Editorial Commentary: Management of Hepatitis C Virus in HIV-Infected Patients in the Era of Direct-Acting Antivirals

Hepatitis C virus (HCV) is a bloodborne pathogen most efficiently transmitted through direct blood-to-blood contact. Injection drug use is the principal route of HCV transmission in developed countries [1]. Although sexual transmission of HCV is uncommon among heterosexual couples in monogamous relationships [2], accumulating evidence suggests that among specific high-risk groups, sexual transmission may be a major route for HCV acquisition. Because HCV and human immunodeficiency virus (HIV) can be transmitted by similar mechanisms, HCV infection is relatively common in HIV-infected patients. In the last decade, an increased incidence of acute HCV infection among HIV-positive men who have sex with men (MSM), attributed to sexual exposure, has been documented worldwide [3, 4]. Incidence rates of acute HCV among HIV-infected MSM in the United Sates range from 0.21 to 0.51 cases per 100 person-years with most cases attributed to injection drug use and high-risk sexual practices [5, 6]. The increasing burden of acute HCV among MSM underscores the urgent need for prevention of HCV transmission among those who remain unexposed as well as evaluation and possibly treatment among those already infected. At the same time, this epidemic provides an opportunity to study early phases of HCV infection that have not been well characterized. HIV/HCV-coinfected patients have been shown to have accelerated liver disease compared to those infected only with HCV, and liver-related complications have become a primary cause of hospitalizations and death in HIV-infected individuals in developed countries [7, 8]. HCV treatment efficacy during the chronic phase of the infection is also reduced in HIV/HCV-coinfected patients when pegylated interferon (peg-IFN) and ribavirin (RBV) are used. Sustained virologic response (SVR) to peg-IFN/RBV is achieved in up to 50% of patients monoinfected with HCV genotype 1, the genotype that is most difficult to treat [9, 10], and by only 14%– 29% of those coinfected with HIV [11, 12]. The approval of the first 2 direct-acting antivirals (DAAs) in 2011, telaprevir (TVR) and boceprevir (BOC), began a new era in the treatment of hepatitis C. Both of these agents are NS3/4A protease inhibitors and were approved only for treatment of HCV genotype 1–monoinfected patients. TVR or BOC, when used in combination with peg-IFN and RBV, achieved SVR rates of ≥70% [13–16]. Uptake of DAA treatment in HCV/ HIV-coinfected individuals has lagged, at least in the United States, largely because their use in this population has not yet been approved by the US Food and Drug Administration. Some concerns also exist regarding potential drug–drug interactions between DAAs and certain antiretrovirals as well as overlappingmedication toxicity. The initial phase 2 pilot studies that evaluated triple therapy in coinfected patients reported significant improvement over treatment with pegIFN and RBV. The addition of a DAA to peg-IFN/RBV therapy increased SVR rates from 45% to 74%, in the case of TVR [17], and from 29% to 63% in the case of BOC [18]. More recently, an IFNsparing 24-week regimen comprised of the NS5B polymerase inhibitor sofosbuvir used in combination with RBV has been studied in HIV/HCV-coinfected patients. Among genotype 1–infected individuals who were also infected with HIV, SVR rates of 76% were achieved Received 18 November 2013; accepted 3 December 2013; electronically published 13 December 2013. Correspondence: Andrew Talal, MD, MPH, Division of Gastroenterology, Hepatology and Nutrition, State University of New York at Buffalo, 875 Ellicot St, Ste 6090, Buffalo, NY 14203 (ahtalal@buffalo.edu). Clinical Infectious Diseases 2014;58(6):880–2 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/cid/cit804