Disclosure Statement. Hepatitis C. HIV/HCV Co-infection. Major Hepatitis Viruses. Hepatitis: definition. Hepatitis C and HIV/HCV Coinfection 1

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1 Disclosure Statement Hepatitis C and HIV/HCV Co-infection No conflicts of interest exist between the speaker and any entity No endorsements of any products based on bias exist with the speaker Dell Robertson, PharmD, MHA Florida A&M University College of Pharmacy and Pharmaceutical Sciences Division of Director of Pharmacy Practice Hepatitis: definition Major Hepatitis Viruses Inflammation of the liver caused by many different agents, including: Viruses (A through E) Alcohol Drugs/prescriptions Herbs Genetic disorders Obesity (NASH) Virus Hepatitis A Hepatitis B Hepatitis C Means of transmission Fecal-oral: Contaminated food or water Sexual, mother-to-child, blood exposure (transfusion, IDU, tattoo) Blood exposure (transfusion, IDU, tattoo); sexual, mother-to-child less common Hepatitis C and HIV/HCV Coinfection 1

2 Hepatitis C: A Global Health Problem Million (M) Carriers Worldwide Hepatitis C: United States United States 3-4 M Americas M Western Eastern Europe Europe 5 M 10 M Africa M Far East Asia 60 M Southeast Asia M Australia 0.2 M 3.7 million infected in U.S. (1.8% of population) 25,000-35,000 new infections per year Sixty percent due to injection drug use (IDU) A leading cause of cirrhosis and liver cancer and the most common reason for liver transplantation in the United States 8,000-10,000 deaths from HCV annually HCV-related deaths and transplants projected to triple in next decade World Health Organization. Weekly epidemiological record. 2009;74: CDC. MMWR. 2008; 47(No. RR-19):1-39. NIH Consensus Development Conference Panel Statement Management of Hepatitis C, 2004 Prevalence of HCV infection in selected subgroups in the U.S. Risk factors for Hepatitis C infection Injection drug users: 52-90% Hemophiliacs: 60-85% HIV infected individuals: 9-40% incarcerated HIV+: 50% MSM: 4-8% IVDU 10% Cocaine 10% Exposure to infected 20% 55% sex partner or multiple partners Occupational, hemodialysis, 5% household, perinatal No recognized source modes; 2010 Hepatitis C and HIV/HCV Coinfection 2

3 Natural History of Hepatitis C Most patients with chronic HCV infection are asymptomatic years Acute Hepatitis C Chronic Hepatitis 75%-85 % Cirrhosis 20 % Acute Infection Symptoms may present 4-12 weeks after exposure Most patients are asymptomatic and rarely progress to fulminant disease Most common symptoms malaise, weakness, anorexia, and jaundice Hoofnagle JH Hepatology. 1997;26 (suppl 1): 15S-20S Di Bisceglie, Hepatology, 2000 Chronic Infection Defined as the presence of viral RNA in the serum 6 months or more after initial infection Associated with the long term development of end stage liver disease, cirrhosis, or HCC. Concurrent Alcohol use most likely leads to complications and end stage liver disease Co Infection with HIV increases the probability of developing HCC Hepatitis C: Pathophysiology Hepatitis C virus (HCV) replicates in liver cells (hepatocytes) Immune system responds with inflammation Inflammation leads to fibrosis and eventually, in some cases, cirrhosis (scarring) Hepatitis C and HIV/HCV Coinfection 3

4 Complications of Cirrhosis Edema Dangerous impairment of liver function Inability to clear toxins from the circulation => jaundice; hepatic encephalopathy Inability to synthesize key proteins (albumin, clotting factors) Cancer (hepatocellular carcinoma)- HCC Blockage of portal vein blood flow through the liver, leading to ascites Bacterial peritonitis (infection of the ascites) Esophageal varices Ascites Other Extrahepatic Manifestations of Hepatitis C Hematologic: Cryoglobulinemia lymphoma Rheumatologic: rheumatoid arthritis Renal: Glomerulonephritis Dermatologic: Porphyria cutanea tarda Cutaneous necrotizing vasculitis Lichen planus CNS: depression Systemic: fatigue Management of Hepatitis C. NIH Consensus Statement, Hepatitis C and HIV/HCV Coinfection 4

