Resistance mutation info of drug

Drug General Information
Drug ID D07HVY
Drug Name Efavirenz Drug Info
Synonyms EFV; EFZ; Eravirenz; Stocrin; Sustiva; DMP 266; L 743726; Atripla (TN); DMP-266; L-741211; L-743725; L-743726; Stocrin (TN); Strocin (TM); Sustiva (TM); Sustiva (TN); Efavirenz (JAN/INN); L-743,726; Zoxazin-2-one; Efavirenz, (S)-isomer; Met-SDF-1.beta. & Efavirenz; Met-Stromal Cell-derived Factor-1.beta. (Human) & Efavirenz; (-)-Efavirenz; (4S)-6-Chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one; (4S)-6-Chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one; (4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-1H-3,1-benzoxazin-2-one; (4S)-6-chloro-4-(cyclopropylethynyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one; (S)-6-Chloro-4-(2-cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-ben; (S)-6-Chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one; (S)-6-Chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one; 2H-3,1-Benzoxazin-2-one, 6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-, (4S)-(9; 6-chloro-4-(2-cyclopropyl-1-ethynyl)-4-trifluoromethyl-(4S)-1,4-dihydro-2H-benzo[d][1,3]oxazin-2-one; EFV
Drug Type Small molecular drug
Therapeutic Class Anti-HIV Agents
Structure D07HVY
Drug Resistance Mutations
Target Name HIV Non-Nucleoside reverse transcriptase
Uniprot ID POL_HV1B1(600-1159)
Species Human immunodeficiency virus type 1 (HIV-1)
Reference Sequence PISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALVEICTEMEKEGKISKIGPENPYNTPV
FAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPL
DEDFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQSSMTKILEPFKKQNPDIVI
YQYMDDLYVGSDLEIGQHRTKIEELRQHLLRWGLTTPDKKHQKEPPFLWMGYELHPDKWT
VQPIVLPEKDSWTVNDIQKLVGKLNWASQIYPGIKVRQLCKLLRGTKALTEVIPLTEEAE
LELAENREILKEPVHGVYYDPSKDLIAEIQKQGQGQWTYQIYQEPFKNLKTGKYARMRGA
HTNDVKQLTEAVQKITTESIVIWGKTPKFKLPIQKETWETWWTEYWQATWIPEWEFVNTP
PLVKLWYQLEKEPIVGAETFYVDGAANRETKLGKAGYVTNKGRQKVVPLTNTTNQKTELQ
AIYLALQDSGLEVNIVTDSQYALGIIQAQPDKSESELVNQIIEQLIKKEKVYLAWVPAHK
GIGGNEQVDKLVSAGIRKIL [Human immunodeficiency virus type 1 (H
IV-1)]
Targeted Disease HIV infection
Drug Resistance Mutations
Mutation info Missense: Y188L [555484]
Level of Resistance Reduce EFV susceptibility 5 fold
Mutation info Missense: K103N [555479]
Level of Resistance Reduce EFV susceptibility about 20 fold
Mutation info Missense: V106A [556164]
Level of Resistance Reduce EFV susceptibility 5 fold
Mutation info Missense: K101P [555757]
Level of Resistance Reduce EFV susceptibility >50 fold
Mutation info Missense: L100I [555479]
Level of Resistance High-level resistance
Mutation info Missense: Y181C [555757]
Level of Resistance Reduce EFV susceptibility about 2 fold
Mutation info Missense: V108I [555887]
Level of Resistance Reduce EFV susceptibility about 2 fold
Mutation info Missense: A98G [555544], [555618], [555925]
Level of Resistance Reduce EFV susceptibility about 2-3 fold
Mutation info Missense: N348I [555649], [555651], [555751]
Level of Resistance Reduce EFV susceptibility 2 fold
Mutation info Missense: K101E [555479], [555757], [555773]
Level of Resistance Reduce EFV susceptibility 1-5 fold
Mutation info Missense: G190E [555572], [555737], [555925]
Level of Resistance Confer high-level resistance to EFV
Mutation info Missense: V179E [555510], [555701], [555925]
Level of Resistance Confer low-level resistance to EFV
Mutation info Missense: G190A [555509], [555544], [555618]
Level of Resistance Reduce EFV susceptibility 5-10 fold
Mutation info Missense: G190S [555509], [555544], [555618]
Level of Resistance Reduce EFV susceptibility >50 fold
Mutation info Missense: K103S [555563], [555618], [555962]
