To obtain tolerance, safety, and pharmacokinetic data for oral valacyclovir hydrochloride ( 256U87 ) in HIV-1 infected children with herpes simplex virus infections ( cold sores ) and/or varicella / zoster virus infections ( chicken pox / shingles ). 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.

Condition	Treatment or Intervention	Phase
Herpes Simplex HIV Infections Chickenpox	Drug: Valacyclovir hydrochloride	Phase I

Further Study Details: 

Expected Total Enrollment:  28

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.

Ages Eligible for Study:  4 Years   -   12 Years,  Genders Eligible for Study:  Both

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.

California
      UCSD Med Ctr / Pediatrics / Clinical Sciences, La Jolla,  California,  920930672,  United States
      Harbor - UCLA Med Ctr / UCLA School of Medicine, Los Angeles,  California,  905022004,  United States
      Summitt Med Ctr / San Francisco Gen Hosp, Oakland,  California,  94609,  United States
      Children's Hosp of Oakland, Oakland,  California,  946091809,  United States
      UCLA Med Ctr / Pediatric, Los Angeles,  California,  900951752,  United States
      Children's Hosp of Los Angeles/UCLA Med Ctr, Los Angeles,  California,  900276016,  United States
District of Columbia
      Children's Hosp of Washington DC, Washington,  District of Columbia,  200102916,  United States
Florida
      Univ of Florida Health Science Ctr / Pediatrics, Jacksonville,  Florida,  32209,  United States
Illinois
      Chicago Children's Memorial Hosp, Chicago,  Illinois,  606143394,  United States
Massachusetts
      Children's Hosp of Boston, Boston,  Massachusetts,  021155724,  United States
New York
      Univ of Rochester Med Ctr, Rochester,  New York,  14642,  United States
      Harlem Hosp Ctr, New York,  New York,  10037,  United States
      Bellevue Hosp / New York Univ Med Ctr, New York,  New York,  10016,  United States
      Columbia Presbyterian Med Ctr, New York,  New York,  10032,  United States
      Incarnation Children's Ctr / Columbia Presbyterian Med Ctr, New York,  New York,  10032,  United States
North Carolina
      Duke Univ Med Ctr, Durham,  North Carolina,  277103499,  United States
South Carolina
      Med Univ of South Carolina, Charleston,  South Carolina,  294253312,  United States
Washington
      Children's Hospital & Medical Center / Seattle ACTU, Seattle,  Washington,  981050371,  United States
Puerto Rico
      Univ of Puerto Rico / Univ Children's Hosp AIDS, San Juan,  009365067,  Puerto Rico

Study chairs or principal investigators

Keller MA,  Study Chair
Bryson Y,  Study Chair
Gershon A,  Study Chair

Study ID Numbers:  ACTG 253
Record last reviewed:  December 1997
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00001054
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08