HCV/HIV Coinfection ANTON AND MARGARET FUISZ CHAIR IN MEDICINE. HIV and HCV Share Risk Factors PREVALENCE OF CO-INFECTION BY RISK FACTOR 60%

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1 HCV/HIV Coinfection BRUCE A. LUXON, MD, PHD, FACG ANTON AND MARGARET FUISZ CHAIR IN MEDICINE PROFESSOR AND CHAIRMAN DEPARTMENT OF MEDICINE GEORGETOWN UNIVERSITY HIV and HCV Share Risk Factors PREVALENCE OF CO-INFECTION BY RISK FACTOR 80% 56% 60% 8% MSM PRISONS HEMOPHILIACS IVDU Sherman K, et al. Clin Infect Dis Sulkowski M, et al. Ann Intern Med 2003 Copyright 2015 American College of Gastroenterology 1

2 Entertainment Theme: Bridges Bridges span voids between two solid endpoints Bridges allow one to get to a destination not otherwise obtainable Sometimes a bridge appears too tenuous to merit any kind of passage Bridges have existed since the rise of civilization; yet still can be harrowing and possibly unsafe. And very disorientating to some Worst Bridges Langkawi Sky Bridge. Kedah, Malaysia Built in 2004, this pedestrian bridge is 700 meters above sea level. Recent news is that it was closed as of January 2014 to install sections of glass flooring and opened in March 2015 Copyright 2015 American College of Gastroenterology 2

3 Test for all 3 Infections! HCV HIV HBV Hepatitis C Differs from HIV and HBV No Long-term or Latent Reservoir HBV HIV HCV Host Cell Viral RNA cccdna Proviral DNA Host DNA Nucleus Nucleus Host DNA Nucleus Host DNA TREATMENT Long-term suppression of viral replication TREATMENT Long-term suppression of viral replication TREATMENT Viral Eradication = Cure cccdna = Covalently Closed Circular DNA Copyright 2015 American College of Gastroenterology 3

4 Bruce A. Luxon, MD, PhD, FACG Trift Bridge Effects of HIV on HCV Disease Progression Lower L rate t off spontaneous t clearance l iin acute t HCV Increased HCV-RNA titers Lower response to HCV treatment in past More rapid progression to cirrhosis, ESLD and death Hernandez MD, et al. Curr Opin HIV AIDS 2011;6: Miller MF, et al. Clin Infect Dis 2005;41: Copyright 2015 American College of Gastroenterology 4

5 HCV-Related Liver Failure is the 2 nd Leading Cause of Death: SWISS HIV Cohort Study Percen ntage of Total Deaths 20 19% Non-AIDS Malignancies 16% AIDS 18% Liver Failure And HCC 9% Non-AIDS Infection 7% Substance Use 6% 6% MI Suicide Psychiatric n=459 deaths, representing 5.1% of cohort. Weber R, et al. HIV Med 2013;14: Proportion of Deaths from ESLD Salmon-Ceron. J Hepatol 2005;42: Copyright 2015 American College of Gastroenterology 5

6 HCV Therapy Improves Survival in Co-infection No SVR SVR Limketkai BN, et al. JAMA 2012;308: Worst Bridges Canopy Walk, Ghana Copyright 2015 American College of Gastroenterology 6

7 AASLD/IDSA HCV -- Treatment Guidelines HCV/HIV CO-INFECTION High priority for treatment owing to high risk for complications treatment prioritization regardless of current fibrosis stage HCV/HIV co-infected persons should be treated and retreated t the same as persons without t HIV infection, after recognizing and managing DDI s Unique Patient Populations: Patients with HIV/HCV Coinfection. AASLD-IDSA Guidelines. AASLD/IDSA Recommended Treatment for HCV in HCV/HIV Co-infection Genotype 1a Fixed-dose combination of ledipasvir/sofosbuvir 12 weeks Fixed-dose combination of SOF + daclatasvir 12 weeks, no cirrhosis 24 weeks, +/- ribavirin, cirrhosis Fixed-dose combination paritaprevir/r, ombitasvir/dasabuvir and ribavirin 12 weeks, no cirrhosis 24 weeks, cirrhosis Not Recommended Sofosbuvir + ribavirin for 24 weeks Copyright 2015 American College of Gastroenterology 7

