| Drug General Information |
| Drug ID |
D0O2EM
|
| Drug Name |
Nevirapine |
|
| Synonyms |
NEV; NVP; Viramune; Cahill May Roberts Brand of Nevirapine; Promeco Brand of Nevirapine; BI RG 587; BIRG 0587; BIRG 587; BIRG587; BIRG-0587; BIRG-587; NON-NUCLEOSIDE RT INHIBITOR NEVIRAPINE; Nevirapine & PRO 140; Nevirapine [USAN:INN]; Viramune (TN); Viramune(TM); BI-RG-587; Nevirapine & CD4-IgG; Nevirapine (JAN/USP/INN); Viramune, BI-RG 587, Nevirapine; BI-RG-587 & CD4-IgG; N11-Cyclopropyl-4-methyl-5,11-dihydro-6H-dipyrido[3,2-b:2',3'-e]-[1,4]diazepin-6-one & CD4-immunoadhesin; 11-CYCLOPROPYL-5,11-DIHYDRO-4-METHYL-6H-DIPYRIDO[3,2-B:2',3'-E][1,4]DIAZEPIN-6-ONE; 11-Cyclopropyl-4-methyl-5,11-dihydro-6H-dipyrido[2,3-e:3',2'-b][1,4]diazepin-6-one; 11-Cyclopropyl-4-methyl-5,11-dihydro-6H-dipyrido[2,3-e:3',2'-b][1,4]diazepin-6-one & PRO 140 (Anti-CCR5 monoclonal antibody); 11-Cyclopropyl-4-methyl-5,11-dihydro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one; 11-Cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido(3,2-b:2',3'-e)(1,4)diazepin-6-one |
| Drug Type |
Small molecular drug |
| Therapeutic Class |
Anti-HIV Agents |
| Company |
Boehringer Ingelheim |
| Structure |
|
| Drug Resistance Mutations |
| Target Name |
HIV Non-Nucleoside reverse transcriptase |
Target Info |
| 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 |
[1], [2] |
| Level of Resistance |
Reduce NVP susceptibility >50 fold |
|
| Mutation info |
Missense: K103N |
[3] |
| Level of Resistance |
Reduce NVP susceptibility about 50 fold |
|
| Mutation info |
Missense: V106A |
[4] |
| Level of Resistance |
Reduce NVP susceptibility 50 fold |
|
| Mutation info |
Missense: K101P |
[5] |
| Level of Resistance |
Reduce NVP susceptibility >50 fold |
|
| Mutation info |
Missense: Y181C |
[5] |
| Level of Resistance |
Reduce NVP susceptibility >50 fold |
|
| Mutation info |
Missense: V108I |
[6] |
| Level of Resistance |
Reduce NVP susceptibility about 2 fold |
|
| Mutation info |
Missense: A98G |
[7], [8], [9] |
| Level of Resistance |
Reduce NVP susceptibility about 2-3 fold |
|
| Mutation info |
Missense: K101E |
[3], [5], [10] |
| Level of Resistance |
Reduce NVP susceptibility 3-10 fold |
|
| Mutation info |
Missense: N348I |
[11], [12], [13] |
| Level of Resistance |
Reduce NVP susceptibility 3 fold |
|
| Mutation info |
Missense: K101H |
[5], [10], [14] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: G190E |
[2], [9], [15] |
| Level of Resistance |
Confer high-level resistance to NVP |
|
| Mutation info |
Missense: V179E |
[9], [16], [17] |
| Level of Resistance |
Confer low-level resistance to NVP |
|
| Mutation info |
Missense: G190A |
[7], [8], [18] |
| Level of Resistance |
Reduce NVP susceptibility >50 fold |
|
| Mutation info |
Missense: G190S |
[7], [8], [18] |
| Level of Resistance |
Reduce NVP susceptibility >50 fold |
|
| Mutation info |
Missense: K103T |
[9], [19], [20] |
| Level of Resistance |
Reduce NVP susceptibility 10 fold |
|
| Mutation info |
Missense: K103S |
[8], [19], [21] |
| Level of Resistance |
Cause high-level resistance to NVP |
|
| Mutation info |
Missense: K238T |
[9], [16], [22] |
| Level of Resistance |
Reduce NVP susceptibility about 5 fold |
|
| Mutation info |
Missense: Y318F |
[1], [2] |
| Level of Resistance |
Reduce NVP susceptibility about 5 fold |
|
| Mutation info |
Missense: G190Q |
[18], [21] |
| Level of Resistance |
Confer high-level resistance to NVP |
|
| Mutation info |
Missense: Y188H |
[8], [21] |
| Level of Resistance |
Reduce NVP susceptibility 10 fold |
|
| Mutation info |
Missense: V179D |
[17], [21] |
| Level of Resistance |
Reduce NVP susceptibility 2-5 fold |
|
| Mutation info |
Missense: K238N |
[14], [9] |
| Level of Resistance |
Reduce susceptibility to NVP |
|
| Mutation info |
Missense: L100V |
[23], [9] |
| Level of Resistance |
Reduce NVP susceptibility 5 fold |
|
| Mutation info |
Missense: V106M |
[9], [21] |
| Level of Resistance |
Reduce NVP susceptibility >30 fold |
|
| Mutation info |
Missense: F227L |
[24], [25] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: G190C |
[24], [25] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: G190T |
[24], [25] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: G190V |
[24], [25] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: H221Y |
[24], [25] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: L100I |
[24], [25] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: M230L |
[24], [25] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: P225H |
[24], [25] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: V179F |
