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The Safety and Effectiveness of Valacyclovir HCl in the Treatment of Herpes Simplex or Varicella/Zoster Infections in HIV-1 Infected Children
This study has been terminated.
First Received: November 2, 1999   Last Updated: June 23, 2005   History of Changes
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator: Glaxo Wellcome
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001054
  Purpose

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

Study Type: Interventional
Study Design: Treatment, Open Label, Pharmacokinetics Study
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 28
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   4 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00001054

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

Publications:
Study ID Numbers: ACTG 253
Study First Received: November 2, 1999
Last Updated: June 23, 2005
ClinicalTrials.gov Identifier: NCT00001054     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Herpes Zoster
AIDS-Related Opportunistic Infections
Herpes Simplex
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
valacyclovir
Chickenpox

Additional relevant MeSH terms:
Communicable Diseases
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Infection
Valacyclovir
Therapeutic Uses
Retroviridae Infections
Herpes Simplex
RNA Virus Infections
Immune System Diseases
Skin Diseases
Acquired Immunodeficiency Syndrome
Chickenpox
Antiviral Agents
Pharmacologic Actions
Immunologic Deficiency Syndromes
Herpesviridae Infections
Virus Diseases
Skin Diseases, Viral
Skin Diseases, Infectious
Acyclovir
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections
DNA Virus Infections

ClinicalTrials.gov processed this record on November 27, 2009