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.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Interferon alfa-2a  Drug: Zidovudine  Drug: Zalcitabine	Phase II

Further Study Details: 

Expected Total Enrollment:  60

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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.

Alabama
      Univ of Alabama at Birmingham, Birmingham,  Alabama,  35294,  United States
California
      Univ of California / San Diego Treatment Ctr, San Diego,  California,  921036325,  United States
      UCSD Med Ctr / Pediatrics / Clinical Sciences, La Jolla,  California,  920930672,  United States
Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States

Study chairs or principal investigators

Fischl MA,  Study Chair
Richman DD,  Study Chair

Study ID Numbers:  ACTG 197
Record last reviewed:  February 1995
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000754
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08