This study will evaluate the safety and effectiveness of combination therapy with
peginterferon alpha-2b and ribavirin for treating hepatitis C virus (HCV) infection in
HIV-infected patients. In studies of patients with hepatitis C alone, interferon alpha-2b
plus ribavirin treatment eradicated the HCV in almost half the patients. Peginterferon
alpha-2b is a compound that results from attaching a polyethylene glycol molecule to
interferon alpha-2b. This compound stays in the blood longer than unmodified interferon
alpha-2b, causing a higher blood concentration and thus maintaining activity against the
hepatitis C virus.
HIV-infected patients 21 years of age and older with chronic hepatitis C infection and a
viral load greater than 2000 copies/mL may be eligible for this 2 1/2-year study.
Candidates will be screened with blood and urine tests and possibly a liver biopsy, if a
recent one is not available. The liver biopsy is done to determine the severity of liver
disease. For this test, patients are admitted to the NIH Clinical Center for 1 to 2 days.
A sedative is injected into an arm vein, 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. The patient remains in the hospital overnight for monitoring.
A chest X-ray, electrocardiogram (EKG) and liver ultrasound are also done. Within 4 weeks
of the screening tests, candidates who appear eligible for the study will have a physical
examination, medical history and repeat blood tests. Women who can become pregnant will
have serial pregnancy tests throughout the study.
Patients who meet the study criteria and decide to participate will begin treatment with
weekly injections under the skin of peginterferon alpha-2b and take ribavirin pills twice a
day by mouth. In addition, patients will continue to take all other medications prescribed
by their doctor. Clinic visits will be scheduled as follows:
- Days 1, 3, 5, 7, 10 and 21 - Blood will be drawn for safety tests and to measure blood
levels of HIV and HCV.
- 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 treatment and its effect on the HCV
- Week 48 or end of treatment - Treatment will stop after 48 weeks. At this time, or
earlier for those who do not complete the 48 weeks, patients will return to the clinic
for a routine test.
Hepatitis C infection occurs in one-third of all HIV-infected individuals. Liver disease
has become more clinically significant among patients coinfected with HIV and HCV. Several
studies have shown that coinfected individuals develop earlier and severe liver disease.
Interferon with ribavirin has become the therapy of choice among people with non-genotype
1a. This is a pilot study to address the relationship of clinical response to combination
therapy to the virologic and immunologic parameters. The study will also address the safety
and efficacy of the peginterferon alpha-2b among HIV- infected individuals. The predictive
ability of baseline HCV viral load, rate of decline of HCV viral load, HIV viral load and
CD4 counts to the clinical response of chronic hepatitis to peginterferon and ribavirin will
also be studied. Approximately sixty patients who are infected with both HIV and HCV and
also have evidence of fibrosis will receive peginterferon alpha-2b and ribavirin for 48
weeks. In order to enroll sixty patients for this study, we will be screening a total of
180 patients. During the 72 weeks study these patients will be monitored for HCV viral
load, and other HIV viral load and CD4 counts. Viral kinetics will also be monitored
closely and the slope of second, slower phase decline of HCV viral load, which corresponds
to the rate of infected cell death presumably may lead to sustained hepatitis C virologic
response. The results of the study will enable us to better delineate the possible
predictors of sustained response to peginterferon and ribavirin. The safety and
tolerability of a combination therapy with peginterferon and ribavirin among HIV-infected
individuals on antiretroviral therapy will further define the standard therapy of chronic
hepatitis C in HIV-infected individuals.
- INCLUSION CRITERIA:
Age greater than or equal to 18 years.
Documentation of HIV-1 infection by any licensed ELISA test and confirmed by a Western
Documentation of Hepatitis C infection by demonstration of a positive test for hepatitis C
HCV RNA level greater than 2000 IU/ml by bDNA.
Infected with HCV genotype 1.
Histopathologic features consistent with chronic hepatitis C on liver biopsy at the time
Patients with CD4 greater than 300 cells/mm(3).
Ability to sign informed consent and willingness to comply with the study requirements and
Serum creatinine less than 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 times the NIH upper limit of normal.
Serum lipase less than 1.5 times the NIH upper limit of normal.
Not pregnant or breast-feeding. Pregnancy test must be negative within two weeks prior to
dosing with study medications.
If capable of pregnancy: use of effective contraception during study: effective
contraception methods include abstinence, surgical sterilization of either partner,
barrier methods such as diaphragm, condom, cap or sponge, or use of hormonal contraception
with an anti-HIV regimen that will not alter metabolism of hormonal contraception. This
is advised on the basis of using ribavirin, which may have a potential teratogenic effect
in pregnant women.
Need to have a primary doctor outside OP8 who will be taking care of the patients for
their HIV infection and liver disease.
Willing to designate a person for durable power of attorney on the NIH form for medical
research and medical care purposes at the NIH Clinical Center.
Ability to learn how to safely inject medication subcutaneously.
PT-INR (in the absence of anti-cardiolipin antibody) prolonged by greater than 2 seconds.
Organ transplant recipient.
Elevated alpha-fetoprotein level (greater than 100 ng/mL).
Coexisting neoplastic disease requiring cytotoxic therapy.
Child Pugh's class B.
Severe cardiac or pulmonary decompensation.
Severe liver decompensation or advanced cirrhosis patients.
Severe psychiatric disorder that would interfere with the adherence to protocol
Preexisting autoimmune disorders including inflammatory bowel diseases, psoriasis, and
Preexisting uncontrolled seizure disorder.
Direct bilirubin more than or equal to 2 times ULN.
No patients using long term systemic corticosteroids, immunosuppressives, or cytotoxic
agents within 60 days of enrollment into the trial.
Chronic viral hepatitis of any other etiology other than hepatitis C.
Active systemic infections other than hepatitis C and HIV.
Liver disease caused by reasons other than hepatitis C like HBV, HDV, Wilson's
hemochromatosis, autoimmune hepatitis (ANA greater than 160) except history of
drug-associated hepatitis with discontinuation of the causative agent.
Hepatic mass suggestive of hepatocellular carcinoma.
Current alcohol or substance abuse that potentially could interfere with patient
Significant heart failure.
Evidence of esophageal varices.
Any systemic illness that will make it unlikely that the subject will be able to return to
NIH for the required study visits.
Evidence of gastrointestinal malabsorption or chronic nausea or vomiting.
Male partners of pregnant women.
Currently taking didanosine (ddl or Videx-EC or Videx) as part of antiretroviral regimen.