Human Immunodeficiency Virus (HIV)
Conditions
Keywords
Shedding, Immunogenicity, Safety, HIV infected, Children, Young adults
Brief summary
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
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.
Interventions
BIOLOGICALQuadrivalent Live Attenuated Influenza Vaccine
Sponsors
MedImmune LLC
University of Colorado, Denver
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Masking description
Open label
Eligibility
Sex/Gender
ALL
Age
2 Years to 25 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 21 days | 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. |
| 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. | day 0-21 post-vaccine | 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.) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events Within 14 Days After Vaccination | 14 days after vaccination for AEs; up to 30 days for unscheduled visits | 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. |
| Number of Participants Reaching Seroprotection (HAI ≥ 40) Within the HIV-positive and Control Groups. | 14-21 days | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With PCR-diagnosed Influenza and Clinically-diagnosed Influenza Like Illness. | up to 11 months post-vaccination | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| QLAIV, HIV-infected QLAIV administered to HIV-infected individuals 2 to 25 yoa
Quadrivalent Live Attenuated Influenza Vaccine | 45 |
| QLAIV, HIV-uninfected QLAIV administered to HIV-uninfected individuals 2 to 25 yoa
Quadrivalent Live Attenuated Influenza Vaccine | 56 |
| Total | 101 |
Baseline characteristics
| Characteristic | QLAIV, HIV-infected | QLAIV, HIV-uninfected | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 10 Participants | 22 Participants | 32 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants | 34 Participants | 69 Participants |
| Age, Continuous | 18 years | 10 years | 12 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 13 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants | 43 Participants | 81 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 9 Participants | 30 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) White | 19 Participants | 45 Participants | 64 Participants |
| Region of Enrollment United States | 45 participants | 56 participants | 101 participants |
| Sex: Female, Male Female | 17 Participants | 26 Participants | 43 Participants |
| Sex: Female, Male Male | 28 Participants | 30 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 55 |
| other Total, other adverse events | 17 / 45 | 16 / 55 |
| serious Total, serious adverse events | 1 / 45 | 0 / 55 |
Outcome results
Primary
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.
Time frame: 21 days
Population: HIV-infected and uninfected recipients of QLAIV; one HIV-uninfected subject was lost-to-follow-up after the first follow-up visit following vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| QLAIV, HIV-infected | 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. | Baseline analysis for virus (before vaccine) | 0 Participants |
| QLAIV, HIV-infected | 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. | Shed any virus anytime up to 21 days post-vaccine | 30 Participants |
| QLAIV, HIV-uninfected | 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. | Baseline analysis for virus (before vaccine) | 0 Participants |
| QLAIV, HIV-uninfected | 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. | Shed any virus anytime up to 21 days post-vaccine | 28 Participants |
Primary
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.)
Time frame: day 0-21 post-vaccine
Population: Subjects with data for any of the visits
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| QLAIV, HIV-infected | 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. | Visit 1, day 0 | 0 Participants |
| QLAIV, HIV-infected | 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. | Visit 2, days 2-5 | 30 Participants |
| QLAIV, HIV-infected | 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. | Visit 3, days 7-10 | 13 Participants |
| QLAIV, HIV-infected | 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. | Visit 4, days 14-21 | 1 Participants |
| QLAIV, HIV-uninfected | 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. | Visit 4, days 14-21 | 0 Participants |
| QLAIV, HIV-uninfected | 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. | Visit 1, day 0 | 0 Participants |
| QLAIV, HIV-uninfected | 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. | Visit 3, days 7-10 | 11 Participants |
| QLAIV, HIV-uninfected | 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. | Visit 2, days 2-5 | 27 Participants |
Secondary
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.
