The Role of New HCV Agents in Managing HIV/HCV Coinfection.2014
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This document summarizes a presentation on new agents for treating hepatitis C virus (HCV) infection in patients coinfected with HIV. It discusses FDA-approved regimens containing simeprevir or sofosbuvir, dosing and administration, treatment guidelines from AASLD/IDSA, and clinical trial data on sofosbuvir and simeprevir in HIV/HCV coinfected patients, showing high sustained virologic response rates.
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The Role of New HCV Agents in Managing HIV/HCV Coinfection.2014
- 1. Mark S. Sulkowski, MD Professor of Medicine Medical Director, Viral Hepatitis Center Divisions of Infectious Diseases and Gastroenterology/Hepatology Johns Hopkins University School of Medicine Baltimore, Maryland The Role of New HCV Agents in Managing HIV/HCV Coinfection This activity is supported by an independent educational grant from Gilead Sciences.
- 2. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection About These Slides Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent These slides may not be published or posted online without permission from Clinical Care Options (email permissions@clinicaloptions.com) Disclaimer The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.
- 3. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection Disclosures Mark S. Sulkowski, MD, has disclosed that he has received consulting fees from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck, and Tobira and funds for research support from AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead Sciences, and Merck, and data and safety monitoring board funding has been paid to Johns Hopkins University by Gilead Sciences.
- 4. Background
- 5. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection FDA-Approved Regimens for Simeprevir and Sofosbuvir in Pts With HCV Infection 1. Simeprevir [package insert]. 2. Sofosbuvir [package insert]. Population Regimen Total Treatment Duration Simeprevir GT1, treatment naive and previous relapsers Simeprevir + pegIFN/RBV for 12 wks, followed by pegIFN/RBV for 12 wks 24 wks GT1, previous partial or nonresponders Simeprevir + pegIFN/RBV for 12 wks, followed by pegIFN/RBV for 36 wks 48 wks Sofosbuvir GT1 or GT4* Sofosbuvir + pegIFN alfa/RBV 12 wks GT2 Sofosbuvir + RBV 12 wks GT3 Sofosbuvir + RBV 24 wks HCC awaiting transplantation Sofosbuvir + RBV Up to 48 wks or until transplantation, whichever first *A 24-wk course of sofosbuvir + RBV can be considered in IFN-ineligible GT1 pts.
- 6. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection Simeprevir: Dosing and Administration 3. Simeprevir [package insert]. Characteristic Simeprevir Dose 150 mg/day PO* Formulation 150-mg capsule Dose reductions Never Pills per day 1 With food Take with food PegIFN Either pegIFN acceptable; use according to package instructions RBV Weight-based dosing according to peginterferon used Most common AEs With pegIFN/RBV: rash, pruritus, nausea Drug class PI Additional considerations Strongly consider Q80K testing in patients with genotype 1a infection; if present, consider alternative therapies *Used in combination with both pegIFN and RBV in registrational trials.
- 7. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection Sofosbuvir: Dosing and Administration *Used in combination with RBV ± pegIFN, depending on HCV genotype and other patient characteristics, in registrational trials. 7. Sofosbuvir [package insert]. Characteristic Sofosbuvir Dose 400 mg/day PO* Formulation 400-mg tablet Dose reductions Never Pills per day 1 With food No food restrictions PegIFN Either pegIFN acceptable, use according to package instructions RBV Weight-based dosing according to package instructions; dose reduction required in patients with renal impairment Most common AEs With pegIFN/RBV: fatigue, headache, nausea, insomnia, anemia With RBV: fatigue, headache Drug class NS5B nucleotide inhibitor
- 8. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection Therapeutic Options Are Evolving NS3 Protease Inhibitors NS5A Replication Complex Inhibitors NS5B Nucleoside Inhibitors NS5B Nonnucleoside Inhibitors Other FDA Approved Agents Telaprevir Sofosbuvir Peginterferon Boceprevir Ribavirin Simeprevir Phase III Agents (as of September 2014) Asunaprevir Daclatasvir Dasabuvir Paritaprevir (previously ABT-450) Ledipasvir Beclabuvir (previously BMS-791325) MK-5172 Ombitasvir MK-8742
- 10. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection AASLD/IDSA Guidance: When to Start Treatment in HCV/HIV-Coinfected Patients Treatment is recommended for patients with chronic HCV infection Treatment should be prioritized in patients at high risk for liver-related complications – Includes patients with HCV/HIV coinfection, regardless of fibrosis stage Treating patients at high risk for transmitting HCV to others may decrease transmission and HCV disease prevalence – Includes MSM with high-risk sexual practices and active injection drug users 9. AASLD and IDSA. HCV Management Guidance. September 2014.
- 11. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection AASLD/IDSA Guidance: Recommended Regimens for HCV/HIV-Coinfected Pts *Previous PR nonresponders regardless of IFN eligibility. 12. AASLD and IDSA. HCV Management Guidance. September 2014. Genotype Recommended Regimens Genotype 1 HCV treatment naive and prior PR relapsers IFN eligible Sofosbuvir + pegIFN/RBV for 12 wks IFN ineligible Sofosbuvir + RBV for 24 wks Sofosbuvir + simeprevir ± RBV for 12 wks HCV treatment experienced* Sofosbuvir + simeprevir ± RBV for 12 wks Genotype 2 Regardless of HCV treatment history Sofosbuvir + RBV for 12 wks Genotype 3 Regardless of HCV treatment history Sofosbuvir + RBV for 24 wks Genotype 4 Regardless of HCV treatment history IFN eligible Sofosbuvir + pegIFN/RBV for 12 wks IFN ineligible Sofosbuvir + RBV for 24 wks Genotype 5 or 6 Regardless of HCV treatment history Sofosbuvir + pegIFN/RBV for 12 wks
- 12. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection AASLD/IDSA Guidance: Allowable ARVs in HCV/HIV-Coinfected Pts Receiving DAAs Sofosbuvir: ALL except didanosine, zidovudine, and tipranavir[1] Simeprevir: raltegravir, rilpivirine, maraviroc, enfuvirtide, tenofovir, emtricitabine, lamivudine, and abacavir[15] – Clinically significant drug interactions were observed when simeprevir coadministered with ritonavir or with efavirenz in healthy volunteers[17] 15. AASLD and IDSA. HCV Management Guidance. September 2014. 17. Simeprevir [package insert].
- 13. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection AASLD/IDSA Guidance: HCV Regimens NOT Recommended in HIV-Coinfected Pts The following are NOT recommended for treatment-naive or treatment-experienced HCV/HIV-coinfected patients: – Telaprevir- or boceprevir-containing therapy – Monotherapy with pegIFN, RBV, or a DAA 19. AASLD and IDSA. HCV Management Guidance. September 2014.
