Treatment of Hepatitis C in HIV Patients in the New Era of Direct-Acting Antivirals

Palella F, Baker R, Moorman A, et al. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr. 2006;43:27–34. Weber R, Sabin C, Friis-Moller N, et al. Liver-related deaths in persons infected with the HIV: the D:A:D study. Arch Intern Med. 2006;166:1632–41. Wyatt C, Malvestutto C, Coca S, et al. The impact of hepatitis C virus coinfection on HIV-related kidney disease: a systematic review and meta-analysis. AIDS. 2008;22:1799–807. Peters L, Grint D, Lundgren J, et al. HCV viremia increases the incidence of chronic kidney disease in HIV-infected patients. AIDS. 2012;26:1917–26. Kakinami L, Block R, Adams M, Cohn S, Maliakkal B, Fisher S. Risk of cardiovascular disease in HIV, hepatitis C or HIV/HCV patients compared to the general population. Int J Clin Pract. 2013;67:6–13. Lo Re V, Teal V, Localio A, et al. Risk of hip fracture associated with HCV infection and HCV/HIV coinfection. Hepatology. 2012;56:1688–98. Soriano V, Vispo E, Fernandez-Montero JV, Labarga P, Barreiro P. Update on HIV/HCV coinfection. Curr HIV/AIDS Rep. 2013. doi:10.1007/s11904-013-0169-5. • Soriano V, Sherman K, Rockstroh J, et al. Challenges and opportunities for hepatitis C drug development in HIV-HCV coinfected patients. AIDS. 2011;25:2197–208. This article summarises and discusses the major issues that may complicate the use of direct-acting antivirals in hepatitis C patients with HIV infection. Naggie S, Sulkowski M. Management of patients coinfected with HCV and HIV: a close look at the role for direct-acting antivirals. Gastroenterology. 2012;142:1324–34. Barreiro P, Vispo E, Labarga P, et al. Management and treatment of chronic hepatitis C in HIV patients. Semin Liver Dis. 2012;32:138–46. Witt M, Seaberg E, Darilay A, et al. Incident hepatitis C virus infection in men who have sex with men: a prospective cohort analysis, 1984-2011. Clin Infect Dis. 2013;57:77–84. Sánchez C, Plaza Z, Vispo E, et al. Scaling up epidemics of acute hepatitis C and syphilis in HIV-infected men who have sex with men in Spain. Liver Int. 2013. doi:10.1111/liv.12212. Macías J, Berenguer J, Japón MA, et al. Fast fibrosis progression between repeated liver biopsies in patients coinfected with HIV/hepatitis C virus. Hepatology. 2009;50:1056–63. Fernández-Montero JV, Soriano V. Management of hepatitis C in HIV and/or HBV co-infected patients. Best Pract Res Clin Gastroenterol. 2012;26:517–30. Soriano V, Puoti M, García-Gascó P, et al. Antiretroviral drugs and liver injury. AIDS. 2008;22:1–13. Vispo E, Fernandez-Montero JV, Labarga P, Barreiro P, Soriano V. Low risk of liver toxicity using the most recently approved antiretroviral agents but still increased in HIV-HCV coinfected patients. AIDS. 2013;27:1187–8. Labarga P, Soriano V, Vispo ME, et al. Hepatotoxicity of antiretroviral drugs is reduced after successful treatment of chronic hepatitis C in HIV-infected patients. J Infect Dis. 2007;196:670–6. Torriani F, Rodriguez-Torres M, Rockstroh J, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. 2004;351:438–50. Carrat F, Bani-Sadr F, Pol S, et al. Pegylated interferon alfa-2b vs standard interferon alfa-2b plus ribavirin for chronic hepatitis C in HIV-infected patients: a randomized controlled trial. JAMA. 2004;292:2839–48. Nuñez M, Miralles C, Berdun MA, et al. Role of weight-based ribavirin dosing and extended duration of therapy in chronic hepatitis C in HIV-infected patients: the PRESCO trial. AIDS Res Hum Retrovir. 