Effect of HIV and/or Active Tuberculosis on the Immune Responses to Trivalent Influenza Vaccine (TIV) in Adults (TIV_HIV_TB)

Tracking Information
First Submitted Date ICMJE	February 21, 2013
First Posted Date ICMJE	March 15, 2013
Last Update Posted Date	August 12, 2014
Study Start Date ICMJE	March 2014
Estimated Primary Completion Date	December 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: March 12, 2013)	humoral antibody responses, measured by hemagglutinin inhibition assay (HAI), to each of three strains included in the seasonal non-adjuvanted trivalent influenza vaccine. [ Time Frame: up to 6 weeks after end of the influenza season ]; • To determine the effect of HIV-infection, tuberculosis (TB) and HIV-TB co-infection on humoral antibody responses, measured by hemagglutinin inhibition assay (HAI), to each of three strains included in the seasonal non-adjuvanted trivalent influenza vaccine In this study we will use the following definitions to assess the humoral immune response to TIV: HAI titers <1:10 = seronegative; HAI titers ≥1:10 = seropositive; HAI titers ≥1:40 = sero-protective; sero-response rate (primary outcome measure) will be defined as a titer of ≥1:40 in an individual with baseline titers of <1:10, or >4-fold increase of HAI titers if baseline titers were ≥1:10. Hemagglutination inhibition assays will be performed on serum as per recommended methods. Sera will be titrated against antigens from the influenza vaccine strains included in the 2013 seasonal TIV.
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01811823 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: March 12, 2013)	• To compare the effect of HIV-infection, tuberculosis (TB) and HIV-TB co-infection on vaccine-strain specific cell mediated immune responses, evaluated by ELISPOT assay, following non-adjuvanted TIV vaccination. [ Time Frame: up to 6 weeks after the end of the influenza season ]; • To compare the effect of HIV-infection, tuberculosis (TB) and HIV-TB co-infection on vaccine-strain specific cell mediated immune responses, evaluated by Enzyme-linked immunosorbent spot (ELISPOT) assay, following non-adjuvanted TIV vaccination. The cell mediated Immunity (CMI) evaluations in this study will provide novel information on influenza-specific CMI in individuals with TB. Interferon gama- ELISPOT responses will be assessed on fresh Peripheral Blood Mononuclear Cells (PBMCs). Spots will be visualized with a ELISPOT plate reader. Background (non-specific) spots detected in the medium-containing wells will be subtracted from the wells stimulated with influenza antigens. Results will be reported as Spot forming cell (SFC)/106 PBMCs.
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Effect of HIV and/or Active Tuberculosis on the Immune Responses to Trivalent Influenza Vaccine (TIV) in Adults
Official Title ICMJE	Effect of HIV and/or Active Tuberculosis on the Humoral and Cell Mediated Immune Responses to Un-adjuvanted Trivalent Sub-unit Influenza Vaccine (TIV) in Adults
Brief Summary	Prospective, open-labelled study which will enrol 360 participants in four groups of 80 participants including: HIV-uninfected adults without evidence of TB; HIV-infected adults without any evidence of TB; HIV-uninfected adults with concurrent microbiologic confirmed TB, HIV-infected adults with concurrent microbiologic confirmed TB. Participants will receive the recommended seasonal 2013 un-adjuvanted Trivalent Influenza Vaccine (TIV). At 3 visits, blood will be collected for determination of immune responses. Objective: • To determine the effect of HIV-infection, tuberculosis (TB) and HIV-TB co-infection on immune responses
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 4
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
Condition ICMJE	Influenza; HIV; Tuberculosis
Intervention ICMJE	Biological: Trivalent Inactivated Influenza Vaccine; The study vaccine will be the seasonal 2013 un-adjuvanted TIV which is provided as a 0•5 milliliter suspension of split virus mixture of 15 micrograms each of circulating H1N1- like strain, H3N2- like strain and B - like strain. The WHO recommended vaccine formulation for Southern Hemisphere 2013 Influenza Season contains the following influenza strains: A/California/7/2009 (H1N1)pdm-like virus; A/Victoria/361/2011 (H3N2)-like virus; B/Wisconsin/1/2010-like virus. (Yamagata lineage); Other Name: Vaxigrip
Study Arms	TIV; Trivalent Inactivated Influenza Vaccine The study vaccine will be the seasonal 2013 un-adjuvanted TIV which is provided as a 0•5 milliliter suspension of split virus mixture of 15 micrograms each of circulating H1N1- like strain, H3N2- like strain and B - like strain. The WHO recommended vaccine formulation for Southern Hemisphere 2013 Influenza Season contains the following influenza strains: A/California/7/2009 (H1N1)pdm-like virus; A/Victoria/361/2011 (H3N2)-like virus; B/Wisconsin/1/2010-like virus. (Yamagata lineage); Intervention: Biological: Trivalent Inactivated Influenza Vaccine
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Unknown status
Estimated Enrollment ICMJE; (submitted: March 12, 2013)	360
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	December 2014
Estimated Primary Completion Date	December 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: for HIV-infected subjects: a Cluster of Differntiation4 (CD4+) cell count of >100/ul within the previous 3 months;; able to attend the clinic for immunogenicity and illness visits;; for subjects with TB: having a microbiologic confirmed diagnosis of TB (defined as the presence of acid-fast-bacilli (AFB) on a sputum smear or other specimen and/or a positive culture for M. tuberculosis) within the past 120 days;; Aged 18 to 55 years. Exclusion Criteria: any contraindication to influenza vaccine;; any contraindication to intramuscular injections;; any existing grade 3 or grade 4 laboratory or clinical toxicity as per Division of Acquired Immune Deficiency Syndrome (DAIDS) toxicity tables;; systemic steroid treatment for >21 days within the past 30 days.; pregnancy (a urine Human Chorionic Gonadotropin (βHCG) will be performed on all women of childbearing age to exclude pregnancy)
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 55 Years (Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	South Africa
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01811823
Other Study ID Numbers ICMJE	TIV_HIV_TB
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Michelle Groome, University of Witwatersrand, South Africa
Study Sponsor ICMJE	University of Witwatersrand, South Africa
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Shabir A Madhi, PHD University of Witwatersrand, South Africa
PRS Account	University of Witwatersrand, South Africa
Verification Date	August 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP