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?

This trial explores how the flu vaccine affects the immune system in individuals with and without HIV. Researchers aim to understand how aging and HIV influence the body's response to both standard and high-dose flu vaccines. The trial includes four groups: younger and older individuals, both with and without HIV, who will receive these vaccines. Suitable candidates for this trial are either HIV-positive individuals on treatment or HIV-negative individuals who have not received a flu shot this season. Participants should be prepared to commit to two years of study visits and vaccinations. As a Phase 4 trial, the flu vaccine is already FDA-approved and proven effective, and this research seeks to understand how it benefits more patients.

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.

What is the safety track record for these treatments?

Research has shown that both high-dose and standard-dose flu vaccines are generally safe, even for people with HIV. Studies have found the high-dose flu vaccine safe for people with HIV, though it may slightly increase pain at the injection site. One study noted a small number of deaths, but these were not directly caused by the vaccine.

Research indicates that the standard-dose flu vaccine is also well-tolerated. In people with HIV, it does not significantly affect viral levels in the body. The Centers for Disease Control and Prevention (CDC) recommends that everyone over six months old receive a flu shot annually, unless specific medical reasons advise otherwise.

Overall, both high-dose and standard-dose flu vaccines have a strong safety record and are widely used. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it explores the impact of different doses of the influenza vaccine on immune responses in people with and without HIV. Unlike standard flu vaccination protocols, which typically do not differentiate based on HIV status or age, this approach tailors vaccine doses based on these factors to potentially enhance immune response. By investigating both high and standard doses, the trial aims to determine if a stronger vaccine dose could significantly boost immune defenses in those with HIV, particularly as their immune response may be compromised. This could lead to more personalized vaccination strategies, offering better protection for vulnerable groups.

What evidence suggests that this trial's treatments could be effective for improving immune response to the flu vaccine in HIV-infected individuals?

Research has shown that flu vaccines are effective for people with HIV. In this trial, participants will receive either the standard dose or high-dose flu vaccine. The regular flu shot reduces flu cases in people with HIV, and studies indicate that many individuals with HIV gain strong protection after vaccination. The high-dose flu shot, administered to some participants, slightly enhances the immune response, particularly in older adults. However, the additional benefit of the high-dose shot for older adults with HIV is minimal. Overall, both vaccine types are safe and help prevent the flu. ^{4 6 7 8 9}

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

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4718365/

Influenza vaccination in HIV-positive subjects Generally, vaccination against influenza is well tolerated in both children and adult individuals with HIV and does not induce significant changes in viral ...

2. eatg.org eatg.org/hiv-news/high-dose-flu-vaccine-offers-limited-immune-boost-in-older-adults-with-hiv/

High-dose flu vaccine offers limited immune boost in older ... A new study finds that high-dose influenza vaccines provide minimal added immune benefit in older adults with HIV.

3. tandfonline.com tandfonline.com/doi/full/10.1080/14760584.2016.1254044

Full article: Fluzone® High-Dose Influenza Vaccine IIV3-HD was significantly more effective than IIV3-SD at protecting against influenza during the 6–8 months after vaccination in participants 65–74 and ≥75 ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0264410X18307436

Influenza vaccination for HIV-positive people: Systematic ... The evidence, although limited, suggests that influenza vaccination is effective in preventing influenza infection in HIV-positive adults [5], [ ...

5. withpower.com withpower.com/trial/phase-4-influenza-human-9-2020-1dec2

Influenza Vaccination for HIV-Related Immune Response 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 ...

6. fda.gov fda.gov/media/132238/download

Package Insert - Fluzone High-Dose Quadrivalent Based on data from Fluzone High-Dose, solicited injection site reactions and systemic adverse reactions were slightly more frequent after vaccination with ...

7. sanofi.com sanofi.com/assets/countries/canada/docs/products/vaccines/fluzone-highdose-en.pdf

FLUZONE High-Dose® A total of 23 deaths were reported during Days 29 – 180 post-vaccination: 16 (0.6%). Page 11. Sanofi. Product Monograph. 372 - FLUZONE®High-Dose ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7227622/

Adjuvanted-influenza vaccination in patients infected with HIV Adjuvanted-influenza vaccination showed good general tolerability in patients infected with HIV, with the only significant increase being the rate of local pain ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4899146/

Immunogenicity and Safety of High-Dose Trivalent ... HD TIV was safe and well-tolerated in children and young adults with leukemia, ST, or HIV. Keywords: Influenza vaccine, High dose, Cancer, HIV, Immune response, ...