Simeprevir for the treatment of hepatitis C and HIV/hepatitis C co-infection

Abstract

Hepatitis C virus (HCV) is a major cause of chronic hepatitis in 170 million people worldwide and can progress to fibrosis, cirrhosis, liver failure and hepatocellular carcinoma, a disease process accelerated in HIV co-infection. Approximately 25% of HIV infected people are co-infected with HCV (worldwide prevalence 4–5 million) and up to 16.7% of deaths in this population are attributable to HCV co-infection. Previous treatment options for HCV were limited to pegylated interferon and ribavirin (PEG-IFN/RBV), a combination that demonstrated lower successful cure rates in genotype 1 HCV mono-infection and HIV/HCV co-infection, and is also associated with a considerable adverse side-effect profile. The development of directly acting antivirals (DAAs) offers the first class of drug to achieve good viral suppression in previously hard-to-treat patient groups. We review the benefits, tolerability and drug interactions with concomitant drugs of the DAA simeprevir for patients who have HCV mono-infection and hep C/HIV co-infection.

Keywords::

• co-infection
• directly acting antivirals
• hepatitis C
• HIV
• NS3/4A protease inhibitors
• simeprevir

Financial & competing interests disclosure

S Flanagan has received course sponsorship from Merck. A Crawford-Jones has received travel bursaries, course sponsorship and honoraria from the following companies: Gilead, Viiv and BMS. C Orkin has received travel bursaries, lectureship fees, honoraria, research grants and provided consultancy to the following companies: Gilead, Viiv, GSK, MSD, BI, BMS, Jannsen, Johnson and Johnson, Abbott and Abbvie. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The hepatitis C virus (HCV) is a major cause of chronic hepatitis in 170 million people worldwide and can progress to fibrosis, cirrhosis, liver failure and hepatocellular carcinoma. Progression is accelerated in the context of HIV co-infection. Approximately 25% of HIV-infected people are co-infected with HCV (worldwide prevalence 4–5 million) and up to 16.7% of deaths in this population are attributable to HCV co-infection.

• Previous treatment for HCV was limited to pegylated interferon and ribavirin (PEG-IFN/RBV), a combination that demonstrated lower successful cure rates in genotype 1 HCV monoinfection and HIV/HCV co-infection. Dual therapy is also associated with a considerable adverse side effect profile.

• In 2012, new treatment options of directly acting antivirals (DAAs) became standard of care. The NS3/4A protease inhibitor class offered the first class of drug to achieve good sustained virological responses (SVRs) in previously difficult-to-treat groups such as genotype 1 infection. However, the first-generation drugs were associated with considerable adverse side effect profiles.

• Simeprevir is a NS3/4A protease inhibitor that, in combination with PEG-IFN/RBV, offers good tolerability and SVRs in varied patient populations, in both monoinfected and HIV co-infected groups.

• Genotype 1a-infected patients still remain difficult-to-treat with lower SVR rates achieved in this group. There are also more likely to be poor SVR rates in patients with the Q80K polymorphism at baseline.

• Simeprevir also shows significant drug interaction, especially with certain antiretroviral medications.

• Future studies should assess the of DAA combinations in terms of forgiveness, drug interactions with concomitant medications and in patients more likely not to achieve SVR.

• The direct-acting antivirals are very expensive and out of the reach of many health economies. It is crucial that the clinical and service-user communities continue to work with companies and health systems to facilitate access for all who need it.