8 AASLD/IDSA Recommended Treatment for HCV in HCV/HIV Co-infection Genotype 1b Fixed-dose combination of ledipasvir/sofosbuvir 12 weeks Fixed-dose combination of SOF + daclatasvir 12 weeks, no cirrhosis 24 weeks, +/- ribavirin, cirrhosis Fixed-dose combination paritaprevir/r, ombitasvir/dasabuvir 12 weeks Not Recommended Sofosbuvir + ribavirin for 24 weeks AASLD/IDSA Recommended Treatment for HCV in HCV/HIV Co-infection Genotypes 2 & 3 GENOTYPE 2 SOF + ribavirin for 12 weeks SOF + daclatasvir for 12 to 16 weeks (cirrhosis 16 weeks) GENOTYPE 3 SOF + daclatasvir +/-RIBA for 12 or 24 weeks (cirrhosis 24 weeks) SOF + RIBA+ PEG IFN for 12 weeks Copyright 2015 American College of Gastroenterology 8

9 AASLD/IDSA Recommended Treatment for HCV in HCV/HIV Co-infection Genotypes 4, 5 & 6 GENOTYPE 4 Sofosbuvir/ledipasvir for 12 weeks (PRoD) + ribavirin for 12 weeks Sofosbuvir + ribavirin for 24 weeks GENOTYPE 5 OR 6 SOF + PEG + RIBA for 12 weeks Lack of trials or experience Bridges in the Alps Copyright 2015 American College of Gastroenterology 9

10 Bruce A. Luxon, MD, PhD, FACG Swiss Bridges Sofosbuvir + Ledipasvir in HIV/HCV Co-infection 50 genotype 1 co-infected patients 100% treatment naïve 80% genotype 1a 25% F3 fibrosis No cirrhosis Sofosbuvir + ledipasvir x 12 weeks No ribavirin 13 not on ART therapy (controlled HIV) 37 stable ART therapy AASLD 2014, Abstract 84 Copyright 2015 American College of Gastroenterology 10

11 Sofosbuvir + Ledipasvir for HIV/HCV Co-infection 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% SVR % 97% 13/13 36/37 No ART ART AASLD 2014, Abstract 84 Simeprevir + Sofosbuvir in HIV/HCV Co-infection Not studied in HIV/HCV coinfection Anecdotal SVR rates of 92%, n=12* Response expected to be similar to monoinfected patients DDI between ART and simeprevir limit applicability *Del Bello, AASLD 2014 Be Careful! Copyright 2015 American College of Gastroenterology 11

12 Viekira Pack (PRoD) + Ribavirin for HCV/HIV Co-infection (G1) PRoD Paritaprevir/r i (PI) Ombitasvir (NS5A) Dasabuvir (non-nucleoside NS5B) Weight based ribavirin (1,000 1,200 mg/d) N=63 12 vs. 24 weeks treatment duration 2/3 treatment t t naïve, 1/3 PEG/RIBA failures >90% genotype 1a 19% cirrhosis, 24% African-American Triple attack against virus AASLD 2014; Abstract 1939 PRoD+ Ribavirin for HCV/HIV Coinfection (G1) 100% 80% SVR-12 94% 91% 60% 40% 20% 0% 12 weeks 24 weeks Treatment Duration AASLD 2014; Abstract 1939 Copyright 2015 American College of Gastroenterology 12

13 Does It Work? HCV HIV Co-infection Worst Bridges Copyright 2015 American College of Gastroenterology 13

14 Treatment Effects on HIV No HIV breakthroughs while compliant with ART No change in CD4% Decreased CD4 count due to ribavirin effect PRoD should only be used in patients with controlled HIV infection Ritonavir may select HIV PI resistance Recent Reports: CROI February 2015 ALLY-2: Sofosbuvir + Daclatasvir for HCV/HIV Repeat of trial already reported in NEJM studying mono-infected GT 1, 2, 3 Drugs Sofosbuvir - polymerase inhibitor (NS5A) Daclatasvir - NS5B inhibitor ALLY-2: GT 1,2,3,4; treatment naive or experienced; cirrhotic or non-cirrhotic; all co-infected Treated for 8 or 12 weeks Copyright 2015 American College of Gastroenterology 14

