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Safety of and Immune Response to an H1N1 Influenza Virus Vaccine in HIV Infected Children and Youth

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ClinicalTrials.gov Identifier: NCT00992836
Recruitment Status : Completed
First Posted : October 9, 2009
Results First Posted : February 9, 2012
Last Update Posted : December 17, 2014
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Conditions HIV Infections
H1N1 Influenza Virus
Intervention Biological: Influenza A (H1N1) 2009 monovalent vaccine
Enrollment 155
Recruitment Details Participants were enrolled from 37 sites between October 14, 2009 and November 12, 2009. Participants were stratified by age in three groups: >=4 to < 9 years old, >=9 to < 18 years old and >=18 to <25 years old.
Pre-assignment Details One study participant was inadvertently enrolled with acute illness, was not given any vaccination and was immediately taken off study. A second study participant received the first vaccination but it was discovered that he/she was not compliant with the ARV regimen and was taken off study before receiving the second dose of vaccine.
Arm/Group Title All Study Participants
Hide Arm/Group Description Participants received two doses of the H1N1 influenza virus vaccine, administered 21 days apart. Each dose consisted of two 15-microgram intramuscular injections.
Period Title: Overall Study
Started 155
Received Both Study Vaccinations 150
Completed 150
Not Completed 5
Reason Not Completed
Lost to Follow-up             1
Withdrawal by Subject             2
Protocol Violation             2
Arm/Group Title All Study Participants
Hide Arm/Group Description Participants received two doses of the H1N1 influenza virus vaccine, administered 21 days apart. Each dose consisted of two 15-microgram intramuscular injections.
Overall Number of Baseline Participants 155
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 155 participants
13  (6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 155 participants
Female
76
  49.0%
Male
79
  51.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 155 participants
United States 147
Puerto Rico 8
Age Strata   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 155 participants
>=4 to < 9 years old 54
>=9 to < 18 years old 51
>=18 to < 25 years old 50
[1]
Measure Description: Study participants were stratified by age into three groups.
CD4 Cells Count   [1] 
Mean (Standard Deviation)
Unit of measure:  Cells / mm^3
Number Analyzed 155 participants
568  (242)
[1]
Measure Description: This measures the number of CD4 cells.
Percentage of CD4 Cells   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage
Number Analyzed 155 participants
29  (11)
[1]
Measure Description: This measures the percentage of CD4 cells.
1.Primary Outcome
Title The Number of Participants Who Had at Least One Adverse Event (AE)
Hide Description

Shows the number of participants who had at least one adverse event (AE) in each category. The AEs include: abnormal laboratory values, signs and symptoms, or diagnoses; solicited local AEs; and solicited systemic AEs.

Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.

Time Frame Measured up to 7 months after vaccination
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Study Participants
Hide Arm/Group Description:
All 155 study participants are included in this analysis.
Overall Number of Participants Analyzed 155
Measure Type: Number
Unit of Measure: participants
Overall (New AEs after start of treatment) 113
Grade 4 AEs (New, after start of treatment) 0
Grade 3 AEs (New, after start of treatment) 7
Grade 2 local and systemic AEs to injection 6
2.Primary Outcome
Title The Number of Participants Who Had at Least One AE Attributed to the Study Vaccine
Hide Description Shows the number of participants who experienced any events that were thought to be at least possibly related to study treatment. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
Time Frame Measured up to 7 months after vaccination
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The 154 study participants who received at last one vaccination are included in this analysis.
Arm/Group Title Vaccinated Study Participants
Hide Arm/Group Description:
The 154 study participants who received at last one vaccination are included in this analysis.
Overall Number of Participants Analyzed 154
Measure Type: Number
Unit of Measure: participants
7
3.Primary Outcome
Title Withholding of Second Vaccine Dose Due to Adverse Reactions Attributed to First Dose
Hide Description [Not Specified]
Time Frame Measured at Day 21
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The 154 study participants who received at last one vaccination are included in this analysis.
Arm/Group Title Vaccinated Study Participants
Hide Arm/Group Description:
The 154 study participants who received at last one vaccination are included in this analysis.
Overall Number of Participants Analyzed 154
Measure Type: Number
Unit of Measure: participants
0
4.Primary Outcome
Title Percent of Participants With a Hemagglutinin Inhibition (HAI) Titer of >=40
Hide Description Antibodies to Influenza A (H1N1) 2009 were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640 and >=1280. Seroprotection was defined as having a titer of >=40 following vaccination.
Time Frame Measured at 21 days after first dose and 10 days after second dose
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Hide Analysis Population Description
The HAI titers following the first vaccination were summarized for the eligible study participants who received at least one vaccine and had nonmissing HAI data, and the titers following the second vaccination for the eligible study participants who received both doses of vaccine and had nonmissing HAI data.
Arm/Group Title Overall
Hide Arm/Group Description:
The total N for these analyses were 140 and 142, for the analysis of antibody titers after the first and second vaccinations, respectively.
Overall Number of Participants Analyzed 142
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Post dose 1 (N=140)
72.1
(63.9 to 79.4)
Post dose 2 (N=142)
82.4
(75.1 to 88.3)
5.Secondary Outcome
Title Percent of Participants With an HAI Titer >=40 at Long-term Follow-up
Hide Description [Not Specified]
Time Frame Measured at 6 months after second dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The HAI titers were summarized for the eligible study participants who received both doses of vaccine and had nonmissing HAI data.
Arm/Group Title Overall
Hide Arm/Group Description:
The total N for this analysis was 138, those who received both vaccinations and had nonmissing data.
Overall Number of Participants Analyzed 138
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
57.2
(48.5 to 65.6)
6.Secondary Outcome
Title Geometric Mean Antibody Titers (GMT) HAI
Hide Description Presents the value of the geometric mean titer at each time point.
Time Frame Measured after first and second doses and 6 months after second dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The HAI titers following the first vaccination were summarized for the eligible study participants who received at least one vaccine and had nonmissing HAI data, and the titers following the second vaccination for the eligible study participants who received both doses of vaccine and had nonmissing HAI data.
Arm/Group Title Overall
Hide Arm/Group Description:
The total N for these analyses were 140, 142 and 138, for the analysis of antibody titers after the first and second vaccinations and after 6 months after the second vaccination, respectively.
Overall Number of Participants Analyzed 142
Geometric Mean (95% Confidence Interval)
Unit of Measure: titers
At 21 days after the first vaccination (N=140)
85
(65 to 111)
At 10 days after the second vaccination (N=142)
127
(101 to 159)
At 6 months after the second vaccination (N=138)
33
(27 to 40)
7.Secondary Outcome
Title Cell-mediated Immune Responses, Measured by B-cell and T-cell Enzyme-linked Immunosorbent Spot (ELISPOT) Assay Values
Hide Description The median and interquartile range (IQR) of B-Cell ELISPOT-measured IgG antibody-secreting cells (ASC)/10^6 peripheral blood mononucleated cell (PBMC) and the median and interquartile range (IQR) of T-Cell ELISPOT-measured pH1N1 IFNgamma spot-forming cells (SFC)/10^6 PBMC.
Time Frame Measured at entry, 21 days after first dose, and 10 days after second dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The participants who had received all doses of vaccine up to that timepoint and had sufficient samples for testing.
Arm/Group Title Overall
Hide Arm/Group Description:
The total N for this analysis was 68, those who received the vaccinations and had enough samples for testing.
Overall Number of Participants Analyzed 68
Median (Inter-Quartile Range)
Unit of Measure: ASC or SFC/10^6 PBMC
IgG ASC/10^6 PBMC, Week 0 (N=46)
6
(2 to 16)
IgG ASC/10^6 PBMC, Post Dose 1 (N=40)
13
(4 to 40)
IgG ASC/10^6 PBMC, Post Dose 2 (N=40)
12
(5 to 25)
pH1N1 IFNgamma SFC/10^6 PBMC, Week 0 (N=68)
317
(117 to 673)
pH1N1 IFNgamma SFC/10^6 PBMC, Post Dose 1 (N=68)
363
(123 to 622)
pH1N1 IFNgamma SFC/10^6 PBMC, Post Dose 2 (N=65)
261
(78 to 525)
8.Secondary Outcome
Title HAI Titers Against Seasonal Influenza Viruses Containing Trivalent Influenza Vaccine (TIV)
Hide Description Presents the value of the median titer as well as the interquartile range at study entry. Antibodies to seasonal Influenza vaccine were measured using an HAI assay. The potential titer read-outs from the assay used were <10 (considered undetectable), 10, 20, 40, 60, 80, 160, 320, 640, and >=1280.
Time Frame Measured at entry, 21 days after first dose, and 10 days and 6 months after second dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The participants who had received all doses of vaccine up to that timepoint and had sufficient samples for testing.
Arm/Group Title Influenza A (H1N1) 2009 Monovalent Vaccine
Hide Arm/Group Description:

All participants received two doses of the H1N1 influenza virus vaccine, administered 21 days apart.

Influenza A (H1N1) 2009 monovalent vaccine: Two doses of vaccine, delivered 21 days apart, with each dose consisting of two 15-microgram intramuscular injections

Overall Number of Participants Analyzed 123
Median (Inter-Quartile Range)
Unit of Measure: titer
Week 0 (N=123)
40
(20 to 80)
Post Dose 1 (N=121)
40
(20 to 80)
Post Dose 2 (N=121)
40
(20 to 80)
6 months Post Dose 2 (N=122)
40
(20 to 80)
9.Secondary Outcome
Title Cell-mediated Immune Responses to Influenza Viruses Contained in TIV and Other Antigens
Hide Description

The TIV assay was not performed due to lack of available cells after completion of other planned assays.

The median and interquartile range (IQR) of T-Cell ELISPOT-measured pH1N1 Granzyme B spot-forming cells (SFC)/10^6 peripheral blood mononucleated cell (PBMC).

The median and interquartile range (IQR) of T-Cell ELISPOT-measured PHA INFgamma spot-forming cells (SFC)/10^6 PBMC.

The median and interquartile range (IQR) of T-Cell ELISPOT-measured PHA Granzyme B spot-forming cells (SFC)/10^6 PBMC.

Time Frame Measured at entry, 21 days after first dose, and 10 days after second dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The participants who had received all doses of vaccine up to that timepoint and had sufficient samples for testing.
Arm/Group Title Overall
Hide Arm/Group Description:
The total N for this analysis was 68, those who received the vaccinations and had enough samples for testing.
Overall Number of Participants Analyzed 68
Median (Inter-Quartile Range)
Unit of Measure: SFC/10^6 PBMC
pH1N1 Granzyme B SFC/10^6 PBMC, Week 0 (N=64)
35
(0 to 220)
pH1N1 Granzyme B SFC/10^6 PBMC, Week 3 (N=62)
26
(0 to 170)
pH1N1 Granzyme B SFC/10^6 PBMC, Week 5 (N=61)
30
(0 to 220)
PHA INFgamma SFC/10^6 PBMC, Week 0 (N=68)
699
(307 to 1010)
PHA INFgamma SFC/10^6 PBMC, Week 3 (N=68)
637
(261 to 965)
PHA INFgamma SFC/10^6 PBMC, Week 5 (N=65)
624
(263 to 1000)
PHA Granzyme B SFC/10^6 PBMC, Week 0 (N=64)
3250
(390 to 7465)
PHA Granzyme B SFC/10^6 PBMC, Week 3 (N=62)
3340
(510 to 7520)
PHA Granzyme B SFC/10^6 PBMC, Week 5 (N=60)
2045
(300 to 7825)
Time Frame Adverse events were collected from the date of enrollment in the study until 6 months after second vaccination.
Adverse Event Reporting Description Include Adverse Events (AEs) of All Grades, Including Abnormal Laboratory Values, Signs and Symptoms, or Diagnoses; Solicited Local AEs and Systemic AEs. Adverse Events were graded using the DAIDS Grading Severity of AEs (see Link under More Information), as follows: grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death.
 
