A Phase I Open-Labeled Study of Long Term Combined or Alternating Foscarnet/Ganciclovir Maintenance Therapy for AIDS Patients With CMV Retinitis After Ganciclovir Induction Therapy

Inclusion Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

- Chemotherapy for Kaposi's sarcoma (excluding interferon) if patient is
hematologically stable for at least 30 days prior to entry.

- Zidovudine (AZT), dideoxyinosine (ddI), dideoxycytidine (ddC) after first two weeks
of study period if absolute neutrophil count is > 1000 cells/mm3 and hemoglobin = or
> 8 g/dl.

- Vancomycin.

- Fluconazole or investigational triazoles (e.g., itraconazole, SCH 39304) for
disseminated fungal infection.

- Pneumocystis carinii pneumonia prophylaxis (except parenteral pentamidine).

- Acyclovir or other appropriate medication may be instituted in the event of the
appearance of Herpes simplex virus

- (HSV) or Varicella zoster virus (VZV) infections.

- G-CSF or GM-CSF for grade 4 neutropenia.

Concurrent Treatment:

Allowed:

- Recombinant human erythropoietin.

Prior Medication: Required:

- Completion of 14-day course of intravenous ganciclovir induction therapy (2.5 mg/kg
IV q8h or 5 mg/kg q12h for 14 days) or foscarnet induction therapy (60 mg/kg q8h
adjusted for renal function for 14 days) within 1 week prior to study entry. Patients
who do not initiate the study immediately upon completing ganciclovir induction
therapy should receive a maintenance ganciclovir regimen of 5 mg/kg/day or 6
mg/kg/day 5 x week or a foscarnet regimen of 90-120 mg/kg/day until initiating study
drug.

Patients must:

- Have a diagnosis of cytomegalovirus retinitis and HIV infection.

- Be capable of giving informed consent. Patients < 18 years of age may participate
with the consent of parent, guardian, or person with power of attorney.

Allowed:

- History of seizure disorder or a central nervous system (CNS) mass lesion.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

- Evidence of tuberculous, diabetic or hypertensive retinopathy.

- Osteomalacia, neoplasm metastatic to bone or other bone disease.

- Any clinically significant pulmonary or neurologic impairment (for example, patients
who are intubated or comatose).

- Retinal detachment.

- Corneal, lens, or vitreous opacification precluding funduscopic exam.

Concurrent Medication:

Excluded:

- Immunomodulators, biologic response modifiers or investigational agents not
specifically allowed.

- Aminoglycosides, amphotericin B, probenecid, parenteral pentamidine.

- Zidovudine (AZT), dideoxyinosine (ddI), dideoxycytidine (ddC) until completion of
second week of maintenance therapy. ddC use is discouraged but not prohibited
because of paucity of experience of this drug with ganciclovir and foscarnet.

Anti-cytomegalovirus (CMV) therapy:

- Ganciclovir, CMV hyperimmune serum/globulin, interferons, immunomodulators.

- Prophylactic antiviral therapy with acyclovir.

Patients with the following are excluded:

- Active AIDS-defining opportunistic infection requiring therapy that is currently
causing nephrotoxicity or myelosuppression.

- Known hypersensitivity to either of the study therapies.

Prior Medication:

Excluded:

- Foscarnet or ganciclovir for CMV retinitis (excluding the 14-day induction period).

Prior Treatment:

Excluded:

- Cytomegalovirus (CMV) hyperimmune globulin within 14 days prior to study entry.