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 D0I1FQ
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.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.