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.]