A Study of Cidofovir in HIV-Infected Children With Cytomegalovirus (CMV) Disease

Concurrent Medication:

Allowed:

• Ganciclovir therapy (for patients on Part A).[AS PER AMENDMENT 1/7/98:

Ganciclovir required during sequential single-dose phase.]

• Antiretroviral medications, including protease inhibitors.
• Antibacterials except for aminoglycosides.
• IVIG.
• Antihistamines, antiemetics, and acetaminophen.

Patients must have:

• Documented laboratory evidence of HIV-1 infection as demonstrated by:

\< 18 months of age:

• a positive viral culture and a second confirmatory test (from a later date) of either a positive viral culture, p24 antigen, or PCR. Confirmatory tests must be completed at an ACTG certified laboratory.

>= 18 months of age:

• criteria as stated for \< 18 months or 2 positive tests for HIV antibody obtained after 18 months of age (drawn from two different dates). HIV antibody tests must be determined by a federally licensed ELISA. One of the two positive HIV antibody tests must be confirmed by any of the confirmatory tests (Western blot or IFA).

Part A:

• End-organ CMV disease documented by histopathologic diagnosis or by compatible clinical disease with positive CMV culture and/or CMV PCR and the need to administer anti-CMV agents as determined by the patient's physician.

Part B:

• CMV retinitis documented by retinal exam and requiring anti-CMV agents as determined by the patient's physician. Patients with CMV retinitis who successfully complete Part A without significant toxicity are eligible to participate in Part B.
• Signed, informed consent from a parent or legal guardian for patients \< 18 years of age.

[AS PER AMENDMENT 1/7/98:

• Documented active or inactive CMV retinitis (by retinal examination) and the need to administer anti-CMV agents as determined by the subject's physician. Subjects may be receiving either induction or maintenance ganciclovir at entry (such therapy must be completed prior to proceeding to the multi-dosing phase).]

Prior Medication:

Required:

• Ganciclovir therapy upon entry (for patients in Part A).

Allowed:

• Ganciclovir therapy upon entry (for patients in Part B). NOTE: Patients in Part B will not be allowed to receive concomitant CMV therapy once study drug is started.

[AS PER AMENDMENT 1/7/98:

• Patients are required to receive ganciclovir during the sequential single-dose phase but must not receive concurrent CMV therapy once the multi-dosing phase is initiated.]

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions are excluded:

• Acute infections requiring treatment during the study period.

Concurrent Medication:

Excluded:

• Cancer chemotherapeutic agents. [AS PER AMENDMENT 1/7/98:Anti-cancer therapy prohibited during multi-dosing phase.]

Excluded within 7 days prior to enrollment:

• Foscarnet therapy.
• Drugs known to cause nephrotoxicity such as amphotericin B, aminoglycosides, vancomycin, or IV pentamidine.
• Other local or systemic anti-CMV medications (except concomitant ganciclovir for patients treated on Part A).

Patients with the following prior conditions are excluded:

• Previous hypersensitivity reaction to probenecid and/or serious allergic reaction (e.g., anaphylactic reaction, hypotension, laryngospasm, exfoliative dermatitis) to sulfa-containing medications.

[AS PER AMENDMENT 1/7/98:

• Pre-existing uveitis/iritis as determined by slit-lamp exam.
• Intraocular pressure \< 4 mm Hg prior to enrollment.]