Influenza Vaccination for HIV-Related Immune Response

Overseen By Suresh Pallikkuth, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Miami

Must be taking: Antiretrovirals

Must not be taking: Steroids, Immunosuppressives

Disqualifiers: Immunodeficiency, Active malignancies, Drug abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot be on steroids or other medications that suppress or modify the immune system.

How does the high-dose influenza vaccine differ from standard treatments for HIV-related immune response?

The high-dose influenza vaccine, such as Fluzone High-Dose, contains a higher amount of hemagglutinin, which can enhance the immune response in older adults and potentially in those with HIV. This higher dose aims to improve the vaccine's effectiveness in individuals with weakened immune systems, like those with HIV, compared to standard-dose vaccines. ^{1 2 3 4 5}

Who Is on the Research Team?

Savita Pahwa, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for people aged ≤35 or ≥65 years, with or without HIV. HIV+ individuals must be on ART for at least a year, have a CD4 count >200/mm3, and an undetectable viral load. Participants should not have other immune disorders, be taking immunosuppressants, have active cancer, drug abuse history or received this season's flu shot.

Inclusion Criteria

For HIV negative participants: Documented negative HIV test at the time of study entry, either by any licensed ELISA. Individuals age: ≤35 years and ≥65 years. No history of other immunodeficiency disorders. Not on steroid or other immunosuppressive/immunomodulators medications. No active malignancies. Agreeable to receive both regular standard (STD-TIV) and high dose (HD-TIV) influenza vaccination. Agreeable to participate in study for a complete course of study full visits including 2 consecutive flu seasons. Able to provide informed consent.

I am HIV positive, on treatment for over a year, with a CD4 count over 200 and an undetectable viral load.

Exclusion Criteria

You can't get the flu shot, don't take your HIV medication regularly, can't understand what the study is about, already got the flu shot this year, or have a history of drug abuse, including cocaine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Vaccination

Participants receive the standard dose flu vaccine

1 day

1 visit (in-person)

Follow-up Post Initial Vaccination

Participants are monitored for immune response to the standard dose flu vaccine

6 months

High Dose Vaccination

Participants who did not respond to the standard dose receive the high dose flu vaccine

1 day

1 visit (in-person)

Follow-up Post High Dose Vaccination

Participants are monitored for immune response to the high dose flu vaccine

6 months

What Are the Treatments Tested in This Trial?

Interventions

• High dose influenza vaccination
• Standard dose influenza vaccination

Trial Overview The study aims to understand how aging and HIV affect the body's defense against flu by comparing immune responses to standard-dose (STD-TIV) and high-dose (HD-TIV) influenza vaccinations in both HIV infected and non-infected participants over two flu seasons.

How Is the Trial Designed?

Group I: Young HIV positive group Experimental Treatment 2 Interventions

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.

Group II: Old HIV positive group Experimental Treatment 2 Interventions

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.

Group III: Old HIV negative group Experimental Treatment 2 Interventions

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.

Group IV: Young HIV negative group Active Control 2 Interventions

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.

High dose influenza vaccination is already approved in United States, Canada for the following indications:

Approved in United States as Fluzone High-Dose for:

• Prevention of disease caused by influenza A subtype viruses and type B virus in individuals 65 years of age and older

Approved in Canada as Fluzone High-Dose for:

• Prevention of disease caused by influenza A subtype viruses and type B virus in individuals 65 years of age and older

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Published Research Related to This Trial

In a study involving 2670 healthy adults aged 65 and older, the quadrivalent high-dose influenza vaccine (IIV4-HD) demonstrated non-inferior immunogenicity compared to the licensed trivalent high-dose vaccine (IIV3-HD) for all four influenza strains.

IIV4-HD showed superior immune responses for both B strains compared to IIV3-HD that did not contain the same B-lineage strain, while maintaining a similar safety profile, indicating it is a more effective option without added safety risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of high-dose quadrivalent influenza vaccine in adults ≥65 years of age: A phase 3 randomized clinical trial. Chang, LJ., Meng, Y., Janosczyk, H., et al.[2020]

In a study involving 256 participants, the MF59-adjuvanted vaccine (Fluad) demonstrated better immunogenicity compared to the non-adjuvanted vaccine (Agrippal) in healthy individuals, although the clinical significance of this difference remains uncertain due to nonstandard measurement methods.

Both vaccines were found to be safe and well-tolerated, with no significant adverse effects on HIV-1-infected individuals' viremia or CD4+ cell counts, supporting their use in this high-risk population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of two influenza virus subunit vaccines, with or without MF59 adjuvant, administered to human immunodeficiency virus type 1-seropositive and -seronegative adults. Durando, P., Fenoglio, D., Boschini, A., et al.[2021]

Annual influenza vaccination is generally safe and well tolerated in individuals with HIV, showing no significant long-term effects on viral load or CD4+ cell counts, although a transient increase in viral replication may occur.

Immunogenicity studies indicate that while some influenza vaccines elicit an adequate immune response in HIV-positive individuals, split/subunit vaccines are less effective, prompting the exploration of new strategies to enhance immune responses in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza vaccination in HIV-positive subjects: latest evidence and future perspective. Ceravolo, A., Orsi, A., Parodi, V., et al.[2021]

The study involving 661 children aged 6 months to under 18 years demonstrated that the high-dose quadrivalent influenza vaccine (IIV4-HD) is safe, with no serious adverse events reported and similar rates of mild reactions compared to the standard-dose vaccine.

IIV4-HD at a dose of 60 µg significantly improved immune responses, particularly in younger children (6 months to <3 years), showing higher antibody titers against various influenza strains compared to the standard-dose vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of high doses of quadrivalent influenza vaccine in children 6 months through Chang, LJ., Anderson, EJ., Jeanfreau, R., et al.[2021]

Fluzone® High Dose, approved by the FDA for individuals 65 and older, contains four times more hemagglutinin than standard vaccines, leading to a stronger immune response against influenza.

A recent randomized controlled trial showed that this high-dose vaccine maintains a favorable safety profile while enhancing immunologic response, supporting its use in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the vaccination of the elderly against influenza: role of a high-dose vaccine. Sullivan, SJ., Jacobson, R., Poland, GA.[2010]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of high-dose quadrivalent influenza vaccine in adults ≥65 years of age: A phase 3 randomized clinical trial. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of two influenza virus subunit vaccines, with or without MF59 adjuvant, administered to human immunodeficiency virus type 1-seropositive and -seronegative adults. [2021]

3. Italy pubmed.ncbi.nlm.nih.gov

Influenza vaccination in HIV-positive subjects: latest evidence and future perspective. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of high doses of quadrivalent influenza vaccine in children 6 months through [2021]

5. England pubmed.ncbi.nlm.nih.gov

Advances in the vaccination of the elderly against influenza: role of a high-dose vaccine. [2010]