A Pharmacokinetic and Tolerance Study of Oral Ganciclovir in HIV-Infected Children With Asymptomatic Cytomegalovirus Infection and Low CD4 Cell Counts or Quiescent Cytomegalovirus Disease

A Pharmacokinetic and Tolerance Study of Oral Ganciclovir in HIV-Infected Children With Asymptomatic Cytomegalovirus Infection and Low CD4 Cell Counts or Quiescent Cytomegalovirus Disease

PRIMARY: To determine the pharmacokinetics, MTD, and long-term safety and tolerance of oral ganciclovir in HIV-infected infants, children, and adolescents.

SECONDARY: To evaluate the effect of oral ganciclovir on the virologic parameters of CMV.

Maintenance treatment with intravenous (IV) ganciclovir for cytomegalovirus retinitis in AIDS patients is now standard therapy, but daily IV therapy can be complicated by catheter infections and thrombosis. An oral regimen of ganciclovir has been administered safely in adult AIDS patients and may be of significant benefit to children and infants as well.

Maintenance treatment with intravenous (IV) ganciclovir for cytomegalovirus retinitis in AIDS patients is now standard therapy, but daily IV therapy can be complicated by catheter infections and thrombosis. An oral regimen of ganciclovir has been administered safely in adult AIDS patients and may be of significant benefit to children and infants as well.

Patients are assigned to 1 of 5 (PER AMENDMENT 10/24/95, was 4) oral (syrup or capsules) dose levels following a single intravenous dose of ganciclovir. Treatment continues for 72 (PER AMENDMENT 10/24/95, was 24 weeks) weeks after the last patient has been enrolled.

Inclusion Criteria

Concurrent Medication:

PER AMENDMENT 10/24/95: Allowed:

• All antiretroviral agents and other medications except those listed under Exclusion - Concurrent Medications.
• Didanosine. However, patients receiving both drugs (didanosine and ganciclovir) should be monitored for toxicity.
• Amphotericin B is allowed but requires additional monitoring.

Patients must have:

• HIV infection.
• CMV infection.
• CD4 count < 150 cells/mm3 or < 15 percent AND/OR quiescent CMV disease.
• NO loss of sight from CMV retinitis.
• NO acute opportunistic infection.
• Life expectancy at least to study completion.
• Consent of parent or guardian.

NOTE:

• Infants < 6 months of age at enrollment must have been >= 36 weeks gestational age at birth.

NOTE:

• Patients may co-enroll in other ACTG protocols that do not involve the administration of disallowed medications.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Loss of sight in one eye for any reason, with evidence of CMV retinitis in the other eye.
• Acute or chronic diarrhea that would affect absorption.
• Clinical or laboratory toxicities of grade 3 or worse.

Concurrent Medication:

Excluded:

• Foscarnet.
• Acyclovir.
• Interferon.
• Myelotoxic agents for malignancy or other condition.
• Other agents with anti-CMV activity. (NOTE:

Enrollment of patients on IVIG must be discussed with protocol chair.)

• Imipenem/cilastatin sodium.

Prior Medication:

Excluded within 30 days prior to study entry:

• G-CSF or GM-CSF.