Treatment of chronic HCV genotype 1 coinfection.

Abstract

Several all-oral direct-acting antiviral (DAA) combination therapies including two fixed-dose combinations (FDCs) have been recently licensed for treatment of hepatitis C virus (HCV) genotype 1 infection. Results of pivotal trials with these new compounds are now also available in human immunodeficiency virus (HIV)/HCV-coinfected patients, highlighting that, in the DAA era, differences no longer do exist in efficacy between HCV-monoinfected and HIV/HCV-coinfected patients. This review will give an overview of the key DAA-containing studies in HIV/HCV genotype 1 coinfection and give guidance on how and when these should be used in clinical practice. Simplified DAA-based and potentially interferon-free HCV therapy regimens are characterized by smaller pill burden, better tolerability, shorter treatment durations, and higher cure rates. With first pilot studies in HCV treatment-naive and treatment-experienced persons with HCV/HIV coinfection demonstrating sustained virological response rates above 95%, interferon (IFN)-free DAA combinations should be considered the new standard of care for chronic HCV. Per both European and US treatment guidelines, HCV treatment indications and DAA drug selection in HIV-coinfected patients are no longer different from HCV-monoinfected patients as cure rates in HCV-monoinfected and HCV-coinfected patients are superimposable. Drug-drug interactions with the new DAAs and concomitant antiretroviral therapy, however, have to be checked carefully prior to selecting DAAs due to commonly shared metabolization pathways. In countries with access to the new DAAs, interferon-free DAA combination therapy for HCV genotype 1 infection is strongly recommended. Agents should be selected based upon HCV genotype and according to current guidelines. Potential drug-drug interactions between HIV antiretrovirals and HCV therapy need to be checked, and if necessary, combination antiretroviral therapy (cART) has to be adapted to the respective HCV therapy. Key Points• HCV treatment in HIV-coinfected patients is the same as in HCV-monoinfected patients as response rates under DAA in the setting of HIV coinfection have been as good as in HCV-monoinfected patients. • IFN-free DAA combinations should be considered standard of care for chronic HCV genotype 1 coinfection. • Drug-drug interactions with the new DAAs and concomitant antiretroviral therapy have to be accounted for due to shared metabolic pathways via the cytochrome p450 system and drug transporters. • Major limitations in treatment uptake are access to DAA which is increasingly driven by the cost of the medications.