Influenza Vaccine in HIV

A Controlled Trial to Assess the Immunogenicity and Efficacy of Three Vaccine Dosing Strategies in HIV Infected Adults

The purposes of this research study are:

1. to see if there is a difference in the quantity of protective influenza antibodies produced by different doses of the Fluviral vaccine
2. to see if these different vaccine dosing schedules reduce flu-like illness and/or reduce laboratory documented influenza in HIV Infected adults.

Study Overview

• Status: Completed
• Conditions: HIV; Influenza
• Intervention / Treatment: Biological: Fluviral

Detailed Description

Immune compromised individuals are at risk for infection with influenza and more likely to manifest more severe symptoms of influenza disease. Furthermore, they are influenza vaccine hyporesponsive in comparison to healthy, adult immune competent individuals. One population of immune compromised Canadians at risk for severe influenza disease is those living with HIV infection. At least 56,000 Canadians are HIV infected [1]. This population is at risk for more severe influenza illness. Influenza viral replication and shedding is prolonged and the duration of influenza symptomatology is longer in those with HIV [2, 3]. Furthermore, influenza-related mortality rates in HIV infected individuals are increased [4]. The HIV population is known to be hyporesponsive to vaccinations, including influenza. The efficacy of influenza vaccines is compromised, in part, by reduced antibody responses observed in HIV infected individuals [5]. Nevertheless, influenza vaccination is recommended for HIV-infected individuals [6, 7]. The Centers of Disease Control guidelines state: "Influenza can result in serious illness and because vaccination with inactivated influenza vaccine might result in the production of protective antibody titers, vaccination might benefit HIV-infected persons. Therefore, influenza vaccination is recommended". As influenza vaccination is the cornerstone of public health interventions intended to protect the population against influenza, vaccine hyporesponsiveness in immune compromised populations represents a significant concern. Given the risk of influenza exposure in general as well as concerns related to poor vaccine efficacy and more severe influenza disease in immune compromised populations such as those living with HIV, strategies to improve vaccine efficacy are required.

Therefore a total of 5 conditions provide justification for a trial to be conducted at this time:

1. current standard treatment with influenza vaccine is less efficacious when used in particular subgroups of immune compromised individuals, such as those diagnosed with HIV
2. there exists a significant burden of influenza infection in HIV patients that must be addressed in terms of identifying an effective treatment strategy
3. past randomized trials of influenza vaccination in HIV patients are of limited comparability to today's relevant base of patients, and alternative vaccination strategies require assessment
4. efficacy of booster doses of influenza vaccine in HIV patients remains in question as a consequence of methodologic shortcomings in terms of both design aspects and outcomes measured of past studies
5. there is a paucity of published evidence assessing the efficacy of an increased, double-dose of influenza vaccine in this patient population.

References

1. Boulos, D., et al., Estimates of HIV prevalence and incidence in Canada, 2005. Can Commun Dis Rep, 2006. 32(15): p. 165-74.
2. Safrin, S., J.D. Rush, and J. Mills, Influenza in patients with human immunodeficiency virus infection. Chest, 1990. 98(1): p. 33-7.
3. Radwan, H.M., et al., Influenza in human immunodeficiency virus-infected patients during the 1997-1998 influenza season. Clin Infect Dis, 2000. 31(2): p. 604-6.
4. Zanetti, A.R., et al., Safety and immunogenicity of influenza vaccination in individuals infected with HIV. Vaccine, 2002. 20 Suppl 5: p. B29-32.
5. Malaspina, A., et al., Compromised B cell responses to influenza vaccination in HIV-infected individuals. J Infect Dis, 2005. 191(9): p. 1442-50.
6. Health Canada Progress towards Canadian target coverage rates in Influenza and Pneumococcal Immunications., in Available at: http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/01vol27/dr2710eb.htlm. Accessed 8 December 2006. 2006.
7. Prevention and Control of Influenza. Recommendations of the advisory committee on immunization practice, in Centers for Disease Control and Prevention. Morbidity and Morality Weekly Report. 2006. p. Vol 55/RR-10.

