Naturally occurring resistance-associated variants to NS3/4A protease and NS5A inhibitors in patients with HIV/HCV co-infection or HCV infection alone

Haohui DENG; Shuifeng LI; Qianchang FENG; Linghua LI

doi:10.3969/j.issn.1001-5256.2022.02.015

Volume 38 Issue 2

Feb. 2022

Turn off MathJax

Article Contents

Article Navigation > Journal of Clinical Hepatology > 2022 > 38(2): 328-333

PDF( 1939 KB)

Naturally occurring resistance-associated variants to NS3/4A protease and NS5A inhibitors in patients with HIV/HCV co-infection or HCV infection alone

DOI: 10.3969/j.issn.1001-5256.2022.02.015

Infectious Disease Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China

Research funding:

Medical Scientific Research Foundation of Guangdong Province, China (B2021302);

Chinese 13th Five-Year National Science and Technology Major Project (2017ZX10202101-003);

National Natural Science Foundation of China (82072265);

Guangzhou Basic Research Program on People's Livelihood Science and Technology (202002020005)

More Information

Corresponding author: LI Linghua, llheliza@126.com
Received Date: 2021-05-04
Accepted Date: 2021-06-05
Published Date: 2022-02-20

Abstract

Abstract

Objective To investigate the difference in naturally occurring resistance-associated variants (RAVs) between the patients with HIV/HCV co-infection and those with HCV infection alone by detecting the drug resistance loci associated with HCV NS3/4A protease and NS5A inhibitors. Methods A total of 246 patients with HIV/HCV co-infection or HCV infection alone who were hospitalized or attended the outpatient service in Guangzhou Eighth People's Hospital, Guangzhou Medical University, from January 2016 to January 2020 were enrolled in this study. Serum samples were collected and next-generation sequencing (Illumina platform, PE250) was used for sequencing. The two groups of patients were compared in terms of RAVs associated with NS3/4A protease and NS5A inhibitors approved in China, and the drugs for analysis included asunaprevir/daclatasvir (ASV/DCV) and elbasvir/grazoprevir (EBR/GZR) for HCV genotype 1b and glecaprevir/pibrentasvir (GLE/PIB) for pan-genotypes. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results Among the 246 serum samples included in this study, 239 samples (97.2%) were successfully amplified by PCR and sequenced, with 102 samples from the patients with HIV/HCV co-infection and 137 from the patients with HCV infection alone. The analysis of RAVs associated with ASV/DCV and EBR/GZR showed that Y56F, Q80K/L, and S122N/R/T associated with ASV and GZR and L31M and Y93H associated with DCV and EBR were observed in patients with HIV/HCV (genotype 1b) co-infection or HCV (genotype 1b) infection alone; 2 patients with HIV/HCV co-infection had the RAVs of Y56F+Y93H associated with EBR/GZR, and 2 with HCV infection alone had the RAVs of Q80L+L31M and Y56F+Y93H, respectively, associated with EBR/GZR, with no significant difference in RAVs between the two groups (both P > 0.05). The analysis of RAVs associated with GLE/PIB for pan-genotypes showed that 3 patients with PIB-associated Y93H RAV were observed among the patients with HCV genotype 3a infection, among whom 2 had HIV/HCV co-infection and 1 had HCV infection alone (P=0.590), and in addition, no RAVs associated with GLE/PIB were observed. Conclusion There is no significant difference in naturally occurring RAVs associated with HCV NS3/4A protease and NS5A inhibitors between the patients with HIV/HCV co-infection and those with HCV infection alone.
- HIV,
- Hepacivirus,
- Direct Antiviral Drugs,
- Drug Resistance Variation

FullText(HTML)

References(17)

