Shedding, Immunogenicity and Safety of Quadrivalent Live Intranasal Influenza Vaccine (QLAIV) in HIV-infected Children and Young Adults

Study Overview
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Brief Summary
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The goal of this study is to determine if there is a difference in shedding (primary objective) and in immunogenicity and safety (secondary objectives) between HIV-positive and HIV-negative children and young adults who are receiving the quadrivalent live-attenuated influenza vaccine (QLAIV).

Detailed Description
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QLAIV is an intranasal vaccine that works by using 4 different attenuated strains of influenza virus that will replicate in the nose and stimulate an immune response in recipients that should protect them if they are infected with one of those strains of influenza in the future. A couple of studies have shown an increase in duration that the viruses remain in the nose in immunocompromised people. Those studies were done using the trivalent vaccine, so the investigators would like to evaluate the quadrivalent vaccine, and there is still a need for additional data to help understand the duration of shedding. If shedding is prolonged in HIV-infected children and young adults, it would be important to know for contacts of those individuals who are very immunocompromised. Shedding will be measured by looking for influenza RNA in nasopharyngeal swabs taken at baseline, 2-5 days, 7-10 days and 14-21 days after the intranasal immunization. The live-attenuated influenza vaccines have been shown to have increased effectiveness in children and they stimulate the immune system in a different way than the inactivated influenza vaccines (TIV or QIV). In this study, the investigators will have the opportunity to compare the immunogenicity of QLAIV, measured at baseline and 14-21 days post-vaccination, in HIV-infected and uninfected children, adolescents and young adults. Although prior studies of LAIV in HIV-infected and other immunocompromised children and adults have not shown any increase in serious adverse events, safety will be actively monitored for the first 30-45 days through a study-specific questionnaire administered at each clinic or phone visit and by asking the subjects to keep a diary of side effects. Safety will be monitored passively throughout the course of the study.

Official Title
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Shedding, Immunogenicity and Safety of Quadrivalent Live Intranasal Influenza Vaccine (QLAIV) in HIV-infected Children and Young Adults

Conditions
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Human Immunodeficiency Virus (HIV)

Intervention / Treatment
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* Biological: Quadrivalent Live Attenuated Influenza Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 2-25 Only supposed to get one dose of vaccine for upcoming influenza season No viral respiratory symptoms at time of immunization HIV-infected group: must have: HIV-infection documented by 2 tests such as positive serology, positive HIV DNA or positive HIV RNA; must thave a CD4>25% or 500, or must have CD4>15% or 200 and be on HAART Healthy controls: no major medical problems affecting the immune system Recruited among: HIV-unifected clients of the Children's Immunodeficiency Program(CHIP), Children's Hospital Colorado Child Health Clinic and Adolescent Clinics. Exclusion Criteria: History of: reactive airway disease, recurrent wheezing, or asthma Active wheezing at time of immunization On any antiviral agents active against influenza (amantadien/rimantadine, zanamavir, oseltamivir) at time of immunization or planned over 21 days of shedding collection Receipt of IVIG within 3 months prior to enrollment Plan to receive IVIG during the 4 weeks after immunization Moderate to severely immunocompromised individual living in the home Pregnant Breastfeeding Plan to start immunosupressive medications or stop HAART over the 4 weeks following immmunization Temperature > 100F or 37.8C Rhinorrhea or cough not related to allergies at the time of immunization History of fungal sinusitis History of Guillain-Barre Syndrome Current on antibiotics Currently taking aspirin On an investigational drug at the time of immunization or planned over the 28 days of shedding collection On any experimental medication at time of immunization or planned over 21 days of shedding collection

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: QLAIV, HIV-infected<br>QLAIV administered to HIV-infected individuals 2 to 25 yoa | Biological: Quadrivalent Live Attenuated Influenza Vaccine<br> <br> * Other names: QLAIV;|
| Active Comparator: QLAIV, HIV-uninfected<br>QLAIV administered to HIV-uninfected individuals 2 to 25 yoa | Biological: Quadrivalent Live Attenuated Influenza Vaccine<br> <br> * Other names: QLAIV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Shedding for at Least One of the Influenza Strains Included in the QLAIV in the First 21 Days After Vaccine Administration Days in HIV-positive and Control Groups. | Measure PCR positivity for any of the influenza subtypes included in QLAIV between baseline (day 0) and the last study visit at 14-21 days after vaccine. Compare number of participants with PCR positivity for any of the vaccine-strain influenza virus strains in each patient group. | 21 days | 
| Number of Participants With Shedding for at Least One of the Influenza Strains Included in the QLAIV Vaccine at Each of the 4 Study Visits, Days 0 (Baseline), 2-5, 7-10, and 14-21 in HIV-positive and Control Groups. | Measure PCR positivity for any of the influenza subtypes included in QLAIV at visit 1 (day 0), visit 2 (days 2-5), visit 3 (days 7-10) and visit 4 (days 14-21). Compare number of participants with shedding for any subtype in each patient group. (The study was powered based on the 7-10 day data.) | day 0-21 post-vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events Within 14 Days After Vaccination | The investigators will compare the number of adverse events (AE) reported by AE category within 14 days after vaccination as reported by each participant. Data will reflect whether a participant ever reported the AE, and not the number of times the AE was reported. | 14 days after vaccination for AEs; up to 30 days for unscheduled visits | 
| Number of Participants Reaching Seroprotection (HAI ≥ 40) Within the HIV-positive and Control Groups. | The investigators will measure hemagglutinin inhibition (HAI) on blood samples #2 (14-21 days after vaccination) for all participants. The investigators will also compare the number of participants reaching HAI ≥ 40 for each virus sub-type contained in the vaccine. | 14-21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Shedding, Immunogenicity, Safety, HIV infected, Children, Young adults