A Phase I/II Study of Cidofovir for HIV-Infected Children With Invasive CMV (Cytomegalovirus) Disease

Inclusion Criteria

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.]

History of severe allergic reactions to study medication Currently pregnant or breastfeeding Recent participation in another clinical trial within the last 30 days Presence of uncontrolled medical conditions that could affect safety