Treatment of Patients with HCV and HIV

Transcription

1 Treatment of Patients with HCV and HIV BRUCE A. LUXON, MD, PHD, FACG ANTON AND MARGARET FUISZ CHAIR IN MEDICINE PROFESSOR AND CHAIRMAN DEPARTMENT OF MEDICINE GEORGETOWN UNIVERSITY Four Questions Is HIV/HCV a common and important co-infection? Does HIV increase the morbidity and mortality of HCV infection? Can HCV be safely and effectively treated in HIV/HCV co-infected patients? Does successful HCV treatment alter the mortality and morbidity of HIV/HCV co-infection? Page 1 of 19

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 they still can be harrowing and possibly unsafe. And very disorientating to some Four Questions Is HIV/HCV a common and important co-infection? Does HIV increase the morbidity and mortality of HCV infection? Can HCV be safely and effectively treated in HIV/HCV co-infected patients? Does successful HCV treatment alter the mortality and morbidity of HIV/HCV co-infection? Page 2 of 19

3 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 Test for all 3 Infections! HCV HIV HBV Page 3 of 19

4 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 Four Questions Is HIV/HCV a common and important co-infection? Does HIV increase the morbidity and mortality of HCV infection? Can HCV be safely and effectively treated in HIV/HCV co-infected patients Does successful HCV treatment alter the mortality and morbidity of HIV/HCV co-infection? Page 4 of 19

5 Effects of HIV on HCV Disease Progression Lower rate of spontaneous clearance in acute 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: HCV-Related Liver Failure is the 2 nd Leading Cause of Death: SWISS HIV Cohort Study Percentage of Total Deaths % 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: Page 5 of 19

6 Cause of Death in HIV-infected Patients: Effect of HCV and HBV Infections Salmon-Ceron. J Hepatol 2005;42: Four Questions Is HIV/HCV a common and important co-infection? Does HIV increase the morbidity and mortality of HCV infection? Can HCV be safely and effectively treated in HIV HCV co-infected patients Does successful HCV treatment alter the mortality and morbidity of HIV/HCV co-infection? Page 6 of 19

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 the same as persons without HIV infection, after recognizing and managing DDI s Unique Patient Populations: Patients with HIV/HCV Coinfection. AASLD-IDSA Guidelines. Pre Treatment Evaluation: What Is New? Need to know Genotype OLD Previous treatment Resistance profiles OLD New Cirrhosis OLD Page 7 of 19

8 What Has Changed Recently? Longer treatment 12, 16, 24 weeks Ribavirin may be added Very simplified treatment algorithms Genotype 1a Daclatasvir and sofosbuvir NEW 12 weeks: No cirrhosis 24 weeks: Cirrhosis Weight-based ribavirin may be added to avoid resistance, especially in cirrhotics Elbasvir and grazoprevir NEW Check baseline resistance 12 weeks, no resistance, with or without cirrhosis If resistance to elbasvir, add ribavirin and treat for 16 weeks Page 8 of 19

9 Genotype 1b Daclatasvir and sofosbuvir NEW 12 weeks: No cirrhosis 24 weeks: Cirrhosis Weight-based ribavirin may be added to avoid resistance, especially in cirrhotics Elbasvir and grazoprevir NEW Check baseline resistance 12 weeks, with or without cirrhosis Genotype 2 Daclatasvir and sofosbuvir NEW 12 weeks without cirrhosis weeks with cirrhosis Sofosbuvir and ribavirin OLD 12 weeks: No cirrhosis weeks: Cirrhosis Page 9 of 19

10 Genotype 3 Daclatasvir and sofosbuvir (FDA approved) --NEW 12 weeks: No cirrhosis 24 weeks: Cirrhosis Weight-based ribavirin may be added to avoid resistance, especially in cirrhotics Genotype 4 Ledipasvir and sofosbuvir OLD 12 weeks Elbasvir and grazoprevir New 12 weeks with or without cirrhosis Page 10 of 19

11 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 Sofosbuvir + Ledipasvir for HIV/HCV Co-infection 100% 80% SVR % 97% 60% 40% 20% 0% 13/13 36/37 No ART ART AASLD 2014, Abstract 84 Page 11 of 19

12 Safety Ledipasvir/Sofosbuvir Combination No changes in CD4 counts or CD4% No AE-related treatment discontinuation No hyperbilirubinemia Side effects in at >5%: Nasal congestion Sore throat Fatigue Diarrhea Nausea Headaches AASLD 2014, abstract #84 PRoD + Ribavirin for HCV/HIV Co-infection (G1) PRoD Paritaprevir/r (PI) Ombitasvir (NS5A) Dasabuvir (non-nucleoside NS5B) Triple attack against virus Weight based ribavirin (1,000 1,200 mg/d) N=63 12 vs. 24 weeks treatment duration 2/3 treatment naïve, 1/3 PEG/RIBA failures >90% genotype 1a 19% cirrhosis, 24% African American AASLD 2014; Abstract 1939 Page 12 of 19

13 PRoD+ Ribavirin for HCV/HIV Coinfection (G1) 100% 80% 60% 40% 20% SVR-12 94% 91% 0% 12 weeks 24 weeks Treatment Duration AASLD 2014; Abstract 1939 Sofosbuvir and Daclatasvir 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 Page 13 of 19

14 ALLY-2 Results SVR Results Naïve 12 Weeks Experienced 12 Weeks GT GT1a GT1b GT GT GT No cirrhosis Cirrhosis Naïve 8 Weeks Treatment Effects on HIV No HIV breakthroughs if compliant with ART No change in CD4% PRoD should only be used in patients with controlled HIV infection Ritonavir may select HIV PI resistance Page 14 of 19

15 Drug-Drug Interactions AASLD /IDSA Guidelines April 2016 Page 15 of 19

16 AASLD /IDSA Guidelines April 2016 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 patients even with less severe fibrosis stages due to increased risk for complications Page 16 of 19

17 Four Questions Is HIV/HCV a common and important co-infection? Does HIV increase the morbidity and mortality of HCV infection? Can HCV be safely and effectively treated in HIV HCV co-infected patients? Does successful HCV treatment alter the mortality and morbidity of HIV/HCV co-infection? Curing HCV in HIV co-infected patients improves outcomes Lower rates of hepatic decompensation Lower rates of HCC Lower rates of liver-related mortaitlity Now Lower adverse events Better response rates Improved acceptance of treatment Pre DAA Era Page 17 of 19

18 HCV Treatment Prevents Decompensation In Co-Infected Patients Increased probability of remaining free of hepatic decompensation HCV Therapy Improves Survival in Co-infection No SVR SVR Limketkai BN, et al. JAMA 2012;308: Page 18 of 19

19 Summary 1. HIV co-infection is an indication to treat HCV Regardless of fibrosis 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 Page 19 of 19