1. Updated Guidelines for Managing HIV/HCV Co-Infection John J Faragon, PharmD, BCPS, AAHIV-P Regional Pharmacy Director, NY/NJ AIDS Education and Training Center Pharmacist, HIV Medicine, Albany Medical Center

2. www.hcvguidelines.org Released 1/29/14!

3. Abbreviations  BOC – boceprevir  DAA – direct acting antiviral  IFN – interferon  PEG – pegylated interferon  RBV WB – ribavirin, weight based dosing  RGT – response guided therapy  SMV – simeprevir  SOF – sofosbuvir  TVR – telaprevir www.hcvguidelines.org

4. 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 www.hcvguidelines.org

5. 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 www.hcvguidelines.org

6. Drug Interactions Considerations  Sofosbuvir  Substrate for P-glycoprotein and breast cancer resistance protein  Intracellular metabolism mediated by hydrolase and nucleotide phosphorylation pathways  Minimal drug interactions expected  Simeprevir  Mild inhibitor of CYP1A2 activity and intestinal CYP3A4  Does not affect hepatic CYP3A4 activity  Inhibits OATP1B1/3 and P-glycoprotein  Multiple drug interactions expected www.hcvguidelines.org

7. Sofosbuvir and HIV Medications (1 of 2) Concurrent MedicationRecommendation HIV Protease Inhibitors All HIV PIs, with or without ritonavir, except tipranavir  Concurrent use at standard doses acceptable. Interactions not expected based upon metabolism of sofosbuvir. Tipranavir (Aptivus®)  Co-administration not recommended HIV Non Nucleoside Reverse Transcriptase Inhibitors All NNRTIs  Concurrent use at standard doses acceptable. www.nynjaetc.org

8. Sofosbuvir and HIV Medications (2 of 2) Concurrent MedicationRecommendation 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. www.nynjaetc.org

9. Simeprevir and HIV Medications (1 of 2) Concurrent MedicationRecommendation 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. Co- administration not recommended. Rilpivirine (Edurant®)  Concurrent use at standard doses acceptable. www.nynjaetc.org

10. Simeprevir and HIV Medications (2 of 2) Concurrent MedicationRecommendation 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. www.nynjaetc.org

11. HIV/HCV Co-Infection, GT1 PreferredAlternative 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 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 x 48 weeks, SMV x 12 weeks + PEG/RBV x 48 wks www.hcvguidelines.org

12. HIV/HCV Co-Infection, GT2 PreferredAlternative All patients, regardless of treatment history: SOF + RBV(WB) x 12 weeks 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 24-48 weeks, or any regimen with TVR, BOC, or SMV www.hcvguidelines.org

13. HIV/HCV Co-Infection, GT3 PreferredAlternative All patients, regardless of treatment history: SOF + RBV(WB) x 24 weeks 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 24 - 48 weeks, Any regimen with TVR, BOC, or SMV www.hcvguidelines.org

14. HIV/HCV Coinfection, GT4 PreferredAlternative All patients, regardless of treatment history: IFN eligible: SOF + PEG/RBV(WB) x 12 weeks IFN ineligible: SOF + RBV(WB) x 24 weeks None Not Recommended: PEG/RBV x 48 weeks, any regimen with TVR or BOC www.hcvguidelines.org

15. HIV/HCV Coinfection, GT 5,6 PreferredAlternative All patients, regardless of treatment history: SOF + PEG/RBV(WB) x 12 weeks None Not Recommended: PEG/RBV x 48 weeks, any regimen with TVR, BOC, or SMV www.hcvguidelines.org

16. HIV/HCV NOT Recommended Not Recommended for treatment-naïve or treatment-experienced patients: PEG/RBV with or without telaprevir or boceprevir for 24 to 48 weeks Monotherapy with PEG, RBV, or a DAA www.hcvguidelines.org

17. Other Drug Interactions with Sofosbuvir Medication and or ClassRationale for Avoiding with Sofosbuvir Anticonvulsants – carbamazepine, oxcarbazepine, phenobarbital, phenytoin  Co-administration with these medications is likely to reduce concentrations of sofosbuvir leading to reduced sofosbuvir efficacy. Co-administration not recommended. Antimycobacterials – rifampin, rifabutin, rifapentin  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 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. www.nynjaetc.org

18. Other Drug Interactions with Simeprevir (1 of 2) Medication and or ClassRationale for Avoiding with Simeprevir Anticonvulsants - carbamazepine, oxcarbazepine, phenobarbital, phenytoin  Co-administration with these medications is likely to reduce concentrations of simeprevir and lead to reduced simeprevir efficacy. Co-administration not recommended. Antibiotics – clarithromycin, erythromycin, telithromycin  Co-administration with these medications is likely to increase concentrations of either simeprevir or the antibiotic due to CYP3A4 and P-glycoprotein (P-gp) inhibition. Co-administration not recommended. Antifungals – fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole  Co-administration with these medications is likely to increase concentrations of simeprevir due to CYP3A4 inhibition from the antifungals. Co-administration not recommended. Antimycobacterials – rifampin, rifabutin, rifapentine  Co-administration with these medications is likely to reduce concentrations of simeprevir and lead to reduced simeprevir efficacy. Co-administration not recommended. www.nynjaetc.org

19. Other Drug Interactions with Simeprevir (2 of 2) Medication and or ClassRationale for Avoiding with Simeprevir Corticosteroids – dexamethasone  Co-administration with dexamethasone is likely to decrease concentrations of simeprevir and lead to reduced simeprevir efficacy. Co-administration not recommended. Propulsive – cisapride  Co-administration with cisapride may result in increased concentrations of cisapride leading to potential cardiac arrhythmias. Herbal products – Milk Thistle, St. John’s Wort  Co-administration with milk thistle is likely to increase concentrations of simeprevir. Co-administration not recommended.  Co-administration with St. John’s Wort is likely to reduce concentrations of simeprevir leading to reduced simeprevir efficacy, due to intestinal P-glycoprotein (P-gp) induction associated with St. John’s Wort. www.nynjaetc.org

20. Select HIV/HCV Resources

21. www.nynjaetc.org

22. CLICK HERE

23. www.nynjaetc.org CLICK HERE

24. NY/NJ AETC – www.nynjaetc.org