Grazoprevir/elbasvir in peginterferon alfa plus ribavirin experienced patients with chronic genotype 1 HCV/HIV co-infection: a non-randomized, open-label clinical trial

Yi-Chun Lin, Shih-Wei Li, Shin-Yen Ku, Hui-Ting Hsieh, Mei-Hui Lin, Shu-Yin Chang, Wei-Wei Wu, Na-Lee Sun, Shu-Hsing Cheng, Chien-Yu Cheng, Yi-Chun Lin, Shih-Wei Li, Shin-Yen Ku, Hui-Ting Hsieh, Mei-Hui Lin, Shu-Yin Chang, Wei-Wei Wu, Na-Lee Sun, Shu-Hsing Cheng, Chien-Yu Cheng

Abstract

Background and aims: We aimed to evaluate the efficacy and tolerability of grazoprevir/elbasvir in patients with chronic genotype 1 hepatitis C virus (HCV) and HIV co-infection who experienced peginterferon alfa plus ribavirin (PegIFN/RBV) (clinicaltrials.gov NCT03098121). Methods: This non-randomized, open-label trial study was conducted in Taoyuan General Hospital. HIV-infected patients were screened for HCV antibody since June 1, 2012, and HCV and HIV co-infected patients were tested for HCV RNA. The subjects who experienced PegIFN/RBV were enrolled in the study, and of whom with chronic genotype 1a or 1b received grazoprevir 100 mg and elbasvir 50 mg in a fixed-dose combination tablet once daily with or without ribavirin for 12 to 16 weeks. Results: Of 2,419 HIV-infected patients, 40 patients with chronic genotype 1 HCV and HIV co-infection who failed PegIFN/RBV treatment were enrolled. Sixteen patients had genotype 1a and 24 patients had genotype 1b, with or without cirrhosis. The median age was 42 (41-47) years, and 5 patients (12.5%) were diagnosed with liver cirrhosis (child Pugh score A). The median CD4 count was 504 cells/μL (321-689). All patients (100%) had HIV viral load <200 copies/mL, and HCV viral load was 6.3 log10 IU/mL (3.98-7.12). At the end of treatment, all patients (100%, 40/40) had undetectable HCV viral load, and 95.0% (38/40) of patients achieved sustained virologic response at 12 weeks. Conclusion: Grazoprevir/elbasvir was effective in genotype 1 patients co-infected with HIV with or without cirrhosis. This finding is consistent with that of previous trials of this regimen in monoinfected population.

Keywords: HCV genotype 1; HCV/HIV co-infection; PEGylated interferon plus ribavirin; direct-acting antiviral; grazoprevir and elbasvir; hepatitis C.

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Flowchart of enrollment of patients with chronic genotype 1 HCV and HIV co-infection who failed peginterferon alfa plus ribavirin treatment. Abbreviations: HCV, hepatitis C virus; GT, genetype; pegIFN/RBV, peginterferon alfa plus ribavirin; SVR, sustained virologic response.
Figure 2
Figure 2
Improvement of fibrosis-4 score after treatment of grazoprevir and elbasvir with or without ribavirin. Abbreviations: EOT, end of treatment; SVR 12, sustained virologic response at 12 week.

