Immunogenicity and Safety of a 9-valent Human Papillomavirus Vaccine in HIV-positive Women

Study Overview
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Brief Summary
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In adult HIV-positive patients, data on the safety and immunogenicity of the quadrivalent HPV (qHPV) vaccine have been reported with excellent results (13 14); also, the results of a clinical trial of qHPV vaccine conducted in seropositive patients older than 36 years (WLHIV and MSM) have been published. Even now, there is not a trial about immunogenicity and safety of a 9-valent human papillomavirus vaccine in HIV-positive women; for this reason, the investigators plan to conduct this clinical trial. HYPOTHESYS: The administration of Nonavalent HPV vaccine (HPV-9) in adult women living with HIV will produce antibodies against nine genotypes of HPV, thus preventing the acquisition of new infections by those genotypes. Besides, this will prevent the cervical and anal dysplasia in these women.

Detailed Description
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This is a phase IV (post-authorization study), open, single-arm trial of 9-valent human papillomavirus (9-HPV) vaccine in HIV-positive women. The recruitment and follow-up period will be 6 and 30 months, respectively. At the initial clinical visit (V0), the conditions and objectives of the study were explained. The details were summarised in a document, which was presented to the patient who then signed the informed consent form. 2 mucosa samples were taken from the anal canal for the detection and genotyping of the HPV and for anal cytology; and high resolution anoscopy will be carried out. The patients will send to gynaecologist for exploration. Finally, full blood haemogram and blood chemistry analysis were measured, together with cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8) lymphocytes counts, HIV viral load (VL) and antibodies against 9 genotypes of the 9-HPV vaccine. 9-HPV vaccine will be administered at day 1 (V1), month 2 (V2) and month 6 (V3). Flow of subjects through the study in graphic 1. Settings and locations: The patients who enrolled were HIV-positive women that were attending the Infectious Diseases Service of the University Hospital Virgen de las Nieves, Granada (Spain), Hospitalary Complex Ciudad de Jaén (Spain) and University hospital San Cecilio, Granada (Spain). The purposes of the study were explained to the potential participants who then underwent screening, and enrolled if they met the inclusion criteria for the trial. They were asked to sign the fully informed consent form. The study will be conducted in compliance with ethical and moral principles stated in the Declaration of Helsinki as well as the current Spanish Laws on Biomedical Research(LEY 14/2007, de 3 de julio). Data were coded to ensure anonymity. SAMPLE SIZE CONSIDERATIONS: Currently, the rate of infections in unvaccinated women in the participating centers is 46.4% (12). The efficacy rate of the tetravalent vaccine in the prevention of cervical cancer is close to 100% and in the appearance of external anal lesions in men, around 85% (21). Considering that in our study population, the effectiveness is at least 75%, to achieve an accuracy of 5% in the estimation of a proportion through a normal 95% asymptotic confidence interval, assuming that the proportion is 11, 6% (25% of 46.4%), it will be necessary to include 158 women in the study. To this sample size will be added 10% in anticipation of possible losses in the follow-up or dropouts. DATA COLLECTION: All data were collected and coded to ensure anonymity according to the current legal requirements in Spain and European Union (EU) (GDPR Regulation (EU) 2016/679). At the initial clinical visit (V0), the conditions and objectives of the study were explained to subjects. The details were summarised in a document, which was presented to the patient who then signed the informed consent form.

Official Title
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Immunogenicity and Safety of a 9-valent Human Papillomavirus Vaccine in HIV-positive Women.

Conditions
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HIV Infections, HPV Infection

Intervention / Treatment
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* Biological: Human Papillomavirus 9-valent Vaccine, Recombinant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-positive women patients of ≥18 years of age who, at the time of study inclusion were not infected simultaneously by the 16, 18 genotypes of HPV in vagina and/or anus. Exclusion Criteria: WLHIV patients who had simultaneous anal infection with the 16, 18, 31, 33, 45, 52 y 58 genotypes. - WLHIV diagnosed in V0 of ASCC or anal HSIL. Active opportunist infection at the time of recruitment into the study. Cd4 count < 200 cel/µL. History of allergy to aluminium and/or yeast extract excipient.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a phase IV (post-authorization study), open, single-arm trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Only arm<br>Single arm, Receiving treatment | Biological: Human Papillomavirus 9-valent Vaccine, Recombinant<br>* Vaccine administrated<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibodies against the 9 genotypes of the qHPV vaccine | immunogenicity of a 9-valent human papillomavirus vaccine in HIV-positive women older than ≥18 years | 30 months | 
| Incidence of Treatment-Emergent Adverse Events of a 9-valent human papillomavirus vaccine in HIV-positive women older than ≥18 years | Number of Participants With Any Adverse Event (AE) | Through study completion, up to 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| new HPV genotypes | acquisition rate of HPV genotypes of anal and cervical mucosa. | Determined at 12th, 24th, 30th month | 
| Data analysis of risk factors in subject who acquire HPV genotypes from data recorded at follow-up visits via survey. | The survey asks about HPV risk factors. | 30 months | 
| progression to dysplastic lesions | rate of progression to dysplastic lesions (LSIL, high grade squamous intraepithelial lesion (HSIL) and Cancer) anal and cervical after vaccination. | Determined at 12th, 24th, 30th month |