5 Diagnostic Approach: Elevated ALT Levels with Risk Factors for HCV Negative <5% chance of hepatitis C Elevated ALT levels + risk factors for hepatitis Anti-HCV (EIA) testing Positive Diagnosis of hepatitis C>95% certain Refer to specialist for evaluation and treatment Hepatitis C: Diagnosis Antibody test (EIA) Indicates past or active infection Unlike hepatitis B, presence of antibodies does not confer immunity HCV RNA test (PCR) Confirms active infection, infectivity to others Quantitative or qualitative RNA tests exist; the former is more often used because it provides a potentially useful viral load measurement Predictors of Advanced Disease Person infected years Person with long history of moderate to high alcohol consumption Lab values that suggest cirrhosis: low platelets, low albumin, high bilirubin, AST level higher than ALT level Liver Biopsy Provides information regarding Degree of inflammation Stage of fibrosis or scarring Presence/absence of cirrhosis Helps determine Prognosis Cause of liver disease Need for treatment Hepatitis C and HIV/HCV Coinfection 5

6 Predictors of Virologic Response Viral Factors Host Factors Types of Hep C Hepatitis C has six major types called genotypes Genotype Viral Load Age Cirrhosis Race Gender Weight Genotype 1: by far the most common type in the US. Genotype 2, 3, or 4: needs six months of treatment Hepatitis C Treatment Decisions Do not treat patients with Advanced cirrhosis Severe depression/psychiatric disorder Low blood counts Thyroid disease, untreated Autoimmune diseases Alcohol/drug dependency Pregnancy Treatment Outcomes RVR: Rapid Virologic Response, Undetectable HCV RNA at week 4 of treatment EVR: early viral response, undetectable at 12 weeks, > 2 log reduction from baseline ETR: end of treatment response: undetectable at end of treatment 24 or 48 week course, depending on genotype SVR: undetectable 6 months after tx. Complete IL28B genotyping for GT1 predicts response to therapy Hepatitis C and HIV/HCV Coinfection 6

7 Recommended Standard Therapy Pegylated interferon- IV [IFN] Ribavirin- 200 mg tablets (Copegus), [RBV] Oral Protease Inhibitors for Chronic HCV Telaprevir-Incivek [TVR] Boceprevir- Victrelis [BOC] Simeprevir- Olysio [SMV] Sofosbuvir- Solvadi [SOF] Hepatitis C PEGYLATED INTERFERON Pegylated interferon Complexed w/polyethylene glycol (PEG) More stable blood levels, thus more effective Weekly injection Better compliance? ( regular interferon was dosed 3x per week!) Side effects similar Prevention of Chronic Infection or maintain a Sustained Virologic Response (SVR) in Chronic Infection Treatment Goals Sustained Virologic Response Rates Prevent progression of scarring Eradicate virus Prevent complications of end stage liver disease % Patie ents 60% 40% 20% 30% n = % n = % n = 453 0% PEG-IFN IFN + RBV PEG-IFN + RBV Fried MW et al. DDW Hepatitis C and HIV/HCV Coinfection 7

8 ients % of Pati Sustained Response According to Genotype 21% n = 145 PEG-IFN IFN + RBV 37% n = % n = % n = 69 61% n = 145 Genotype 1 Genotype 2, 3 PEG-IFN + RBV 76% n = 140 Fried MW et al. DDW Side Effects of Interferon Flu-like symptoms Alopecia Headache Thyroiditis Fatigue or asthenia Myalgia, arthralgia Nausea Fever, chills Diarrhea Neuropsychiatric disorders Depression Mood lability Brain Fog Injection-site reaction Lab alterations Neutropenia Anemia Thrombocytopenia PEGASYS (peginterferon alfa-2a) [package insert]. Nutley, NJ: Hoffmann-La Roche; PEG-Intron (peginterferon alfa-2b) [package insert]. Kenilworth, NJ: Schering Corporation; Side Effects of Ribavirin Hemolytic anemia Teratogenicity Cough and dyspnea Rash and pruritus Insomnia Anorexia Hepatitis C INTERFERON AND RIBAVIRIN Serious, less common side effects Bacterial infections Thyroid disease Se ere depression s icide Severe depression, suicide Seizures Vision or hearing loss Kidney or heart failure Fetal abnormalities/fetal loss COPEGUS (ribavirin, USP) [package insert]. Nutley, NJ: Hoffmann-La Roche; Hepatitis C and HIV/HCV Coinfection 8

