Use of a Varicella-Zoster Virus (VZV) Vaccine to Prevent Shingles in HIV-Infected Children Who Have Already Had Chickenpox
Condition: HIV Infections; Chickenpox
MeSH terms: Chickenpox; Herpes Zoster
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to see if the varicella-zoster virus (VZV) vaccine will be safe
      and if it can help prevent shingles in HIV-infected children who have already had chickenpox.

      VZV is the virus that causes chickenpox. If this virus is reactivated in the body, it can
      also cause shingles. Shingles is common in children with HIV who have had chickenpox,
      although it is usually not life-threatening. The VZV vaccine used in this study may be able
      to prevent HIV-positive children who have had chickenpox from developing shingles.
    

Detailed description: 
      Varicella (chickenpox) results from primary infection with VZV. Varicella, a common and
      usually benign illness in normal children, is more severe in HIV-infected children and may
      result in other conditions such as HZ (shingles). HZ is due to reactivation of latent VZV
      acquired during varicella and is common in HIV-infected children who have had natural
      varicella. While HZ is not likely to be life-threatening in these children, it does cause
      considerable morbidity and interferes with quality of life. Use of a live-attenuated VZV
      vaccine may be able to boost immunity in these children.

      Two immunologic cohorts are enrolled. Cohort A includes children with a CD4 cell percentage
      greater than or equal to 20 percent that has been documented as stable for at least the 6
      months prior to the time varicella developed (confirmed by a minimum of 2 tests) and a CD4
      cell percentage greater than [AS PER AMENDMENT 10/27/99: or equal to] 15 percent that has
      been documented as stable for at least the 6 months prior to enrollment (confirmed by a
      minimum of 2 tests). Cohort B includes children with a CD4 cell percentage greater than or
      equal to 10 percent and less than 15 percent that has been documented as stable for at least
      the 6 months prior to the time varicella developed and stable for at least the 6 months prior
      to enrollment (confirmed by a minimum of 2 tests). [AS PER AMENDMENT 4/20/01: Cohort B
      includes children who have a CD4 cell percentage less than 15% documented by a minimum of 1
      but preferably 2 tests within 1 year of onset of varicella (i.e., within 1 year before to 1
      year after varicella) and a CD4 cell percentage greater than or equal to 15% documented by a
      minimum of 2 tests at the time of enrollment.] A pilot study precedes the full study. [AS PER
      AMENDMENT 10/27/99: The pilot study for Cohort A precedes the full study for Cohort A and the
      pilot study for Cohort B. The pilot study for Cohort B precedes the full study for Cohort B.]
      The pilot study includes 10 children from each cohort who receive live-attenuated VZV at
      Weeks 0 and 8. If 3 pilot-study patients in a cohort meet a toxicity endpoint related to the
      vaccine, the dose regimen has failed the safety criteria for that cohort. [AS PER AMENDMENT
      10/27/99: If 3 children in the pilot study for Cohort A meet a toxicity endpoint deemed to be
      related to the vaccine, the dose regimen has failed safety criteria for both cohorts. If 3
      children in the pilot phase of Cohort B meet a toxicity endpoint deemed related to the
      vaccine, the dose regimen has failed the safety criteria for Cohort B.] If, at 12 weeks after
      immunization, at least 5 pilot-study patients in a cohort respond and the safety profile is
      deemed adequate, the pilot study extends into a full study with the immunization of an
      additional 20 patients from that cohort. [AS PER AMENDMENT 10/27/99: If, at Week 12, at least
      5 pilot-study patients in Cohort A meet immunologic criteria and the safety profile is deemed
      adequate, then the full study for Cohort A and the pilot study for Cohort B opens. If the
      same immunologic and safety criteria are met for the pilot study for Cohort B, then the full
      study for Cohort B opens.] If either cohort shows an inadequate immunologic response or
      safety profile, the study team reviews the results to determine if another regimen should be
      considered. In the full study, patients receive 2 immunizations, at Weeks 0 and 8. Varicella
      antibody titers and in vitro responder cell frequency (RCF) assays are measured at Weeks 0,
      4, 8, 12, 24, 52, 78, and 104. Symptoms, HIV progression, and VZV presence are monitored
      throughout the study.
    

Intervention name(s): Varicella Virus Vaccine (Live)
Intervention type(s): Biological
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Antibodies, Viral; Chickenpox; Chickenpox Vaccine