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Differences in Response to the Flu Vaccine Among Adults With HIV and Without HIV in Uganda

Primary Purpose

HIV, Acquired Immunodeficiency Syndrome, Influenza

Status

Completed

Phase

Not Applicable

Locations

Uganda

Study Type

Interventional

Intervention

Seasonal trivalent inactivated influenza vaccine (Vaxigrip®)

About this trial

This is an interventional basic science trial for HIV focused on measuring immunization

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

For HIV uninfected group
- Confirmation of HIV-1 infection from medical records
For HIV infected on HAART group
- Confirmation of HIV-1 infection from medical records
- Participants must be on HAART for at least 6 months prior to enrollment
- A CD4 T-cell count available in the last 6 months
- CD4 T-cell count >350 cells/μL on the eligibility blood specimen
Long-term non-progressor group
- HIV infected for more than 7 years
- No evidence of opportunistic infections in the medical records
- Never received antiretroviral therapy (except anti-retrovirals for prevention of mother-to-infant transmission of HIV)
- A CD4 T-cell count available in the last 6 months
- CD4+ T-cell count slop of ≥0 cells/µl blood from entry into the MU-JHU cohort until the most recent available CD4+ T-cell count.

Exclusion Criteria:

Current moderate or severe acute illness, history of fever or temperature ≥37.5oC within 48 hours prior to vaccination (participants can be re-evaluated at a subsequent visit)
History of systemic disease, including: Guillain-Barré Syndrome; known hepatitis B, or hepatitis C infection; cardiac disease; uncontrolled diabetes mellitus (including gestational diabetes); chronic liver condition; clinically significant renal impairment; clinically significant neurological disorders; active TB within the last year; Cancer. This information will be based on self-reporting and (where possible) will be confirmed by hospital medical records
Received immunoglobulin or other blood product within the preceding 3 months or expected receipt of blood products during the 3 months of follow-up
History of anaphylactic hypersensitivity reactions to egg proteins (eggs or egg products), or any other component of the vaccine including traces (formaldehyde, octoxinol 9 (Triton X-100) and neomycin)
History of severe reaction (including hypersensitivity) after receiving any vaccine
Currently pregnant
In the opinion of the study team it would be unsuitable for the study subjects to receive the vaccine or participate in the study.

Sites / Locations

Makere University- Johns Hopkins University Research Collaboration, at the Mulago National Referral Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Arm Label

HIV uninfected adults

HIV infected adults on HAART

HIV-infected long-term non-progressors

Arm Description

25 HIV uninfected adults enrolled at the Mulago National Referral Hospital complex in Kampala, Uganda will receive seasonal trivalent inactivated influenza vaccine (Vaxigrip®).

25 HIV infected adults enrolled at the Mulago National Referral Hospital complex in Kampala, Uganda will receive seasonal trivalent inactivated influenza vaccine (Vaxigrip®).

10 HIV-infected long-term non-progressor adults enrolled at the Mulago National Referral Hospital complex in Kampala, Uganda will receive seasonal trivalent inactivated influenza vaccine (Vaxigrip®).

Outcomes

Primary Outcome Measures

In group and between group comparison of immune parameters and gene expressions that change significantly following vaccination with the seasonal trivalent influenza vaccine (Vaxigrip®)

Immune parameters or gene expressions that change significantly in groups over baseline post immunization and between the study groups will be analyzed. For immune parameters, we will use a two-sided paired t-test. Fold-change will be combined with the test p-value in a selection criterion as appropriate. The tentative selection criterion is p-value ≤ 0.01 and fold change ≥ 3. For the gene/miRNA expression data, we will use the method Significance Analysis of Microarrays (SAM) with paired design to find differentially expressed genes. False discovery rate (FDR) will be used as selection criterion. The tentative selection criterion is FDR ≤ 0.1.

Proportion of subjects achieving 4-fold or greater hemagglutination inhibition (HAI)antibody titer increases.

