To study the safety, tolerance, pharmacokinetics, and anti-HIV effects of combination zidovudine (AZT) and PMEA (adefovir) therapy.

Patients receive AZT daily and intravenous PMEA three times weekly for 4 weeks. An MTD will be defined for this regimen.

Inclusion Criteria

Concurrent Medication:

Allowed:

• Prophylactic therapy with aerosolized pentamidine, oral trimethoprim/sulfamethoxazole (Bactrim, Septra) or dapsone, and fluconazole or ketoconazole IF on a stable regimen for at least 4 weeks prior to study entry.

Patients must have:

• HIV seropositivity.
• Mean CD4 count <= 500 cells/mm3.
• Been receiving AZT at 500 mg daily for at least 4 weeks prior to study entry.
• Life expectancy of at least 3 months.

NOTE:

• Kaposi's sarcoma is permitted provided patient has not received any systemic therapy for KS within the past 4 weeks. Patients with a history of another malignancy must be disease free for 6 months or more prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Inadequate venous access.
• Active, serious infections (other than HIV infection) requiring parenteral antibiotic therapy.
• Clinically significant cardiac disease, including symptoms of ischemia, congestive heart failure, or clinically significant arrhythmia.
• Active malignancy other than Kaposi's sarcoma.
• Mental incapacity or illness that may affect compliance.

Concurrent Medication:

Excluded:

• ddI or ddC.
• Interferon alpha.
• Ganciclovir.
• Foscarnet.
• Diuretics.
• Investigational agents including d4T.
• Chemotherapeutic agents.
• Amphotericin B.
• Aminoglycoside antibiotics.
• Other nephrotoxic agents.
• Immunomodulatory agents.
• Parenteral therapy for an active, serious infection (other than HIV infection).

Prior Medication:

Excluded within 2 weeks prior to study entry:

• ddI or ddC.
• Interferon alpha.
• Ganciclovir.
• Foscarnet.
• Diuretics.
• Investigational agents including d4T.
• Chemotherapeutic agents.
• Amphotericin B.
• Aminoglycoside antibiotics.
• Other nephrotoxic agents.
• Immunomodulatory agents.

Excluded within 4 weeks prior to study entry:

Systemic therapy for Kaposi's sarcoma.

Required:

• AZT at a stable dose for at least 4 weeks prior to study entry. Current use of illicit drugs (e.g., heroin or cocaine). Ingestion of substantial alcohol.