References

    1. Lavanchy D. The global burden of hepatitis C. Liver Int. 2009;29(Suppl 1):74–81. doi:10.1111/j.1478-3231.2008.01934.x
    1. Alter MJ. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol. 2006;44(Suppl 1):S6–9. doi:10.1016/j.jhep.2005.09.019
    1. Peters L, Klein MB. Epidemiology of hepatitis C virus in HIV-infected patients. Curr Opin HIV AIDS. 2015;10(5):297–302. doi:10.1097/COH.0000000000000181
    1. 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. Lancet Infect Dis. 2016;16(7):797–808. doi:10.1016/S1473-3099(16)30197-9
    1. Rockstroh JK, Peters L, Grint D, et al. Does hepatitis C viremia or genotype predict the risk of mortality in individuals co-infected with HIV? J Hepatol. 2013;59(2):213–220. doi:10.1016/j.jhep.2013.04.005
    1. 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-monoinfected patients: a cohort study. Ann Intern Med. 2014;160(6):369–379.
    1. Bunchorntavakul C, Chavalitdhamrong D, Tanwandee T. Hepatitis C genotype 6: a concise review and response-guided therapy proposal. World J Hepatol. 2013;5(9):496–504. doi:10.4254/wjh.v5.i9.496
    1. Laguno M, Cifuentes C, Murillas J, et al. Randomized trial comparing pegylated interferon alpha-2b versus pegylated interferon alpha-2a, both plus ribavirin, to treat chronic hepatitis C in human immunodeficiency virus patients. Hepatology. 2009;49(1):22–31. doi:10.1002/hep.22598
    1. Chung RT, Andersen J, Volberding P; AIDS Clinical Trials Group A5071 Study Team. Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med. 2004;351(5):451–459. doi:10.1056/NEJMcp041956
    1. Torriani FJ, Rodriguez-Torres M, Rockstroh JK, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. 2004;351(5):438–450. doi:10.1056/NEJMcp041956
    1. Liu JY, Lin HH, Liu YC, et al. Extremely high prevalence and genetic diversity of hepatitis C virus infection among HIV-infected injection drug users in Taiwan. Clin Infect Dis. 2008;46(11):1761–1768. doi:10.1086/587992
    1. Liu CH, Sheng WH, Sun HY, et al. Peginterferon plus ribavirin for HIV-infected patients with treatment-naïve acute or chronic HCV infection in Taiwan: a prospective cohort study. Sci Rep. 2015;5:17410. doi:10.1038/srep17410
    1. Sulkowski MS, Eron JJ, Wyles D, et al. Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial. JAMA. 2015;313(12):1223–1231. doi:10.1001/jama.2015.1328
    1. Wyles DL, Ruane PJ, Sulkowski MS, et al. Daclatasvir plus sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):714–725. doi:10.1056/NEJMoa1503153
    1. Luetkemeyer AF, McDonald C, Ramgopal M, Noviello S, Bhore R, Ackerman P. 12 weeks of daclatasvir in combination with sofosbuvir for HIV-HCV coinfection (ALLY-2 Study): efficacy and safety by HIV combination antiretroviral regimens. Clin Infect Dis. 2016;62(12):1489–1496. doi:10.1093/cid/ciw163
    1. Naggie S, Cooper C, Saag M, et al. Ledipasvir and sofosbuvir for HCV in patients coinfected with HIV-1. N Engl J Med. 2015;373(8):705–713. doi:10.1056/NEJMoa1501315
    1. Osinusi A, Townsend K, Kohli A, et al. Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection. JAMA. 2015;313(12):1232–1239. doi:10.1001/jama.2015.1373
    1. Sulkowski M, Hezode C, Gerstoft J, et al. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and Hiv/hepatitis C virus co-infection (C-WORTHY): a randomized, open-label phase 2 trial. Lancet. 2015;385(9973):1087–1097.
    1. Rockstroh JK, Nelson M, Katlama C, et al. Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial. Lancet HIV. 2015;2(8):e319–327. doi:10.1016/S2352-3018(15)00108-3
    1. Rockstroh JK, Lacombe K, Viani RM, et al. Efficacy and safety of glecaprevir/pibrentasvir in patients coinfected with hepatitis C virus and human immunodeficiency virus Type 1: the EXPEDITION-2 Study. Clin Infect Dis. 2018;67(7):1010–1017. doi:10.1093/cid/ciy220
    1. American Association for the Study of Liver Disease, Infectious Diseases Society of America. HCV guidance: recommendations for testing, managing, and treating hepatitis C virus. 2017. Available from: . Accessed May, 2018.
    1. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2018. J Hepatol. 2018. doi:10.1016/j.jhep.2018.03.026
    1. Kim BK, Kim DY, Park JY, et al. Validation of FIB-4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virus-infected patients. Liver Int. 2010;30(4):546–553. doi:10.1111/j.1478-3231.2009.02192.x
    1. Shah AG, Lydecker A, Murray K, Tetri BN, Contos MJ, Sanyal AJ. Nash Clinical Research Network. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009;7(10):1104–1112. doi:10.1016/j.cgh.2009.05.033
    1. Sulkowsky MS. HCV-HIV co-infected patients: no longer a ‘special’ population? Liver Int. 2016;36(Suppl 1):43–46. doi:10.1111/liv.13021
    1. Cunningham EB, Applegate TL, Lloyd AR, Dore GJ, Grebely J. Mixed HCV infection and reinfection in people who inject drugs–impact on therapy. Nat Rev Gastroenterol Hepatol. 2015;12(4):218–230. doi:10.1038/nrgastro.2015.36
    1. Dirani G, Paesini E, Mascetra E, et al. A novel next generation sequencing assay as an alternative to currently available methods for hepatitis C virus genotyping. J Virol Methods. 2018;251:88–91. doi:10.1016/j.jviromet.2017.09.027
    1. Braun DL, Hampel B, Kouyos R, et al. High cure rates with grazoprevir-elbasvir with or without ribavirin guided by genotypic resistance testing among human immunodeficiency virus/hepatitis C virus–coinfected men who have sex with men. Clin Infect Dis. 2019;68(4):569–576. doi:10.1093/cid/ciy547
    1. Werner CR, Schwarz JM, Egetemeyr DP, et al. Second-generation direct-acting-antiviral hepatitis C virus treatment: efficacy, safety, and predictors of SVR12. World J Gastroenterol. 2016;22(35):8050–8059. doi:10.3748/wjg.v22.i37.8314
    1. Dienstag JL, Ghany MG, Morgan TR; HALT-C Trial Group. A prospective study of the rate of progression in compensated, histologically advanced chronic hepatitis C. Hepatology. 2011;54(2):396–405. doi:10.1002/hep.24370

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