- 14. Clinical Trial Data on New HCV Agents in HCV/HIV-Coinfected Patients
- 15. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection Sofosbuvir + PegIFN/RBV for 12 Wks in Treatment-Naive GT1 HCV Patients 20. Lawitz E, et al. N Engl J Med. 2013;368:1878-1887. 21. Rodriguez-Torres M, et al. ID Week 2013. Abstract 714. P7977-1910 Single-Arm Study in HCV/HIV Coinfection: SVR12[21] 100 80 60 40 20 0 GT1 GT1a GT1b 89 87 100 17/19 13/15 4/4 100 Overall SVR12(%) 89 80 60 40 20 0 GT1 261/292n/N = 90 295/327 NEUTRINO Single-Arm Study in HCV Monoinfection: SVR12[20]
- 16. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection PHOTON-1: Sofosbuvir + RBV in GT1-3 HCV Patients Coinfected With HIV Nonrandomized, open-label phase III study; primary endpoint: SVR12 Stable ART (HIV-1 RNA < 50 copies/mL for > 8 wks before enrollment) – 95% on ART: TDF/FTC, 100%; EFV, 35%; ATV/RTV, 17%; DRV/RTV, 15%; RAL, 16%; RPV, 6% Cirrhosis at baseline: GT1, 4%; GT2/3 tx naive, 10%; GT2/3 tx-exp’d: 24% 22. Sulkowski MS, et al. JAMA. 2014;312:353-361. Wk 24 Sofosbuvir + RBV (n = 114) Sofosbuvir + RBV (n = 41) Sofosbuvir + RBV (n = 68) Wk 12 Tx-naive GT1 Tx-naive GT2/3 Tx-exp’d GT2/3 SVR12, % (n/N) GT1: 76 (87/114) GT2: 88 (23/26) GT3: 67 (28/42) GT2: 92 (22/24) GT3: 94 (16/17) Sofosbuvir 400 mg QD; weight-based RBV 1000 or 1200 mg/day
- 17. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection PHOTON-2: Sofosbuvir + RBV in GT1-4 HCV Patients Coinfected With HIV Nonrandomized, open-label phase III study; primary endpoint: SVR12 Stable ART (HIV-1 RNA < 50 copies/mL for ≥ 8 wks before enrollment) – 97% on ART: TDF/FTC, 100%; EFV, 25%; ATV/RTV, 17%; DRV/RTV, 21%; RAL; 23%; RPV, 5% Cirrhosis at baseline: All pts, 20%; tx-naive patients, 13%; tx-exp’d patients, 45% 29. Molina JM, et al. AIDS 2014. Abstract MOAB0105LB. Wk 24 Sofosbuvir + RBV (n = 200) Sofosbuvir + RBV (n = 55) Sofosbuvir + RBV (n = 19) Wk 12 Tx-naive GT1,3,4 Tx-naive GT2 Tx-exp’d GT2,3 Sofosbuvir 400 mg QD; weight-based RBV 1000 or 1200 mg/day
- 18. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection PHOTON-2: SVR12 by Genotype and Cirrhosis Absolute CD4+ count—but not CD4%—decreased, consistent with effect of RBV on lymphocytes 31. Molina JM, et al. AIDS 2014. Abstract MOAB0105LB. 24-wk noncirrhotic 24-wk cirrhotic 12-wk noncirrhotic 12-wk cirrhotic 0 20 40 60 80 100 Total GT1a GT1b Naive GT1 Naive PatientsWithSVR(%) Exp’d Naive Exp’d Naive GT2 GT3 GT4 89 100 100 100 78 9291 75 83 88 88 65 87 62 100 75 84/ 95 11/ 17 76/ 87 8/ 13 7/ 7 3/ 4 16/ 18 3/ 4 49/ 54 1/ 1 2/ 2 3/ 3 24/ 26 18/ 23 19/ 23 7/ 8
- 19. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection C212 Study: Simeprevir + PegIFN/RBV in GT1 HCV/HIV Coinfection Open-label phase III study in treatment-naive and treatment-experienced pts (N = 106) Response-guided therapy if HCV RNA < LLOQ Wk 4 and < LLOD Wk 12: 89% of treatment-naive pts and previous PR relapsers without cirrhosis met RGT criteria and were eligible for shortened therapy to 24 wks, with 87% achieving SVR12 HCV treatment naive or relapse Partial or null response or cirrhotic RGT Wk 12 Wk 24 Wk 48 Wk 72 SMV/ PR SMV/ PR SMV/ PR PR PR PR Follow-up Follow-up Follow-up 35. Dieterich D, et al. CROI 2014. Abstract 24. Simeprevir dosed 150 mg/day. SVR12, % (n/N) Naive: 79 (42/53) Relapse: 87 (13/15) Partial: 70 (7/10) Null: 57 (16/28)
- 20. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection COSMOS: Sofosbuvir + Simeprevir ± RBV in GT1 HCV Monoinfection SVR in pts with Q80K mutation = 83% to 100% Study investigating SOF + SMV in HCV/HIV-coinfected patients planned[2] SVR12(%) Cohort 1 (F0-F2 Nulls): SVR12[43] (N = 80, all arms) 100 80 60 40 20 0 24-Wk Arms 79 93 96 93 Cohort 2 (F3-F4 Naives/Nulls): SVR12[43] (N = 87, all arms) 100 80 60 40 20 0 93 100 9393 12-Wk Arms SVR12(%) 24-Wk Arms 12-Wk Arms 19/24 26/27 13/14 28/30 16/16 25/27 13/14 43. Lawitz E, et al. Lancet. 2014;[Epub ahead of print]. 49. ClinicalTrials.gov. NCT02206932. SMV + SOF + RBV SMV + SOF 14/15
- 21. Approach to Treatment of HCV/HIV-Coinfected Patients
- 22. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection SVR With Single-DAA Regimens by Genotype: Coinfection vs Monoinfection 52. Dieterich D, et al. CROI 2014. Abstract 24. 53. Jacobson IM, et al. Lancet. 2014;[Epub ahead of print]. 54. Manns M, et al. Lancet. 2014;[Epub ahead of print]. 55. Rodriguez-Torres M, et al. ID Week 2013. Abstract 714. 56. Lawitz E, et al. N Engl J Med. 2013;368:1878-1887. 57. Gane EJ, et al. EASL 2014. Abstract 845. 58. Sulkowski MS, et al. JAMA. 2014;312:353-361. 59. Molina JM, et al. AIDS 2014. Abstract MOAB0105LB. 60. Osinusi A, et al. JAMA. 2013;310:804-811. 61. Zeuzem S, et al. N Engl J Med. 2014;370:1993-2001. SVR Range*, % HIV/HCV Coinfection HCV Monoinfection GT1 GT2 GT3 GT1 GT2 GT3 Simeprevir + PR 74[1] NA NA 80-81[2,3] NA NA Sofosbuvir + PR 89[4] NA NA 89[5] NA 97[6] Sofosbuvir + RBV 76-88[7,8] 88-89[7,8] 67-91[7,8] 68-90[9] 93[10] 85[10] *Treatment-naive patients.
