Clinical trial NCT01484522: Laboratory Study of Licensed H1N1 Influenza Vaccines in HIV-1 Perinatally Infected Children and Youth
Official title: A Laboratory Study to Assess the Immunogenicity of Three Licensed Influenza A (H1N1) 2009 Monovalent Vaccines in HIV-1 Perinatally Infected Children and Youth
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV-1 Infection
H1N1
Influenza
Flu
Keywords: Influenza
Perinatal
immunogenicity
Monovalent vaccine
Children
Youth
H1N1
Adolescent
Flu
Lead sponsor: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Sponsor class: NETWORK
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2011-12-02
Enrollment: 149
Sex: ALL
Minimum age (years): 6
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV-1 perinatally infected children and youth 6 months to 25 years of age.

For inclusion into the study, if perinatal acquisition of HIV infection cannot be confirmed based on the child's medical record, it is acceptable to enroll the child if the investigator's assessment is that the most likely route of infection was perinatal.

Brief summary: The purpose of this research study is to evaluate the immune response to the H1N1 influenza or "flu" vaccine. The "immune response" is how your body recognizes and defends itself against bacteria, viruses, and substances that may be harmful to the body.

HIV-1 infected children typically respond more poorly to vaccines compared to uninfected, healthy children and so this study hopes to learn whether or not the body will successfully produce enough antibodies (proteins that fight infection) that will prevent or fight the H1N1 flu virus. There is no information yet on the safety or immune response to this vaccine in children infected with HIV.

Detailed description: HIV-infected children typically respond poorer to vaccines as compared to normal children. The FDA has currently approved several Influenza A 2009 monovalent vaccines to be used in children and adults. However, little data is available in perinatally infected youth. Therefore, knowledge of the immunogenicity of several of the licensed Influenza A 2009 monovalent vaccines in HIV-infected children and youth is critically important to address the health care needs of this vulnerable population. Efforts are currently underway to evaluate Influenza A 2009 monovalent vaccines in healthy children as well as other populations. This study will assess the immune response following receipt of three Influenza A monovalent vaccines in HIV-1 infected children and youth. Protection of HIV-1 infected children and youth from 2009 H1N1 Influenza A will require knowledge of immunogenicity of these new products in this population. The 2009 (H1N1) Influenza A virus is likely to infect a significant proportion of HIV-1 infected children and youth. Immunogenicity of licensed and commercially available Influenza A 2009 monovalent vaccines must be established in HIV-1 infected children in order to assure that this population is protected. Lack of a protective immune response would support the need for additional measures to protect this high risk population.

Eligibility criteria: Inclusion Criteria:

1. Children and youth 6 months to \<25 years of age at study entry.
2. HIV infection, defined as positive test results obtained from 2 different samples. Tests may include two of the same type OR two different types of tests listed below, as long as there are positive test results obtained from 2 different samples:

   * HIV-1 antibody (ELISA + WB), obtained at age \>18 months
   * HIV-1 culture, any age
   * HIV-1 DNA PCR, any age
   * HIV-1 RNA PCR \>10,000 copies/mL, any age
   * Neutralizable HIV-1 p24 antigen obtained \>28 days of age
3. In the opinion of the investigator, the route of HIV-1 transmission is perinatally acquired.
4. Parent or legal guardian, youth of legal age, or subjects who are emancipated minors, who are willing and able to provide signed informed consent.
5. Planned receipt of one of the following FDA licensed Influenza A (H1N1) 2009 Monovalent Vaccines within 24 hours following study entry:

   * Group A: Influenza A (H1N1) 2009 Monovalent Vaccine (MedImmune FluMist®)
   * Group B: Influenza A (H1N1) 2009 Monovalent Vaccine (Novartis Fluvirin®)
   * Group C: Influenza A (H1N1) 2009 Monovalent Vaccine (Sanofi Pasteur Fluzone®) \*OR has received one of the above vaccines within 4 hours prior to study entry.