9 Hepatitis C INTERFERON AND RIBAVIRIN Requirements of treated patients 6-12 month course Monitoring For side effects: visits and blood tests at 2 and 4 wks, then every 1-3 months For effectiveness: recheck viral level at 6 and 12 months Monitoring the Patient Anemia Bone marrow toxicity Pulmonary disorders Pancreatitis Psychiatric Side Effect Management Aggressive management of side effects increases compliance and treatment success. Anti-depressants depressants, anti-nauseanausea and insomnia meds are helpful. Growth factors: erythropoetin and filgastim are helpful. (off label use) Management of Fatigue Conduct baseline assessment Check hydration status and diet Advise patients t to: Avoid strenuous activities, incorporate relaxing activities in daily regimen Plan lighter activities for days after interferon dosing Hepatitis C and HIV/HCV Coinfection 9

10 Management of Depression Assess before starting treatment Stabilize on antidepressant before treatment Establish care with counselor, psychiatrist, primary care giver before treatment Immediate evaluation if suicidal. May need to discontinue treatment. Management of Cough Assess for pneumonia Rule out other causes (eg, allergies, bronchial infections) Advise patients to: Increase daily fluid intake, use humidifier, use cough drops or nonsedating cough medications Hep C and HIV Topics Interactions of viruses Treatment decisions Drug interactions Hepatitis C HIV/HCV COINFECTION 10%-30% w/ HIV also have HCV Rate of HCV depends on risk factor Hemophiliacs >90% IDUs 70%-90% MSM 5%-10% Hepatitis C and HIV/HCV Coinfection 10

11 HCV/HIV Coinfection HIV accelerates Hep C liver disease (may cut time to cirrhosis in half!) Hep C may impair immune reconstitution after HAART HCC may occur at an earlier age with coinfection Hepatitis C HIV/HCV COINFECTION HCV liver disease is more severe in HIV+ HCV liver disease is now more important HIV deaths are decreasing Deaths related to liver disease are increasing Effect of HCV infection on HIV/AIDS progression is not known Hepatitis C HIV/HCV COINFECTION HIV treatments can cause liver problems/liver enzyme elevations In some studies these liver problems are increased in those w/hcv Some report worsening of HCV liver disease after HIV treatment is started HIV/HCV Treatment Predictors of success in achieving a sustained viral response: CD4 count greater than 500 HIV RNA levels below 10,000 copies No alcohol consumption Hepatitis C and HIV/HCV Coinfection 11

12 Drug interactions in Co-infection Drug interactions ddi and d4t plus interferon/ribavirin appear to cause mitochondrial toxicity result: lactic acidosis, peripheral neuropathy Avoid starting these drugs if plan to treat HCV later Clinical manifestations: pancreatitis, hepatitis, myopathy, peripheral neuropathy and lactic acidosis Drug interactions Monitor serum lactate and amylase monthly Consider changing HAART before starting combination therapy Discontinue all meds immediately if lactate rising Treatment Decisions Treat Hep. C first? (if HIV stable, if CD4 count good) Treat HIV first? (if immune compromised) Hepatitis C and HIV/HCV Coinfection 12

13 Sofosbuvir + PEG + RBV: Treatment-Naive HCV GT 1,4,5,6 NEUTRINO Trial: Results NEUTRINO: SVR 12 by Genotype Sofosbuvir + PEG + RBV: Treatment-Naive HCV GT 1,4,5,6 NEUTRINO Trial: Results NEUTRINO: SVR 12 by Race 261/292 27/28 7/7 248/273 47/54 GT = genotype Source: Lawitz E, et al. N Engl J Med. 2013;368: Source: Lawitz E, et al. N Engl J Med. 2013;368: Sofosbuvir + PEG + RBV: Treatment-Naive HCV GT 1,4,5,6 NEUTRINO Trial: Results NEUTRINO: SVR 12 by Liver Disease 252/273 43/54 Sofosbuvir + PEG + RBV: Treatment-Naive HCV GT 1,4,5,6 NEUTRINO Trial: Adverse Events Event SOF + PEG + RBV (n=327) Discontinuation due to adverse event 5 (2%) Fatigue 192 (59%) Headache 118 (36%) Nausea 112 (34%) Rash 59 (18%) Hemoglobin < 10 g/dl 74 (23%) Neutropenia 54 (17%) Influenza-like illness 51 (16%) Depression 31 (9.5%) Insomnia 81 (41%) Rates of adverse events shown in triple therapy did not exceed rates seen in dual therapy (Peg + RBV) arm of FISSION. Source: Lawitz E, et al. N Engl J Med. 2013;368: Source: Lawitz E, et al. N Engl J Med. 2013;368: Hepatitis C and HIV/HCV Coinfection 13

14 Sofosbuvir + PEG + RBV: Treatment-Naive HCV GT 1,4,5,6 NEUTRINO Trial: Conclusions Treatment Naïve Conclusions: In the open-label, single-group study, 12 weeks of treatment with sofosbuvir plus peginterferonribavirin had high efficacy in previously untreated patients with genotype 1 or 4 infection, with apparent reductions in adverse effects. Sofosbuvir + RBV in Treatment-Naïve Genotypes 2,3 FISSION Trial* *Note: Published in NEJM in tandem with NEUTRINO Trial (Genotypes 1,4,5,6) Lawitz E, et al. N Engl J Med. 2013;368: *Note: This conclusion pertains to both the NEUTRINO and FISSION trials, which were published in tandem Source: Lawitz E, et al. N Engl J Med. 2013;368: Sofosbuvir + Ribavirin for Treatment-Naïve HCV GT 2 or 3 FISSION Trial: Features FISSION Trial: Features Design: Randomized, controlled, open-label phase 3 non-inferiority trial comparing sofosbuvir + ribavirin versus PEG + ribavirin in HCV GT 2,3 Setting: 97 sites in US, Australia, New Zealand, Italy, Sweden, and the Netherlands, enrolled Dec 2011-May 2012 Entry Criteria - Treatment-naïve, chronic HCV Genotype 2 or 3 - HCV RNA 10,000 IU/ml Patient Characteristics - N = 499 HCV-monoinfected patients - HCV Genotype: 2 (28%); 3 (72%) - IL28B Genotype: 57% non-cc - Age and Sex: mean age 48 (range 19-77); 66% male - Race: 87% white; 3.4% black - Liver disease: 20% had cirrhosis Primary End-Point: SVR12 Source: Lawitz E, et al. N Engl J Med. 2013;368: Week 0 12 N =256 N =243 Sofosbuvir + Ribavirin for Treatment-Naïve HCV GT 2 or 3 FISSION Trial: Design Sofosbuvir + RBV (weight-based) Peginterferon + RBV (fixed-dose) Source: Lawitz E, et al. N Engl J Med. 2013;368: SVR12 Drug Dosing Sofosbuvir: 400 mg once daily Peginterferon alfa-2a: 180 µg once weekly Weight-based Ribavirin (in 2 divided doses): 1000 mg/day if < 75 kg or 1200 mg/day if 75 kg Fixed-dose Ribavirin (in 2 divided doses): 800 mg/day SVR12 Hepatitis C and HIV/HCV Coinfection 14

