Clinical trial NCT01916759: 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
Overall status: COMPLETED
Phase: NA
Conditions: HIV
Acquired Immunodeficiency Syndrome
Influenza
Keywords: immunization
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Makerere University
First posted: 2013-08-06
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

1. For HIV uninfected group

   * Confirmation of HIV-1 infection from medical records
2. 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
3. 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:

1. 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)
2. 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
3. Received immunoglobulin or other blood product within the preceding 3 months or expected receipt of blood products during the 3 months of follow-up
4. 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)
5. History of severe reaction (including hypersensitivity) after receiving any vaccine
6. Currently pregnant
7. In the opinion of the study team it would be unsuitable for the study subjects to receive the vaccine or participate in the study.

Primary outcomes:
measure: In group and between group comparison of immune parameters and gene expressions that change significantly following vaccination with the seasonal trivalent influenza vaccine (Vaxigrip®)
timeFrame: From baseline (Day 0) to 100 days post vaccination
measure: Proportion of subjects achieving 4-fold or greater hemagglutination inhibition (HAI)antibody titer increases.
timeFrame: From baseline (Day 0) to 100 days following primary vaccination
measure: Calculating correlation coefficient between the immune parameter and vaccine immunogenicity, as measured by the humoral immune response against seasonal influenza.
timeFrame: From baseline (Day 0) to 100 days post vaccination
measure: 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
timeFrame: From baseline (Day 0) to Day 28 post vaccination
measure: Correlation between microbiata status and the quality of immune response elicited in vaccinated individuals
timeFrame: From baseline (Day 0) to Day 28 post vaccination
Secondary outcomes:
Other outcomes:
Locations:
city: Kampala
country: Uganda
facility: Makere University- Johns Hopkins University Research Collaboration, at the Mulago National Referral Hospital
Study officials:
affiliation: Emory Unversity
name: Saad B Omer, MBBS,MPH,PhD
role: PRINCIPAL_INVESTIGATOR
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