Pegylated Interferon Alfa-2a Maintenance Therapy and Liver Disease Progression in People Infected With Both HIV and Hepatitis C Virus (HCV)

NCT00078403 | Completed Phase 2 Results

• 2 other identifiers: A517810008
• Study Type: interventional
• Target: 333
• Locations: 2 countries
• Sites: 37

Brief Summary

Infection with both HIV and hepatitis C virus (HCV) may result in serious and sometimes fatal liver disease. The purpose of this study was to test the effectiveness of long-term pegylated interferon alfa-2a (PEG-IFN) and ribavirin treatment in slowing liver disease progression in people infected with both HIV and HCV.

Conditions

HIV Infections; Hepatitis C; Liver Disease

Keywords

Treatment Experienced

Outcome Measures

Primary Outcomes (1)

• Time-scaled Change in Metavir Liver Fibrosis Score (SCMFS)

  SCMFS is the difference between the Metavir fibrosis scores of the study exit and study entry liver biopsies where the difference is scaled to one year. The SCMFS assesses the annualized change in the severity of liver fibrosis on a continuous scale from -4.0 Metavir units per year (reduced fibrosis over time, a positive study outcome) to +4.0 Metavir units per year (increased fibrosis over time).

  Baseline and at week 72 or premature discontinuation

Secondary Outcomes (17)

• Number of Participants With Detectable HCV Viral Load (>= 60 IU/mL)

  Arms A and B: Weeks 0, 12, 24, 48 and 72; Arm C: Weeks 0, 12, 24, 36, 60, 72, 84

• Time-scaled Change in Ishak Liver Inflammation Score (SCIIS)

  Baseline and at week 72 or premature discontinuation

• Number of Participants With Anemia

  Up to 96 weeks

• Number of Participants With Neutropenia

  Up to 96 weeks

• Number of Participants With Thrombocytopenia

  Up to 96 weeks

Study Arms (3)

Arm A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN)

EXPERIMENTAL

At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA \>=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to receive the pegylated interferon (PEG-IFN) 180 mcg weekly for 72 weeks.

Drug: Peginterferon alfa-2a; Drug: Ribavirin

Arm B: OL (PEG-IFN, RBV) then OL Randomized (Observation)

EXPERIMENTAL

At week 12 (end of the initial run-in period - Step 1) participants were found to have detectable HCV RNA (HCV RNA \>=600 IU/mL) and had less than a 2 log10 decrease in HCV RNA from baseline. For Step 2, participants were randomized to 72 weeks of observation (no treatment).

Drug: Peginterferon alfa-2a; Drug: Ribavirin

Arm C: OL (PEG-IFN, RBV) then OL (PEG-IFN, RBV)

EXPERIMENTAL

At week 12 (end of initial run-in period, Step 1) participants were found to have undetectable HCV RNA (HCV RNA \<600 IU/mL) or at least a 2 log10 decrease in HCV RNA from baseline. Participants entered Step 3 and were assigned to continue the run-in treatment (PEG-IFN 180 mcg weekly \& RBV1-1.2 g/day based on weight) for a total of 72 weeks. At week 36, participants who had detectable HCV RNA (HCV RNA \>=60 IU/mL using a qualitative assay) could enter Step 2 and be randomized to OL PEG-IFN or Observation.

Drug: Peginterferon alfa-2a; Drug: Ribavirin

Interventions

Peginterferon alfa-2a DRUG

180 mcg PEG-IFN subcutaneously

Arm A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN); Arm B: OL (PEG-IFN, RBV) then OL Randomized (Observation); Arm C: OL (PEG-IFN, RBV) then OL (PEG-IFN, RBV)

Ribavirin DRUG

One tablet or capsule containing ribavirin 200 mg

Arm A: Open Label (OL) (PEG-IFN, RBV); OL Randomized (PEG-IFN); Arm B: OL (PEG-IFN, RBV) then OL Randomized (Observation); Arm C: OL (PEG-IFN, RBV) then OL (PEG-IFN, RBV)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV infected
• Stable antiretroviral therapy for at least 8 weeks prior to study entry OR have not received any antiretroviral therapy for at least 4 weeks prior to entry
• HIV viral load less than 50,000 copies/ml within 6 weeks prior to study entry
• CD4 count greater than 200 cells/mm\^3 within 6 weeks prior to study entry
• Hepatitis C virus (HCV) infected
• Either HCV treatment naive OR previously treated with interferon (IFN), PEG-IFN, IFN and ribavirin, or PEG-IFN and ribavirin for at least 12 weeks and HCV RNA positive following their last course of HCV treatment
• Chronic liver disease consistent with chronic viral hepatitis
• At least stage I fibrosis on a liver biopsy obtained within 104 weeks of study entry
• If at stage VI fibrosis, Child-Pugh-Turcotte (CPT) score of 5 or less and no more than Child-Pugh Class A
• Liver enzyme (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], and alkaline phosphatase) levels 10 times or less than upper limit of normal
• Agree to use acceptable methods of contraception
• Currently enrolled in Step 1 or received 12 weeks of PEG-IFN plus ribavirin outside this study
• Detectable HCV viral load and \<2 log10 decrease from baseline in plasma/serum HCV viral load at Week 12.
• On Step 1 study treatment for no longer than 18 weeks
• Currently enrolled in Step 1

You may not qualify if:

• Have received HCV treatment within 4 weeks of study entry. Participants currently receiving treatment for HCV, if non-EVRs, were considered for direct entry into Step 2, without the run-in period in Step 1.
• Could not tolerate treatment with PEG-IFN, defined as missing 3 or more consecutive PEG-IFN doses during the first 12 weeks or a total of 5 doses prior to Step 3 entry. Participants who have missed doses of ribavirin will not be excluded from Step 3 entry.
• Use of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) within 14 days prior to study entry
• Alpha feto protein level 400 ng/ml or greater within 24 weeks prior to study entry, or alpha feto protein level greater than 50 ng/ml and less than 400 ng/ml (unless computed tomography \[CT\] scan or magnetic resonance imaging \[MRI\] shows no evidence of hepatic tumor) within 24 weeks prior to study entry
• Decompensated liver disease, including presence or history of ascites, variceal bleeding, and brain or nervous system damage as a result of liver damage
• Other causes of significant liver disease, including hepatitis A or B, excess iron deposits in the liver (hemochromatosis), or homozygote alpha-1 antitrypsin deficiency
• Use of systemic corticosteroids, interferon gamma, TNF-alpha inhibitors, rifampin, rifabutin, pyrazinamide, isoniazid, ganciclovir, or hydroxyurea within 2 weeks prior to study entry
• Known allergy/sensitivity to PEG-IFN alfa-2a or ribavirin or their formulations
• History of uncontrolled seizure disorders
• Clinically active thyroid disease. Thyroid hormone replacement therapy is permitted, but thyroid-stimulating hormone (TSH) and free thyroxine index (FTI) must be in normal range.
• History of autoimmune processes, including Crohn's disease, ulcerative colitis, severe psoriasis, and rheumatoid arthritis, that may be made worse by interferon use
• Any systemic antineoplastic or immunomodulatory treatment or radiation within 24 weeks prior to study entry
• Malignancy
• Active coronary artery disease within 24 weeks prior to study entry
• Acute or active AIDS-defining opportunistic infections within 12 weeks of study entry

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (37)

Alabama Therapeutics CRS

Birmingham, Alabama, 35924-2050, United States

Location

University of Southern California CRS

Los Angeles, California, 90033-1079, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

Stanford AIDS Clinical Trials Unit CRS

Palo Alto, California, 94304-5350, United States

Location

UCSD Antiviral Research Center CRS

San Diego, California, 92103, United States

Location

Ucsf Hiv/Aids Crs

San Francisco, California, 94110, United States

Location

Santa Clara Valley Med. Ctr.

San Jose, California, 95128, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

Location

Georgetown University CRS (GU CRS)

Washington D.C., District of Columbia, 20007, United States

Location

Univ. of Hawaii at Manoa, Leahi Hosp.

Honolulu, Hawaii, 96816, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, 46202-5250, United States

Location

Indiana Univ. School of Medicine, Wishard Memorial

Indianapolis, Indiana, 46202-5250, United States

Location

Johns Hopkins University CRS

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hosp. ACTG CRS

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, 02215, United States

Location

Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110-1010, United States

Location

Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.

Omaha, Nebraska, 68198-9500, United States

Location

Beth Israel Med. Ctr., ACTU

New York, New York, 10003, United States

Location

Weill Cornell Chelsea CRS

New York, New York, 10011, United States

Location

NY Univ. HIV/AIDS CRS

New York, New York, 10016, United States

Location

Weill Cornell Uptown CRS

New York, New York, 10021, United States

Location

Columbia P&S CRS

New York, New York, 10032-3732, United States

Location

Trillium Health ACTG CRS

Rochester, New York, 14607, United States

Location

McCree McCuller Wellness Ctr. at the Connection, Infectious Disease Unit

Rochester, New York, 14642, United States

Location

Univ. of Rochester ACTG CRS

Rochester, New York, 14642, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

Location

Cincinnati CRS

Cincinnati, Ohio, 45267-0405, United States

Location

MetroHealth CRS

Cleveland, Ohio, 44109, United States

Location

Univ. of Pennsylvania Health System, Presbyterian Med. Ctr.

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

The Miriam Hospital Clinical Research Site (TMH CRS) CRS

Providence, Rhode Island, 02906, United States

Location

Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, 37204, United States

Location

Univ. of Texas Southwestern Med. Ctr., Amelia Court Continuity Clinic

Dallas, Texas, 75235-9173, United States

Location

Univ. of Texas Medical Branch, ACTU

Galveston, Texas, 77555-0435, United States

Location

Puerto Rico AIDS Clinical Trials Unit CRS

San Juan, 00935, Puerto Rico

Location

Related Publications (14)

• Brau N. Treatment of chronic hepatitis C in human immunodeficiency virus/hepatitis C virus-coinfected patients in the era of pegylated interferon and ribavirin. Semin Liver Dis. 2005 Feb;25(1):33-51. doi: 10.1055/s-2005-864780.

  PMID: 15731996 BACKGROUND

• Borgia G, Reynaud L, Gentile I, Piazza M. HIV and hepatitis C virus: facts and controversies. Infection. 2003 Aug;31(4):232-40. doi: 10.1007/s15010-003-3131-4.

  PMID: 14562947 BACKGROUND

• Khalili M, Bernstein D, Lentz E, Barylski C, Hoffman-Terry M. Pegylated interferon alpha-2a with or without ribavirin in HCV/HIV coinfection: partially blinded, randomized multicenter trial. Dig Dis Sci. 2005 Jun;50(6):1148-55. doi: 10.1007/s10620-005-2723-5.

  PMID: 15986873 BACKGROUND

• Neau D, Trimoulet P, Winnock M, Rullier A, Le Bail B, Lacoste D, Ragnaud JM, Bioulac-Sage P, Lafon ME, Chene G, Dupon M; ROCO Study Group. Comparison of 2 regimens that include interferon-alpha-2a plus ribavirin for treatment of chronic hepatitis C in human immunodeficiency virus-coinfected patients. Clin Infect Dis. 2003 Jun 15;36(12):1564-71. doi: 10.1086/375067. Epub 2003 Jun 3.

  PMID: 12802757 BACKGROUND

• Torriani FJ, Ribeiro RM, Gilbert TL, Schrenk UM, Clauson M, Pacheco DM, Perelson AS. Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) dynamics during HCV treatment in HCV/HIV coinfection. J Infect Dis. 2003 Nov 15;188(10):1498-507. doi: 10.1086/379255. Epub 2003 Nov 13.

  PMID: 14624375 BACKGROUND

• Torriani FJ, Rodriguez-Torres M, Rockstroh JK, Lissen E, Gonzalez-Garcia J, Lazzarin A, Carosi G, Sasadeusz J, Katlama C, Montaner J, Sette H Jr, Passe S, De Pamphilis J, Duff F, Schrenk UM, Dieterich DT; APRICOT Study Group. Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. 2004 Jul 29;351(5):438-50. doi: 10.1056/NEJMoa040842.

  PMID: 15282351 BACKGROUND

• The Division of AIDS Table for Grading the Severity of Adult Adverse Events (DAIDS AE Grading Table), August 1992.

  BACKGROUND

• Manual for Expedited Reporting of Adverse Events to Division of AIDS (DAIDS EAE Manual), May 2004.

  BACKGROUND

• Butt AA, Umbleja T, Andersen JW, Chung RT, Sherman KE; ACTG A5178 Study Team. The incidence, predictors and management of anaemia and its association with virological response in HCV / HIV coinfected persons treated with long-term pegylated interferon alfa 2a and ribavirin. Aliment Pharmacol Ther. 2011 Jun;33(11):1234-44. doi: 10.1111/j.1365-2036.2011.04648.x. Epub 2011 Mar 29.

  PMID: 21535051 RESULT

• Sherman KE, Andersen JW, Butt AA, Umbleja T, Alston B, Koziel MJ, Peters MG, Sulkowski M, Goodman ZD, Chung RT; AIDS Clinical Trials Group A5178 Study Team. Sustained long-term antiviral maintenance therapy in HCV/HIV-coinfected patients (SLAM-C). J Acquir Immune Defic Syndr. 2010 Dec 15;55(5):597-605. doi: 10.1097/QAI.0b013e3181f6d916.

  PMID: 20921898 RESULT

• Chung RT, Umbleja T, Chen JY, Andersen JW, Butt AA, Sherman KE; Actg A5178 Study Team. Extended therapy with pegylated interferon and weight-based ribavirin for HCV-HIV coinfected patients. HIV Clin Trials. 2012 Mar-Apr;13(2):70-82. doi: 10.1310/hct1302-70.

  PMID: 22510354 RESULT

• Butt AA, Umbleja T, Andersen JW, Sherman KE, Chung RT; ACTG A5178 Study Team. Impact of peginterferon alpha and ribavirin treatment on lipid profiles and insulin resistance in Hepatitis C virus/HIV-coinfected persons: the AIDS Clinical Trials Group A5178 Study. Clin Infect Dis. 2012 Sep;55(5):631-8. doi: 10.1093/cid/cis463. Epub 2012 May 4.

  PMID: 22563020 RESULT

• Branch AD, Kang M, Hollabaugh K, Wyatt CM, Chung RT, Glesby MJ. In HIV/hepatitis C virus co-infected patients, higher 25-hydroxyvitamin D concentrations were not related to hepatitis C virus treatment responses but were associated with ritonavir use. Am J Clin Nutr. 2013 Aug;98(2):423-9. doi: 10.3945/ajcn.112.048785. Epub 2013 Jun 5.

  PMID: 23739141 DERIVED

• Shire NJ, Rao MB, Succop P, Buncher CR, Andersen JA, Butt AA, Chung RT, Sherman KE; AIDS Clinical Trials Group 5178 Study Group. Improving noninvasive methods of assessing liver fibrosis in patients with hepatitis C virus/human immunodeficiency virus co-infection. Clin Gastroenterol Hepatol. 2009 Apr;7(4):471-80, 480.e1-2. doi: 10.1016/j.cgh.2008.12.016. Epub 2008 Dec 25.

  PMID: 19268724 DERIVED

MeSH Terms

Conditions

HIV Infections; Hepatitis C; Liver Diseases

Interventions

peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hepatitis, Viral, Human; Flaviviridae Infections; Hepatitis; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Kenneth E. Sherman, MD, PhD

  University of Cincinnati

  STUDY CHAIR

• Raymond Chung, MD

  Harvard/Massachusetts General Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2004
• First Posted: February 25, 2004
• Study Start: July 1, 2004
• Primary Completion: May 1, 2007
• Study Completion: February 1, 2009
• Last Updated: November 8, 2021
• Results First Posted: April 27, 2011

Record last verified: 2016-11

Locations

PR (1); US (36)