Advances in Hepatitis C Virus Treatment for HIV-Infected Persons: Have We Reached the End of the Rainbow? Kara W. Chew, MD, MS Assistant Clinical Professor of Medicine David Geffen School of Medicine at UCLA Los Angeles, California FLOWED: 04/18/2016 Los Angeles, California: April 25, 2016 From KW Chew, MD, MS, at Los Angeles, CA: April 25, 2016, IAS-USA. Learning Objectives After attending this presentation, participants will be able to: Conduct the initial evaluation for hepatitis C virus (HCV) including hepatic fibrosis assessment Select between treatment options for genotype 1 HCV in HIV/HCV-coinfected patients List treatment options for genotype 2, 3, or 4 HCV infection Slide 2 of 9 From KW Chew, MD, MS, at Los Angeles, CA: April 25, 2016, IAS-USA. Evaluation for advanced fibrosis is recommended for all Necessary to determine the appropriate HCV treatment strategy – – Impacts treatment options Depending on the genotype and regimen: Treatment duration may need to be extended Addition of ribavirin may need to be considered Additional management necessary for advanced fibrosis/cirrhosis – – – – Screening for hepatocellular carcinoma Screening for esophageal varices Monitoring of hepatic function Counseling to avoid NSAIDs, limit acetaminophen use, avoid raw shellfish Slide 3 of 9 From KW Chew, MD, MS, at Los Angeles, CA: April 25, 2016, IAS-USA. Recommended approach for fibrosis assessment • Combining direct biomarkers and transient elastography is most efficient • If discordant, consider liver biopsy • If direct biomarkers or transient elastography not available, combine indirect serum biomarkers • If indeterminate, consider liver biopsy AASLD/IDSA, hcvguidelines.org, Boursier Hepatology 2012 Slide 4 of 9 From KW Chew, MD, MS, at Los Angeles, CA: April 25, 2016, IAS-USA. Key considerations when choosing between HCV treatment regimens Drug interactions between ART and HCV DAAs Drug interactions between HCV DAAs and drugs for comorbidities – E.g. PPIs, statins, anticonvulsants, dihydropyridines, rifampin, digoxin Comorbidities: – Cardiac disease (anemia with RBV, drug interactions with cardiac meds) – Renal insufficiency (limited data for most DAAs with advanced kidney disease/ESRD, increased tenofovir levels with coadministration of ledipasvir with TDF) Slide 5 of 9 From KW Chew, MD, MS, at Los Angeles, CA: April 25, 2016, IAS-USA. Drug-drug interactions between ART and HCV treatment HCV regimen Allowed ART Comments Ledipasvir/sofosbuvir Most ART allowed (LDV/SOF) Interaction between ledipasvir and TDF, ledipasvir and cobicistat LDV increases tenofovir levels – avoid coadmin with TDF if CrCL <60 mL/min and avoid LDV + TDF with ritonavir- or cobicistat-boosted ART Elbasvir/grazoprevir Raltegravir, dolutegravir, rilpivirine, tenofovir, abacavir, emtricitabine, enfuvirtide, lamivudine, NO HIV-1 protease inhibitors or efavirenz Paritaprevir/ritonavir/ ombitasvir + dasabuvir Atazanavir, dolutegravir, raltegravir, emtricitabine, lamivudine, tenofovir, enfuvirtide NO efavirenz If ritonavir in ART regimen, hold ritonavir in ART for dose due with HCV treatment Simeprevir Raltegravir, (dolutegravir), rilpivirine, maraviroc, abacavir, emtricitabine, tenofovir, lamivudine, enfuvirtide NO HIV-1 protease inhibitors or efavirenz Daclatasvir (DCV) -Note standard DCV dose is 60 mg Slide 6 of 9 No restrictions Dose adjustment with select ART DCV dose to 30 mg with r/ATV, IDV, NFV, SQV, cobi-containing ART (except DRVcobi). DCV dose to 90 mg with efavirenz, From KW Chew, MD, MS, at Los Angeles, CA: April 25, 2016, IAS-USA. etravirine, nevirapine Treatment recommendations - HCV genotype 3 Treatment naïve and PEG-IFN/RBV experienced noncirrhotic Treatment naïve compensated cirrhotic PEG-IFN/RBV treatment experienced compensated cirrhotic Sofosbuvir + WBR + PEG-IFN x 12 weeks (IA) Sofosbuvir/RBV experienced noncirrhotic or cirrhotic Daclatasvir + sofosbuvir x 12 weeks (IA) Sofosbuvir + WBR + PEG-IFN x 12 weeks (IA) Sofosbuvir + WBR + PEG-IFN x 12 weeks (IA) Daclatasvir + Daclatasvir + Daclatasvir + sofosbuvir +/- WBR sofosbuvir + WBR x sofosbuvir + WBR x x 24 weeks (IIaB) 24 weeks (IIaB) 24 weeks (IIaC) Sofosbuvir + WBR + PEG-IFN x 12 weeks (IIaC) WBR = weight-based ribavirin, RBV = ribavirin; Strength of recommendation provided by Class (I, IIa/b, III) AASLD/IDSA HCV Guidance and Level (A, B, C), PEG-IFN= pegylated interferon Slide 7 of 9 From KW Chew, MD, MS, at Los Angeles, CA: April 25, 2016, IAS-USA. Determining treatment response and post-treatment follow-up Quantitative HCV RNA at week 4 on treatment and 12 weeks after treatment completion (SVR12 determination) Can consider HCV RNA at end of treatment and 24 weeks after end of treatment (SVR24) – >99% concordance between SVR12 and SVR24 Remind patients that treatment cure does not = HCV immunity High rates of reinfection in HIV/HCV co-infected persons – – HIV+ MSM without IDU, 2-year cumulative reinfection rates 25-33% Continue to review risk factors Ongoing cirrhosis/chronic liver disease management Slide 8 of 9 Yoshida et al, Hepatology 2015, Martin et al, AIDS 2013, Lambers et al, AIDS 2011, AASLD/IDSA HCV guidance From KW Chew, MD, MS, at Los Angeles, CA: April 25, 2016, IAS-USA. Management of treatment failures Optimal retreatment strategy unknown If urgent to retreat: Resistance testing for NS3 and NS5A resistance mutations – Include RBV on retreatment – Consider PEG-IFN – Consider a clinical trial – AASLD/IDSA HCV Guidance, hcvguidelines.org Slide 9 of 9 From KW Chew, MD, MS, at Los Angeles, CA: April 25, 2016, IAS-USA.