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

Study Overview
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Brief Summary
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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.

Official Title
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Immune Response to Bivalent and Tetravalent Human Papillomavirus Vaccine in HIV Infected Adults

Conditions
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HIV, Human Papillomavirus

Intervention / Treatment
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* Biological: Gardasil
* Biological: Cervarix


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gardasil®<br> | Biological: Gardasil<br>* Subjects will receive three doses of the study vaccine administered intramuscularly according to a Day 0, Week 6, and Month 6 vaccination schedule.<br>* Other names: Tetravalent HPV vaccine;|
| Experimental: Cervarix®<br> | Biological: Cervarix<br>* Subjects will receive three doses of the study vaccine administered intramuscularly according to a Day 0, Week 6, and Month 6 vaccination schedule.<br>* Other names: Bivalent HPV vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |