| Drug General Information |
| Drug ID |
D0D9HW
|
| Drug Name |
Tenofovir |
|
| Synonyms |
Apropovir; PMPA; TFV; Tenefovir; GS 1275; GS 1278; GS1278; GNA & Tenofovir; HHA & Tenofovir; KS-5021; Viread (TN); Viread, Tenofovir; D,L-Tenofovir; PMPA-(R); Phosphonic acid, [[2-(6-amino-9H-purin-9; [(2R)-1-(6-aminopurin-9-yl)propan-2-yl]oxymethylphosphonic acid; Phosphonic acid, [[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl]-(9CI); Phosphonic acid, [[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl]-& Galanthus nivalis agglutinin (GNA); Phosphonic acid, [[(1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy]methyl]-& Hippeastrum hybrid agglutinin(HHA); (R)-9-(2-Phosphonomethoxypropyl)adenine; (R)-9-(2-Phosphonylmethoxypropyl)adenine; (R)-PMPA |
| Drug Type |
Small molecular drug |
| Therapeutic Class |
Anti-HIV Agents |
| Company |
Gilead Sciences |
| Structure |
|
| Drug Resistance Mutations |
| Target Name |
HIV 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
PLVKLWYQLEKEPIVGAETFYVDGAANRETKLGKAGYVTN [Human immunodefici
ency virus type 1 (HIV-1)]
|
| Targeted Disease |
HIV infection |
| Drug Resistance Mutations |
| Mutation info |
Missense: Y115F |
[1] |
| Mutation Frequency |
9 out of 11 samples |
| Level of Resistance |
Reduce ABC susceptibility 3 fold |
|
| Mutation info |
Missense: K65R |
[1] |
| Mutation Frequency |
7 out of 19 samples |
| Level of Resistance |
High-level resistance |
|
| Mutation info |
Missense: M184V |
[2], [3] |
| Level of Resistance |
Confer reduce susceptibility to TDF |
|
| Mutation info |
Missense: K65N |
[4], [5], [6] |
| Level of Resistance |
Reduce susceptibility to TDF |
|
| Mutation info |
Missense: Q151M |
[2], [3], [7] |
| Level of Resistance |
Confer low-level resistance to TDF |
|
| Mutation info |
Missense: K70E |
[3], [2] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: K70G |
[3], [2] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: K70N |
[3], [2] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: K70Q |
[3], [2] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: K70R |
[3], [2] |
| Level of Resistance |
Confer low-level resistance to TDF |
|
| Mutation info |
Missense: K70S |
[3], [2] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: K70T |
[3], [2] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: M184* |
[3], [2] |
|
| Mutation info |
Missense: M41L |
[3], [2] |
|
| Mutation info |
Missense: T210W |
[3], [2] |
|
| Mutation info |
Missense: T215F |
[3], [2] |
|
| Mutation info |
Missense: F77L + F116Y + Q151M |
[3], [8] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: T215Y |
[3], [8] |
|
| Mutation info |
Missense: L74I |
[9] |
| Mutation Frequency |
3-20% of the samples |
|
| Mutation info |
Missense: L74V |
[10] |
|
| 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 |
Deletion: D67 |
[3], [8] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Deletion: K70 |
[3], [8] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Deletion: S68 |
[3], [8] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Insertion: T69 |
[3], [8] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Deletion: T69 |
[3], [8] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: K65R |
[11] |
| Mutation Frequency |
7 out of 19 samples |
|
| Mutation info |
Missense: M184I |
[11] |
|
| Mutation info |
Missense: E138A |
[7] |
|
| Mutation info |
Missense: H221Y |
[7] |
|
| Mutation info |
Missense: K101E |
[7] |
|
| Mutation info |
Missense: V106M |
[7] |
|
| Mutation info |
Missense: Y181C |
[7] |
|
| References |
| REF 1 |
High prevalence of the K65R mutation in HIV-1 subtype C infected patients failing tenofovir-based first-line regimens in South Africa. PLoS One. 2015 Feb 6;10(2):e0118145.
|
| REF 2 |
The population genetics of drug resistance evolution in natural populations of viral, bacterial and eukaryotic pathogens. Mol Ecol. 2016 Jan;25(1):42-66.
|
| REF 3 |
The HIVdb system for HIV-1 genotypic resistance interpretation. Intervirology. 2012;55(2):98-101.
|
| REF 4 |
A rare HIV reverse transcriptase mutation, K65N, confers reduced susceptibility to tenofovir, lamivudine and didanosine. AIDS. 2006 Mar 21;20(5):787-9.
|
| REF 5 |
In vitro human immunodeficiency virus type 1 resistance selections with combinations of tenofovir and emtricitabine or abacavir and lamivudine. Antimicrob Agents Chemother. 2006 Dec;50(12):4087-95.
|
| REF 6 |
Reverse transcriptase mutation K65N confers a decreased replication capacity to HIV-1 in comparison to K65R due to a decreased RT processivity. Virology. 2011 May 25;414(1):34-41.
|
| REF 7 |
HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. J Acquir Immune Defic Syndr. 2017 Jun 1;75(2):e45-e54.
|
| REF 8 |
HIV-1 drug resistance and resistance testing. Infect Genet Evol. 2016 Dec;46:292-307.
|
| REF 9 |
Identification of alternative amino acid substitutions in drug-resistant variants of the HIV-1 reverse transcriptase. AIDS. 2006 Jul 13;20(11):1515-20.
|
| REF 10 |
Impact of human immunodeficiency virus type 1 reverse transcriptase inhibitor drug resistance mutation interactions on phenotypic susceptibility. AIDS Res Hum Retroviruses. 2008 Oct;24(10):1291-300.
|
| REF 11 |
Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy. AIDS. 2013 Feb 20;27(4):553-61.
|