Proportion of subjects in different study groups achieving 4-fold or greater hemagglutination inhibition (HAI)antibody titer increases will be tabulated at each time point (Days 0, 1, 3, 7, 14, 28 and 100) and plotted across time. Fisher's exact test will be used to make comparisons between the study groups.

Calculating correlation coefficient between the immune parameter and vaccine immunogenicity, as measured by the humoral immune response against seasonal influenza.

For immune parameters, we will calculate the correlation coefficient between the immune parameter and vaccine immunogenicity, as measured by the humoral immune response against seasonal influenza. The p-values associated with the correlation coefficients will be used to select immune parameters that are associated with the respective adaptive immune responses. The tentative selection criterion is p-value ≤ 0.01. For gene expression data, we will use the method Significance Analysis of Microarrays (SAM) with quantitative outcome to identify genes that are significantly associated with the immune response. False discovery rate (FDR) will be used as selection criterion. The tentative selection criterion is FDR ≤ 0.1.

Characterization of the gut microbiota to determine compositional differences between HIV-uninfected adults versus HIV-infected adults on HAART versus HIV-infected long-term non-progressors

Gut mircobiota will be characterized to determine what compositional differences exist between HIV-uninfected adults versus HIV-infected adults on HAARt versus HIV-infected long-term non-progressors at baseline (Day 0), Day 7 and Day 28 post vaccination

Correlation between microbiata status and the quality of immune response elicited in vaccinated individuals

Determine whether the status of the microbita correlates with the quality of immune responses elicited in vaccinated individuals

Secondary Outcome Measures

Full Information

NCT ID

NCT01916759

First Posted

February 25, 2013

Last Updated

April 22, 2014

Sponsor

Emory University

Collaborators

Makerere University

1. Study Identification

Unique Protocol Identification Number

NCT01916759

Brief Title

Differences in Response to the Flu Vaccine Among Adults With HIV and Without HIV in Uganda

Official Title

Systems Biological Responses to Influenza Vaccination in an HIV-infected and HIV-uninfected Adult Population in Kampala, Uganda

Study Type

Interventional

2. Study Status

Record Verification Date

April 2014

Overall Recruitment Status

Completed

Study Start Date

June 2013 (undefined)

Primary Completion Date

December 2013 (Actual)

Study Completion Date

March 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Emory University

Collaborators

Makerere University

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

To use a systems biological approach to study the molecular signatures of innate and adaptive responses to vaccination in a HIV infected versus uninfected adult population in Kampala, Uganda.

Detailed Description

This longitudinal, observational cohort study will be conducted at the Makerere University- Johns Hopkins University Research Collaboration, at the Mulago National Referral Hospital complex in Kampala Uganda. The study will consist of 2 groups. One group will consist of 25 healthy HIV uninfected adults and the other arm will consist of 35 HIV infected adults. Within the HIV infected arm there will be two groups, 25 HIV infected adults and 10 long term non-progressors. Vaccinees will receive a primary immunization at day 0, and blood samples will be obtained at days 0, 1, 3, 7, 14, 28 and 100 after immunization. We will analyze the early molecular signatures (identified by microarray analyses, as well as by FACS analyses of innate immune cells and luminex analyses of cytokines and chemokines) that correlate and predict the later immune responses.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV, Acquired Immunodeficiency Syndrome, Influenza

Keywords

immunization

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

63 (Actual)

8. Arms, Groups, and Interventions

Arm Title

HIV uninfected adults

Arm Type

Other

Arm Description

25 HIV uninfected adults enrolled at the Mulago National Referral Hospital complex in Kampala, Uganda will receive seasonal trivalent inactivated influenza vaccine (Vaxigrip®).

Arm Title

HIV infected adults on HAART

Arm Type

Other

Arm Description

25 HIV infected adults enrolled at the Mulago National Referral Hospital complex in Kampala, Uganda will receive seasonal trivalent inactivated influenza vaccine (Vaxigrip®).

