The Safety and Effectiveness of a Two-Drug Combination in the Treatment of Patients With Hepatitis C Plus Advanced HIV Infections

A Phase I Pilot Study of the Safety and Efficacy of Interferon Alfa-2b (IFN Alfa-2b) in Combination With Nucleoside Analog Therapy in Patients With Combined Hepatitis C (HCV) and Advanced Human Immunodeficiency Virus (HIV) Infections

To investigate the toxicity of interferon alfa-2b ( IFN alfa-2b ) in combination with nucleoside analog therapy in HIV-positive patients with chronic hepatitis C. To determine the efficacy of treatment with IFN alfa-2b for chronic hepatitis C in patients with advanced HIV infections treated with nucleoside analog therapy.

IFN alfa-2b has HIV inhibitory properties and has also been approved for treatment of chronic hepatitis C. Studies have shown that IFN alfa-2b is effective in asymptomatic HIV-positive patients with chronic hepatitis C, but the drug's benefit against hepatitis C in patients with advanced HIV infection has not been determined.

IFN alfa-2b has HIV inhibitory properties and has also been approved for treatment of chronic hepatitis C. Studies have shown that IFN alfa-2b is effective in asymptomatic HIV-positive patients with chronic hepatitis C, but the drug's benefit against hepatitis C in patients with advanced HIV infection has not been determined.

Patients receive interferon alpha-2b subcutaneously 3 times weekly for 6 months. If no response is seen after 18 weeks of therapy or if an initial response is followed by relapse while on therapy, dose is increased. Patients who require a dose escalation should continue on IFN alfa-2b for an additional 6 months. All patients will also receive available nucleoside analog therapy ( zidovudine, didanosine, zalcitabine ) at currently accepted doses as clinically appropriate.

Inclusion Criteria

Concurrent Medication:

Allowed:

• Treatment or suppression of opportunistic infections with standard drugs.
• Pneumovax, HIB, tetanus, influenza, and hepatitis B vaccines.
• Clinically indicated antibiotics.
• Short courses of steroids (< 21 days) for acute problems not related to hepatitis C.
• Other regularly prescribed medications such as analgesics, nonsteroidal anti-inflammatory agents, antipyretics, allergy medications, and oral contraceptives.

Patients must have:

• HIV positivity.
• Documented hepatitis C virus.
• CD4 count <= 200 cells/mm3.
• No severe liver disease (Grade C Childs-Pugh classification) or chronic liver disease not caused by hepatitis C.
• Willingness to be followed for the duration of treatment and follow-up period.

Prior Medication:

Allowed:

• Prior AZT, ddI, and ddC.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Hepatitis B (HBsAg positive).
• Autoimmune hepatitis (FANA titer >= 1:160 and anti-smooth muscle antibody titer >= 1:160).
• Wilson's disease.
• alpha-1 antitrypsin deficiency.
• Hemochromatosis.
• Malignancy requiring systemic chemotherapy.

Concurrent Medication:

Excluded:

• Nonnucleoside analog therapy for HIV.
• Biologic response modifiers.
• Systemic cytotoxic chemotherapy.
• Chronic systemic steroid use.

Concurrent Treatment:

Excluded:

• Radiation therapy other than local irradiation to the skin.

Prior Medication:

Excluded:

• Prednisone within 12 weeks prior to study entry (if patient has received prior daily doses for 1 month or longer duration).
• Acute therapy for an infection within 2 weeks prior to study entry.