- 23. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection Considerations When Managing HCV/HIV-Coinfected Patients Drug–drug interactions among HCV antivirals and antiretrovirals are expected and may be difficult to predict – CYP3A4 inhibition (ritonavir); induction (efavirenz) – Must study the DAA regimen + ART regimen in healthy volunteers However, long-term adherence to ART/clinic visits also demonstrate ability to adhere to HCV therapy
- 24. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection Drug–Drug Interactions With ARVs 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 63. Sofosbuvir [package insert]. 64. Simeprevir [package insert]. 65. Kirby B, et al. AASLD 2012. Abstract 1877. 66. Ouwerkerk-Mahadevan S, et al. IDSA 2012. Abstract 49.
- 25. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection Considerations Regarding Treatment Initiation in HCV/HIV-Coinfected Pts Is the pt ready and able to start therapy? Pts not receiving ART – Treat HCV now and defer ART? Pts receiving ART – Is there an HCV regimen available that can be coadministered with current ART or is ART switch needed? – Should ART interruption ever be considered? – Associated with increased risk of OI/death in HIV infected pts[1] – Associated with increased risk of fibrosis progression in HCV/HIV- coinfected pts[2] 69. El-Sadr WM, et al. N Engl J Med. 2006;355:2283-2296. 70. Thorpe J, et al. AIDS. 2011;25:967-975.
- 26. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection Forthcoming DAAs Sofosbuvir/ledipasvir Paritaprevir/RTV/ombitasvir + dasabuvir Daclatasvir – Use of daclatasvir + sofosbuvir ± RBV resulted in SVR12 in 98% of GT1 monoinfected pts, 92% of GT2 monoinfected pts, 89% of GT3 monoinfected pts[1] – Phase III ALLY 2 study evaluating daclatasvir + sofosbuvir in HCV/HIV-coinfected patients ongoing (NCT02032888)[2] 71. Sulkowski MS, et al. N Engl J Med. 2014;370:211-221. 72. ClinicalTrials.gov. NCT02032888.
- 27. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection ERADICATE: SOF/LDV in ARV-Treated and Untreated HCV/HIV-Coinfected Patients Single-arm phase II trial in GT1, HCV treatment-naive, coinfected pts – ARV-untreated pts: stable CD4+ and HIV-1 RNA < 500 c/mL, or CD4+ > 500 cells/mm3 ; – ARV-treated patients: CD4+ > 100 cells/mm3 , HIV-1 RNA < 40 c/mL, stable ARV regimen for ≥ 8 wks (TDF, FTC, EFV, RPV, RAL only) Primary endpoint: SVR12 ARV use in 37 ARV-treated patients: EFV (41%), RAL (27%), RPV (21%), RPV and RAL (8%), EFV and RAL (3%) SOF/LDV FDC Wk 12 73. Osinusi A, et al. EASL 2014. Abstract O14. Sofosbuvir/ledipasvir 400/90 mg FDC tablet once daily. Patients with GT1 HCV and HIV coinfection (N = 50) SVR12, % 100 in ARV-untreated pts; NA in ARV-treated pts
- 28. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection TURQUOISE I: Paritaprevir/RTV/Ombitasvir + Dasabuvir + RBV in GT1 HCV/HCV Pts Open-label phase II/III trial in GT1, DAA-naive, coinfected pts – HIV-1 RNA < 40 c/mL on ATV or RAL regimen; CD4+ count ≥ 200 or CD4+% ≥ 14% Primary endpoint: SVR12 19% of patients per arm had cirrhosis Paritaprevir/RTV/Ombitasvir + Dasabuvir + RBV (n = 32) Paritaprevir/RTV/Ombitasvir + Dasabuvir + RBV (n = 31) Wk 24 75. Sulkowski M, et al. AIDS 2014. Abstract MOAB0104LB. Paritaprevir/RTV/ombitasvir 150/100/25 mg QD FDC; dasabuvir 250 mg BID; RBV 1000-1200 mg/day. DAA-naive HIV-coinfected pts with HCV GT1 (N = 63) Wk 12 SVR12, % 93.5 NA
- 29. clinicaloptions.com/hepatitis Clinical Focus: The Role of New HCV Agents in Managing HIV/HCV Coinfection Summary
- 30. Go Online for More CCO Coverage of Hepatitis C! CME-certified educational modules Downloadable PowerPoint slides for your own use clinicaloptions.com/hepatitis
Editor's Notes
- Welcome to this concise educational activity focusing on the latest expert recommendations for the treatment of hepatitis C virus (HCV)/HIV coinfection and data from key clinical trials that inform this guidance.
- This slide lists the disclosure information of the faculty and staff involved in the development of these slides.
- The first section of this module summarizes important prescribing information for current antiviral agents and HCV/HIV coinfection management guidance from the American Association for the Study of Liver Diseases (AASLD)/Infectious Diseases Society of America (IDSA).
- FDA, US Food and Drug Administration; GT, genotype; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; IFN, interferon; pegIFN, peginterferon; RBV, ribavirin. In late 2013, the US Food and Drug Administration (FDA) approved 2 new antiviral drugs for the treatment of chronic HCV infection. The first of these drugs is the protease inhibitor (PI) simeprevir. This drug is in the same family as the first-generation agents telaprevir and boceprevir and is approved for the treatment of patients with genotype 1 HCV infection.[1] Simeprevir is administered once daily in combination with peginterferon and ribavirin for 24 or 48 weeks using a classical response-guided therapy paradigm. The second new drug to receive FDA approval in late 2013 is sofosbuvir, a first-in-class nucleotide analogue polymerase inhibitor approved for use in combination with ribavirin as part of the first all-oral FDA-approved regimens for patients with genotype 2 or 3 HCV infection, including those with hepatocellular carcinoma awaiting liver transplantation.[2] Sofosbuvir is also indicated in combination with peginterferon/ ribavirin for 12 weeks of therapy in patients with genotype 1 or 4 HCV infection. This indication represents a major paradigm shift by reducing the duration of treatment for genotype 1 HCV infection to 12 weeks.
