66K |
[10], [11] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: V151A |
[10], [11] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: V151L |
[10], [11] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: Y143A |
[10], [11] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: Y143G |
[10], [11] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: Y143H |
[10], [11] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: Y143K |
[10], [11] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: Y143S |
[10], [11] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: E157Q |
[5] |
| Level of Resistance |
Reduce RAL susceptibility 2-3 fold |
|
| Mutation info |
Missense: S230R |
[3] |
| Level of Resistance |
Low-level resistance |
|
| References |
| REF 1 |
Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med. 2008 Jul 24;359(4):355-65.
|
| REF 2 |
Genotypic/phenotypic patterns of HIV-1 integrase resistance to raltegravir. J Antimicrob Chemother. 2010 Mar;65(3):425-33.
|
| REF 3 |
HIV-1 integrase inhibitor resistance and its clinical implications. J Infect Dis. 2011 May 1;203(9):1204-14.
|
| REF 4 |
Broad phenotypic cross-resistance to elvitegravir in HIV-infected patients failing on raltegravir-containing regimens. Antimicrob Agents Chemother. 2012 Jun;56(6):2873-8.
|
| REF 5 |
Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro. Antimicrob Agents Chemother. 2008 Apr;52(4):1351-8.
|
| REF 6 |
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 7 |
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 8 |
Drug resistance profiles for the HIV integrase gene in patients failing raltegravir salvage therapy. HIV Med. 2008 Oct;9(9):765-70.
|
| REF 9 |
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 Apr 1;53(4):456-63.
|
| REF 10 |
The HIVdb system for HIV-1 genotypic resistance interpretation. Intervirology. 2012;55(2):98-101.
|
| REF 11 |
Resistance to direct-acting antiviral agents: clinical utility and significance. Curr Opin HIV AIDS. 2015 Sep;10(5):381-9.
|
