Efficacy of switching to co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide combined with sofosbuvir/velpatasvir in treatment of previously untreated chronic hepatitis C patients with HIV/HCV co-infection and its influence on blood lipid levels

Bianli DANG; Wenzhen KANG; Mingyuan BI; Jianhui LI; Zhaoyun CHEN; Shupeng LI; Qing LIU; Yongtao SUN; Weiping CAI; Wen KANG

doi:10.3969/j.issn.1001-5256.2022.03.010

Volume 38 Issue 3

Mar. 2022

Turn off MathJax

Article Contents

Article Navigation > Journal of Clinical Hepatology > 2022 > 38(3): 541-546

PDF( 1942 KB)

Efficacy of switching to co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide combined with sofosbuvir/velpatasvir in treatment of previously untreated chronic hepatitis C patients with HIV/HCV co-infection and its influence on blood lipid levels

DOI: 10.3969/j.issn.1001-5256.2022.03.010

1.
Department of Infectious Diseases, Tangdu Hospital, Air Force Medical University, Xi'an 710038, China
2.
Infecctious Disease Center, The Sixth People's Hospital of Zhengzhou, Zhengzhou 450015, China
3.
Infectious Disease Center, Guangzhou Eighth People's Hospital, Guangzhou 510060, China

Research funding:

National Science and Technology Major Project during the 13^th Five-Year Plan Period (2017ZX10202101-003-007);

National Science and Technology Major Project during the 13^th Five-Year Plan Period (2017ZX10202101-004-005);

National Science and Technology Major Project during the 13^th Five-Year Plan Period (2017ZX10202203-008-003);

National Science and Technology Major Project during the 13^th Five-Year Plan Period (2017ZX10202102-002-001)

More Information

Corresponding author: KANG Wen, 82399536@qq.com(ORCID:0000-0002-4818-8183)
Received Date: 2021-07-21
Accepted Date: 2021-11-12
Published Date: 2022-03-20

Abstract

Abstract

Objective To investigate the efficacy of switching to co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/c/F/TAF) combined with sofosbuvir/velpatasvir (SOF/VEL) in the treatment of previously untreated chronic hepatitis C patients with HIV/HCV co-infection and the changes in blood lipid levels. Methods This prospective cohort study was conducted among 10 previously untreated chronic hepatitis C patients with HIV/HCV co-infection who attended Department of Infectious Diseases in Tangdu Hospital from July 2019 to May 2021 and achieved continuous HIV suppression after antiretroviral treatment (ART). As for anti-HIV therapy, the ART regimen was switched to the E/c/F/TAF regimen for 32 weeks, and for anti-HCV therapy, the SOF/VEL regimen was started since week 4 after switching and lasted for 12 weeks. Related indices were monitored before and after switching to E/c/F/TAF for anti-HCV therapy and SOF/VEL for anti-HCV therapy, including body weight, body mass index, HCV genotype, alpha-fetoprotein, liver stiffness measurement, CD4⁺T cell count, CD4⁺T/CD8⁺T ratio, hepatic and renal function parameters, blood lipids, HIV RNA, HCV RNA, SVR12, SVR24, and adverse reactions. The Mann-Whitney U test was used for comparison of continuous data between two groups, and a Spearman correlation analysis was performed. Results After 4 weeks of treatment with E/c/F/TAF, 10 patients (HCV genotypes 2a and 1b) had HIV RNA below the lower limit of detection (20 IU/ml) and a significant reduction in albumin (Z=-2.801, P=0.003 7), with the other indices remaining stable, and the patients reported significant improvements in the adverse events of anti-HIV therapy with the former ART regimen. After 4 weeks of E/c/F/TAF combined with SOF/VEL, the patients had HCV RNA below the lower limit of detection (15 IU/ml), and both SVR12 and SVR24 reached 100%; after 12 weeks of anti-HCV therapy, there were significant reductions in alanine aminotransferase (Z=-2.732, P=0.004 8) and aspartate aminotransferase (Z=-2.501, P=0.010 7) and significant increases in total cholesterol (TC) (Z=-2.797, P=0.003 9) and low-density lipoprotein cholesterol (LDL-C) (Z=-2.343, P=0.018 5), with a significantly positive correlation between them (r=0.87, P < 0.001), and all the other indices were normal. Conclusion For previously untreated chronic hepatitis C patients with HIV/HCV co-infection, switching to E/c/F/TAF combined with SOF/VEL has good efficacy, tolerability, and safety, and the combination of the two regimens can avoid drug interaction, achieve a high HCV cure rate, and maintain HIV suppression. Transient increases in TC and LDL-C are observed during combination treatment, which suggests dyslipidemia caused by HCV infection and the pharmacological action of this regimen.
- Hepacivirus,
- HIV Infections,
- Antiviral Agents,
- Treatment Outcome