2007;23:972–82. Labarga P, Barreiro P, da Silva A, et al. Comparison of high ribavirin induction versus standard ribavirin dosing, plus peginterferon-alfa for the treatment of chronic hepatitis C in HIV-infected patients: the PERICO trial. J Infect Dis. 2012;206:961–8. Soriano V, Puoti M, Peters M, et al. Care of patients coinfected with HIV and HCV: 2007 updated recommendations from the HCV-HIV international panel. AIDS. 2007;21:1073–89. EACS guidelines. (www.europeanaidsclinicalsociety.org). Updated version November 2012. Medrano J, Neukam K, Rallon N, et al. Modeling the probability of SVR to therapy with pegylated interferon plus ribavirin in patients coinfected with HCV and HIV. Clin Infect Dis. 2010;51:1209–16. Medrano J, de Ledinghen V, Taupin J-L et al. Baseline prediction of response to pegIFN-RBV in chronic hepatitis C using the Prometheus score. 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2012). Boston, Nov 9-13, 2012. Abstract 657. • Sulkowski M, Pol S, Mallolas J, et al. Boceprevir versus placebo with pegylated interferon alfa-2b and ribavirin for treatment of hepatitis C virus genotype 1 in patients with HIV: a randomised, double-blind, controlled phase 2 trial. Lancet Infect Dis. 2013;13:597–605. This is the pivotal study demonstrating the efficacy and safety of boceprevir in coinfected patients. • Sulkowski M, Sherman K, Dieterich D, et al. Telaprevir in combination with peginterferon and ribavirin for chronic HCV genotype 1 infection in HIV-infected patients. Ann Intern Med. 2013. doi:10.7326/0003-4819-159-2-201307160-00654. This is the pivotal study demonstrating the efficacy and safety of telaprevir in coinfected patients. Hulskotte E, Feng H, Xuan F, et al. Pharmacokinetic interactions between the hepatitis C virus protease inhibitor boceprevir and ritonavir-boosted HIV-1 protease inhibitors atazanavir, darunavir, and lopinavir. Clin Infect Dis. 2013;56:718–26. van Heeswijk R, Beumont M, Kauffman R, et al. Review of drug interactions with telaprevir and antiretrovirals. Antivir Ther. 2013. doi:10.3851/IMP2527. de Kanter C, Blonk M, Colbers A, et al. Lack of a clinically significant drug-drug interaction in healthy volunteers between the hepatitis C virus protease inhibitor boceprevir and the HIV integrase inhibitor raltegravir. Clin Infect Dis. 2013;56:300–6. Crauwels H, van Heeswijk R, Stevens M, et al. Clinical perspective on drug‑drug interactions with the non-nucleoside reverse transcriptase inhibitor rilpivirine. AIDS Rev. 2013;15:87–101. Benito JM, Sanchez-Parra C, Barreiro P, et al. Triple combination therapy for hepatitis C with telaprevir exhibits greater early antiviral activity than with boceprevir. Antivir Ther. 2013. doi:10.3851/IMP2614. Cachay E, Wyles D, Torriani F, et al. High incidence of serious adverse events in HIV-infected patients treated with a telaprevir-based HCV treatment regimen. AIDS. 2013 Jul 24. [Epub ahead of print]. Cotte L, Braun J, Lascoux-Combe C, et al. High early virological response with telaprevir-pegylated interferon-ribavirin in treatment-experienced HCV genotype 1/HIV coinfected patients: ANRS HC26 TelapreVIH study. CROI 2013. March 3-6 2013. Atlanta, GA. Abstract 36. Poizot-Martin I, Bellissant E, Piroth L, et al. ANRS HC27 BocepreVIH interim analysis: high early virologic response with boceprevir + pegylated interferón + ribavirin in HCV/HCV coinfected patients with previous failure to pegylated interferon + ribavirin. CROI 2013, Atlanta, GA. March 3-6 2013. Abstract 37. Poveda E, Vispo E, Barreiro P, et al. Predicted effect of direct-acting antivirals in the current HIV-HCV coinfected population in Spain. Antivir Ther. 2012;17:571–5. Vispo E, Rallon N, Labarga P, Barreiro P, Benito JM, Soriano V. Different impact of IL28B polymorphisms on response to peginterferon plus ribavirin in HIV-positive patients infected with HCV subtypes 1a or 1b. J Clin Virol. 