Level of Resistance Cause high-level resistance to EFV
Mutation info Missense: K238T [555510], [555581], [555925]
Level of Resistance Reduce EFV susceptibility about 5 fold
Mutation info Missense: G190Q [555509], [555962]
Level of Resistance Confer high-level resistance to EFV
Mutation info Missense: Y188H [555618], [555962]
Level of Resistance Reduce EFV susceptibility 5 fold
Mutation info Missense: V179D [555701], [555962]
Level of Resistance Reduce EFV susceptibility 2-5 fold
Mutation info Missense: K238N [555726], [555925]
Level of Resistance Reduce susceptibility to EFV
Mutation info Missense: L100V [555914], [555925]
Level of Resistance Reduce EFV susceptibility 10 fold
Mutation info Missense: V106M [555925], [555962]
Level of Resistance Reduce EFV susceptibility >30 fold
Mutation info Missense: F227L [556228], [556246]
Level of Resistance Low-level resistance
Mutation info Missense: G190C [556228], [556246]
Level of Resistance High-level resistance
Mutation info Missense: G190T [556228], [556246]
Level of Resistance High-level resistance
Mutation info Missense: G190V [556228], [556246]
Level of Resistance High-level resistance
Mutation info Missense: K103R + V179D [556228], [556246]
Level of Resistance Low-level resistance
Mutation info Missense: K103T [556228], [556246]
Level of Resistance Low-level resistance
Mutation info Missense: M230L [556228], [556246]
Level of Resistance Intermediate resistance
Mutation info Missense: P225H [556228], [556246]
Level of Resistance Intermediate resistance
Mutation info Missense: V106A + F227L [556228], [556246]
Level of Resistance Low-level resistance
Mutation info Missense: Y181F [556228], [556246]
Level of Resistance Low-level resistance
Mutation info Missense: Y181G [556228], [556246]
Level of Resistance Low-level resistance
Mutation info Missense: Y181I [556228], [556246]
Level of Resistance Intermediate resistance
Mutation info Missense: Y181S [556228], [556246]
Level of Resistance Low-level resistance
Mutation info Missense: Y181V [556228], [556246]
Level of Resistance Intermediate resistance
Mutation info Missense: Y188F [556228], [556246]
Level of Resistance High-level resistance
Mutation info Missense: K103H [555563]
Level of Resistance Reduce EFV susceptibility 20 fold
Mutation info Missense: Y188C [555962]
Level of Resistance Reduce EFV susceptibility 20 fold
Mutation info Missense: E138G [556038]
Level of Resistance Reduce EFV susceptibility 2 fold
Mutation info Missense: F227C [556038]
Level of Resistance Reduce EFV susceptibility 4-5 fold
Mutation info Missense: M230I [556038]
Level of Resistance Reduce EFV susceptibility 11 fold
References
Ref 550326Approved antiretroviral drugs. Antiretroviral Drugs. Company report of AVERT. 2009.
Ref 555479Human immunodeficiency virus type 1 mutations selected in patients failing efavirenz combination therapy. Antimicrob Agents Chemother. 2000 Sep;44(9):2475-84.
Ref 555484Genotypic correlates of phenotypic resistance to efavirenz in virus isolates from patients failing nonnucleoside reverse transcriptase inhibitor therapy. J Virol. 2001 Jun;75(11):4999-5008.
Ref 555509Amino acid substitutions at position 190 of human immunodeficiency virus type 1 reverse transcriptase increase susceptibility to delavirdine and impair virus replication. J Virol. 2003 Jan;77(2):1512-23.
Ref 555510Human immunodeficiency virus reverse transcriptase and protease sequence database. Nucleic Acids Res. 2003 Jan 1;31(1):298-303.
Ref 555544Distribution of human immunodeficiency virus type 1 protease and reverse transcriptase mutation patterns in 4,183 persons undergoing genotypic resistance testing. Antimicrob Agents Chemother. 2004 Aug;48(8):3122-6.