15 Sofosbuvir + Ribavirin for Treatment-Naïve HCV GT 2 or 3 FISSION Trial: Results FISSION: HCV RNA <25 IU/ml by Study Timepoint (GT 2, 3 Combined) Sofosbuvir + Ribavirin for Treatment-Naïve HCV GT 2 or 3 FISSION Trial: Results FISSION: SVR12 by Genotype 249/ / / / / / / /243 68/70 52/67 102/ /176 RBV = Ribavirin; PEG = Peginterferon RBV = Ribavirin; PEG = Peginterferon Source: Lawitz E, et al. N Engl J Med. 2013;368: Source: Lawitz E, et al. N Engl J Med. 2013;368: Event Sofosbuvir + Ribavirin for Treatment-Naïve HCV GT 2 or 3 FISSION Trial: Adverse Effects Sofosbuvir + RBV (n=256) PEG + RBV (n=243) Discontinuation due to adverse event 3 (1%) 26 (11%) Fatigue 92 (36%) 134 (55%) Headache 64 (25%) 108 (44%) Nausea 46 (18%) 70 (29%) Pruritus 19 (7%) 42 (17%) Hemoglobin < 10 g/dl 23 (9%) 35 (14%) Neutropenia 0 30 (12%) Influenza-like illness 7 (3%) 43 (18%) Depression 14 (5.5%) 34 (14%) Insomnia 31 (12%) 70 (29%) Source: Lawitz E, et al. N Engl J Med. 2013;368: Sofosbuvir FDA Approved, December 6, 2013 FDA Panel recommended approval October 25, 2013 Recommendation covers both use with interferon-based therapy for treatment-naive people with HCV genotypes 1 or 4 Also use in dual therapy with ribavirin for people with easier-to-treat HCV genotypes 2 or 3 - the first approved interferon-free regimen Gilead Sciences. FDA Advisory Committee Supports Approval of Gilead s Sofosbuvir for Chronic Hepatitis C Infection. Press release. October 25, Accessed June 4, Hepatitis C and HIV/HCV Coinfection 15

16 Sofosbuvir Key Points Indication NS5B nucleotide polymerase inhibitor for the treatment of chronic HCV as a component of combination anitiviral treatment regimen 400 mg tablet, once daily dosing, with no food restrictions HCV Mono-infected and HCV/HIV Co-infected Genotype 1 or 4 Treatment Sofosbuvir + PEGinterferon + ribavirin Duration 12 weeks Genotype 2 Sofosbuvir + ribavirin 12 weeks Genotype 3 Sofosbuvir + ribavirin 24 weeks Sofosbuvir Key Points Sofosbuvir + ribavirin ALONE for 24 weeks can be considered for GT1 if intolerant to interferon No dosage recommendation can be made in patients with severe renal impairment or ESRD up to 20 fold increase in SOF metabolite Contraindications Monotherapy, also ribavirin birth defects Accessed June 4, Accessed June 4, Sofosbuvir Key Points Adverse Events Headache and fatigue most common Anemia and insomnia, nausea when adding peginterferon + ribavirin Additional info HIV/HCV coinfection studied, also data on patients with HCC awaiting liver transplantation studied Drug Interactions Intestinal PGP inducers likely to reduce levels ie rifampin, St Johns Wort Accessed June 4, 2014 PHOTON-1 Trial in HIV/HCV Co-infection Open-label, phase 3 study of sofosbuvir plus weightbased ribavirin in coinfection, genotypes 1, 2 or 3. GT1, Naive GT2/3, Naive GT2/3, Experienced Week SOF + RBV, n=114 SOF + RBV, n=68 SOF + RBV, n=41 Naggie S et al. CROI 2014; Abst 26. SVR 12 SVR Hepatitis C and HIV/HCV Coinfection 16