2012;55:58–61. Barreiro P, Cornelli B, Maida I, et al. Performance of boceprevir or telaprevir in triple therapy with peginterferon and ribavirin in routine clinical practice. EACS. 2013. doi:10.1016/S1473-3099(13)70162-2. Soriano V, Labarga P, Fernández-Montero JV, et al. The changing face of hepatitis C in the new era of direct-acting antivirals. Antivir Res. 2013;97:36–40. Dieterich D, Rockstroh J, Orkin C, et al. Simeprevir with pegylated interferon/ribavirin in patients co-infected with chronic hepatitis C and HIV-1: week-24 interim analysis of the TMC435-C212 study. Program and abstracts of the 20th Conference on Retroviruses and Opportunistic Infections; March 3-6, 2013; Atlanta, GA. Abstract 154LB. Dieterich D, Soriano V, Nelson M, et al. STARTVerso 4: high rates of early virologic response in hepatitis C virus genotype 1/HIV co-infected patients treated with faldaprevir + pegylated interferon and ribavirin. Program and abstracts of the 20th Conference on Retroviruses and Opportunistic Infections; March 3-6, 2013; Atlanta, Georgia. Abstract 40LB. Rockstroh J, Nelson M, Soriano V, et al. STARTVerso 4 Phase III trial of faldaprevir once-daily plus peginterferon alfa-2a and ribavirin in patients with HIV and HCV genotype 1 coinfection: end of treatment response. EACS, Brussels, Belgium. Oct 2013. (in press). Sabo J, Kort J, Haschke M, et al. Pharmacokinetic interactions of darunavir/ritonavir, efavirenz, and tenofovir with the HCV protease inhibitor faldaprevir in healthy volunteers. CROI 2013, Atlanta, GA. March 3-6 2013. Abstract 35. Scheel T, Rice C. Understanding the hepatitis C virus life cycle paves the way for highly effective therapies. Nat Med. 2013;19:837–49. Lok A, Gardiner D, Lawitz E, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012;366:216–24. Suzuki Y, Ikeda K, Suzuki F, et al. Dual oral therapy with daclatasvir and asunaprevir for patients with HCV genotype 1b infection and limited treatment options. J Hepatol. 2013. doi:10.1016/j.jhep.2012.09.037. Soriano V, Vispo E, de Mendoza C, et al. Hepatitis C therapy with HCV NS5B polymerase inhibitors. Expert Opin Pharmacother. 2013;14:1161–70. Lawitz E, Mangia A, Wyles D, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368:1878–87. Jacobson I, Gordon S, Kowdley K, et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013;368:1867–77. Kowdley K, Lawitz E, Crespo I, et al. Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naïve patients with hepatitis C genotype 1 infection (ATOMIC): an open-label, randomized, multicentre phase 2 trial. Lancet. 2013;381:2100–7. Rodriguez-Torres M, Gonzalez A, Rodriguez J, et al. HIV/HCV coinfected and HCV monoinfected patients have similar early HCV viral kinetics with the potent HCV nucleotide polymerase inhibitor sofosbuvir. ICAAC 2012, San Francisco, CA; Sept 9-12 2012 [abstract H-1921a]. Poordad F, Lawitz E, Kowdley K, et al. Exploratory study of oral combination antiviral therapy for hepatitis C. N Engl J Med. 2013;368:45–53. Gane E. Future perspectives: towards interferon-free regimens for HCV infection. Antivir Ther. 2012;17:1201–10. Sulkowski M, Gardiner D, Rodriguez-Torres M, et al. High rate of sustained virologic response with the all-oral combination of daclatasvir (NS5A inhibitor) plus sofosbuvir (nucleotide NS5B inhibitor), with or without ribavirin, in treatment-naive patients chronically infected with HCV genotypes 1, 2, or 3. 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2012). Boston, November 9-13, 2012. Abstract LB-2. Kowdley K, Lawitz E, Poordad F, et al. A 12-week interferon-free treatment regimen with ABT-450/r, ABT-267, ABT-333 and ribavirin achieves SVR rates (observed data) of 99% in treatment-naive patients and 93% in prior null responders with HCV genotype 1 infection. 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2012). Boston, November 9-13, 2012. Abstract LB-1. Zeuzem S, Soriano V, Asselah T, et al. Interferon-free treatment with faldaprevir and BI 207127 for genotype 1 HCV infection. N Engl J Med. 2013;369:630–9. Cohen M, Chen Y, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365:493–505. Barreiro P, Duerr A, Beckerman K, Soriano V. Reproductive options for HIV-serodiscordant couples. AIDS Rev. 2006;8:158–70. Thomas D. Global control of hepatitis C: where challenge meets opportunity. Nat Med. 2013;19:850–8. Centers for Disease Control and Prevention. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945–1965. MMWR. 2012;61(RR-4):1–32. Grebely J, Matthews G, Lloyd A, et al. Elimination of hepatitis C virus infection among people who inject drugs through treatment as prevention: feasibility and future requirements. Clin Infect Dis. 2013 Jun 27. [Epub ahead of print]. Martin N, Vickerman P, Grebely J, et al. HCV treatment for prevention among people who inject drugs: modeling treatment scale-up in the age of direct-acting antivirals. Hepatology. 2013. doi:10.1002/hep.26431. Soriano V, Perelson A, Zoulim F. Why are there different dynamics in the selection of drug resistance in HIV and hepatitis B and C viruses? J Antimicrob Chemother. 2008;62:1–4. Ralston R, Jacobson I, Scull M. The conundrum of relapse in STAT-C therapy: does HCV play the Red Queen or Rip Van Winkle? Semin Liver Dis. 2011;31:410–9. Rutter K, Hofer H, Beinhardt S, et al. Durability of SVR in chronic hepatitis C patients treated with peginterferon/ribavirin in combination with a direct-acting antiviral. Aliment Pharmacol Ther. 2013;38:118–23. Lawitz E, Poordad F, Kowdley K, et al. A phase 2a trial of 12-week interferon-free therapy with two direct-acting antivirals (ABT-450/r, ABT-072) and ribavirin in IL28B C/C patients with chronic hepatitis C genotype 1. J Hepatol. 2013. doi:10.1016/j.jhep.2013.02.009. Soriano V, Vispo E, de Mendoza C, et al. Very late relapse after discontinuation of antiviral therapy for chronic hepatitis C. Antivir Ther. 2013. doi:10.3851/IMP2659. De Rosa F, Audagnotto S, Bargiacchi O, et al. Resolution of HCV infection after highly active antiretroviral therapy in a HIV-HCV coinfected patient. J Infect. 2006;53:e215–8. Endo T, Fujimoto K, Nishio M, et al. Case report: clearance of hepatitis C virus after changing the HAART regimen in a patient infected with hepatitis C virus and the HIV. J Med Virol. 2009;81:979–82. Falconer K, Gonzalez V, Reichard O, Sandberg J, Alaeus A. Spontaneous HCV clearance in HCV/HIV-1 coinfection associated with normalized CD4 counts, low level of chronic immune activation and high level of T cell function. J Clin Virol. 2008;41:160–3. Fialaire P, Payan C, Vitour D, et al. Sustained disappearance of hepatitis C viremia in patients receiving protease inhibitor treatment for HIV infection. J Infect Dis. 1999;180:574–5. Perez-Olmeda M, Garcia-Samaniego J, Soriano V. Hepatitis C viraemia in HIV-HCV co-infected patients having immune restoration with highly active antiretroviral therapy. AIDS. 2000;14:212. Ranieri R, Santambrogio C, Veronelli A, Pontiroli A. Hepatitis C viremia persistently suppressed by HAART. Clin Infect Dis. 2003;36:1086–7. Torti C, Barnes E, Quiros-Roldan E, Puoti M, Carosi G, Klenerman P. Suppression of hepatitis C virus replication is maintained long term following HAART therapy, in an individual with HCV/HIV co-infection. Antivir Ther. 2004;9:139–42. Zeitoun J, Mallet V, Chaix ML, Viard J, Blanche S, Pol S. Stable recovery from HCV in HIV-HCV co-infection under antiretroviral therapy. J Clin Virol. 2007;40:71–3. Weissbrich B, Langmann P, Schubert J, Jassoy C, Klinker H. Resolution of HCV infection in a HIV-infected patient under HAART after several hepatitis flare-ups. Eur J Med Res. 2003;8:495–8. Manfredi R, Dentale N, Calza L. Spontaneous clearance of chronic hepatitis C infection in a patient with a 20-year-old HIV-hepatitis C co-infection and chronic active hepatitis. Int J STD AIDS. 2012;23:e48–50. Yokozaki S, Takamatsu J, Nakano I, et al. Immunologic dynamics in hemophiliac patients infected with hepatitis C virus and HIV: influence of antiretroviral therapy. Blood. 2000;96:4293–9. Vispo E, Barreiro P, Plaza Z, et al. Spontaneous HCV clearance in HIV patients with chronic hepatitis C on antiretroviral therapy. EACS, Brussels, Belgium. Oct 2013 (in press). Guedj J, Dahari H, Rong L, et al. Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life. Proc Natl Acad Sci U S A. 2013;110:3991–6.