Updated Guidelines for Managing HIV/HCV Co-Infection

Updated Guidelines for Managing HIV/HCV Co-Infection

John J Faragon, PharmD, BCPS, AAHIV-PRegional Pharmacy Director, NY/NJ AIDS Education and Training Center Pharmacist, HIV Medicine, Albany Medical Center

www.hcvguidelines.orgReleased 1/29/14!

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

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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


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


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 expectedwww.hcvguidelines.org

Sofosbuvir and HIV Medications (1 of 2)

Concurrent Medication RecommendationHIV Protease InhibitorsAll 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 recommendedHIV Non Nucleoside Reverse Transcriptase InhibitorsAll NNRTIs Concurrent use at standard doses acceptable.

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Sofosbuvir and HIV Medications (2 of 2)

Concurrent Medication RecommendationHIV Integrase Strand Transfer InhibitorsDolutegravir (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 InhibitorsMaraviroc (Selzentry®) Concurrent use at standard doses acceptable. Interactions not

expected based upon metabolism of sofosbuvir.HIV Nucleoside/Nucleotide Reverse Transcriptase InhibitorsAll NRTIs Concurrent use at standard doses acceptable. Interactions not

expected based upon metabolism of sofosbuvir.

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Simeprevir and HIV Medications (1 of 2)

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. Co-administration not recommended.

Rilpivirine (Edurant®) Concurrent use at standard doses acceptable.

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Simeprevir and HIV Medications (2 of 2)

Concurrent Medication RecommendationHIV Integrase Strand Transfer InhibitorsDolutegravir (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 InhibitorsMaraviroc (Selzentry®) Concurrent use at standard doses acceptable. Interactions not

expected based upon metabolism of simeprevir.HIV Nucleoside/Nucelotide Reverse Transcriptase InhibitorsAll NRTIs Concurrent use at standard doses acceptable. Interactions not

expected based upon metabolism of simeprevir.

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HIV/HCV Co-Infection, GT1Preferred AlternativeTreatment-naïve, prior PEG/RBV relapsers, IFN eligible: SOF + PEG/RBV(WB) x 12 weeks

IFN ineligible: SOF + RBV(WB) x 24 weeksSOF + SMV ± RBV(WB) x 12 weeksTreatment 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 weeksIFN ineligible: None

Treatment experienced, prior PEG/RBVnonrespondersIFN eligible: SOF + PEG/RBV(WB) x 12 WeeksIFN 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


HIV/HCV Co-Infection, GT2Preferred AlternativeAll patients, regardless of treatment history:SOF + RBV(WB) x 12 weeks

Treatment naive and prior PEG/RBV relapsers:None

Treatment experienced, prior PEG/RBVNonresponders:

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


HIV/HCV Co-Infection, GT3Preferred AlternativeAll patients, regardless of treatment history:SOF + RBV(WB) x 24 weeks

Treatment naïve, PEG/RBV relapsers: None

Treatment experienced, prior PEG/RBVNonresponders:

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


HIV/HCV Coinfection, GT4Preferred AlternativeAll 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


HIV/HCV Coinfection, GT 5,6Preferred AlternativeAll 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


HIV/HCV NOT RecommendedNot Recommended for treatment-naïve or treatment-experienced patients:PEG/RBV with or without telaprevir or boceprevir for 24 to 48 weeksMonotherapy with PEG, RBV, or a DAA


Other Drug Interactions with Sofosbuvir

Medication and or Class Rationale 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.

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Other Drug Interactions with Simeprevir (1 of 2)

Medication and or Class Rationale 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.

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Other Drug Interactions with Simeprevir (2 of 2)

Medication and or Class Rationale 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.

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Select HIV/HCV Resources

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NY/NJ AETC – www.nynjaetc.org

Updated Guidelines for Managing HIV/HCV Co-Infection

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