15 ALLY-2 Results SVR Results Naïve 12 Weeks Experienced 12 Weeks GT GT1a GT1b GT GT GT No cirrhosis Cirrhosis Naïve 8 Weeks The Sky Bridge Copyright 2015 American College of Gastroenterology 15

16 Drug-Drug Interactions DDI Considerations with HIV Drugs Efavirenz Induces CYP 450, lowers levels l of PI s and SOF Zidovudine (AZT) Increased risk of anemia; caution with ribavirin Ritonavir Blocks CYP 3A4, raises levels of PI s GI side effects at higher doses Viekira Pak contains a ritonavir-boosted PI do not administer with other HIV ritonavir-boosted PI s Copyright 2015 American College of Gastroenterology 16

17 DDI Considerations With HIV Drugs (2) DDI (didanosine) Risk of lactic acidosis when combined with ribavirin Tripanavir Do not co-administer with sofosbuvir Ledipasvir/sofosbuvir Tenofovir levels may rise if used with an ART regimen that includes a boosted PI Rifampin, rifabutin, rifapentine Do not use with any DDA-based HCV regimens Drug-drug Interactions with Anti-retroviral Drugs ARV Simeprevir Sofosbuvir DTG No interaction expected No interaction expected RAL Use standard doses Use standard doses EFV Do not coadminister Use standard doses DLV, ETR, NVP Do not coadminister Use standard doses RPV Use standard doses Use standard doses Any PI Do not coadminister DRV/RTV Do not coadminister Use standard doses RTV Do not coadminister Use standard doses TPV/RTV Do not coadminister Do not coadminister TDF Use standard doses Use standard doses COBI Do not coadminister Use standard doses Sofosbuvir [package insert]. Simeprevir [package insert]. Kirby B, et al. AASLD Abstract Ouwerkerk-Mahadevan S, et al. IDSA Abstract 49. Copyright 2015 American College of Gastroenterology 17

18 DDI Sofosbuvir + Ledipasvir DO NOT USE WITH: Tipranavir/ritonavir Concern for lower levels of sofosbuvir/ledipasvir Effavirenz/emtricitabine/tenofovir DF (ATRIPLA ) Elvitegravir/cobicistat/emtricitabine/tenofovir DF (STRIBILD ) Regimens containing Tenofovir DF + ritonavir- boosted PI Concern for increased tenofovir blood levels Monitor renal function, avoid if CrCl <60 ml/min DDI Viekira Pak DO NOT USE WITH: Ritonavir-boosted PI s Switch to unboosted PI s; administer PI with AM dose of Viekira Pak Rilpivirine Increased levels of rilpivirine QT prolongation Darunavir/ritonavir Lower levels of darunavir Lopinavir/ritonavir Higher levels of paritaprevir and ritonavir Efavirenz Ketoconazole Do not administer with ketoconazole dose >200mg/d Higher levels of ketoconazole Viekira Pak Prescribing Information, AbbVie Inc.; Dec 2014 Copyright 2015 American College of Gastroenterology 18

19 Worst Bridges HIV/HCV Treatments Recommended by AASLD-ISDA Guidelines Treat all genotypes as you would for mono-infected patients Do not shorten to 8 weeks of therapy in co-infected patients Be very careful about drug-drug interactions Get an ID /HIV expert to help change ART regimens if necessary Treat co-infected even in less severe fibrosis stages due to increased risk for complications Copyright 2015 American College of Gastroenterology 19

20 Summary 1. HIV co-infection is an indication to treat HCV Regardless of fibrosis i stage 2. Interferon-free options are available and preferred Similar SVR rates to mono-infected patients 3. Adverse event profile similar to mono-infected patients Low discontinuation rates High bilirubin levels with certain ARV s do not reflect hepatotoxicity 4. DDI s deserve careful attention and coordination with HIV-treaters Questions?? Copyright 2015 American College of Gastroenterology 20