• Study Type: Interventional
• Enrollment (Actual): 285
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2R 0X7
      • Southern Alberta Clinic
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • BC Center for Excellence in HIV/Aids
    • Vancouver, British Columbia, Canada, V6Z 2C7
      • Downtown Immunodeficiency Clinic / UBC
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • QEII HSC, Victoria General Hospital Site
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • McMaster University Medical Center
    • London, Ontario, Canada, N5Y 3H6
      • Infectious Disease Care Program
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital, General Campus
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network
    • Toronto, Ontario, Canada, K1N 6N5
      • University of Ottawa Health Services
    • Toronto, Ontario, Canada, M2N 3M5
      • Sunnybrook Health Science Center
    • Windsor, Ontario, Canada, N8W 1E3
      • HIV Care Program - Windsor Regional Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2X 2P4
      • Immunodeficiency Service, Montreal Chest Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 - < 60 years
• HIV positive
• Able to provide signed, informed consent.

Exclusion Criteria:

• Receipt or anticipated requirement of any blood product, vaccine, or immunoglobulin preparation within one month of study vaccine administration until completion of study.
• Immunosuppressive therapy including prednisone, immune modulators, subjects undergoing dialysis, autoimmune dysfunction (including rheumatoid arthritis, lupus erythematosus, multiple sclerosis)
• Alcohol consumption > 4 drinks per day (1 drink is equal to a 12-ounce can of beer, or a 5-ounce glass of wine or one cocktail with 1 1/2-ounces alcohol)
• History of cancer, with the exception of cutaneous cancers including Kaposi Sarcoma, basal cell carcinoma and non-invasive HPV-related malignancy
• Known or suspected hypersensitivity to any component of the study vaccines, including chicken eggs or egg products and thimerosol
• History of immediate hypersensitivity reaction and/or reaction resulting in neurological symptoms to a previous dose of any influenza vaccine
• Presentation with or any recent history (within 24 hours) of any febrile illness (> 38 C) or symptoms of significant local or systemic infection - such subjects will be deferred from enrollment at least until one week after the illness has resolved
• Any other condition which in the opinion of the Investigator might interfere with evaluation of the study objectives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Biological: Fluviral; Other Names: non applicable
Active Comparator: Fluviral	Biological: Fluviral; Other Names: non applicable

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Immunogenicity measured by haemagglutination inhibition (HI)	baseline, week 4, week 8 and week 20.

Secondary Outcome Measures

Outcome Measure	Time Frame
Frequencies of laboratory confirmed influenza and Frequencies clinical/respiratory illness	event driven

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Collaborators: Ontario HIV Treatment Network; Public Health Agency of Canada (PHAC); CIHR Canadian HIV Trials Network
• Investigators: Principal Investigator: Curtis Cooper, MD, OHRI

Publications and helpful links

General Publications

• Cooper C, Thorne A, Klein M, Conway B, Boivin G, Haase D, Shafran S, Zubyk W, Singer J, Halperin S, Walmsley S; CIHR Canadian HIV Trials Network Influenza Vaccine Research Group. Immunogenicity is not improved by increased antigen dose or booster dosing of seasonal influenza vaccine in a randomized trial of HIV infected adults. PLoS One. 2011 Mar 25;6(3):e17758. doi: 10.1371/journal.pone.0017758.
• Nosyk B, Sharif B, Sun H, Cooper C, Anis AH; CIHR Canadian HIV Trials Network Influenza Vaccine Research Group. The cost-effectiveness and value of information of three influenza vaccination dosing strategies for individuals with human immunodeficiency virus. PLoS One. 2011;6(12):e27059. doi: 10.1371/journal.pone.0027059. Epub 2011 Dec 6.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: October 1, 2008
• First Submitted That Met QC Criteria: October 1, 2008
• First Posted (Estimate): October 2, 2008

Study Record Updates

• Last Update Posted (Actual): April 28, 2017
• Last Update Submitted That Met QC Criteria: April 26, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: HIV; Efficacy; Influenza; Influenza Vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: CTN237