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

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).

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus (HIV)
• Intervention / Treatment: Biological: Quadrivalent Live Attenuated Influenza Vaccine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80045
      • University of Colorado Denver

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: QLAIV, HIV-infected; QLAIV administered to HIV-infected individuals 2 to 25 yoa	Biological: Quadrivalent Live Attenuated Influenza Vaccine; Other Names: FluMist Quadrivalent; QLAIV
Active Comparator: QLAIV, HIV-uninfected; QLAIV administered to HIV-uninfected individuals 2 to 25 yoa	Biological: Quadrivalent Live Attenuated Influenza Vaccine; Other Names: FluMist Quadrivalent; QLAIV

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With PCR-diagnosed Influenza and Clinically-diagnosed Influenza Like Illness.	Compare numbers of participants with influenza diagnosed by PCR and with clinically-diagnosed influenza between the two groups. Data was taken from Influenza Infection Questionnaires #1 and #2. The last questionnaire (#2) was administered between May 15 and June 10, 2014 (after the vaccine). Data is reported as PCR-confirmed influenza and clinically-diagnosed influenza (subject told had influenza without confirmatory testing).	up to 11 months post-vaccination

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: MedImmune LLC
• Investigators: Principal Investigator: Adriana Weinberg, MD, University of Colorado, Denver; Study Chair: Myron Levin, MD, University of Colorado, Denver; Study Director: Donna Curtis, MD,MPH, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2013
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: June 15, 2015
• First Submitted That Met QC Criteria: June 15, 2015
• First Posted (Estimate): June 18, 2015

Study Record Updates

• Last Update Posted (Actual): November 20, 2017
• Last Update Submitted That Met QC Criteria: October 17, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Safety; Children; Immunogenicity; Young adults; HIV infected; Shedding
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: 13-1752