The Impact of HAART on Response to Hepatitis C Treatment in Patients Taking Peginterferon Alpha-2b and Ribavirin

NCT00031343 | Completed Phase 2

• 2 other identifiers: 02013902-I-0139
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate how controlling HIV infection with HAART (highly active antiretroviral therapy) affects the response to hepatitis C treatment with peginterferon alpha-2b and ribavirin in HIV-infected patients with chronic hepatitis C. HIV worsens liver disease caused by hepatitis C. Since treatment of HIV infection with HAART improves immune function, it may be beneficial to start HAART before treating HCV. HIV-infected patients 18 years of age and older with chronic hepatitis C infection may be eligible for this study. Patients must have an HCV viral load greater than 2000 copies/mL and a CD4 count that is either more than 500 cells/mm3, or more than 350 cells/mm3 with an HIV viral load no greater than 40,000 particles/mL. Candidates will be screened for current or previous diseases, conditions or treatments that may exclude them from this study. Screening includes a medical history and physical examination, eye examination, blood and urine tests, chest X-ray, electrocardiogram (EKG), liver ultrasound, and, possibly, a liver biopsy, if a recent one is not available. The liver biopsy is optional and is done to determine the severity of liver disease. Patients will be sedated for this test. The skin in the area over the biopsy site is numbed with a local anesthetic, and a needle is inserted rapidly into and out of the liver to obtain a small tissue sample. Patients remain in the hospital overnight for monitoring. Women of childbearing age will have a pregnancy test. Patients enrolled in the study will be randomly assigned to one of the following treatment groups: 1) pegylated interferon and ribavirin for 48 weeks (control group); or 2) HAART for 6 months, followed by 48 weeks of pegylated interferon and ribavirin. HAART group - Patients taking HAART will be followed in the clinic every 2 weeks for the first month and then monthly for the next 5 months. After 6 months of HAART they will begin taking pegylated interferon and ribavirin and will follow the dosing and follow-up schedule outlined below for patients in the control group. Control group - Patients will have weekly injections under the skin of peginterferon alpha-2b and ribavirin pills daily by mouth. Clinic visits will be scheduled as follows:

• Days 1, 3, 7, and 21 - Blood will be drawn for safety tests and to measure blood levels of HIV and HCV. HCV medications will be injected on days 7 and 21.
• Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 52, 56, and 64 - Blood and urine tests will be done to determine the side effects of pegylated interferon and ribavirin treatment and its effect on the HCV infection. Eye examinations will be done every 3 months.
• Week 48 or end of treatment - Treatment with pegylated interferon and ribavirin will stop after 48 weeks. At this time (or earlier for those who do not complete the 48 weeks of treatment), patients will return to the clinic for a routine visit, blood tests (including a test for hepatitis B) and abdominal ultrasound. Patients may also be hospitalized for 2 days for a repeat optional liver biopsy.
• Week 72 and extended follow-up visits - At week 72, patients will return for blood tests and a routine clinic visit. HCV viral load will be measured. Follow-up visits every 3 months for an additional year will include a blood test to measure HCV viral load and a complete physical examination.

Conditions

HIV Infections; Hepatitis C

Keywords

Liver Disease; Virologic Response; Immune Mechanisms; Eradication; Antiviral Therapy; HIV; Hepatitis C; HCV; Coinfection

Interventions

highly active antiretroviral therapy (HAART) DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 18 years
• Documentation of HIV-1 infection by a licensed ELISA test and confirmed by a Western Blot
• CD4 greater than or equal to 500 cells/mm(3) or CD4 greater than or equal to 350 cells/mm(3) and HIV VL less than or equal to 40,000 copies per milliliter
• CD4 nadir not below 200 cells/mm(3)
• If not HAART naive, history of HIV VL suppression while on HAART treatment.
• Patients who are currently on HAART but do not meet criteria for the initiation of HAART according to current DHHS guidelines must be willing to come off their regimen 3 months prior to study initiation.
• Documentation of Hepatitis C infection by demonstration of a positive test for hepatitis C antibody.
• HCV RNA level greater than 2000 copies per milliliter by polymerase chain reaction
• Patients naive to HCV treatment at time of enrollment.
• Serum creatinine less than or equal to 1.5 mg/dL
• Serum phosphorus greater than or equal to 2.2 mg/dL (normal range NIH 2.3-4.3 mg/dL)
• Neutrophil count greater than or equal to 1000 cells/mm(3)
• Platelets greater than or equal to 75,000/mm(3)
• Hemoglobin greater than or equal to 8.0 mg/dL
• ALT less than 7 X the NIH upper limit of normal

You may not qualify if:

• PT-INR (in the absence of anti-cardiolipin Ab) by greater than or equal to 2.
• Organ transplant recipient
• Recent HIV seroconverters (must be 6 months or more with documented HIV diagnosis).
• Patients who are medically indicated to begin HAART therapy
• Elevated alpha-fetoprotein level (greater than or equal to 100 ng/mL).
• Coexisting neoplastic disease requiring cytotoxic therapy.
• Have had cancer other than Kaposi's sarcoma of the skin, other skin cancers treated by resection, Bowen's disease, or localized cervical or anal cancer in the 5 years prior to enrollment
• Have had significant renal dysfunction within the previous 12 months or evidence of significant protein wasting
• Severe cardiac or pulmonary decompensation as assessed by the PI.
• Severe liver decompensation or advanced cirrhosis patients
• Severe psychiatric disorder that would interfere with the adherence to protocol requirements.
• Autoimmune disorders including inflammatory bowel diseases, and optic neuritis as assessed by the PI.
• Uncontrolled seizure disorder
• Severe retinopathy.
• Direct bilirubin more than or equal to 2 times ULN.

Sponsors & Collaborators

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

Study Sites (1)

National Institute of Allergy and Infectious Diseases (NIAID)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• National Institutes of Health Consensus Development Conference Panel statement: management of hepatitis C. Hepatology. 1997 Sep;26(3 Suppl 1):2S-10S. doi: 10.1002/hep.510260701.

  PMID: 9305656 BACKGROUND

• Alter MJ, Mast EE. The epidemiology of viral hepatitis in the United States. Gastroenterol Clin North Am. 1994 Sep;23(3):437-55.

  PMID: 7989088 BACKGROUND

• Alter MJ, Margolis HS, Krawczynski K, Judson FN, Mares A, Alexander WJ, Hu PY, Miller JK, Gerber MA, Sampliner RE, et al. The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team. N Engl J Med. 1992 Dec 31;327(27):1899-905. doi: 10.1056/NEJM199212313272702.

  PMID: 1280771 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Hepatitis C; Liver Diseases; Coinfection

Interventions

Antiretroviral Therapy, Highly Active

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)

Drug Therapy, Combination; Drug Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 2, 2002
• First Posted: March 4, 2002
• Study Start: February 1, 2002
• Study Completion: April 1, 2004
• Last Updated: March 4, 2008

Record last verified: 2004-04

Locations

US (1)