References

[1]	Chinese Society of Hepatology and Chinese Society of Infectious Diseases. Guideline of prevention and treatment for hepatitis C (2019 version)[J]. J Clin Hepatol, 2019, 35(12): 2670-2686. DOI: 10.3969/j.issn.1001-5256.2019.12.008. 中华医学会肝病学分会, 中华医学会感染病学分会. 丙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35(12): 2670-2686. DOI: 10.3969/j.issn.1001-5256.2019.12.008.
[2]	AIDS and Hepatitis C Professional Group and Society of Infectious Diseases, Chinese Medical Association, Chinese Center for Disease Control and Prevention. Chinese guidelines for diagnosis and treatment of HIV/AIDS (2018)[J]. Chin J Infect Dis, 2018, 36(12): 705-724. DOI: 10.3760/cma.j.issn.1000-6680.2018.12.001. 中华医学会感染病学分会艾滋病丙型肝炎学组, 中国疾病预防与控制中心. 中国艾滋病诊疗指南(2018版)[J]. 中华传染病杂志, 2018, 36(12): 705-724. DOI: 10.3760/cma.j.issn.1000-6680.2018.12.001.
[3]	SORBO MC, CENTO V, DI MAIO VC, et al. Hepatitis C virus drug resistance associated substitutions and their clinical relevance: Update 2018[J]. Drug Resist Updat, 2018, 37: 17-39. DOI: 10.1016/j.drup.2018.01.004.
[4]	IKEGAMI T, UEDA Y, AKAMATSU N, et al. Asunaprevir and daclatasvir for recurrent hepatitis C after liver transplantation: A Japanese multicenter experience[J]. Clin Transplant, 2017, 31(11): e13109. DOI: 10.1111/ctr.13109.
[5]	SUDA G, FURUSYO N, TOYODA H, et al. Daclatasvir and asunaprevir in hemodialysis patients with hepatitis C virus infection: A nationwide retrospective study in Japan[J]. J Gastroenterol, 2018, 53(1): 119-128. DOI: 10.1007/s00535-017-1353-y.
[6]	NG TI, KRISHNAN P, PILOT-MATIAS T, et al. In vitro antiviral activity and resistance profile of the next-generation hepatitis C virus NS5A inhibitor pibrentasvir[J]. Antimicrob Agents Chemother, 2017, 61(5): e02558-16. DOI: 10.1128/AAC.02558-16.
[7]	NG TI, TRIPATHI R, REISCH T, et al. In vitro antiviral activity and resistance profile of the next-generation hepatitis C virus NS3/4A protease inhibitor glecaprevir[J]. Antimicrob Agents Chemother, 2018, 62(1): e01620-17. DOI: 10.1128/AAC.01620-17.
[8]	DENG HH, XU M, LIU HY, et al. HCV NS5A and NS5B inhibitor natural resistance mutations in patients with chronic hepatitis C and hepatitis C cirrhosis[J]. J Trop Med, 2020, 20(4): 484-488. DOI: 10.3969/j.issn.1672-3619.2020.04.014. 邓浩辉, 许敏, 刘惠媛, 等. 慢性丙型肝炎和丙型肝炎肝硬化患者HCV NS5A和NS5B抑制剂天然耐药变异分析[J]. 热带医学杂志, 2020, 20(4): 484-488. DOI: 10.3969/j.issn.1672-3619.2020.04.014.
[9]	DENG HH, XU M, LOU Y, et al. Analysis of resistance mutations in patients with persistent low viral load during antiviral therapy with tebivudine alone or in combination with adefovir dipivoxil[J]. Chin J Hepatol, 2019, 27(10): 802-805. DOI: 10.3760/cma.j.issn.1007-3418.2019.10.013. 邓浩辉, 许敏, 楼燕, 等. 替比夫定单药或联合阿德福韦酯抗病毒治疗过程中持续低病毒载量者耐药变异分析[J]. 中华肝脏病杂志, 2019, 27(10): 802-805. DOI: 10.3760/cma.j.issn.1007-3418.2019.10.013.
[10]	SARRAZIN C, DVORY-SOBOL H, SVAROVSKAIA ES, et al. Prevalence of resistance-associated substitutions in HCV NS5A, NS5B, or NS3 and outcomes of treatment with ledipasvir and sofosbuvir[J]. Gastroenterology, 2016, 151(3): 501-512. e1. DOI: 10.1053/j.gastro.2016.06.002.
[11]	OMATA M, KANDA T, WEI L, et al. APASL consensus statements and recommendation on treatment of hepatitis C[J]. Hepatol Int, 2016, 10(5): 702-726. DOI: 10.1007/s12072-016-9717-6.
[12]	SHIN SK, LEE JW, RA H, et al. Durability of sustained virologic response and improvement of fibrosis markers after daclatasvir and asunaprevir treatment in genotype 1b hepatitis C virus-infected patients: A real life and multicenter study[J]. J Korean Med Sci, 2019, 34(41): e264. DOI: 10.3346/jkms.2019.34.e264.
[13]	QUARANTA MG, ROSATO S, FERRIGNO L, et al. Real-life use of elbasvir/grazoprevir in adults and elderly patients: A prospective evaluation of comedications used in the PITER cohort[J]. Antivir Ther, 2020, 25(2): 73-81. DOI: 10.3851/IMP3350.
[14]	LIU CH, LIU CJ, HUNG CC, et al. Glecaprevir/pibrentasvir for patients with chronic hepatitis C virus infection: Real-world effectiveness and safety in Taiwan[J]. Liver Int, 2020, 40(4): 758-768. DOI: 10.1111/liv.14295.
[15]	ZENG ZJ, DAI J, CHEN HC, et al. Naturally occurring resistance-associated variants to NS5A inhibitor in HIV-1 and HCV co-infected intravenous drug users in Yunnan province[J]. Chin J AIDS STD, 2019, 25(9): 911-916. DOI: 10.13419/j.cnki.aids.2019.09.10. 曾志君, 戴洁, 陈会超, 等. 静脉注射吸毒者HIV-1/HCV共感染的HCVNS5A抑制剂天然耐药相关变异分析[J]. 中国艾滋病性病, 2019, 25(9): 911-916. DOI: 10.13419/j.cnki.aids.2019.09.10.
[16]	CHEN M, CHEN HC, DAI J, et al. Naturally occurring resistance associated variations for HCV NS3 protease inhibitors among intravenous drug users co-infected with HIV-1 and HCV in Yunnan province[J]. Chin J AIDS STD, 2018, 24(6): 548-552. DOI: 10.13419/j.cnki.aids.2018.06.05. 陈敏, 陈会超, 戴洁, 等. 静脉注射吸毒者HIV-1/HCV共感染的HCV NS3蛋白酶抑制剂天然耐药相关变异分析[J]. 中国艾滋病性病, 2018, 24(6): 548-552. DOI: 10.13419/j.cnki.aids.2018.06.05.
[17]	DENG H, DENG X, LIU Y, et al. Naturally occurring antiviral drug resistance in HIV patients who are mono-infected or co-infected with HBV or HCV in China[J]. J Med Virol, 2018, 90(7): 1246-1256. DOI: 10.1002/jmv.25078.

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Tables(6)

Get Citation

PDF

XML

Article Metrics

Article views (379) PDF downloads(35)

Naturally occurring resistance-associated variants to NS3/4A protease and NS5A inhibitors in patients with HIV/HCV co-infection or HCV infection alone

DOI: 10.3969/j.issn.1001-5256.2022.02.015

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Naturally occurring resistance-associated variants to NS3/4A protease and NS5A inhibitors in patients with HIV/HCV co-infection or HCV infection alone

DOI: 10.3969/j.issn.1001-5256.2022.02.015

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content