Clinical trial NCT00091702: Safety of and Immune Response to Two Influenza Vaccines in HIV Infected Children and Adolescents
Official title: A Phase I/II Randomized Trial of the Safety and Immunogenicity of Cold Adapted Influenza Vaccine (FluMist) in HIV-Infected Children and Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV Infections
Influenza
Keywords: FluMist
Influenza Vaccine
Adolescent
Treatment Experienced
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2004-09-20
Enrollment: 300
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to compare two flu vaccines to determine their safety and ability to stimulate an immune response in HIV infected children and adolescents. This study will also determine how often and how long people who receive a vaccine are able to spread flu vaccine virus to other people.

Detailed description: Influenza virus infections are common among children, particularly during the winter season. The infections are often mild, but more serious cases can cause a number of complications, including respiratory illnesses and bacterial infections. HIV infected children may have an increased risk for developing influenza-related bacterial complications, and influenza infections among this population may lead to more rapid disease progression. The current standard of care for HIV infected children is vaccination with an inactivated influenza vaccine (IAIV). However, IAIV is limited in its ability to stimulate the immune systems of HIV infected children with advanced disease. FluMist, a cold-adapted live attenuated influenza vaccine, is both immunogenic and effective in HIV infected children; unfortunately, FluMist is associated with viral shedding, a period of time when the influenza virus used to produce the vaccine may be transmitted to other people. This study will compare the safety and immunogenicity of IAIV and FluMist in HIV infected children and adolescents. This study will also determine the prevalence and duration of FluMist viral shedding in HIV infected children and adolescents who have received the vaccination.

Participants in this study will be randomly assigned to one of two arms. Arm A participants will receive FluMist; Arm B participants will receive IAIV. A single immunization will occur on Day 0 of the study. Arm A participants will have study visits on Days 3, 14, and 28 or home visits on Days 3 and 14. Participants in Arm B will have a study visit on Day 28. A physical exam will be performed at the initial study visit; blood will be collected at study start and at each visit thereafter. Phone calls will be made to participants throughout the study. All participants will have a final study visit after 6 months.

Eligibility criteria: Inclusion Criteria:

* HIV infected
* Stable highly active antiretroviral therapy (HAART) regimen for at least 16 weeks with no changes in therapy anticipated
* Meet certain CD4 cell count and CD4% requirements
* Viral load of less than 60,000 copies/ml within 60 days prior to study start
* Received inactivated influenza vaccine (IAIV) in at least one of the past 2 years
* Written informed consent of parent or legal guardian
* Availability of parent or legal guardian to be contacted by phone

Exclusion Criteria:

* Immunosuppressive or immunomodulatory therapy within 60 days prior to immunization or immunological testing
* Aspirin or aspirin-containing therapy at the time of vaccination or planned within 42 days after immunization
* History of hypersensitivity to any component of IAIV or FluMist
* History of Guillain-Barre syndrome
* Receipt of any inactivated vaccine within 14 days prior to the study vaccination
* Receipt of any live vaccine within 30 days prior to the study vaccination
* Plans to receive any vaccine within the 30 days following the vaccination
* Receipt of any additional influenza vaccine for the duration of the study
* Prophylactic use of drugs with anti-influenza activity
* Moderate chronic pulmonary disease, obstructive or restrictive
* Cardiopulmonary disease affecting normal childhood activity
* Medically-diagnosed wheezing, bronchodilator use, or steroid use within the past 42 days
* Medical illness associated with suppression of T-cell immunity
* Pregnancy, breast-feeding, or unwillingness to use acceptable methods of contraception for 3 months following vaccination
* Severely immunosuppressed household member
* Receipt of any blood products within 3 months prior to vaccination or expected receipt during the study, including the 6-month follow-up period
* Significant fever or illness within 72 hours prior to vaccination
* Any other condition that would interfere with the study