- AE, adverse event; pegIFN, peginterferon; PI, protease inhibitor; PO, orally; RBV, ribavirin. The approved simeprevir dose is 150 mg/day, given as a single capsule.[3] The medication should be taken with food. In the registration trials, simeprevir in combination with peginterferon and weight-based ribavirin was associated with photosensitivity reactions, rash, nausea, and occasional pruritus.[4] In addition, patients infected with genotype 1a HCV are strongly recommended to have baseline resistance testing for the Q80K mutation, which occurs in approximately 30% to 40% of all patients with genotype 1 HCV infection in the United States.[5] When present, Q80K reduces the effectiveness of simeprevir in combination with peginterferon/ribavirin. Therefore, the FDA prescribing information recommends that patients infected with genotype 1a HCV that harbors the Q80K mutation not be treated with simeprevir in combination with peginterferon/ribavirin.[6]
- AE, adverse event; HCV, hepatitis C virus; pegIFN, peginterferon; PO, orally; RBV, ribavirin. Sofosbuvir is also administered once daily as a 400-mg tablet that can be taken with or without food.[7] It was studied in the registrational trials with weight-based ribavirin either alone or in combination with peginterferon.
- FDA, US Food and Drug Administration. The approval of these 2 agents in late 2013 marked the beginning of a period of rapid transformation in HCV therapeutic options. In May 2011, telaprevir and boceprevir were approved for HCV treatment, and by late 2013, these medications had already been supplanted by sofosbuvir and simeprevir as optimal first-line therapy options. Also in 2013, the ability to treat hepatitis C without using interferon became feasible for the first time in the history of hepatitis C therapeutics. Further evolution of HCV therapy continues into 2014 and 2015 when oral direct-acting antivirals (DAA) combinations that include NS5A inhibitors such as daclatasvir, ledipasvir, and ombitasvir are expected to become available. Additional PIs as well as nonnucleoside polymerase inhibitors are also anticipated in the near future. It is clear that therapeutic regimens in HCV will continue to evolve quite rapidly.
- Shortly after the approval of sofosbuvir and simeprevir, the AASLD/IDSA developed recommendations to help clinicians navigate these new therapeutic options and optimize patient outcomes.[8] This guidance differs from traditional published guidelines in that the format is intended to allow rapid dissemination of updates as new data from peer-reviewed evidence become available. Therefore, the guidance panel opted to use an Internet-based “living document” that can be frequently updated rather than a published document in a print journal.
- AASLD, American Association for the Study of Liver Diseases; HCV, hepatitis C virus; IDSA, Infectious Diseases Society of America; MSM, men who have sex with men. The AASLD/IDSA guidance includes a section specific for the management of HCV/HIV-coinfected patients.[9] The recommendations address who should receive treatment, when treatment should be initiated, and which regimens should be used. It is important to note that the guidance recommends treatment for all patients with chronic HCV infection, including patients at low-/immediate-risk for liver-related complications. However, it is recommended that patients at high risk for liver-related complications should receive the highest priority for hepatitis C treatment.[10] For patients with HCV monoinfection, high risk generally refers to more advanced fibrosis, severe cryoglobulinemia, or membranoproliferative glomerulonephritis. However, based on the recognition that HIV is associated with rapid acceleration of liver disease, HCV/HIV-coinfected patients represent a group who should be prioritized for HCV treatment regardless of fibrosis stage. Patients at high risk for transmitting HCV to others represent another high-priority treatment group. HIV-infected men who have sex with men are included in this group based on well-documented outbreaks of sexually transmitted HCV within this population, as are active injection drug users. The justification for this guidance is that effective treatment of HCV leading to virologic cure in high-risk transmission groups may prevent further transmission.[11]
- AASLD, American Association for the Study of Liver Diseases; HCV, hepatitis C virus; IDSA, Infectious Diseases Society of America; IFN, interferon; pegIFN, peginterferon; PR, peginterferon/ribavirin; RBV, ribavirin. The recommended treatment options for HCV/HIV-coinfected patients generally mirror the treatment recommendations for HCV-monoinfected patients.[12] Of note, the recommendations include some of the first-ever interferon-free treatment options, including the off-label combination of sofosbuvir and simeprevir with or without ribavirin for interferon-ineligible patients with genotype 1 HCV, and various durations of sofosbuvir plus ribavirin for genotypes 2-4 HCV. Patients ineligible for interferon are generally those with psychiatric disease or other comorbidities such as autoimmune conditions that preclude the use of interferon. For patients coinfected with genotype 1 HCV/HIV who are naive to HCV therapy or who have experienced relapse to previous peginterferon/ribavirin, sofosbuvir plus peginterferon/ribavirin for 12 weeks is recommended if they are interferon eligible, whereas interferon-ineligible patients in this group should receive either sofosbuvir plus ribavirin for 24 weeks or the off-label combination of sofosbuvir and simeprevir with or without ribavirin for 12 weeks.[13] Genotype 1 HCV/HIV–coinfected patients with nonresponse to previous peginterferon/ribavirin therapy should be treated with the interferon-free regimen of sofosbuvir and simeprevir with or without ribavirin for 12 weeks. Sofosbuvir plus ribavirin is the recommended regimen for genotype 2 or 3 HCV/HIV coinfection but with a different duration for each genotype: 12 weeks for genotype 2 HCV and 24 weeks for genotype 3 HCV.[14] Patients with genotype 4 HCV/HIV coinfection should be treated with sofosbuvir plus peginterferon/ribavirin for 12 weeks if they are eligible for interferon and with sofosbuvir plus ribavirin for 24 weeks if they are ineligible for interferon. Although sofosbuvir is not FDA approved for use in genotypes 5 and 6 HCV, the AASLD/IDSA guidance panel recommends sofosbuvir plus peginterferon/ribavirin for 12 weeks in patients with genotype 5 or 6 HCV/HIV coinfection.
- AASLD, American Association for the Study of Liver Diseases; ARV, antiretroviral; DAA, direct-acting antiviral; HCV, hepatitis C virus; IDSA, Infectious Diseases Society of America. A critical issue in treating HCV/HIV-coinfected patients is preventing drug–drug interactions between antiretroviral agents and DAAs, and the prescribing information for each of these medications provides information about known interactions. Sofosbuvir is renally metabolized and is a substrate of P-glycoprotein. Coadministration with tipranavir, therefore, is not recommended, as tipranavir is an inducer of intestinal P-glycoprotein and is expected to reduce sofosbuvir exposure.[15] Didanosine and zidovudine do not have specific interactions with sofosbuvir but rather should not be used with interferon and/or ribavirin. Simeprevir has a more complicated drug interaction profile that includes interactions with drugs that inhibit and/or are metabolized by CYP3A4. As such, the list of allowable antiretroviral agents in combination with simeprevir is somewhat shorter and includes rilpivirine, raltegravir, maraviroc, and enfuvirtide as well as nucleos(t)ide analogue reverse transcriptase inhibitors.[16] It is important to note that studies evaluating simeprevir in combination with ritonavir in healthy volunteers demonstrated significantly increased plasma concentrations of simeprevir.[17] As a result, ritonavir-boosted HIV PIs should not be used in combination with simeprevir. Similarly, coadministration of efavirenz with simeprevir led to reduced simeprevir levels, leading to the recommendation that this combination should be avoided.[18]
- AASLD, American Association for the Study of Liver Diseases; DAA, direct-acting antiviral; HCV, hepatitis C virus; IDSA, Infectious Diseases Society of America; pegIFN, peginterferon; RBV, ribavirin. The AASLD/IDSA guidance panel agreed that the May 2011 breakthrough therapies telaprevir and boceprevir are no longer recommended,[19] reflecting a markedly rapid transformation as noted earlier: In the span of 2.5 years, telaprevir and boceprevir went from breakthrough HCV drugs to agents that are no longer recommended for use in HCV-infected patients, with or without HIV coinfection.
- HCV, hepatitis C virus. The next section of this module examines the key data that formed the basis of the AASLD/IDSA recommendations.
- HCV, hepatitis C virus; pegIFN, peginterferon; RBV, ribavirin; SVR, sustained virologic response. The single-arm NEUTRINO study evaluated sofosbuvir plus peginterferon/ribavirin for 12 weeks in 327 HCV-monoinfected patients. The overall sustained virologic response (SVR) rate was 90%; among those with genotype 1 HCV, it was 89%.[20] No large study has evaluated this 12-week triple regimen specifically in HCV/HIV-coinfected patients. However, a smaller single-center study yielded remarkably similar results in HCV/HIV-coinfected patients. Rates of SVR in this study were 87% among patients with genotype 1a HCV/HIV coinfection and 100% (4/4) in patients with genotype 1b HCV/HIV coinfection.[21]
- ART, antiretroviral therapy; ATV, atazanavir; DRV, darunavir; EFV, efavirenz; FTC, emtricitabine; GT, genotype; HCV, hepatitis C virus; QD, once daily; RAL, raltegravir; RBV, ribavirin; RPV, rilpivirine; RTV, ritonavir; SVR, sustained virologic response; TDF, tenofovir; Tx, treatment. PHOTON-1 was an open-label phase III study of sofosbuvir plus ribavirin for patients coinfected with HIV and genotype 1, 2, or 3 HCV. Enrolled patients were allowed to be receiving a wide range of antiretroviral therapies, reflecting the lack of interactions between sofosbuvir and most HIV drugs, and the vast majority (95%) was receiving antiretroviral treatment.[22] Overall, the study enrolled 114 HCV treatment–naive patients with genotype 1 HCV who received 24 weeks of therapy. There were also 68 HCV treatment–naive patients with genotype 2 or 3 HCV who were treated for 12 weeks. The study enrolled a third group of patients with genotype 2 or 3 HCV who had experienced treatment failure with previous peginterferon/ribavirin therapy; this group received 24 weeks of treatment. Overall, the SVR rate with this interferon-free regimen was quite good, at 76% in patients with genotype 1 HCV/HIV coinfection.[23] This result was similar to that of the SPARE study, which reported an SVR24 rate of 68% with the same regimen in patients with genotype 1 HCV monoinfection.[24] For HCV treatment–naive patients with genotype 2 HCV/HIV coinfection in PHOTON-1, the recommended duration of 12 weeks resulted in an 88% rate of SVR or HCV cure.[25] Not surprisingly, when HCV treatment–naive patients with genotype 3 HCV/HIV coinfection were treated for only 12 weeks, the SVR rate was lower at 67%.[26] The VALENCE trial, a large study that tested sofosbuvir and ribavirin for 24 weeks in patients with HCV monoinfection, had demonstrated that patients with genotype 3 HCV infection had improved SVR rates with extended therapy.[27] Indeed, in the treatment-experienced patient group treated for 24 weeks in PHOTON-1, patients with genotype 3 HCV experienced a 94% SVR rate, although it is important to note that the number of patients in this group was low.[28]
- ART, antiretroviral therapy; ATV, atazanavir; DRV, darunavir; EFV, efavirenz; FTC, emtricitabine; GT, genotype; HCV, hepatitis C virus; QD, once daily; RAL, raltegravir; RBV, ribavirin; RPV, rilpivirine; RTV, ritonavir; SVR, sustained virologic response; TDF, tenofovir; Tx, treatment. The PHOTON-2 trial was a nonrandomized, open-label phase II study with a similar design to PHOTON-1. Patients were receiving stable antiretroviral therapy with suppressed HIV-1 RNA. Cirrhosis was present in 20% of all patients, 45% of treatment-experienced patients, and 13% of treatment-naive patients.[29] The study design of PHOTON-2 was slightly modified from that of PHOTON-1 because of the knowledge that patients with genotype 3 HCV require 24 weeks of treatment. In addition, patients with genotype 4 HCV/HIV coinfection were included in this trial. Therefore, in PHOTON-2 treatment-naive patients coinfected with genotype 1, 3, or 4 HCV/HIV and treatment-experienced patients coinfected with genotype 2 or 3 HCV/HIV were treated with sofosbuvir and ribavirin for 24 weeks, whereas treatment-naive patients coinfected with genotype 2 HCV and HIV received 12 weeks of sofosbuvir and ribavirin.[30]
- GT, genotype; RBV, ribavirin; SVR, sustained virologic response. This study was larger than PHOTON-1, but the response rates were quite similar. When SVR rates were evaluated by cirrhosis status and HCV genotype, among treatment-naive patients with genotype 1 HCV/HIV coinfection, the SVR rate was 88% in those without cirrhosis and 65% in those with cirrhosis.[31] A similar pattern was seen when this population was further divided according to genotype 1 subtype, although caution is warranted in interpreting the subtype 1b data because there were only 7 noncirrhotic patients and 4 cirrhotic patients in that group, which is reflective of the relatively low prevalence of subgenotype 1b in Europe and Australia where the majority of study participants were enrolled. Among treatment-naive patients with genotype 2 HCV/HIV coinfection—a so-called easy-to-treat patient population—the overall SVR rates were 89% without cirrhosis and 100% in the 1 patient with cirrhosis.[32] There were also very few treatment-experienced patients with genotype 2 HCV/HIV coinfection, making it difficult to draw conclusions from the SVR rates. Cirrhosis also did not appear to affect HCV treatment response among treatment-naive patients with genotype 3 HCV/HIV coinfection. Among treatment-experienced patients in this genotype group, the SVR rate was 92% without cirrhosis but 78% in the 23 cirrhotic patients.[33] Treatment-naive patients with genotype 4 HCV/HIV coinfection represent an important population in this study because previous data in this group were limited. The results demonstrated an 83% SVR rate with 24 weeks of sofosbuvir plus ribavirin in the absence of cirrhosis and an 88% SVR rate in patients with cirrhosis.[34] Overall, data from PHOTON-1 and PHOTON-2 provide support for the AASLD/IDSA guidance on sofosbuvir plus ribavirin regimens in HCV/HIV-coinfected patients.
- GT, genotype; HCV, hepatitis C virus; LLOD, lower limit of detection; LLOQ, lower limit of quantification; pegIFN, peginterferon; PR, peginterferon/ribavirin; RBV, ribavirin; RGT, response-guided therapy; SMV, simeprevir; SVR, sustained virologic response. The open-label phase III C212 study assessed simeprevir plus peginterferon/ribavirin in 106 patients with genotype 1 HCV and HIV coinfection.[35] The study enrolled both treatment-naive and treatment-experienced patients. In the AASLD/IDSA guidance document, this is not a recommended regimen.[36] However, this study did provide important data on the compatibility between simeprevir and antiretroviral therapy, leading to the allowable agents mentioned earlier. In addition, it provided some very encouraging data on the likelihood of SVR with this regimen. C212 used a response-guided therapy paradigm in which patients received simeprevir once daily plus peginterferon/ribavirin for 12 weeks followed by either 12 or 24 weeks of peginterferon/ribavirin alone, depending on whether HCV RNA decreased to below the lower limit of quantification at treatment Week 4.[37] The overall SVR rate for HCV treatment–naive patients was 79%,[38] which is very similar to the response rates seen in the QUEST-1 and QUEST-2 studies evaluating this regimen in HCV-monoinfected patients.[39.40] Among previous relapsers, the SVR rate was 87%.[41] The important point of this study is that it provided useful information on the efficacy and tolerability of simeprevir in this patient population. Overall, the investigators observed generally favorable safety, tolerability, and efficacy outcomes similar to those in HCV-monoinfected patients.
- GT, genotype; HCV, hepatitis C virus; RBV, ribavirin; SMV, simeprevir; SOF, sofosbuvir; SVR, sustained virologic response. The COSMOS study did not enroll HCV/HIV-coinfected patients, yet the AASLD/IDSA guidance panel adopted the COSMOS regimen—sofosbuvir plus simeprevir with or without ribavirin—as a recommended option for interferon-ineligible and treatment-experienced patients with genotype 1 HCV/HIV coinfection.[42] The COSMOS trial enrolled 167 patients into 2 cohorts. Cohort 1 included null responders to previous peginterferon/ribavirin with F0-F2 liver disease. This group received 12 or 24 weeks of simeprevir plus sofosbuvir, 2 pills once daily, with or without ribavirin, and the resulting SVR rates were 93% to 96% in the 12-week treatment groups.[43] Extending the treatment duration to 24 weeks did not increase the SVR rate. This regimen offers a shorter duration of therapy than the PHOTON trials,[44,45] in which these patients would have received 24 weeks of treatment with sofosbuvir and ribavirin. Also note that the COSMOS trial achieved these results among previous null responders with HCV monoinfection, whereas PHOTON-1 and PHOTON-2 enrolled only treatment-naive patients with genotype 1 HCV/HIV coinfection. Cohort 2 of COSMOS included patients with bridging fibrosis and cirrhosis who were either treatment naive or null responders to previous peginterferon/ribavirin, and this group achieved very similar outcomes. Twelve weeks of therapy yielded a 93% SVR rate with or without ribavirin and was comparable to the response rates obtained with 24 weeks of treatment.[46] However, it is important to note that viral relapse occurred more frequently in patients treated for 12 weeks in both cohorts; the best outcomes were seen among those treated for 24 weeks. The study did not yield a firm answer on the need for ribavirin. The ribavirin-free arms appeared to do just as well as the ribavirin-containing arms, but the randomization was 2:1, resulting in approximately 15 patients in each of the ribavirin-free groups.[47] Therefore, only small numbers of patients were treated without ribavirin. That limitation prevented the AASLD/IDSA guidance panel from offering conclusive recommendations about the need for ribavirin.[48] A study investigating sofosbuvir plus simeprevir in HCV/HIV-coinfected patients is planned.[49]
- HCV, hepatitis C virus. The next section of this program will review important considerations when selecting a treatment regimen for patients with HCV/HIV coinfection.
- DAA, direct-acting antiviral; GT, genotype; HCV, hepatitis C virus; NA, not available; PR, peginterferon/ribavirin; RBV, ribavirin; SVR, sustained virologic response. The data reviewed thus far highlight an important point regarding HCV/HIV-coinfected patients, namely, that they are no longer a special population when it comes to the ability to achieve SVR. In the days of peginterferon/ribavirin, it became clear in clinical trials that this group of patients did not achieve SVR at the same rate as HCV-monoinfected patients. This was perhaps best seen when comparing the NR16071 trial of peginterferon alfa-2a and ribavirin in monoinfected patients[50] to the APRICOT study of the same regimen in coinfected patients.[51] Response rates were remarkably lower in the coinfected patient groups. Yet, when one compares response rates for simeprevir plus peginterferon/ribavirin, sofosbuvir plus peginterferon/ribavirin, or sofosbuvir and ribavirin alone in monoinfected and coinfected patients, they are very similar in both patient groups,[52-61] indicating that using a potent oral DAA with or without peginterferon seems to overcome the negative impact of HIV coinfection on HCV treatment efficacy.
- ART, antiretroviral therapy; DAA, direct-acting antiviral; HCV, hepatitis C virus. Perhaps the only major distinctive consideration when treating an HCV/HIV-coinfected vs an HCV-monoinfected patient is drug interactions between the hepatitis C antivirals and the HIV antiretroviral regimen. It has been known for a number of years that antiretroviral regimens, particularly those that include ritonavir-boosted HIV PIs or the nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz, which is an inducer of CYP3A4, can lead to fairly significant drug–drug interactions that either prevent coadministration of some agents or raise particular safety concerns. Therefore, it was expected that some combinations of hepatitis C DAAs and antiretroviral drugs would have adverse interactions, and simeprevir is a good example where that has been observed. To successfully treat a coinfected patient, clinicians need both reliable data on efficacy, safety, and tolerability—the type of data derived from clinical trials—and an abundance of data on the combination of antiretroviral drugs and hepatitis C DAA regimens in healthy volunteers. The latter studies should involve comparisons of the entire hepatitis C regimen and the entire HIV regimen. These studies should be undertaken early, before there is widespread use of HCV drugs in patients receiving antiretrovirals. One advantage that HCV/HIV-coinfected patients have over HCV-monoinfected patients is that, in general, if they have been receiving antiretroviral therapy successfully for several years, they have proven their ability to engage with the healthcare system and adhere to healthcare as well as a daily medication regimen. By contrast, many HCV-monoinfected patients initiating first-time therapy have not been challenged with the burden of taking pills every day.
- ARV, antiretroviral; COBI, cobicistat; DLV, delavirdine; DRV, darunavir; DTG, dolutegravir; EFV, efavirenz; ETR, etravirine; NVP, nevirapine; RTV, ritonavir; PI, protease inhibitor; RAL, raltegravir; RPV, rilpivirine; TDF, tenofovir; TPV, tipranavir. This slide highlights what is currently known about antiretroviral drug interactions with simeprevir and sofosbuvir. In general, permissible antiretroviral agents in combination with sofosbuvir plus simeprevir include raltegravir, rilpivirine, and tenofovir.[63-66] Essentially, the use of NNRTIs and ritonavir-boosted HIV PIs is not recommended.