Arm Title

HIV-infected long-term non-progressors

Arm Type

Other

Arm Description

Intervention Type

Drug

Intervention Name(s)

Seasonal trivalent inactivated influenza vaccine (Vaxigrip®)

Intervention Description

Administer seasonal trivalent inactivated influenza vaccine (Vaxigrip®) and collect blood specimens at 0, 1, 3, 7, 14, 28 and 100 days following vaccination.

Primary Outcome Measure Information:

Title

In group and between group comparison of immune parameters and gene expressions that change significantly following vaccination with the seasonal trivalent influenza vaccine (Vaxigrip®)

Description

Time Frame

From baseline (Day 0) to 100 days post vaccination

Title

Proportion of subjects achieving 4-fold or greater hemagglutination inhibition (HAI)antibody titer increases.

Description

Time Frame

From baseline (Day 0) to 100 days following primary vaccination

Title

Calculating correlation coefficient between the immune parameter and vaccine immunogenicity, as measured by the humoral immune response against seasonal influenza.

Description

Time Frame

From baseline (Day 0) to 100 days post vaccination

Title

Characterization of the gut microbiota to determine compositional differences between HIV-uninfected adults versus HIV-infected adults on HAART versus HIV-infected long-term non-progressors

Description

Time Frame

From baseline (Day 0) to Day 28 post vaccination

Title

Correlation between microbiata status and the quality of immune response elicited in vaccinated individuals

Description

Determine whether the status of the microbita correlates with the quality of immune responses elicited in vaccinated individuals

Time Frame

From baseline (Day 0) to Day 28 post vaccination

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: For HIV uninfected group Confirmation of HIV-1 infection from medical records For HIV infected on HAART group Confirmation of HIV-1 infection from medical records Participants must be on HAART for at least 6 months prior to enrollment A CD4 T-cell count available in the last 6 months CD4 T-cell count >350 cells/μL on the eligibility blood specimen Long-term non-progressor group HIV infected for more than 7 years No evidence of opportunistic infections in the medical records Never received antiretroviral therapy (except anti-retrovirals for prevention of mother-to-infant transmission of HIV) A CD4 T-cell count available in the last 6 months CD4+ T-cell count slop of ≥0 cells/µl blood from entry into the MU-JHU cohort until the most recent available CD4+ T-cell count. Exclusion Criteria: Current moderate or severe acute illness, history of fever or temperature ≥37.5oC within 48 hours prior to vaccination (participants can be re-evaluated at a subsequent visit) History of systemic disease, including: Guillain-Barré Syndrome; known hepatitis B, or hepatitis C infection; cardiac disease; uncontrolled diabetes mellitus (including gestational diabetes); chronic liver condition; clinically significant renal impairment; clinically significant neurological disorders; active TB within the last year; Cancer. This information will be based on self-reporting and (where possible) will be confirmed by hospital medical records Received immunoglobulin or other blood product within the preceding 3 months or expected receipt of blood products during the 3 months of follow-up History of anaphylactic hypersensitivity reactions to egg proteins (eggs or egg products), or any other component of the vaccine including traces (formaldehyde, octoxinol 9 (Triton X-100) and neomycin) History of severe reaction (including hypersensitivity) after receiving any vaccine Currently pregnant In the opinion of the study team it would be unsuitable for the study subjects to receive the vaccine or participate in the study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Saad B Omer, MBBS,MPH,PhD

Organizational Affiliation

Emory Unversity

Official's Role

Principal Investigator

Facility Information:

Facility Name

Makere University- Johns Hopkins University Research Collaboration, at the Mulago National Referral Hospital

City

Kampala

Country

Uganda

12. IPD Sharing Statement

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Differences in Response to the Flu Vaccine Among Adults With HIV and Without HIV in Uganda

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