To study the safety, tolerance, pharmacokinetics, and anti-HIV effects of PMEA ( adefovir ) when administered daily by intravenous (IV) and/or subcutaneous (SC) injection in patients with advanced HIV disease.

Patients receive a single IV or SC dose of PMEA daily for 4 weeks. A maximum tolerated dose will be defined for these regimens.

Inclusion Criteria

Concurrent Medication:

Allowed:

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

Patients must have:

• HIV seropositivity.
• Elevated p24 antigen (> 40 pg/ml).
• Mean CD4 count <= 100 cells/mm3.
• Life expectancy of at least 3 months.

Prior Medication:

Allowed:

• Other prior antiretroviral therapy.
• Prophylactic therapy with aerosolized pentamidine, oral trimethoprim/sulfamethoxazole (Bactrim, Septra) or dapsone, and fluconazole or ketoconazole.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

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

Concurrent Medication:

Excluded:

• Investigational agents other than stavudine (d4T).
• Interferon-alpha.
• Ganciclovir.
• Foscarnet.
• Diuretics.
• Amphotericin B.
• Aminoglycoside antibiotics.
• Other nephrotoxic agents.
• Acyclovir at doses >= 2 g/day.

Prior Medication:

Excluded within 2 weeks prior to study entry:

• Investigational agents other than stavudine (d4T).
• Interferon-alpha.
• Ganciclovir.
• Foscarnet.
• Diuretics.
• Amphotericin B.
• Aminoglycoside antibiotics.
• Other nephrotoxic agents.

Excluded within 4 weeks prior to study entry:

• Systemic therapy for Kaposi's sarcoma. Substance abuse.