A Phase I Trial to Evaluate the Pharmacokinetics, Safety, and Tolerance of Valacyclovir HCl in HIV-1 Infected Children With Herpes Simplex Infections or Varicella/Zoster Infections
Valacyclovir hydrochloride
Varicella Zoster Virus Infection+26
+ Blood-Borne Infections
+ Urogenital Diseases
Treatment Study
Summary
Varicella and zoster are common problems in HIV-infected children. It is believed that chronic oral therapy with acyclovir may result in subtherapeutic concentrations of acyclovir, resulting in resistance to that drug. Valacyclovir hydrochloride, which converts to acyclovir in the body, increases acyclovir bioavailability by 3-5 fold. In the first cohort, patients with stable herpes simplex virus receive valacyclovir hydrochloride at 1 of 2 doses, depending on body surface area (BSA), for 10 days. If acceptable safety is seen at this dose level, a second cohort of patients with stable herpes simplex virus receive a higher dose, depending on BSA, for 10 days. A third cohort of patients with varicella or zoster receive a selected dose based on results from the previous cohorts.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 4 to 12 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
Inclusion Criteria Concurrent Medication: Allowed: Antiretrovirals. PCP prophylaxis. IVIG, G-CSF, and erythropoietin. Concurrent Treatment: Allowed: Transfusions. Patients must have: Localized mucocutaneous herpes simplex OR undisseminated varicella or zoster. HIV positive. NOTE: Varicella patients must NOT have AIDS. CD4 count >= 100 cells/mm3 (herpes simplex or zoster patients) OR >= 250 cells/mm3 (varicella patients). BSA > 0.6 m2. Ability to swallow solid dosage formulations. Prior Medication: Allowed: Prior VZV immune globulin and/or IVIG. Antiretrovirals if at a stable dose for at least 14 days. Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Clinical evidence of pneumonitis. Severe abdominal pain or back pain. Encephalopathy. Hemorrhagic varicella. Zoster involving ophthalmic branch of trigeminal nerve. Severe gastrointestinal disorder. Concurrent Medication: Excluded: Agents with potential activity against HSV or VZV, such as acyclovir, famciclovir, ganciclovir, foscarnet, and sorivudine. Probenecid. Aspartamine within 48 hours prior to pharmacokinetic samplings. Patients with the following prior conditions are excluded: Grade 2 creatinine value within the past 30 days. Grade 3 hematologic or hepatic values within the past 30 days. Prior hypersensitivity and/or allergic reaction to acyclovir. Grade 3 or 4 mental status changes within the past 30 days. Prior Medication: Excluded: Acyclovir within 1 week prior to study entry. Steroids within 4 weeks prior to onset of varicella lesions.