17 PHOTON-1: Results PHOTON-1: Results Allowable ARVs: NRTIs, atazanavir/r, darunavir/r, rilpivirine & raltegravir Most virologic failures had relapse No sofosbuvir resistance seen Naggie S et al. CROI 2014; Abst Naggie S et al. CROI 2014; Abst Patients, % AEs PHOTON-1 Adverse Events 24 Weeks SOF+RBV(n=155) 12 Weeks SOF+RBV(n=68) Fatigue Insomnia Headache Nausea Diarrhea 11 9 Irritability URI Grade 3-4 AEs Serious AEs 6 7 Treatment DC due to AEs 3 4 Death 0 1 Medications to Avoid with Sofosbuvir Medication and or Class Rationale for Avoiding with Sofosbuvir Anticonvulsants carbamazepine, oxcarbazepine, Co-administration with these medications is likely to reduce concentrations of sofosbuvir leading to reduced sofosbuvir efficacy. Co-administration not recommended. phenobarbital, phenytoin Antimycobacterials Co-administration with these medications is likely to reduce rifampin, rifabutin, rifapentin concentrations of sofosbuvir leading to reduced sofosbuvir efficacy due to intestinal P-glycoprotein (P-gp) induction from rifampin. Herbal products St. John s Wort Co-administration with these medications is likely to reduce concentrations of sofosbuvir leading to reduced sofosbuvir efficacy due to intestinal P-glycoprotein (P-gp) induction associated with St. John s Wort. Naggie S et al. CROI 2014; Abst Hepatitis C and HIV/HCV Coinfection 17

18 Sofosbuvir and HIV Medications Sofosbuvir and HIV Medications Concurrent Medication Recommendation HIV Protease Inhibitors All HIV PIs, with or without ritonavir, except Concurrent use at standard doses acceptable. Interactions not expected based upon metabolism of sofosbuvir. tipranavir Tipranavir (Aptivus ) Co administration not recommended HIV Non Nucleoside Reverse Transcriptase Inhibitors All NNRTIs Concurrent use at standard doses acceptable. Concurrent Medication Recommendation HIV Integrase Strand Transfer Inhibitors Dolutegravir (Tivicay ) Concurrent use at standard doses acceptable. Interactions not expected based upon metabolism of sofosbuvir. Elvitegravir (contained in Stribild ) Concurrent use at standard doses acceptable. Interactions not expected based upon metabolism of sofosbuvir. Raltegravir (Isentress ) Concurrent use at standard doses acceptable. HIV Entry Inhibitors Maraviroc (Selzentry ) Concurrent use at standard doses acceptable. Interactions not expected based upon metabolism of sofosbuvir. HIV Nucleoside/Nucleotide Reverse Transcriptase Inhibitors All NRTIs Concurrent use at standard doses acceptable. Interactions not expected based upon metabolism of sofosbuvir. HIV/HCV Co-Infection, GT1 Preferred Treatment-naïve, prior PEG/RBV relapsers, IFN eligible: SOF + PEG/RBV(WB) x 12 weeks IFN ineligible: SOF + RBV(WB) x 24 weeks SOF + SMV ± RBV(WB) x 12 weeks Treatment experienced, prior PEG/RBV nonresponders, regardless of IFN eligibility: SOF + SMV ± RBV(WB) x 12 weeks Alternative Treatment-naïve, prior PEG/RBV relapsers, IFN eligible: SMV x 12 weeks + PEG/RBV(WB) x 24 weeks IFN ineligible: None Treatment experienced, prior PEG/RBV nonresponders IFN eligible: SOF + PEG/RBV(WB) x 12 Weeks IFN ineligible: SOF + RBV(WB) x 24 Weeks Not Recommended: TVR + PEG/RBV x 24 or 48 weeks (RGT), BOC + PEG/RBV x 28 or 48 weeks (RGT) PEG/RBV 48 k SMV 12 k + PEG/RBV 48 k Hepatitis C and HIV/HCV Coinfection 18

