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Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance
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| Zeitschriftentitel: | Liver International |
|---|---|
| Personen und Körperschaften: | , , , , , , , |
| In: | Liver International, 40, 2020, 1, S. 83-91 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
|
| Schlagwörter: |
| author_facet |
Jiang, Dong Wang, Jianghua Zhao, Xuesen Li, Yuxin Zhang, Qun Song, Chuan Zeng, Hui Wang, Xianbo Jiang, Dong Wang, Jianghua Zhao, Xuesen Li, Yuxin Zhang, Qun Song, Chuan Zeng, Hui Wang, Xianbo |
|---|---|
| author |
Jiang, Dong Wang, Jianghua Zhao, Xuesen Li, Yuxin Zhang, Qun Song, Chuan Zeng, Hui Wang, Xianbo |
| spellingShingle |
Jiang, Dong Wang, Jianghua Zhao, Xuesen Li, Yuxin Zhang, Qun Song, Chuan Zeng, Hui Wang, Xianbo Liver International Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance Hepatology |
| author_sort |
jiang, dong |
| spelling |
Jiang, Dong Wang, Jianghua Zhao, Xuesen Li, Yuxin Zhang, Qun Song, Chuan Zeng, Hui Wang, Xianbo 1478-3223 1478-3231 Wiley Hepatology http://dx.doi.org/10.1111/liv.14241 <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Tenofovir disoproxil fumarate (TDF) imposes a high genetic barrier to drug resistance and potently inhibits replication of multidrug‐resistant hepatitis B virus. Few clinical cases with confirmed TDF‐resistance have been reported to date.</jats:p></jats:sec><jats:sec><jats:title>Methods and Results</jats:title><jats:p>Here, we report viral rebound in a patient with chronic hepatitis B who underwent TDF monotherapy and harboured a quadruple mutant consisting of classic entecavir (ETV)‐resistance mutations (rtL180M/T184L/M204V) together with an rtA200V mutation in the reverse transcriptase gene. Sequencing analysis revealed that this quadruple mutant emerged as a major viral population. In vitro phenotyping demonstrated that the rtL180M/T184L/A200V/M204V mutant had moderate resistance to TDF treatment, with a 4.52‐fold higher half maximal effective concentration than that of wild‐type virus. Importantly, this patient with TDF resistance achieved virological suppression after TDF/ETV combination rescue therapy.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>An rtL180M/T184L/A200V/M204V mutant with moderate resistance to TDF monotherapy was selected during sequential nucleoside analogue (NA) treatment in a stepwise manner. ETV/TDF combination therapy effectively suppressed replication of this TDF‐resistant mutant. Our studies provide novel insights into the treatment of NA‐naïve patients as well as patients with TDF resistance.</jats:p></jats:sec> Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance Liver International |
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Medizin |
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| imprint |
Wiley, 2020 |
| imprint_str_mv |
Wiley, 2020 |
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1478-3223 1478-3231 |
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1478-3223 1478-3231 |
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2020 |
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Liver International |
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49 |
| title |
Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance |
| title_unstemmed |
Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance |
| title_full |
Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance |
| title_fullStr |
Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance |
| title_full_unstemmed |
Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance |
| title_short |
Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance |
| title_sort |
entecavir resistance mutations rtl180m/t184l/m204v combined with rta200v lead to tenofovir resistance |
| topic |
Hepatology |
| url |
http://dx.doi.org/10.1111/liv.14241 |
| publishDate |
2020 |
| physical |
83-91 |
| description |
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Tenofovir disoproxil fumarate (TDF) imposes a high genetic barrier to drug resistance and potently inhibits replication of multidrug‐resistant hepatitis B virus. Few clinical cases with confirmed TDF‐resistance have been reported to date.</jats:p></jats:sec><jats:sec><jats:title>Methods and Results</jats:title><jats:p>Here, we report viral rebound in a patient with chronic hepatitis B who underwent TDF monotherapy and harboured a quadruple mutant consisting of classic entecavir (ETV)‐resistance mutations (rtL180M/T184L/M204V) together with an rtA200V mutation in the reverse transcriptase gene. Sequencing analysis revealed that this quadruple mutant emerged as a major viral population. In vitro phenotyping demonstrated that the rtL180M/T184L/A200V/M204V mutant had moderate resistance to TDF treatment, with a 4.52‐fold higher half maximal effective concentration than that of wild‐type virus. Importantly, this patient with TDF resistance achieved virological suppression after TDF/ETV combination rescue therapy.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>An rtL180M/T184L/A200V/M204V mutant with moderate resistance to TDF monotherapy was selected during sequential nucleoside analogue (NA) treatment in a stepwise manner. ETV/TDF combination therapy effectively suppressed replication of this TDF‐resistant mutant. Our studies provide novel insights into the treatment of NA‐naïve patients as well as patients with TDF resistance.</jats:p></jats:sec> |