FullText(HTML)

References(33)

References

[1]	COLLINS LF, ADEKUNLE RO, CARTWRIGHT EJ. Metabolic syndrome in HIV/HCV co-infected patients[J]. Curr Treat Options Infect Dis, 2019, 11(4): 351-371. DOI: 10.1007/s40506-019-00207-3.
[2]	NAGGIE S, LUSK S, THOMPSON JW, et al. Metabolomic signature as a predictor of liver disease events in patients with HIV/HCV coinfection[J]. J Infect Dis, 2020, 222(12): 2012-2020. DOI: 10.1093/infdis/jiaa316.
[3]	KUTI MA, AKINYEMI JO, OGUNBOSI BO, et al. HCV co-infection is associated with metabolic abnormalities among HAART naive HIV-infected persons[J]. Niger J Clin Pract, 2017, 20(7): 799-803. DOI: 10.4103/1119-3077.212444.
[4]	FELMLEE DJ, HAFIRASSOU ML, LEFEVRE M, et al. Hepatitis C virus, cholesterol and lipoproteins-impact for the viral life cycle and pathogenesis of liver disease[J]. Viruses, 2013, 5(5): 1292-1324. DOI: 10.3390/v5051292.
[5]	PLATT L, EASTERBROOK P, GOWER E, et al. Prevalence and burden of HCV co-infection in people living with HIV: A global systematic review and meta-analysis[J]. Lancet Infect Dis, 2016, 16(7): 797-808. DOI: 10.1016/S1473-3099(15)00485-5.
[6]	LO RE V 3rd, KALLAN MJ, TATE JP, et al. Hepatic decompensation in antiretroviral-treated patients co-infected with HIV and hepatitis C virus compared with hepatitis C virus-monoinfected patients: A cohort study[J]. Ann Intern Med, 2014, 160(6): 369-379. DOI: 10.7326/M13-1829.
[7]	SMITH CJ, RYOM L, WEBER R, et al. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D∶A∶D): A multicohort collaboration[J]. Lancet, 2014, 384(9939): 241-248. DOI: 10.1016/S0140-6736(14)60604-8.
[8]	HINO N, SASAKI R, TAKAHASHI Y, et al. Treatment of hepatitis C virus infection with direct-acting antiviral agents elevates the serum small-dense low-density lipoprotein cholesterol level[J]. Intern Med, 2021, 60(2): 191-199. DOI: 10.2169/internalmedicine.5563-20.
[9]	BAGELLA P, SQUILLACE N, RICCI E, et al. Lipid profile improvement in virologically suppressed HIV-1-infected patients switched to dolutegravir/abacavir/lamivudine: Data from the SCOLTA project[J]. Infect Drug Resist, 2019, 12: 1385-1391. DOI: 10.2147/IDR.S203813.
[10]	GRAF C, WELZEL T, BOGDANOU D, et al. Hepatitis C clearance by direct-acting antivirals impacts glucose and lipid homeostasis[J]. J Clin Med, 2020, 9(9): 2702. DOI: 10.3390/jcm9092702.
[11]	HUNT PW, LEE SA, SIEDNER MJ. Immunologic biomarkers, morbidity, and mortality in treated HIV infection[J]. J Infect Dis, 2016, 214(Suppl 2): s44-s50. DOI: 10.1093/infdis/jiw275.
[12]	YAN XJ, YANG Y. Research progress on the application of liver transplantation in HIV combined with HCV positive patients[J]. Ogran Transplantation, 2020, 11(6): 677-684. DOI: 10.3969/j.issn.1674-7445.2020.06.005. 颜曦婧, 杨扬. 肝移植治疗HIV合并HCV阳性患者的研究进展[J]. 器官移植, 2020, 11(6): 677-684. DOI: 10.3969/j.issn.1674-7445.2020.06.005.