- ART, antiretroviral therapy; HCV, hepatitis C virus; OI, opportunistic infection. In addition to consideration of the AASLD/IDSA guidance, available data on the safety, tolerability, and efficacy of simeprevir and sofosbuvir in HCV/HIV-coinfected patients and known interactions between these drugs and antiretroviral agents, there are several important questions to consider before initiating HCV therapy in this population. These questions include: Is the patient ready, willing, and able to add hepatitis C treatment to their antiretroviral regimen, and are they committed to finishing a course of treatment? A course of treatment can be curative, but like any therapy, to be successful, the patient must adhere and complete the full duration of treatment. For patients not receiving antiretroviral therapy, there may be a reason to treat the hepatitis C first, deferring antiretroviral therapy. Although my general recommendation is that HCV-infected patients coinfected with HIV receive antiretroviral therapy based on study findings that have demonstrated a substantial reduction in the risk of liver mortality and morbidity over time,[67,68] one could certainly defer initiation of HIV treatment until HCV treatment has been completed. For HCV/HIV-coinfected patients who are receiving antiretroviral therapy, the recommendation is to ensure that they are on a regimen that can be safely coadministered with anti-HCV therapy, which may require switching the antiretroviral therapy. In that case, I generally recommend a direct consultation between the hepatitis C treater and the HIV treater, if they are different healthcare providers. The key questions to ask are: Is this a safe combination to switch to? Will it achieve/maintain HIV-1 RNA suppression? And can the patient tolerate it? I generally like to keep patients on the new HIV regimen for 1 month and to check their HIV-1 RNA level to confirm virologic suppression before initiating hepatitis C treatment. I do not believe it makes sense from a practical perspective to switch the HIV regimen and start hepatitis C treatment the same day. That approach makes adverse effects more difficult to manage and interpret. It is important to stress that interrupting antiretroviral therapy so that a patient can receive HCV treatment without concern for drug-drug interactions is not a recommended strategy based on findings from several studies showing that HIV therapy interruptions are associated with an increased risk of death in HIV-monoinfected patients[69] and an increased risk of liver disease progression in HCV/HIV-coinfected patients.[70]
- DAA, direct-acting antiviral; GT, genotype; HCV, hepatitis C virus; RBV, ribavirin; RV, ritonavir; SVR, sustained virologic response. As noted earlier, there has been and continues to be a rapid transformation in the treatment of HCV, raising the question of how long the current recommendations for sofosbuvir plus peginterferon/ribavirin or sofosbuvir plus simeprevir for genotype 1 HCV/HIV coinfection will reign as the “standard of care.” The answer is probably less than 1 year. It is anticipated that a single-tablet combination of sofosbuvir and ledipasvir, a nucleotide polymerase inhibitor and an NS5A inhibitor, will be approved by the FDA by October 2014. In addition, it is anticipated that a second highly effective regimen, ritonavir-boosted paritaprevir (formerly ABT-450) plus ombitasvir and dasabuvir, will be approved by the FDA by the end of 2014 . This regimen includes the coformulation of paritaprevir/ritonavir and ombitasvir as 2 tablets once daily, plus dasabuvir, a nonnucleoside polymerase inhibitor, as 1 tablet twice daily. Patients with genotype 1a HCV will likely receive ribavirin with this combination. Also in 2014, the FDA may approve daclatasvir, an NS5A inhibitor that was approved in Europe in August 2014. Daclatasvir plus sofosbuvir was highly effective in HCV-monoinfected patients[71] and is being tested in HCV/HIV-coinfected patients in the ongoing phase III study known as ALLY 2.[72]
- AE, adverse event; ARV, antiretroviral; EFV, efavirenz; FDC, fixed-dose combination; FTC, emtricitabine; GT, genotype; HCV, hepatitis C virus; LDV, ledipasvir; NA, not yet available; RAL, raltegravir; RPV, rilpivirine; SOF, sofosbuvir; SVR, sustained virologic response; TDF, tenofovir. How well are these regimens expected to perform in HCV/HIV-coinfected patients? Preliminary data from the ongoing phase II ERADICATE study were presented at the annual meeting of the European Association for the Study of the Liver in April 2014 (Capsule Summary).[73] [Coder: link to http://www.clinicaloptions.com/Hepatitis/Conference%20Coverage/London%202014/Highlights/Capsules/14.aspx] In this single-arm study, treatment-naive patients with HIV and genotype 1 HCV coinfection with stage 0-3 fibrosis were treated with a single-tablet sofosbuvir/ledipasvir regimen. The study investigators enrolled both patients who were and were not receiving HIV antiretroviral therapy. Permitted antiretroviral agents included efavirenz, rilpivirine, raltegravir, tenofovir DF, and emtricitabine. Of the 50 patients enrolled, 37 were receiving antiretroviral drugs, and 13 were not receiving antiretroviral therapy. At the end of treatment, all patients responded, and thus far SVR12 has been achieved by 100% of the patients that have reached that time point.[74] However, it should be noted that at the time of the presentation, not all 50 patients had reached SVR12; nonetheless, no virologic failures had occurred at that time.
- ATV, atazanavir; BID, twice daily; DAA, direct-acting antiviral; FDC, fixed dose combination; GT, genotype; HCV, hepatitis C virus; NA, not yet available; RAL, raltegravir; RBV, ribavirin; RTV, ritonavir; QD, once daily; SVR, sustained virologic response. TURQUOISE-I is an open-label phase II/III trial of the combination of paritaprevir/ritonavir/ombitasvir and dasabuvir with ribavirin in 63 DAA-naive patients coinfected with genotype 1 HCV and HIV (Capsule Summary).[75] [Coder: Link to http://www.clinicaloptions.com/HIV/Conference%20Coverage/AIDS%202014/Highlights%20of%20AIDS%202014/Capsules/MOAB0104LB.aspx] All patients had stably suppressed HIV-1 RNA with either atazanavir- or raltegravir-based regimens. Unlike the ERADICATE study, this study did allow patients with cirrhosis, and overall 19% of enrolled patients had cirrhosis. Patients were randomized to either 12 or 24 weeks of the triple-DAA regimen plus ribavirin. At the time of the presentation, SVR12 data were available from the 12-week treatment arm, with 93.5% of 31 patients achieving SVR12.[76] Of 32 patients treated for 24 weeks, SVR12 data are awaited, but the SVR4 rate was very good at 97%. For more information about this study, go online to http://clinicaloptions.com/HIV/Conference%20Coverage/AIDS%202014/Highlights%20of%20AIDS%202014/Capsules/MOAB0104LB.aspx.