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB, Dept. of Ped., Div. of Infectious Diseases
state: Alabama
city: Mobile
country: United States
facility: Univ. of South Alabama College of Medicine, Southeast Ped. ACTU
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hosp.
state: Arizona
city: Long Beach
country: United States
facility: Long Beach Memorial Med. Ctr., Miller Children's Hosp.
state: California
city: Los Angeles
country: United States
facility: Usc La Nichd Crs
state: California
city: Los Angeles
country: United States
facility: UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
state: California
city: Oakland
country: United States
facility: Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.
state: California
city: Orange
country: United States
facility: Children's Hosp. of Orange County
state: California
city: San Diego
country: United States
facility: UCSD Maternal, Child, and Adolescent HIV CRS
state: California
city: San Francisco
country: United States
facility: UCSF Pediatric AIDS CRS
state: California
city: Torrance
country: United States
facility: Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases
state: California
city: Aurora
country: United States
facility: Univ. of Colorado Denver NICHD CRS
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Med. Ctr.
state: Connecticut
city: New Haven
country: United States
facility: Yale Univ. School of Medicine - Dept. of Peds., Div. of Infectious Disease
state: Connecticut
city: Washington
country: United States
facility: Children's National Med. Ctr. Washington DC NICHD CRS
state: District of Columbia
city: Washington
country: United States
facility: Children's National Med. Ctr., ACTU
state: District of Columbia
city: Washington
country: United States
facility: Howard Univ. Washington DC NICHD CRS
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: South Florida CDC Ft Lauderdale NICHD CRS
state: Florida
city: Fort Lauderdale
country: United States
facility: Children's Diagnostic & Treatment Ctr. of South Florida
state: Florida
city: Gainesville
country: United States
facility: Univ. of Florida College of Medicine-Dept of Peds, Div. of Immunology, Infectious Diseases & Allergy
state: Florida
city: Jacksonville
country: United States
facility: Univ. of Florida Jacksonville NICHD CRS
state: Florida
city: Miami
country: United States
facility: Univ. of Miami Ped. Perinatal HIV/AIDS CRS
state: Florida
city: Tampa
country: United States
facility: USF - Tampa NICHD CRS
state: Florida
city: Augusta
country: United States
facility: Med. College of Georgia School of Medicine, Dept. of Peds., Div. of Infectious Diseases
state: Georgia
city: Columbus
country: United States
facility: Columbus Regional HealthCare System, The Med. Ctr.
state: Georgia
city: Chicago
country: United States
facility: Chicago Children's CRS
state: Illinois
city: Chicago
country: United States
facility: Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program
state: Illinois
city: Chicago
country: United States
facility: Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease
state: Illinois
city: New Orleans
country: United States
facility: Tulane/LSU Maternal/Child CRS
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases
state: Maryland
city: Baltimore
country: United States
facility: Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology
state: Maryland
city: Boston
country: United States
facility: HMS - Children's Hosp. Boston, Div. of Infectious Diseases
state: Massachusetts
city: Boston
country: United States
facility: BMC, Div. of Ped Infectious Diseases
state: Massachusetts
city: Lawrence
country: United States
facility: Lawrence Family Health Ctr., Essex St. Clinic
state: Massachusetts
city: Lowell
country: United States
facility: Lowell Community Health Ctr.
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Health, Baystate Med. Ctr.
state: Massachusetts
city: Worcester
country: United States
facility: WNE Maternal Pediatric Adolescent AIDS CRS
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hospital of Michigan NICHD CRS
state: Michigan
city: Saint Louis
country: United States
