Tfh Dysfunction in HIV and Aging

Phase 4

Recruiting

• Conditions: Human Influenza
• Interventions: Biological: Standard dose influenza vaccination; Biological: High dose influenza vaccination

• Registration Number: NCT04487041
• Lead Sponsor: University of Miami

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-07-22
• Study First Submitted QC: 2020-07-22
• Study First Posted: 2020-07-27
• Study Start: 2020-10-30
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-22
• Last Update Posted: 2023-09-25
• Primary Completion: 2025-09-30
• Study Completion: 2025-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 400

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Young HIV positive group	High dose influenza vaccination	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.
Old HIV negative group	Standard dose influenza vaccination	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.
Young HIV negative group	Standard dose influenza vaccination	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.
Young HIV negative group	High dose influenza vaccination	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.
Young HIV positive group	Standard dose influenza vaccination	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.
Old HIV positive group	High dose influenza vaccination	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.
Old HIV negative group	High dose influenza vaccination	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.
Old HIV positive group	Standard dose influenza vaccination	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants with Vaccine Response	Month 13 (1 month post high-dose flu vaccination)	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.
Change in HAI antibody response	Baseline to Month 6 (post standard dose flu vaccination), Baseline to Month 18 (post high-dose flu vaccination)	Change in mean titers of Hemagglutination inhibition (HAI) antibody response will be measured using serum sample.
Change in neutralization antibody response	Baseline to Month 6 (post standard dose flu vaccination), Baseline to Month 18 (post high-dose flu vaccination)	Change in mean titers of neutralization antibody response will be measured using serum sample.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Miami; 🇺🇸 Miami, Florida, United States