Clinical trial NCT01386164: Immune Response to Bivalent and Tetravalent Human Papillomavirus Vaccine in HIV Infected Adults
Official title: Immune Response to Bivalent and Tetravalent Human Papillomavirus Vaccine in HIV Infected Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV
Human Papillomavirus
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
First posted: 2011-06-30
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Geometric mean titres of serum HPV-16 and HPV-18 antibody titers on measured by Pseudovirion-Based Neutralization Assay (PBNA)
timeFrame: Day 0, Day 45, Day 180, Day 210 and Day 365
Secondary outcomes:
measure: Geometric mean titres of serum HPV-31, HPV-33, HPV-45, HPV-52 and HPV-58 antibody measured by Pseudovirion-Based Neutralization Assay (PBNA)
timeFrame: Day 0, Day 45, Day 180, Day 210 and Day 365
measure: Avidity of HPV-16 and -18 serum antibodies measured by ELISA
timeFrame: Day 0, Day 45, Day 180, Day 210 and Day 365
measure: Frequencies of HPV-16 and HPV-18 T-cells measured by flow cytometry
timeFrame: Day 0, Day 45, Day 180, Day 210 and Day 365
measure: Frequencies of HPV-16 and -18 specific B-cells measured by B-cell ELISPOT
timeFrame: Day 0, Day 45, Day 180, Day 210 and Day 365
measure: B-cell profile measured by Flow cytometry
timeFrame: Day 0, Day 45, Day 180, Day 210 and Day 365
measure: Secretion of pro- and antiinflammatory cytokines from PBMC's stimulated with innate stimuli measured by Luminex or Elisa
timeFrame: Day 0, Day 45, Day 180, Day 210 and Day 365
measure: Type-specific HPV-DNA from cervical and genital swab material
timeFrame: Day 0 and Day 210
measure: CD4 cell count and HIV viral load
timeFrame: Day 0, Day 45, Day 180, Day 210 and Day 365
measure: Occurrence and intensity of solicited local symptoms
timeFrame: Day 0-6 after each vaccination
measure: Occurrence, intensity and relationship to vaccination of solicited general symptoms
timeFrame: Day 0-6 after each vaccination
measure: Occurrence of SAEs
timeFrame: Throughout the active phase of the study (up to Day 210)
measure: Occurrence of clinically relevant abnormalities in hematological and biochemical parameters
timeFrame: Throughout the active phase of the study (up to Day 210)
measure: Geometric mean titres of HPV-16 and HPV-18 and total Immunoglobulin G (IgG) titers in cervicovaginal secretion (CVS) from female participants
timeFrame: Day 0, Day 210 and Day 365
measure: Geometric mean titres of serum HPV-6 and HPV-11 antibody measured by a competitive Luminex immunoassay (cLIA)
timeFrame: To be measured at day 0, day 45, day 180, day 210 and day 365
measure: % of participants seropositive for anti-HPV-6, -11 -18, -31, -33, -45, -52 and -58
timeFrame: Day 0, Day 45, Day 180, Day 210, Day 365
Other outcomes:
Locations:
city: Aarhus N
country: Denmark
facility: Department of Infectious Diseases, Aarhus University Hospital
Study officials:
affiliation: Department of Infectious Diseases, Aarhus University Hospital, Denmark
name: Lars Østergaard, MD,PhD,DmSC
role: STUDY_DIRECTOR
affiliation: Department of Infectious Diseases, Aarhus University Hospital, Denmark
name: Lars Toft, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.