The Safety and Effectiveness of Valacyclovir HCl in the Treatment of Herpes Simplex or Varicella/Zoster Infections in HIV-1 Infected Children

NCT ID: NCT00001054

Last Updated: 2021-11-04

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Completion Date: 2001-01-31

Brief Summary

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.

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.

Conditions

Herpes Simplex; HIV Infections; Chickenpox

Keywords

Herpes Zoster; AIDS-Related Opportunistic Infections; Herpes Simplex; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; valacyclovir; Chickenpox

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Valacyclovir hydrochloride

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 4 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Glaxo Wellcome

INDUSTRY

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Keller MA

Role: STUDY_CHAIR

Bryson Y

Role: STUDY_CHAIR

Gershon A

Role: STUDY_CHAIR

Countries

Puerto Rico; United States

References

von Seidlein L, Gillette SG, Bryson Y, Frederick T, Mascola L, Church J, Brunell P, Kovacs A, Deveikis A, Keller M. Frequent recurrence and persistence of varicella-zoster virus infections in children infected with human immunodeficiency virus type 1. J Pediatr. 1996 Jan;128(1):52-7. doi: 10.1016/s0022-3476(96)70427-4.

Reference Type: BACKGROUND

PMID: 8551421 (View on PubMed)

Cohen JI, Brunell PA, Straus SE, Krause PR. Recent advances in varicella-zoster virus infection. Ann Intern Med. 1999 Jun 1;130(11):922-32. doi: 10.7326/0003-4819-130-11-199906010-00017.

Reference Type: BACKGROUND

PMID: 10375341 (View on PubMed)

Other Identifiers

11230

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 253

Identifier Type: -

Identifier Source: org_study_id