Arm/Group Title All Study Participants
Hide Arm/Group Description Participants received two doses of the H1N1 influenza virus vaccine, administered 21 days apart. Each dose consisted of two 15-microgram intramuscular injections.
All-Cause Mortality
All Study Participants
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
All Study Participants
Affected / at Risk (%)
Total   6/155 (3.87%) 
Blood and lymphatic system disorders   
Neutropenia  1  1/155 (0.65%) 
General disorders   
Gait disturbance  1  1/155 (0.65%) 
Infections and infestations   
Herpes zoster  1  1/155 (0.65%) 
Musculoskeletal and connective tissue disorders   
Muscular weakness  1  1/155 (0.65%) 
Nervous system disorders   
Syncope  1  1/155 (0.65%) 
VIIth nerve paralysis  1  1/155 (0.65%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
All Study Participants
Affected / at Risk (%)
Total   113/155 (72.90%) 
Ear and labyrinth disorders   
Ear pain  1  10/155 (6.45%) 
Gastrointestinal disorders   
Abdominal pain  1  11/155 (7.10%) 
Diarrhoea  1  16/155 (10.32%) 
Nausea  1  12/155 (7.74%) 
Vomiting  1  18/155 (11.61%) 
General disorders   
Adverse event  1  20/155 (12.90%) 
Fatigue  1  11/155 (7.10%) 
Pyrexia  1  19/155 (12.26%) 
Infections and infestations   
Otitis media  1  11/155 (7.10%) 
Investigations   
Alanine aminotransferase increased  1  11/155 (7.10%) 
Aspartate aminotransferase increased  1  9/155 (5.81%) 
Neutrophil count decreased  1  21/155 (13.55%) 
Musculoskeletal and connective tissue disorders   
Pain in extremity  1  12/155 (7.74%) 
Nervous system disorders   
Headache  1  29/155 (18.71%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  51/155 (32.90%) 
Nasal congestion  1  35/155 (22.58%) 
Oropharyngeal pain  1  32/155 (20.65%) 
Rhinorrhoea  1  19/155 (12.26%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Melissa Allen, Director, IMPAACT Operations Center
Organization: Family Health International (FHI 360)
Phone: 919-405-1429
Publications of Results:
Flynn P, Nachman S, Spector SA, Cunningham CK, Weinberg A, Pass R, Muresan P, Levy W, Siberry G, Handelsman E for the IMPAACT P1088 and P1089 Teams: Safety and Immunogenicity of 2009 H1N1 Influenza Immunization in HIV-1 Perinatally Infected Children and Youth. Presented at the IDSA conference, October 2010.
Flynn PM, Nachman S, Spector SA, Cunningham CK, Weinberg A, Pass R, Muresan P, Levy W, Petzold E, Heckman B, Siberry G, Handelsman E for the IMPAACT P1088 and P1089 Teams. 2009 Influenza A (H1N1) Immunization in HIV-1 Perinatally Infected Children and Youth. Presented at the Retroviruses Conference, Feb 2010.
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00992836     History of Changes
Other Study ID Numbers: P1088
10840 ( Registry Identifier: DAIDS ES Registry Number )
IMPAACT P1088
First Submitted: October 8, 2009
First Posted: October 9, 2009
Results First Submitted: August 23, 2011
Results First Posted: February 9, 2012
Last Update Posted: December 17, 2014