Exclusion Criteria:

1. Has a history of probable or proven pandemic 2009 H1N1 Influenza A virus infection prior to study entry.
2. Has received seasonal FluMist vaccine within 2 weeks prior to study entry.
3. Has received any 2009 H1N1 vaccines prior to the day of entry.
4. Has received any immunoglobulin or blood products within 3 months prior to study entry.
5. Has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the study.
6. Use of anti-cancer chemotherapy or radiation therapy within the 36 months preceding study entry, or has immunosuppression as a result of an underlying illness or treatment (other than HIV-1 infection).
7. Has an active neoplastic disease.
8. Long term use of glucocorticoids, including oral or parenteral prednisone or equivalent (more than or equal to 2 mg/kg per day or more than or equal to 20 mg total dose) for more than 2 weeks in the past 6 months, or high-dose inhaled steroids (\>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (nasal and topical steroids are allowed).

Primary outcomes:
measure: The short term immune response following immunization with a licensed Influenza A (H1N1) 2009 Monovalent Vaccine administered as a single dose in perinatally HIV-1 infected children and youth aged >10 to <25 years.
timeFrame: 8 months
measure: The short term immune response following second immunization with a licensed Influenza A (H1N1) 2009 Monovalent Vaccine in perinatally HIV-1 infected children > 6 months to < 10 years of age.
timeFrame: 8 months
Secondary outcomes:
measure: The immune response following first immunization with a licensed Influenza A (H1N1) 2009 monovalent vaccine in children aged > 6 months to < 10 years of age.
timeFrame: 8 months
measure: Persistence of antibody responses 7 months after receipt of the first immunization with a licensed Influenza A (H1N1) 2009 monovalent vaccine.
timeFrame: 8 months
measure: Immune responses with CD4+ cell count and timing of seasonal trivalent influenza vaccine (TIV).
timeFrame: 8 months
measure: Immune responses with CD4 percent and timing of seasonal trivalent influenza vaccine (TIV).
timeFrame: 8 months
measure: Immune responses with ARV use and timing of seasonal trivalent influenza vaccine (TIV).
timeFrame: 8 months
measure: Immune responses with plasma HIV-1 RNA concentration and timing of seasonal trivalent influenza vaccine (TIV).
timeFrame: 8 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ. of Alabama Birmingham NICHD CRS (5096)
state: Alabama
city: Los Angeles
country: United States
facility: USC/Los Angeles County Medical Center NICHD CRS
state: California
city: San Francisco
country: United States
facility: University of California San Francisco NICHD CRS (5091)
state: California
city: Aurora
country: United States
facility: University of Colorado Denver NICHD CRS (5052)
state: Colorado
city: Miami
country: United States
facility: University of Miami Pediatric/Perinatal HIV/AIDS (4201)
state: Florida
city: Tampa
country: United States
facility: University of South Florida Tampa (5018)
state: Florida
city: Chicago
country: United States
facility: Chicago Children's CRS (4001)
state: Illinois
city: Boston
country: United States
facility: Children's Hospital of Boston NICHD CRS (5009)
state: Massachusetts
city: Worcester
country: United States
facility: WNE Maternal Pediatric Adolescent AIDS CRS
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University/Children's Hospital of Michigan NICHD CRS
state: Michigan
city: Newark
country: United States
facility: NJ Med School CRS (2802)
state: New Jersey
city: Bronx
country: United States
facility: Jacobi Medical Center Bronx (5013)
state: New York
city: New York
country: United States
facility: New York University NY (5012)
state: New York
city: Stony Brook
country: United States
facility: SUNY Stony Brook (5040)
state: New York
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia (6701)
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude/UTHSC CRS (6501)
state: Tennessee
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico Pediatric HIV/AIDS Research (6601)
Study officials:
affiliation: St. Jude Childrens Research Hospital
name: Patricia M. Flynn, M.D.
role: STUDY_CHAIR
References: