A Randomized, Double-Blind Phase II/III Trial of Monotherapy vs. Combination Therapy With Nucleoside Analogs in HIV-Infected Persons With CD4 Cells of 200-500/mm3

A Randomized, Double-Blind Phase II/III Trial of Monotherapy vs. Combination Therapy With Nucleoside Analogs in HIV-Infected Persons With CD4 Cells of 200-500/mm3

To determine the efficacy and safety of zidovudine ( AZT ) versus didanosine ( ddI ), AZT plus ddI, and AZT plus zalcitabine ( ddC ) in preventing disease progression in HIV-infected patients with CD4 counts of 200-500 cells/mm3.

Patients are randomized to receive AZT alone, AZT and ddI, AZT and ddC, or ddI alone for at least 2 years. Patients who develop AIDS or whose CD4 count falls to 50 percent or less of baseline are crossed over to another treatment arm.

PER AMENDMENT 4/5/95: Study treatment will be available until 10/31/95 at the latest for patients still taking study medications on 4/30/95, so that follow-up trials may be completed and approved.

Inclusion Criteria

Concurrent Medication:

Allowed:

• PCP prophylaxis, M. tuberculosis prophylaxis, short courses of acyclovir, chronic suppressive acyclovir, pneumovax or Hib vaccine, antibiotics, rEPO and G-CSF for grade 3 or worse anemia and neutropenia, systemic corticosteroids for < 21 days, regularly prescribed medications, and vitamins or herbal therapies.

Patients must have:

• HIV infection without AIDS with CD4 200-500 cells/mm3.

PER AMENDMENT 4/5/95:

• Patients must have remained on ACTG 175 study treatment through 4/30/95 and meet toxicity management criteria for continuing treatment. Subjects taking ACTG 175 crossover treatment are eligible.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions are excluded:

• Current AIDS-related condition other than minimal KS, grade 2 or worse peripheral neuropathy, and malignancy requiring systemic therapy.

Concurrent Medication:

Excluded:

• Other anti-HIV drugs, biologic response modifiers other than rEPO and G-CSF, systemic cytotoxic chemotherapy, chronic systemic corticosteroids, or any drug that affects AZT glucuronidation or clearance.

Concurrent Treatment:

Excluded:

• Radiotherapy other than limited local therapy to skin.

Patients with the following prior conditions are excluded:

• AIDS-related condition other than minimal KS; intolerance to AZT, ddI, or ddC at study doses; and acute or chronic pancreatitis.

Prior Medication:

Excluded:

• Acute therapy for an infection or other medical illness within the past 14 days.

Current alcohol abuse.