Time frame: 14-21 days
Population: The total number of participants analyzed reflect the number of subjects for whom there was a blood sample from the 4th visit at day 14-21.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| QLAIV, HIV-infected | Number of Participants Reaching Seroprotection (HAI ≥ 40) Within the HIV-positive and Control Groups. | H1N1 | 35 Participants |
| QLAIV, HIV-infected | Number of Participants Reaching Seroprotection (HAI ≥ 40) Within the HIV-positive and Control Groups. | H3N2 | 27 Participants |
| QLAIV, HIV-infected | Number of Participants Reaching Seroprotection (HAI ≥ 40) Within the HIV-positive and Control Groups. | B-Victoria | 7 Participants |
| QLAIV, HIV-infected | Number of Participants Reaching Seroprotection (HAI ≥ 40) Within the HIV-positive and Control Groups. | B-Yamagata | 7 Participants |
| QLAIV, HIV-uninfected | Number of Participants Reaching Seroprotection (HAI ≥ 40) Within the HIV-positive and Control Groups. | B-Yamagata | 7 Participants |
| QLAIV, HIV-uninfected | Number of Participants Reaching Seroprotection (HAI ≥ 40) Within the HIV-positive and Control Groups. | H1N1 | 35 Participants |
| QLAIV, HIV-uninfected | Number of Participants Reaching Seroprotection (HAI ≥ 40) Within the HIV-positive and Control Groups. | B-Victoria | 4 Participants |
| QLAIV, HIV-uninfected | Number of Participants Reaching Seroprotection (HAI ≥ 40) Within the HIV-positive and Control Groups. | H3N2 | 35 Participants |
Secondary
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.
Time frame: 14 days after vaccination for AEs; up to 30 days for unscheduled visits
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| QLAIV, HIV-infected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Temperature >100F | 0 Participants |
| QLAIV, HIV-infected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Runny nose | 17 Participants |
| QLAIV, HIV-infected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Nasal congestion | 17 Participants |
| QLAIV, HIV-infected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Sore throat | 6 Participants |
| QLAIV, HIV-infected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Headache | 8 Participants |
| QLAIV, HIV-infected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Muscle aches | 8 Participants |
| QLAIV, HIV-infected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Decrease in energy | 11 Participants |
| QLAIV, HIV-infected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Decreased appetite | 6 Participants |
| QLAIV, HIV-infected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Any other symptom | 9 Participants |
| QLAIV, HIV-infected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Unscheduled medical visits in 30 days post vaccine | 2 Participants |
| QLAIV, HIV-uninfected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Decreased appetite | 2 Participants |
| QLAIV, HIV-uninfected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Temperature >100F | 1 Participants |
| QLAIV, HIV-uninfected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Muscle aches | 2 Participants |
| QLAIV, HIV-uninfected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Runny nose | 16 Participants |
| QLAIV, HIV-uninfected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Unscheduled medical visits in 30 days post vaccine | 10 Participants |
| QLAIV, HIV-uninfected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Nasal congestion | 16 Participants |
| QLAIV, HIV-uninfected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Decrease in energy | 3 Participants |
| QLAIV, HIV-uninfected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Sore throat | 5 Participants |
| QLAIV, HIV-uninfected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Any other symptom | 5 Participants |
| QLAIV, HIV-uninfected | Number of Participants With Adverse Events Within 14 Days After Vaccination | Headache | 8 Participants |
p-value: <0.05Chi-squared, Corrected
Other Pre-specified
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).
Time frame: up to 11 months post-vaccination
Population: Number of participants analyzed reflects the number of subjects who participated in the end-of-season interview.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| QLAIV, HIV-infected | Number of Participants With PCR-diagnosed Influenza and Clinically-diagnosed Influenza Like Illness. | PCR-confirmed influenza | 0 Participants |
| QLAIV, HIV-infected | Number of Participants With PCR-diagnosed Influenza and Clinically-diagnosed Influenza Like Illness. | clinically-diagnosed influenza | 2 Participants |
| QLAIV, HIV-uninfected | Number of Participants With PCR-diagnosed Influenza and Clinically-diagnosed Influenza Like Illness. | PCR-confirmed influenza | 1 Participants |
| QLAIV, HIV-uninfected | Number of Participants With PCR-diagnosed Influenza and Clinically-diagnosed Influenza Like Illness. | clinically-diagnosed influenza | 2 Participants |