The Effectiveness of Three Drug Combinations in HIV-Infected Patients Who Have Taken Zidovudine for More Than 12 Weeks

Inclusion Criteria

Concurrent Medication:

Required for patients whose CD4 count falls below 200 cells/mm3:

• PCP prophylaxis with TMP/SMX, aerosolized pentamidine, or dapsone.

Allowed:

• Atovaquone, IV pentamidine, trimethoprim-dapsone, clindamycin-primaquine, trimetrexate, or TMP/SMX for acute PCP.
• Topical antifungals, clotrimazole, ketoconazole, fluconazole, and amphotericin B for mucosal and esophageal candidiasis.
• Itraconazole.
• Amphotericin B.
• Rifabutin.
• Isoniazid.
• Pyrazinamide.
• Clofazimine.
• Clarithromycin.
• Azithromycin.
• Ethambutol.
• Amikacin.
• Ciprofloxacin.
• Ofloxacin.
• Pyrimethamine.
• Sulfadiazine.
• Clindamycin.
• Ganciclovir.
• G-CSF.
• Acyclovir (up to 1000 mg/day).
• Erythropoietin.
• Antibiotics for bacterial infections.
• Antipyretics.
• Analgesics.
• Antiemetics.
• Rifampin.

Concurrent Treatment:

Allowed:

• Local radiation therapy.

Patients must have:

• HIV infection.
• CD4 count 300-600 cells/mm3.
• More than 12 weeks (was 24 weeks, AMENDED 3/31/96) of total prior AZT ( > 500 mg/day without serious adverse event). Subjects must be actively taking ZDV for at least 4 continuous weeks up to the time of study entry.
• No prior or current history of AIDS.
• No active opportunistic infection.
• Life expectancy of at least 2 years.
• Consent of patient and parent or guardian if less than 18 years of age.

NOTE:

• Protocol is approved for prisoner enrollment.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Malignancy requiring systemic cytotoxic chemotherapy.
• Serious underlying medical condition other than HIV that would reduce life expectancy to < 2 years.

Concurrent Medication:

Excluded:

• Antiretrovirals other than study drugs.
• Foscarnet.

Patients with the following prior conditions are excluded:

• Unexplained temperature >= 38.5 C for 7 days or chronic diarrhea (>= three stools daily) for 15 days, if occurring within 30 days prior to study entry.
• History of acute or chronic pancreatitis.
• History of grade 2 or higher peripheral neuropathy.
• History of grade 3 or worse intolerance to 500-600 mg/day AZT.

Prior Medication:

Excluded:

(within 30 days prior to study entry)

• Prior ddI, ddC, 3TC or d4T (more than 2 weeks total).
• Non-nucleoside reverse transcriptase inhibitor or protease inhibitor.
• Biologic response modifiers such as interferon and IL-2.
• Other experimental therapy.