A Randomized Phase II Study of Two Doses of Interferon Alfa-2a (IFN Alfa-2a) in Combination With Zidovudine (AZT) and Dideoxycytidine (ddC) Versus AZT and ddC Only in Patients With HIV Infection and Less Than 400 CD4 Cells/mm3

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 2

Conditions: HIV Infections

Treatments: Drug: Zalcitabine; Drug: Interferon alfa-2a; Drug: Zidovudine

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT00000754

11173 (Registry Identifier)

ACTG 197

Details and patient eligibility

About

To determine the safety and efficacy of two doses of interferon alfa-2a ( IFN alfa-2a ) in combination with zidovudine ( AZT )/zalcitabine ( ddC ) versus AZT/ddC only in patients with HIV infection and CD4 count < 400 cells/mm3.

AZT and ddC inhibit HIV by acting as reverse transcriptase chain terminators, while IFN alfa-2a inhibits translation of viral proteins. Combining agents that act at different sites of viral replication may improve HIV inhibition and produce more effective and sustained anti-HIV effects.

Full description

AZT and ddC inhibit HIV by acting as reverse transcriptase chain terminators, while IFN alfa-2a inhibits translation of viral proteins. Combining agents that act at different sites of viral replication may improve HIV inhibition and produce more effective and sustained anti-HIV effects.

Patients are randomly assigned to one of three treatment arms to receive AZT/ddC alone or combined with one of two doses of IFN alfa-2a. Treatment continues for up to 12 months after enrollment of the last patient. Patients are followed at 2, 4, and 8 weeks and every 8 weeks thereafter. Mean duration of follow-up is expected to be 13 months.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• Isoniazid for < grade 2 peripheral neuropathy (if patient is also taking 50 mg/day pyridoxine).
• Phenytoin for < grade 2 peripheral neuropathy.
• A 21-day course of adjuvant systemic corticosteroid therapy for moderate to severe Pneumocystis carinii pneumonia (PCP).
• Chemoprophylaxis for PCP, candidiasis, herpes simplex infection (up to 1 g acyclovir daily), and Mycobacterium tuberculosis.

Patients must have:

• HIV infection.
• CD4 count < 400 cells/mm3 within 30 days prior to study entry.

NOTE:

• Minimal Kaposi's sarcoma is allowed.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

• Active opportunistic infection requiring acute therapy.
• Need for maintenance therapy for cytomegalovirus infection, toxoplasmic encephalitis, or mycobacterial infection.
• Malignancy (other than minimal Kaposi's sarcoma) requiring therapy.
• Grade 2 or worse peripheral neuropathy.

Concurrent Medication:

Excluded:

• Other antiretroviral drugs, biologic response modifiers, cytotoxic chemotherapy, or investigational drugs (unless approved by the protocol chairs).
• Recombinant erythropoietin, G-CSF, or GM-CSF.
• Drugs that cause peripheral neuropathy, e.g., gold, hydralazine, nitrofurantoin, vincristine, cisplatin, disulfiram, and diethyldithiocarbamate (unless approved by the protocol chairs).

Concurrent Treatment:

Excluded:

• Radiation therapy (unless approved by the protocol chairs).

Patients with the following prior conditions are excluded:

• History of intolerance to AZT at 600 mg/day or less.
• Unexplained temperature of 38.5 degrees C persisting for 14 days or longer.
• Unexplained, chronic diarrhea defined as 3 or more stools per day persisting for 14 days or longer.

Prior Medication:

Excluded:

• Acute therapy for opportunistic infection within 14 days prior to study entry.
• Prior ddC, ddI, or IFN alfa-2a.

Active substance abuse.