Immune Response to Bivalent and Tetravalent Human Papillomavirus Vaccine in HIV Infected Adults (HIPAVAC)

The purpose of this study is to analyze and compare the immunogenicity of Bivalent and Tetravalent vaccines against Human Papillomavirus in HIV-infected adult persons.

Study Overview

• Status: Completed
• Conditions: HIV; Human Papillomavirus
• Intervention / Treatment: Biological: Gardasil; Biological: Cervarix

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Department of Infectious Diseases, Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV positive subjects.
• Age above 18 at the time of the first vaccination.
• Written informed consent obtained from the subject.
• Subjects whom the investigator believes can and will comply with the requirements of the protocol.
• If currently on antiretroviral therapy (ART), subjects must be compliant to triple therapy (highly active ART) and have undetectable viral load for a period of six months prior to study entry.
• Female subjects of non-childbearing potential may be enrolled in the study.
• Female subjects of childbearing potential may be enrolled in the study, if the subject has a negative pregnancy test at screening and on the day of vaccination, and has agreed to continue adequate contraception during the entire treatment period.

Exclusion Criteria:

• Previous vaccination against HPV, or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period (Day 0 to Month 12).
• Pregnant or breastfeeding female.
• Previous enrollment in the study.
• Subjects whom the investigator believes cannot and/or will not comply with the requirements of the protocol (i.e. because of abuse of drugs or alcohol, dementia or given medical, psychiatric, social or work related conditions).
• Chronic administration of immunosuppressive drugs
• Cancer or autoimmune disease
• Previous allergic reaction to vaccination
• Known allergy towards on or more components of either of the test drugs.

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
Experimental: Gardasil®	Biological: Gardasil; Subjects will receive three doses of the study vaccine administered intramuscularly according to a Day 0, Week 6, and Month 6 vaccination schedule.; Other Names: Tetravalent HPV vaccine
Experimental: Cervarix®	Biological: Cervarix; Subjects will receive three doses of the study vaccine administered intramuscularly according to a Day 0, Week 6, and Month 6 vaccination schedule.; Other Names: Bivalent HPV vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Geometric mean titres of serum HPV-16 and HPV-18 antibody titers on measured by Pseudovirion-Based Neutralization Assay (PBNA)	Day 0, Day 45, Day 180, Day 210 and Day 365

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric mean titres of serum HPV-31, HPV-33, HPV-45, HPV-52 and HPV-58 antibody measured by Pseudovirion-Based Neutralization Assay (PBNA)		Day 0, Day 45, Day 180, Day 210 and Day 365
Avidity of HPV-16 and -18 serum antibodies measured by ELISA		Day 0, Day 45, Day 180, Day 210 and Day 365
Frequencies of HPV-16 and HPV-18 T-cells measured by flow cytometry		Day 0, Day 45, Day 180, Day 210 and Day 365
Frequencies of HPV-16 and -18 specific B-cells measured by B-cell ELISPOT		Day 0, Day 45, Day 180, Day 210 and Day 365
B-cell profile measured by Flow cytometry		Day 0, Day 45, Day 180, Day 210 and Day 365
Secretion of pro- and antiinflammatory cytokines from PBMC's stimulated with innate stimuli measured by Luminex or Elisa		Day 0, Day 45, Day 180, Day 210 and Day 365
Type-specific HPV-DNA from cervical and genital swab material		Day 0 and Day 210
CD4 cell count and HIV viral load		Day 0, Day 45, Day 180, Day 210 and Day 365
Occurrence and intensity of solicited local symptoms	Participants will complete a vaccination diary with regards to local symptoms. Number and intensity of local symptoms will be listed and summarized.	Day 0-6 after each vaccination
Occurrence, intensity and relationship to vaccination of solicited general symptoms	Participants will complete a vaccination diary with regards to general symptoms. Number and intensity of generalized symptoms will be listed and summarized in a form.	Day 0-6 after each vaccination
Occurrence of SAEs		Throughout the active phase of the study (up to Day 210)
Occurrence of clinically relevant abnormalities in hematological and biochemical parameters	Clinical significant changes in hemoglobin, ALAT, basic phosphatase and creatinine compared to baseline values will be listed and summarized.	Throughout the active phase of the study (up to Day 210)
Geometric mean titres of HPV-16 and HPV-18 and total Immunoglobulin G (IgG) titers in cervicovaginal secretion (CVS) from female participants		Day 0, Day 210 and Day 365
Geometric mean titres of serum HPV-6 and HPV-11 antibody measured by a competitive Luminex immunoassay (cLIA)		To be measured at day 0, day 45, day 180, day 210 and day 365
% of participants seropositive for anti-HPV-6, -11 -18, -31, -33, -45, -52 and -58	% of participants seropositive for anti-HPV-6, -11 as measured by a competitive Luminex immunoassay (cLIA) and % of participants seropositive for anti-HPV-18, -31, -33, -45, -52 and -58 antibodies as measured by either Pseudovirion-Based Neutralization Assay (PBNA)	Day 0, Day 45, Day 180, Day 210, Day 365

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital
• Investigators: Study Director: Lars Østergaard, MD,PhD,DmSC, Department of Infectious Diseases, Aarhus University Hospital, Denmark; Principal Investigator: Lars Toft, MD, Department of Infectious Diseases, Aarhus University Hospital, Denmark

Publications and helpful links

General Publications

• Toft L, Tolstrup M, Muller M, Sehr P, Bonde J, Storgaard M, Ostergaard L, Sogaard OS. Comparison of the immunogenicity of Cervarix(R) and Gardasil(R) human papillomavirus vaccines for oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults. Hum Vaccin Immunother. 2014;10(5):1147-54. doi: 10.4161/hv.27925. Epub 2014 Feb 19.
• Toft L, Storgaard M, Muller M, Sehr P, Bonde J, Tolstrup M, Ostergaard L, Sogaard OS. Comparison of the immunogenicity and reactogenicity of Cervarix and Gardasil human papillomavirus vaccines in HIV-infected adults: a randomized, double-blind clinical trial. J Infect Dis. 2014 Apr 15;209(8):1165-73. doi: 10.1093/infdis/jit657. Epub 2013 Nov 23.

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: June 22, 2011
• First Submitted That Met QC Criteria: June 29, 2011
• First Posted (Estimate): June 30, 2011

Study Record Updates

• Last Update Posted (Estimate): August 16, 2013
• Last Update Submitted That Met QC Criteria: August 15, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: LTN0001