Tfh Dysfunction in HIV and Aging

The purpose of this research is to evaluate blood samples from HIV infected and non-HIV infected people to understand how aging and HIV infection affect the immune responses (body defenses against infection) to the flu vaccine.

Study Overview

• Status: Recruiting
• Conditions: Human Influenza
• Intervention / Treatment: Biological: Standard dose influenza vaccination; Biological: High dose influenza vaccination

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Suresh Pallikkuth, PhD; Phone Number: 3052435315; Email: spallikkuth@med.miami.edu

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami
      • Contact: Suresh Pallikkuth, PhD; Phone Number: 305-243-5315; Email: spallikkuth@med.miami.edu
      • Principal Investigator: Savita Pahwa, MD
      • Sub-Investigator: Suresh Pallikkuth, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. For HIV positive participants:

   • HIV infection, as documented by any licensed ELISA test kit. Participants on ART as a result of prior HIV documented infection will not be required to provide proof of diagnosis of HIV infection.

   • Additional criteria for HIV positive

     1. on ART for at least 1 year. Occasional viral blips up to 1000 copies/ml also acceptable provided the patients are on continuing treatment,
     2. Cluster of differentiation 4 (CD4) count available in the prior 6 months and >200/mm3
     3. Undetectable viral load (< 40 copies/mL). Blips of <1000 copies/mL will be allowed.

2. For HIV negative participants:

   • Documented negative HIV test at the time of study entry, either by any licensed ELISA.

3. For all participants:

   1. Individuals age: ≤35 years and ≥65 years.
   2. No history of other immunodeficiency disorders
   3. Not on steroid or other immunosuppressive/immunomodulators medications.
   4. No active malignancies.
   5. Agreeable to receive both regular standard (STD-TIV) and high dose (HD-TIV) influenza vaccination.
   6. Agreeable to participate in study for a complete course of study full visits including 2 consecutive flu seasons.
   7. Able to provide informed consent.

Exclusion criteria

1. Contraindication to receive influenza vaccination.
2. Non-adherence to ART for HIV positive
3. Unable to provide informed consent.
4. Influenza vaccination already given during the current vaccination season.
5. Known drug abuse including cocaine by history

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Young HIV negative group; HIV uninfected participants that are 18-35 years of age will receive the standard dose flu vaccine. Participants who did not respond to the standard dose flu vaccination, as defined by less than a four-fold increase in flu antibody titer from baseline, will then receive the high dose flu vaccination 1 year after initial standard dose flu vaccination. Participants who respond to the standard dose flu vaccination will not receive the high dose flu vaccination.	Biological: Standard dose influenza vaccination; Single 0.5 ml injection administered intramuscularly into participant's deltoid muscle; Other Names: Fluzone quadrivalent; Biological: High dose influenza vaccination; 4 times more concentrated single 0.7 ml injection administered intramuscularly into participant's deltoid muscle; Other Names: Fluzone high dose quadrivalent
Experimental: Young HIV positive group; HIV infected viral suppressed participants, who are on anti-retroviral therapy (ART) aged 18-35 years of age, will receive the standard dose flu vaccine first followed by the high dose flu vaccine 1 year after initial standard dose.	Biological: Standard dose influenza vaccination; Single 0.5 ml injection administered intramuscularly into participant's deltoid muscle; Other Names: Fluzone quadrivalent; Biological: High dose influenza vaccination; 4 times more concentrated single 0.7 ml injection administered intramuscularly into participant's deltoid muscle; Other Names: Fluzone high dose quadrivalent
Experimental: Old HIV negative group; HIV uninfected participants that are 65 years and older will receive the standard dose flu vaccine first followed by the high dose flu vaccine 1 year after initial standard dose.	Biological: Standard dose influenza vaccination; Single 0.5 ml injection administered intramuscularly into participant's deltoid muscle; Other Names: Fluzone quadrivalent; Biological: High dose influenza vaccination; 4 times more concentrated single 0.7 ml injection administered intramuscularly into participant's deltoid muscle; Other Names: Fluzone high dose quadrivalent
Experimental: Old HIV positive group; HIV infected viral suppressed participants, who are on anti-retroviral therapy (ART) aged 65 years and older, will receive the standard dose flu vaccine first followed by the high dose flu vaccine 1 year after initial standard dose.	Biological: Standard dose influenza vaccination; Single 0.5 ml injection administered intramuscularly into participant's deltoid muscle; Other Names: Fluzone quadrivalent; Biological: High dose influenza vaccination; 4 times more concentrated single 0.7 ml injection administered intramuscularly into participant's deltoid muscle; Other Names: Fluzone high dose quadrivalent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HAI antibody response	Change in mean titers of Hemagglutination inhibition (HAI) antibody response will be measured using serum sample.	Baseline to Month 6 (post standard dose flu vaccination), Baseline to Month 18 (post high-dose flu vaccination)
Change in neutralization antibody response	Change in mean titers of neutralization antibody response will be measured using serum sample.	Baseline to Month 6 (post standard dose flu vaccination), Baseline to Month 18 (post high-dose flu vaccination)
Percentage of Participants with Vaccine Response	Percentage of participants that are vaccine responders and non-responders will be reported. Response is evaluated using seroconversion to the flu vaccine using serum sample.	Month 13 (1 month post high-dose flu vaccination)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of T-follicular helper (Tfh) cells	Percentage of Tfh cells as measured using peripheral blood samples	Month 13 (1 month post high-dose flu vaccination)
Percentage of B cells	Percentage of B cells as measured using peripheral blood samples	Month 13 (1 month post high-dose flu vaccination)
Percentage of monocytes	Percentage of monocytes as measured using peripheral blood samples	Month 13 (1 month post high-dose flu vaccination)
Percentage of Tfh cells producing cytokines	Percentage of Tfh cells producing cytokines as measured using peripheral blood samples	Month 13 (1 month post high-dose flu vaccination)

Collaborators and Investigators

• Sponsor: University of Miami
• Investigators: Principal Investigator: Savita Pahwa, MD, University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2020
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: July 22, 2020
• First Submitted That Met QC Criteria: July 22, 2020
• First Posted (Actual): July 27, 2020

Study Record Updates

• Last Update Posted (Actual): September 25, 2023
• Last Update Submitted That Met QC Criteria: September 22, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: HIV; Aging; immune function; flu vaccination; high dose vaccination
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: 20200752

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No