[13]	SIKAVI C, CHEN PH, LEE AD, et al. Hepatitis C and human immunodeficiency virus coinfection in the era of direct-acting antiviral agents: No longer a difficult-to-treat population[J]. Hepatology, 2018, 67(3): 847-857. DOI: 10.1002/hep.29642.
[14]	POL S, PARLATI L. Treatment of hepatitis C: The use of the new pangenotypic direct-acting antivirals in "special populations"[J]. Liver Int, 2018, 38(Suppl 1): 28-33. DOI: 10.1111/liv.13626.
[15]	BERENGUER J, RODRíGUEZ E, MIRALLES P, et al. Sustained virological response to interferon plus ribavirin reduces non-liver-related mortality in patients coinfected with HIV and hepatitis C virus[J]. Clin Infect Dis, 2012, 55(5): 728-736. DOI: 10.1093/cid/cis500.
[16]	BERENGUER J, RODRÍGUEZ-CASTELLANO E, CARRERO A, et al. Eradication of hepatitis C virus and non-liver-related non-acquired immune deficiency syndrome-related events in human immunodeficiency virus/hepatitis C virus coinfection[J]. Hepatology, 2017, 66(2): 344-356. DOI: 10.1002/hep.29071.
[17]	ROCKSTROH JK. Optimal therapy of HIV/HCV co-infected patients with direct acting antivirals[J]. Liver Int, 2015, 35(Suppl 1): 51-55. DOI: 10.1111/liv.12721.
[18]	European Association for the Study of the Liver. EASL clinical practice guidelines: Management of hepatitis C virus infection[J]. J Hepatol, 2011, 55(2): 245-264. DOI: 10.1016/j.jhep.2011.02.023.
[19]	SCHLABE S, ROCKSTROH JK. Advances in the treatment of HIV/HCV coinfection in adults[J]. Expert Opin Pharmacother, 2018, 19(1): 49-64. DOI: 10.1080/14656566.2017.1419185.
[20]	AIDS and Hepatitis C Professional Group, 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.
[21]	MA CT, WANG Q, ZHANG YK, et al. Analysis on the composition of free antiviral drugs for AIDS treatment in China from 2009 to 2019[J]. China Med Herald, 2021, 18(17): 157-160, 168, 198. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202117038.htm 马春涛, 王强, 张煜昆, 等. 2009—2019年我国艾滋病免费抗病毒治疗药品构成分析[J]. 中国医药导报, 2021, 18(17): 157-160, 168, 198. https://www.cnki.com.cn/Article/CJFDTOTAL-YYCY202117038.htm
[22]	HEZODE C, REAU N, SVAROVSKAIA ES, et al. Resistance analysis in patients with genotype 1-6 HCV infection treated with sofosbuvir/velpatasvir in the phase Ⅲ studies[J]. J Hepatol, 2018, 68(5): 895-903. DOI: 10.1016/j.jhep.2017.11.032.
[23]	MILLER MM. Sofosbuvir-velpatasvir: A single-tablet treatment for hepatitis C infection of all genotypes[J]. Am J Health Syst Pharm, 2017, 74(14): 1045-1052. DOI: 10.2146/ajhp60632.
[24]	ASSELAH T, SHAFRAN SD, BOURGEOIS S, et al. Deferred treatment with a fixed-dose combination of sofosbuvir-velpatasvir for chronic hepatitis C virus genotype 1, 2, 4 and 6 infection[J]. J Viral Hepat, 2019, 26(10): 1229-1232. DOI: 10.1111/jvh.13159.