19 Preferred HIV/HCV Co-Infection, GT2 All patients, regardless of treatment history: SOF + RBV(WB) x 12 weeks Alternative Treatment naive and prior PEG/RBV relapsers: None Treatment experienced, prior PEG/RBV Nonresponders: IFN eligible: SOF + PEG/RBV(WB) X 12 Weeks IFN ineligible: None Not Recommended: PEG/RBV x weeks, or any regimen with TVR, BOC, or SMV HIV/HCV Co-Infection, GT3 Preferred All patients, regardless of treatment history: SOF + RBV(WB) x 24 weeks Alternative Treatment naïve, PEG/RBV relapsers: None Treatment experienced, prior PEG/RBV Nonresponders: IFN eligible: SOF + PEG/RBV(WB) X 12 weeks IFN ineligible: None Not Recommended: PEG/RBV x weeks, Any regimen with TVR, BOC, or SMV HIV/HCV Coinfection, GT4 Preferred All patients, regardless of treatment history: IFN eligible: SOF + PEG/RBV(WB) x 12 weeks Alternative None IFN ineligible: SOF + RBV(WB) x 24 weeks Not Recommended: PEG/RBV x 48 weeks, any regimen with TVR or BOC HIV/HCV Coinfection, GT 5,6 Preferred All patients, regardless of treatment history: SOF + PEG/RBV(WB) x 12 weeks Alternative None Not Recommended: PEG/RBV x 48 weeks, any regimen with TVR, BOC, or SMV Hepatitis C and HIV/HCV Coinfection 19

20 Simeprevir and HIV Medications Simeprevir and HIV Medications Concurrent Medication Recommendation HIV Protease Inhibitors All HIV PIs Significant increases or decreases in simeprevir levels expected when used with any HIV protease inhibitor, when used with or without ritonavir. Co-administration not recommended HIV Non Nucleoside Reverse Transcriptase Inhibitors Efavirenz (Sustiva ), Etravirine (Intelence ), Nevirapine (Viramune ) Significant reductions in simeprevir levels and reduced simeprevir efficacy due to CYP3A4 induction. Coadministration not recommended. Rilpivirine (Edurant ) Concurrent use at standard doses acceptable. Concurrent Medication Recommendation HIV Integrase Strand Transfer Inhibitors Dolutegravir (Tivicay ) Concurrent use at standard doses acceptable. Interactions not expected based upon metabolism of simeprevir. Elvitegravir (contained in Stribild ) Significant increase in simeprevir levels expected when used with a cobicistat containing regimen. Co-administration not recommended. Raltegravir (Isentress ) Concurrent use at standard doses acceptable. HIV Entry Inhibitors Maraviroc (Selzentry ) Concurrent use at standard doses acceptable. Interactions not expected based upon metabolism of simeprevir. HIV Nucleoside/Nucelotide Reverse Transcriptase Inhibitors All NRTIs Concurrent use at standard doses acceptable. Interactions not expected based upon metabolism of simeprevir. Standard Dosing Sofosbuvir 400mg once daily Simeprevir 150mg once daily Peg Interferon 180mcg once weekly Ribavirin weight based dosing <75kg 1000mg daily in divided doses 75 kg 1200mg daily in divided doses IFN Ineligible Definitions Intolerance to IFN Autoimmune hepatitis and other autoimmune disorders Hypersensitivity to PEG or any of its components Decompensated hepatic disease History of depression, or clinical features consistent with depression A baseline neutrophil count below 1500/μL, a baseline platelet count below 90,000/μL or baseline hemoglobin below 10 g/dl A history of preexisting cardiac disease Hepatitis C and HIV/HCV Coinfection 20

21 Summary SVR was significantly higher for PEGASYS (40 kda) + COPEGUS compared to conventional combination therapy Overall: 40% vs 12%; P < Genotype 1: 29% vs 7% Genotype 2/3: 62% vs 20% Adverse event profile of PEGASYS (40kDa) + COPEGUS is generally similar to IFN + RBV therapy Only 15% of patients discontinued for adverse events or laboratory abnormalities Hepatitis C/HIV SUMMARY HIV+ persons have worse liver disease Treatment should be considered Expect greater side effects, possible interactions with HIV medications Clinical Pearls for the Pharmacist Special tests: abdominal ultrasounds/egd/liver biopsy Combination therapy management Vaccinations: HAV, HBV, pneumovax? Education Team Work Physician/PA/NP providers Nutritionists Social workers/case Managers Mental health: psychiatrist/counselors Pharmacists Hepatitis C and HIV/HCV Coinfection 21

22 Questions Hepatitis C and HIV/HCV Coinfection 22