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.

Condition	Treatment or Intervention	Phase
HIV Infections Chickenpox	Vaccine: Varicella Virus Vaccine (Live)	Phase I

Further Study Details: 

Expected Total Enrollment:  60

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.

Ages Eligible for Study:  2 Years   -   18 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Children may be eligible for this study if they:

• Are 2 to 18 years old (need consent of parent or guardian if under 18).
• Are HIV-positive.
• Are VZV-positive.
• Have a CD4 cell percentage of at least 15 percent at the time of enrollment. (This criterion reflects a change from the original CD4 cell percentage.)
• Have been receiving stable anti-HIV therapy for at least 3 months, with no plans to change these medications.
• Had chickenpox at least 6 months prior to study entry.
• Were at least 1 year old when they had chickenpox.
• Agree to use a barrier method of birth control (such as a condom) during the study.

Exclusion Criteria

Children will not be eligible for this study if they:

• Have an active infection within 72 hours of study entry.
• Have a fever over 101 F within 72 hours of study entry.
• Were exposed to chickenpox or shingles within 4 weeks prior to study entry.
• Have ever had shingles.
• Live with someone who has HIV, or who has a weak immune system, and has never had chickenpox.
• Have taken certain medications that affect the immune system, such as steroids, within 30 days of study entry.
• Have taken or are planning to take VZIG or IVIG within 1 year prior to or 2 months after a study vaccination.
• Are allergic to the vaccine, or to neomycin.
• Have received or expect to receive another vaccine within 30 days prior to or 30 days after a study vaccination.
• Have ever received a chickenpox vaccine.
• Are taking aspirin or expect to use aspirin 6 weeks after a study vaccination.
• Have taken or plan to take any anti-herpes drugs within 1 week before or 3 weeks after a study vaccination.
• Have received or plan to receive a blood transfusion within 1 year before or 2 months after a study vaccination.
• Have certain medical problems that would interfere with the study.
• Are pregnant or breast-feeding.

Alabama
      Univ of Alabama at Birmingham - Pediatric, Birmingham,  Alabama,  35233,  United States
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
      Children's Hosp of Oakland, Oakland,  California,  946091809,  United States
      UCLA Med Ctr / Pediatric, Los Angeles,  California,  900951752,  United States
      Long Beach Memorial (Pediatric), Long Beach,  California,  90801,  United States
      Los Angeles County - USC Med Ctr, Los Angeles,  California,  90033,  United States
Colorado
      Children's Hosp of Denver, Denver,  Colorado,  802181088,  United States
Connecticut
      Yale Univ Med School, New Haven,  Connecticut,  06504,  United States
      Connecticut Children's Med Ctr, Farmington,  Connecticut,  060303805,  United States
District of Columbia
      Howard Univ Hosp, Washington,  District of Columbia,  20060,  United States
      Children's Hosp of Washington DC, Washington,  District of Columbia,  200102916,  United States
Florida
      Univ of Miami (Pediatric), Miami,  Florida,  33161,  United States
      Univ of Florida Health Science Ctr / Pediatrics, Jacksonville,  Florida,  32209,  United States
      North Broward Hosp District, Fort Lauderdale,  Florida,  33311,  United States
      Sacred Heart Children's Hosp / CMS of Florida, Pensacola,  Florida,  32503,  United States
Georgia
      Emory Univ Hosp / Pediatrics, Atlanta,  Georgia,  30306,  United States
      Med College of Georgia, Augusta,  Georgia,  30912,  United States
Illinois
      Chicago Children's Memorial Hosp, Chicago,  Illinois,  606143394,  United States
      Cook County Hosp, Chicago,  Illinois,  60612,  United States
      Univ of Illinois College of Medicine / Pediatrics, Chicago,  Illinois,  60612,  United States
      Univ of Chicago Children's Hosp, Chicago,  Illinois,  606371470,  United States
Louisiana
      Tulane Univ / Charity Hosp of New Orleans, New Orleans,  Louisiana,  701122699,  United States
Maryland
      Johns Hopkins Hosp - Pediatric, Baltimore,  Maryland,  212874933,  United States
Massachusetts
      Children's Hosp of Boston, Boston,  Massachusetts,  021155724,  United States
      Boston City Hosp / Pediatrics, Boston,  Massachusetts,  02118,  United States
      Baystate Med Ctr of Springfield, Springfield,  Massachusetts,  01199,  United States
      Univ of Massachusetts Med School, Worcester,  Massachusetts,  016550001,  United States
Michigan
      Children's Hosp of Michigan, Detroit,  Michigan,  48201,  United States
New Jersey
      Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark,  New Jersey,  071032714,  United States
      UMDNJ - Robert Wood Johnson Med School / Pediatrics, New Brunswick,  New Jersey,  089030019,  United States
      Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl, Newark,  New Jersey,  07103,  United States
      Cooper Hosp - Univ Med Ctr / UMDNJ - New Jersey Med Schl, Camden,  New Jersey,  08103,  United States
New York
      Harlem Hosp Ctr, New York,  New York,  10037,  United States
      SUNY - Brooklyn, Brooklyn,  New York,  11203,  United States
      North Shore Univ Hosp, Great Neck,  New York,  11021,  United States
      Schneider Children's Hosp, New Hyde Park,  New York,  11040,  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
      Children's Hosp at Albany Med Ctr, Albany,  New York,  12208,  United States
      SUNY Health Sciences Ctr at Syracuse / Pediatrics, Syracuse,  New York,  13210,  United States
      Bronx Lebanon Hosp Ctr, Bronx,  New York,  10457,  United States
      Incarnation Children's Ctr / Columbia Presbyterian Med Ctr, New York,  New York,  10032,  United States
      State Univ of New York at Stony Brook, Stony Brook,  New York,  117948111,  United States
      Univ of Rochester Med Ctr, Rochester,  New York,  146420001,  United States
      New York Hosp - Cornell Med Ctr, New York,  New York,  10021,  United States
North Carolina
      Duke Univ Med Ctr, Durham,  North Carolina,  277103499,  United States
Pennsylvania
      Children's Hosp of Philadelphia, Philadelphia,  Pennsylvania,  191044318,  United States
      Saint Christopher's Hosp for Children, Philadelphia,  Pennsylvania,  191341095,  United States
South Carolina
      Med Univ of South Carolina, Charleston,  South Carolina,  294253312,  United States
Tennessee
      Saint Jude Children's Research Hosp of Memphis, Memphis,  Tennessee,  381052794,  United States
      Vanderbilt Univ Med Ctr, Nashville,  Tennessee,  372322581,  United States
Texas
      Texas Children's Hosp / Baylor Univ, Houston,  Texas,  77030,  United States
Virginia
      Med College of Virginia, Richmond,  Virginia,  23219,  United States
Washington
      Children's Hospital & Medical Center / Seattle ACTU, Seattle,  Washington,  981050371,  United States
Puerto Rico
      San Juan City Hosp, San Juan,  009367344,  Puerto Rico
      Univ of Puerto Rico / Univ Children's Hosp AIDS, San Juan,  009365067,  Puerto Rico

Study chairs or principal investigators

Anne Gershon,  Study Chair

Study ID Numbers:  ACTG 391; PACTG 391
Record last reviewed:  January 2005
Last Updated:  April 7, 2005
Record first received:  January 17, 2000
ClinicalTrials.gov Identifier:  NCT00001125
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08