facility: Washington Univ. School of Medicine at St. Louis, St. Louis Children's Hosp.
state: Missouri
city: Newark
country: United States
facility: NJ Med. School CRS
state: New Jersey
city: Bronx
country: United States
facility: Bronx-Lebanon Hosp. IMPAACT CRS
state: New York
city: Bronx
country: United States
facility: Jacobi Med. Ctr. Bronx NICHD CRS
state: New York
city: Bronx
country: United States
facility: Jacobi Med. Ctr.
state: New York
city: Brooklyn
country: United States
facility: SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS
state: New York
city: New York
country: United States
facility: Nyu Ny Nichd Crs
state: New York
city: New York
country: United States
facility: Mt. Sinai School of Medicine, Div. of Ped. Infectious Diseases
state: New York
city: New York
country: United States
facility: Harlem Hosp. Ctr. NY NICHD CRS
state: New York
city: New York
country: United States
facility: Columbia IMPAACT CRS
state: New York
city: Rochester
country: United States
facility: Strong Memorial Hospital Rochester NY NICHD CRS
state: New York
city: Stony Brook
country: United States
facility: SUNY Stony Brook NICHD CRS
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Med. Univ., Dept. of Peds.
state: New York
city: Chapel Hill
country: United States
facility: UNC at Chapel Hill School of Medicine - Dept. of Peds., Div. of Immunology & Infectious Diseases
state: North Carolina
city: Durham
country: United States
facility: DUMC Ped. CRS
state: North Carolina
city: Philadelphia
country: United States
facility: The Children's Hosp. of Philadelphia IMPAACT CRS
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude/UTHSC CRS
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Hosp. CRS
state: Texas
city: Norfolk
country: United States
facility: Children's Hosp. of the King's Daughters, Infectious Disease
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital CRS
state: Washington
city: Seattle
country: United States
facility: UW School of Medicine - CHRMC
state: Washington
city: San Juan
country: Puerto Rico
facility: Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp. PR NICHD CRS
Study officials:
affiliation: University of Colorado, Denver
name: Myron J. Levin, MD
role: STUDY_CHAIR
References:
citation: Gunthard HF, Wong JK, Spina CA, Ignacio C, Kwok S, Christopherson C, Hwang J, Haubrich R, Havlir D, Richman DD. Effect of influenza vaccination on viral replication and immune response in persons infected with human immunodeficiency virus receiving potent antiretroviral therapy. J Infect Dis. 2000 Feb;181(2):522-31. doi: 10.1086/315260.
citation: Belshe RB, Mendelman PM, Treanor J, King J, Gruber WC, Piedra P, Bernstein DI, Hayden FG, Kotloff K, Zangwill K, Iacuzio D, Wolff M. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children. N Engl J Med. 1998 May 14;338(20):1405-12. doi: 10.1056/NEJM199805143382002.
citation: King JC Jr, Fast PE, Zangwill KM, Weinberg GA, Wolff M, Yan L, Newman F, Belshe RB, Kovacs A, Deville JG, Jelonek M; HIV Influenza Study Group. Safety, vaccine virus shedding and immunogenicity of trivalent, cold-adapted, live attenuated influenza vaccine administered to human immunodeficiency virus-infected and noninfected children. Pediatr Infect Dis J. 2001 Dec;20(12):1124-31. doi: 10.1097/00006454-200112000-00006.
citation: King JC Jr, Treanor J, Fast PE, Wolff M, Yan L, Iacuzio D, Readmond B, O'Brien D, Mallon K, Highsmith WE, Lambert JS, Belshe RB. Comparison of the safety, vaccine virus shedding, and immunogenicity of influenza virus vaccine, trivalent, types A and B, live cold-adapted, administered to human immunodeficiency virus (HIV)-infected and non-HIV-infected adults. J Infect Dis. 2000 Feb;181(2):725-8. doi: 10.1086/315246.
citation: Weinberg A, Song LY, Walker R, Allende M, Fenton T, Patterson-Bartlett J, Nachman S, Kemble G, Yi TT, Defechereux P, Wara D, Read JS, Levin M; IMPAACT P1057 Team. Anti-influenza serum and mucosal antibody responses after administration of live attenuated or inactivated influenza vaccines to HIV-infected children. J Acquir Immune Defic Syndr. 2010 Oct;55(2):189-96. doi: 10.1097/QAI.0b013e3181e46308.