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| author | Jiang, Dong, Wang, Jianghua, Zhao, Xuesen, Li, Yuxin, Zhang, Qun, Song, Chuan, Zeng, Hui, Wang, Xianbo |
| author_facet | Jiang, Dong, Wang, Jianghua, Zhao, Xuesen, Li, Yuxin, Zhang, Qun, Song, Chuan, Zeng, Hui, Wang, Xianbo, Jiang, Dong, Wang, Jianghua, Zhao, Xuesen, Li, Yuxin, Zhang, Qun, Song, Chuan, Zeng, Hui, Wang, Xianbo |
| author_sort | jiang, dong |
| container_issue | 1 |
| container_start_page | 83 |
| container_title | Liver International |
| container_volume | 40 |
| description | <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Tenofovir disoproxil fumarate (TDF) imposes a high genetic barrier to drug resistance and potently inhibits replication of multidrug‐resistant hepatitis B virus. Few clinical cases with confirmed TDF‐resistance have been reported to date.</jats:p></jats:sec><jats:sec><jats:title>Methods and Results</jats:title><jats:p>Here, we report viral rebound in a patient with chronic hepatitis B who underwent TDF monotherapy and harboured a quadruple mutant consisting of classic entecavir (ETV)‐resistance mutations (rtL180M/T184L/M204V) together with an rtA200V mutation in the reverse transcriptase gene. Sequencing analysis revealed that this quadruple mutant emerged as a major viral population. In vitro phenotyping demonstrated that the rtL180M/T184L/A200V/M204V mutant had moderate resistance to TDF treatment, with a 4.52‐fold higher half maximal effective concentration than that of wild‐type virus. Importantly, this patient with TDF resistance achieved virological suppression after TDF/ETV combination rescue therapy.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>An rtL180M/T184L/A200V/M204V mutant with moderate resistance to TDF monotherapy was selected during sequential nucleoside analogue (NA) treatment in a stepwise manner. ETV/TDF combination therapy effectively suppressed replication of this TDF‐resistant mutant. Our studies provide novel insights into the treatment of NA‐naïve patients as well as patients with TDF resistance.</jats:p></jats:sec> |
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| imprint_str_mv | Wiley, 2020 |
| institution | DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-D161 |
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| spelling | Jiang, Dong Wang, Jianghua Zhao, Xuesen Li, Yuxin Zhang, Qun Song, Chuan Zeng, Hui Wang, Xianbo 1478-3223 1478-3231 Wiley Hepatology http://dx.doi.org/10.1111/liv.14241 <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Tenofovir disoproxil fumarate (TDF) imposes a high genetic barrier to drug resistance and potently inhibits replication of multidrug‐resistant hepatitis B virus. Few clinical cases with confirmed TDF‐resistance have been reported to date.</jats:p></jats:sec><jats:sec><jats:title>Methods and Results</jats:title><jats:p>Here, we report viral rebound in a patient with chronic hepatitis B who underwent TDF monotherapy and harboured a quadruple mutant consisting of classic entecavir (ETV)‐resistance mutations (rtL180M/T184L/M204V) together with an rtA200V mutation in the reverse transcriptase gene. Sequencing analysis revealed that this quadruple mutant emerged as a major viral population. In vitro phenotyping demonstrated that the rtL180M/T184L/A200V/M204V mutant had moderate resistance to TDF treatment, with a 4.52‐fold higher half maximal effective concentration than that of wild‐type virus. Importantly, this patient with TDF resistance achieved virological suppression after TDF/ETV combination rescue therapy.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>An rtL180M/T184L/A200V/M204V mutant with moderate resistance to TDF monotherapy was selected during sequential nucleoside analogue (NA) treatment in a stepwise manner. ETV/TDF combination therapy effectively suppressed replication of this TDF‐resistant mutant. Our studies provide novel insights into the treatment of NA‐naïve patients as well as patients with TDF resistance.</jats:p></jats:sec> Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance Liver International |
| spellingShingle | Jiang, Dong, Wang, Jianghua, Zhao, Xuesen, Li, Yuxin, Zhang, Qun, Song, Chuan, Zeng, Hui, Wang, Xianbo, Liver International, Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance, Hepatology |
| title | Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance |
| title_full | Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance |
| title_fullStr | Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance |
| title_full_unstemmed | Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance |
| title_short | Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance |
| title_sort | entecavir resistance mutations rtl180m/t184l/m204v combined with rta200v lead to tenofovir resistance |
| title_unstemmed | Entecavir resistance mutations rtL180M/T184L/M204V combined with rtA200V lead to tenofovir resistance |
| topic | Hepatology |
| url | http://dx.doi.org/10.1111/liv.14241 |