Ref 555563Rare mutations at codon 103 of HIV-1 reverse transcriptase can confer resistance to non-nucleoside reverse transcriptase inhibitors. AIDS. 2005 Mar 24;19(6):549-54.
Ref 555572TMC125 displays a high genetic barrier to the development of resistance: evidence from in vitro selection experiments. J Virol. 2005 Oct;79(20):12773-82.
Ref 555581The K101P and K103R/V179D mutations in human immunodeficiency virus type 1 reverse transcriptase confer resistance to nonnucleoside reverse transcriptase inhibitors. Antimicrob Agents Chemother. 2006 Jan;50(1):351-4.
Ref 555618A novel nonnucleoside analogue that inhibits human immunodeficiency virus type 1 isolates resistant to current nonnucleoside reverse transcriptase inhibitors. Antimicrob Agents Chemother. 2007 Feb;51(2):429-37. Epub 2006 Nov 20.
Ref 555649N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. PLoS Med. 2007 Dec;4(12):e335.
Ref 555651Amino acid mutation N348I in the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase confers multiclass resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors. J Virol. 2008 Apr;82(7):3261-70. doi: 10.1128/JVI.01154-07. Epub 2008 Jan 23.
Ref 555701Compilation and prevalence of mutations associated with resistance to non-nucleoside reverse transcriptase inhibitors. Antivir Ther. 2009;14(1):103-9.
Ref 555726Nonpolymorphic human immunodeficiency virus type 1 protease and reverse transcriptase treatment-selected mutations. Antimicrob Agents Chemother. 2009 Nov;53(11):4869-78. doi: 10.1128/AAC.00592-09. Epub 2009 Aug 31.
Ref 555737TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. Antimicrob Agents Chemother. 2010 Feb;54(2):718-27. doi: 10.1128/AAC.00986-09. Epub 2009 Nov 23.
Ref 555751Combinations of mutations in the connection domain of human immunodeficiency virus type 1 reverse transcriptase: assessing the impact on nucleoside and nonnucleoside reverse transcriptase inhibitor resistance. Antimicrob Agents Chemother. 2010 May;54(5):1973-80. doi: 10.1128/AAC.00870-09. Epub 2010 Mar 1.
Ref 555757Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. J Antimicrob Chemother. 2010 Jul;65(7):1477-85. doi: 10.1093/jac/dkq140. Epub 2010 May 12.
Ref 555773Characterization of genotypic and phenotypic changes in HIV-1-infected patients with virologic failure on an etravirine-containing regimen in the DUET-1 and DUET-2 clinical studies. AIDS Res Hum Retroviruses. 2010 Nov;26(11):1197-205. doi: 10.1089/aid.2009.0302. Epub 2010 Sep 20.
Ref 556228The HIVdb system for HIV-1 genotypic resistance interpretation. Intervirology. 2012;55(2):98-101. doi: 10.1159/000331998. Epub 2012 Jan 24.
Ref 555887Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. PLoS One. 2012;7(9):e44333. doi: 10.1371/journal.pone.0044333. Epub 2012 Sep 12.
Ref 555914Quantitative prediction of integrase inhibitor resistance from genotype through consensus linear regression modeling. Virol J. 2013 Jan 3;10:8. doi: 10.1186/1743-422X-10-8.
Ref 555925Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. PLoS Comput Biol. 2013;9(2):e1002899. doi: 10.1371/journal.pcbi.1002899. Epub 2013 Feb 21.
Ref 555962Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing. J Antimicrob Chemother. 2014 Jan;69(1):12-20. doi: 10.1093/jac/dkt316. Epub 2013 Aug 9.
Ref 556038Impact of drug resistance-associated amino acid changes in HIV-1 subtype C on susceptibility to newer nonnucleoside reverse transcriptase inhibitors. Antimicrob Agents Chemother. 2015 Feb;59(2):960-71. doi: 10.1128/AAC.04215-14. Epub 2014 Nov 24.
Ref 556246Development and significance of nucleoside drug resistance in infection caused by the human immunodeficiency virus type 1. Clin Invest Med. 1994 Jun;17(3):226-43.
Ref 556164Convergent combination therapy can select viable multidrug-resistant HIV-1 in vitro. Nature. 1993 Sep 30;365(6445):451-3.

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