[24], [25] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: Y181F |
[24], [25] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: Y181G |
[24], [25] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: Y181I |
[24], [25] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: Y181V |
[24], [25] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: Y188F |
[24], [25] |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: K103R + V179D |
[24], [26] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: K103H |
[19] |
| Level of Resistance |
Reduce NVP susceptibility 20 fold |
|
| Mutation info |
Missense: Y181S |
[27] |
| Level of Resistance |
Reduce NVP susceptibility about 30 fold |
|
| Mutation info |
Missense: Y188C |
[21] |
| Level of Resistance |
Reduce NVP susceptibility >50 fold |
|
| Mutation info |
Missense: E138G |
[28] |
| Level of Resistance |
Reduce NVP susceptibility 2 fold |
|
| Mutation info |
Missense: F227C |
[28] |
| Level of Resistance |
Reduce NVP susceptibility 17 fold |
|
| Mutation info |
Missense: M230I |
[28] |
| Level of Resistance |
Reduce NVP susceptibility 16 fold |
|
| References |
| REF 1 |
A mutation in the 3' region of the human immunodeficiency virus type 1 reverse transcriptase (Y318F) associated with nonnucleoside reverse transcriptase inhibitor resistance. J Virol. 2002 Jul;76(13):6836-40.
|
| REF 2 |
TMC125 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 3 |
Human immunodeficiency virus type 1 mutations selected in patients failing efavirenz combination therapy. Antimicrob Agents Chemother. 2000 Sep;44(9):2475-84.
|
| REF 4 |
Convergent combination therapy can select viable multidrug-resistant HIV-1 in vitro. Nature. 1993 Sep 30;365(6445):451-3.
|
| REF 5 |
Constrained patterns of covariation and clustering of HIV-1 non-nucleoside reverse transcriptase inhibitor resistance mutations. J Antimicrob Chemother. 2010 Jul;65(7):1477-85.
|
| REF 6 |
Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro. PLoS One. 2012;7(9):e44333.
|
| REF 7 |
Distribution 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 8 |
A novel nonnucleoside analogue that inhibits human immunodeficiency virus type 1 isolates resistant to current nonnucleoside reverse transcriptase ... Antimicrob Agents Chemother. 2007 Feb;51(2):429-37.
|
| REF 9 |
Significantly improved HIV inhibitor efficacy prediction employing proteochemometric models generated from antivirogram data. PLoS Comput Biol. 2013;9(2):e1002899.
|
| REF 10 |
Characterization 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.
|
| REF 11 |
N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. PLoS Med. 2007 Dec;4(12):e335.
|
| REF 12 |
Amino 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.
|
| REF 13 |
Combinations 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.
|
| REF 14 |
Nonpolymorphic human immunodeficiency virus type 1 protease and reverse transcriptase treatment-selected mutations. Antimicrob Agents Chemother. 2009 Nov;53(11):4869-78.
|
| REF 15 |
TMC278, 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.
|
| REF 16 |
Human immunodeficiency virus reverse transcriptase and protease sequence database. Nucleic Acids Res. 2003 Jan 1;31(1):298-303.
|
| REF 17 |
Compilation and prevalence of mutations associated with resistance to non-nucleoside reverse transcriptase inhibitors. Antivir Ther. 2009;14(1):103-9.
|
| REF 18 |
Amino 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 19 |
Rare 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 20 |
In vitro selection of mutations in human immunodeficiency virus type 1 reverse transcriptase that confer resistance to capravirine, a novel nonnucl... Antiviral Res. 2006 Jun;70(2):66-74.
|
| REF 21 |
Non-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.
|
| REF 22 |
The 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 23 |
Quantitative prediction of integrase inhibitor resistance from genotype through consensus linear regression modeling. Virol J. 2013 Jan 3;10:8.
|
| REF 24 |
The HIVdb system for HIV-1 genotypic resistance interpretation. Intervirology. 2012;55(2):98-101.
|
| REF 25 |
Evolutionary consequences of drug resistance: shared principles across diverse targets and organisms. Nat Rev Genet. 2015 Aug;16(8):459-71.
|
| REF 26 |
Resistance to direct-acting antiviral agents: clinical utility and significance. Curr Opin HIV AIDS. 2015 Sep;10(5):381-9.
|
| REF 27 |
Phenotypic drug resistance patterns in subtype A HIV-1 clones with nonnucleoside reverse transcriptase resistance mutations. AIDS Res Hum Retroviruses. 2006 Mar;22(3):289-93.
|
| REF 28 |
Impact 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.
|
