Clinical trial NCT00764998: Influenza Vaccine in HIV
Official title: A Controlled Trial to Assess the Immunogenicity and Efficacy of Three Vaccine Dosing Strategies in HIV Infected Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza
HIV
Keywords: Influenza
HIV
Influenza Vaccine
Efficacy
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Ontario HIV Treatment Network
name: Public Health Agency of Canada (PHAC)
name: CIHR Canadian HIV Trials Network
First posted: 2008-10-02
Enrollment: 285
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Immunogenicity measured by haemagglutination inhibition (HI)
timeFrame: baseline, week 4, week 8 and week 20.
Secondary outcomes:
measure: Frequencies of laboratory confirmed influenza and Frequencies clinical/respiratory illness
timeFrame: event driven
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Southern Alberta Clinic
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: BC Center for Excellence in HIV/Aids
state: British Columbia
city: Vancouver
country: Canada
facility: Downtown Immunodeficiency Clinic / UBC
state: British Columbia
city: Halifax
country: Canada
facility: QEII HSC, Victoria General Hospital Site
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster University Medical Center
state: Ontario
city: London
country: Canada
facility: Infectious Disease Care Program
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital, General Campus
state: Ontario
city: Toronto
country: Canada
facility: University of Ottawa Health Services
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Science Center
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Windsor
country: Canada
facility: HIV Care Program - Windsor Regional Hospital
state: Ontario
city: Montreal
country: Canada
facility: Immunodeficiency Service, Montreal Chest Institute
state: Quebec
Study officials:
affiliation: OHRI
name: Curtis Cooper, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.