[25]	GODINHO R, BUGNON S, GRACIN T, et al. Severe rhabdomyolysis-induced acute kidney injury following concomitant use of Genvoya^®(EVG/COBI/FTC/TAF) and simvastatin; a case report[J]. BMC Nephrol, 2019, 20(1): 69. DOI: 10.1186/s12882-019-1257-6.
[26]	POPESCU CI, RIVA L, VLAICU O, et al. Hepatitis C virus life cycle and lipid metabolism[J]. Biology (Basel), 2014, 3(4): 892-921. DOI: 10.3390/biology3040892.
[27]	INOUE T, GOTO T, IIO E, et al. Changes in serum lipid profiles caused by three regimens of interferon-free direct-acting antivirals for patients infected with hepatitis C virus[J]. Hepatol Res, 2018, 48(3): e203-e212. DOI: 10.1111/hepr.12970.
[28]	GONZÁLEZ-ALDACO K, TORRES-REYES LA, OJEDA-GRANADOS C, et al. Immunometabolic effect of cholesterol in hepatitis C infection: Implications in clinical management and antiviral therapy[J]. Ann Hepatol, 2018, 17(6): 908-919. DOI: 10.5604/01.3001.0012.7191.
[29]	BROWN MS, GOLDSTEIN JL. A receptor-mediated pathway for cholesterol homeostasis[J]. Science, 1986, 232(4746): 34-47. DOI: 10.1126/science.3513311.
[30]	MEISSNER EG, LEE YJ, OSINUSI A, et al. Effect of sofosbuvir and ribavirin treatment on peripheral and hepatic lipid metabolism in chronic hepatitis C virus, genotype 1-infected patients[J]. Hepatology, 2015, 61(3): 790-801. DOI: 10.1002/hep.27424.
[31]	BERG T, ANDREONE P, POL S, et al. Low-density lipoprotein and other predictors of response with telaprevir-based therapy in treatment-experienced HCV genotype 1 patients: REALIZE study[J]. Liver Int, 2015, 35(2): 448-454. DOI: 10.1111/liv.12703.
[32]	LU L, WANG M, XIA W, et al. Migration patterns of hepatitis C virus in China characterized for five major subtypes based on samples from 411 volunteer blood donors from 17 provinces and municipalities[J]. J Virol, 2014, 88(13): 7120-7129. DOI: 10.1128/JVI.00414-14.
[33]	NIE B, ZHANG KJ, LIU JB, et al. Prevalence of hepatitis C virus genotype in China patients: A systematic review and Meta-analysis[J]. Lab Med Clin, 2016, 13(20): 2876-2881. https://www.cnki.com.cn/Article/CJFDTOTAL-JYYL201620014.htm 聂滨, 张开炯, 刘靳波, 等. 中国丙型肝炎病毒基因型分布回顾及Meta分析[J]. 检验医学与临床, 2016, 13(20): 2876-2881. https://www.cnki.com.cn/Article/CJFDTOTAL-JYYL201620014.htm

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

Figures(1) / Tables(1)

Get Citation

PDF

XML

Article Metrics

Article views (529) PDF downloads(47)

Efficacy of switching to co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide combined with sofosbuvir/velpatasvir in treatment of previously untreated chronic hepatitis C patients with HIV/HCV co-infection and its influence on blood lipid levels

DOI: 10.3969/j.issn.1001-5256.2022.03.010

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