- ART, antiretroviral therapy; DAA, direct-acting antiviral; HCV, hepatitis C virus; SVR, sustained virologic response. In summary, the current AASLD/IDSA-recommended regimens for patients with HCV/HIV coinfection include sofosbuvir in combination with peginterferon/ribavirin, ribavirin alone, or simeprevir.[77] Simeprevir in combination with peginterferon/ribavirin is an alternative regimen that is not frequently used, and telaprevir and boceprevir have moved from the standard of care to not recommended. The exciting information in terms of the safety, tolerability, and efficacy of these drugs in HCV/HIV-coinfected patients is that outcomes appear to be very similar to those in HCV-monoinfected patients, with no detectable adverse effects of HIV coinfection. The one important challenge that remains in this setting is mitigating drug–drug interactions between hepatitis C and antiretroviral regimens. Indeed, for any patient with HIV infection who is starting hepatitis C treatment, the potential interactions between their antiretroviral drugs and the proposed hepatitis C treatment regimen must be carefully considered. As more HCV drugs become available, it will be possible to pick and choose which regimens offer the best opportunities for efficacy, safety, and tolerability, as well as compatibility with antiretroviral therapy. However, as treatment for hepatitis C will likely be for 12 or 24 weeks, changing the antiretroviral regimen is a reasonable option as well. As more anti-HCV drugs become available, the HCV/HIV-coinfected patient population will continue to have an outstanding opportunity to achieve HCV cure.
- References 1.Simeprevir [package insert]. 2.Sofosbuvir [package insert]. 3.Simeprevir [package insert]. 4.Simeprevir [package insert]. 5.Simeprevir [package insert]. 6.Simeprevir [package insert]. 7.Sofosbuvir [package insert]. 8.AASLD and IDSA. HCV Management Guidance. September 2014. 9.AASLD and IDSA. HCV Management Guidance. September 2014. 10.AASLD and IDSA. HCV Management Guidance. September 2014. 11.AASLD and IDSA. HCV Management Guidance. September 2014. 12.AASLD and IDSA. HCV Management Guidance. September 2014. 13.AASLD and IDSA. HCV Management Guidance. September 2014. 14.AASLD and IDSA. HCV Management Guidance. September 2014. 15.AASLD and IDSA. HCV Management Guidance. September 2014. 16.AASLD and IDSA. HCV Management Guidance. September 2014. 17.Simeprevir [package insert]. 18.Simeprevir [package insert]. 19.AASLD and IDSA. HCV Management Guidance. September 2014. 20.Lawitz E, et al. N Engl J Med. 2013;368:1878-1887. 21.Rodriguez-Torres M, et al. ID Week 2013. Abstract 714. 22.Sulkowski MS, et al. JAMA. 2014;312:353-361. 23.Sulkowski MS, et al. JAMA. 2014;312:353-361. 24.Osinusi A, et al. JAMA. 2013;310:804-811. 25.Sulkowski MS, et al. JAMA. 2014;312:353-361. 26.Sulkowski MS, et al. JAMA. 2014;312:353-361. 27.Zeuzem S, et al. N Engl J Med. 2014;370:1993-2001. 28.Sulkowski MS, et al. JAMA. 2014;312:353-361. 29.Molina JM, et al. AIDS 2014. Abstract MOAB0105LB. 30.Molina JM, et al. AIDS 2014. Abstract MOAB0105LB. 31.Molina JM, et al. AIDS 2014. Abstract MOAB0105LB. 32.Molina JM, et al. AIDS 2014. Abstract MOAB0105LB. 33.Molina JM, et al. AIDS 2014. Abstract MOAB0105LB. 34.Molina JM, et al. AIDS 2014. Abstract MOAB0105LB. 35.Dieterich D, et al. CROI 2014. Abstract 24. 36.AASLD and IDSA. HCV Management Guidance. September 2014. 37.Dieterich D, et al. CROI 2014. Abstract 24. 38.Dieterich D, et al. CROI 2014. Abstract 24. 39.Jacobson IM, et al. Lancet. 2014;384:403-413. 40.Manns M, et al. Lancet. 2014;384:414-426. 41.Dieterich D, et al. CROI 2014. Abstract 24. 42.AASLD and IDSA. HCV Management Guidance. September 2014. 43.Lawitz E, et al. Lancet. 2014;[Epub ahead of print]. 44.Sulkowski MS, et al. JAMA. 2014;312:353-361. 45.Molina JM, et al. AIDS 2014. Abstract MOAB0105LB. 46.Lawitz E, et al. Lancet. 2014;[Epub ahead of print]. 47.Lawitz E, et al. Lancet. 2014;[Epub ahead of print]. 48.AASLD and IDSA. HCV Management Guidance. September 2014. 49.ClinicalTrials.gov. NCT02206932 50.Zeuzem S, et al. Gastroenterology. 2004;127:1724-1732. 51.Torriani FJ, et al. N Engl J Med. 2004;351:438-450. 52.Dieterich D, et al. CROI 2014. Abstract 24. 53.Jacobson IM, et al. Lancet. 2014;[Epub ahead of print]. 54.Manns M, et al. Lancet. 2014;[Epub ahead of print]. 55.Rodriguez-Torres M, et al. ID Week 2013. Abstract 714. 56.Lawitz E, et al. N Engl J Med. 2013;368:1878-1887. 57.Gane EJ, et al. EASL 2014. Abstract 845. 58.Sulkowski MS, et al. JAMA. 2014;312:353-361. 59.Molina JM, et al. AIDS 2014. Abstract MOAB0105LB. 60.Osinusi A, et al. JAMA. 2013;310:804-811. 61.Zeuzem S, et al. N Engl J Med. 2014;370:1993-2001. 62.El-Sadr WM, et al. N Engl J Med. 2006;355:2283-2296. 63.Sofosbuvir [package insert]. 64.Simeprevir [package insert]. 65.Kirby B, et al. AASLD 2012. Abstract 1877. 66.Ouwerkerk-Mahadevan S, et al. IDSA 2012. Abstract 49. 67.Benhamou Y, et al. Hepatology. 2001;34:283-287. 68.Bräu N, et al. J Hepatol. 2006;44:47-55. 69.El-Sadr WM, et al. N Engl J Med. 2006;355:2283-2296. 70.Thorpe J, et al. AIDS. 2011;25:967-975. 71.Sulkowski MS, et al. N Engl J Med. 2014;370:211-221. 72.ClinicalTrials.gov. NCT02032888. 73.Osinusi A, et al. EASL 2014. Abstract O14. 74.Osinusi A, et al. EASL 2014. Abstract O14. 75.Sulkowski M, et al. AIDS 2014. Abstract MOAB0104LB. 76.Sulkowski M, et al. AIDS 2014. Abstract MOAB0104LB. 77.AASLD and IDSA. HCV Management Guidance. September 2014.