Long Term Follow-up of HPV Vaccine in HIV (CTN 236)

Long Term Follow-up Study of CTN 236 - A Study of an HPV VLP Vaccine in a Cohort of HIV Positive Girls and Women

The purpose of this extension study is to determine whether HPV antibody levels in HIV-positive girls and women will decline more rapidly and more significantly than in HIV-negative girls and women and if this decline is determined by HIV parameters.

Study Overview

• Status: Completed
• Conditions: Cervical Cancer; Human Immunodeficiency Virus; Human Papillomavirus Infection; Genital Warts; Cervical Dysplasia

Detailed Description

Study hypothesis: HPV antibody levels in HIV-positive girls and women will decline more rapidly and more significantly than in HIV-negative girls and women and that this decline will be determined by HIV parameters.

Girls and women living with HIV (greater than, or equal to, age 11) attending the HIV treatment clinics in each of the 13 sites across Canada and who enrolled in and received at least one dose of quadrivalent HPV vaccine as part of "A Study of an HPV VLP Vaccine in a Cohort of HIV Positive Girls and Women (CTN 236)" will be offered participation in this long term follow-up study.

OBJECTIVES

Primary:

To measure the antibody response to each genotype contained in the qHPV vaccine to 96 months post first dose of quadrivalent HPV vaccine.

Secondary:

1. To determine the incidence rate and nature of 'breakthrough' HPV incidence and persistent (2 sequential positive HPV DNA in > 6 months) infections of vaccine - non-vaccine-containing high-risk types;
2. To determine the incidence rate of cervical dysplasia (LSIL or greater) and/or vulvar and vaginal dysplasia associated HPV genotypes (both with and without vaccine types; and
3. To determine the incidence rate of external genital warts.

Exploratory:

1. To examine the relationship between HSV-2 serostatus and peak HPV antibody response as well as HPV incidence and persistent infections; and
2. To relate vaginal microbiome profiles to HPV acquisition/persistence and cervical dysplasia.

STUDY DESIGN Phase 3, longitudinal, multi-center, 13 sites, girls and women living with HIV aged 11 years of age and older, received one plus dose of quadrivalent HPV vaccine in the precursor study.

STUDY VISITS 3 possible visits over a total of 5 years

• Visit 8 (month 36)
• Visit 9 (month 48)
• Visit 10 (month 60)
• Visit 11 (month 72)*
• Visit 12 (month 84)*
• Visit 13 (month 96)*

STUDY PROCEDURES:

Informed consent, Medical history, Height & weight, Cervical cytology and HPV DNA (liquid prep method), Gynecological swab for vaginal microbiota, Serology for HPV antibodies, Serology for HSV-2, Lower Urinary Tract Symptoms Survey (at one time-point only for participants 18 years of age and older).

NOTE: Girls who are pre-menarchal and not sexually active will not be asked to undergo any genital examinations or sampling until they become menarchal and sexually active.

DATA COLLECTION Consent and source document templates will be provided by the Study Coordinating Center. Source data will be transferred to paper case report forms and sent to the Study Coordinating Center/CTN where it will be entered into an electronic database.

PRIMARY ENDPOINT The primary endpoint of this study will be the HPV antibody GMT for each of the 4 types contained in the GARDASIL™ vaccine up to month 96 after receiving at least one dose of the vaccine.

SECONDARY ENDPOINTS Incidence rates of: 1) breakthrough incidents and persistent HPV infections; 2) cervical dysplasia; 3) external genital warts

• Study Type: Observational
• Enrollment (Actual): 241

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3N1
      • Oak Tree Clinic, BC Women's Hospital & Health Centre
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • AIDS Research Program & the John Ruedy Immunodeficience Clinic, St. Paul's Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8S 1A4
      • Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7L 5G2
      • Infection & Immunology Clinic, Hotel Dieu
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario (CHEO)
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
    • Toronto, Ontario, Canada, M5G 2N2
      • Toronto General Hospital
    • Toronto, Ontario, Canada, M5C 1K2
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M5G 2N2
      • Maple Leaf Research
    • Windsor, Ontario, Canada, N8W 1E3
      • HIV Care Program
  • Quebec
    • Montréal, Quebec, Canada, H3T 1C5
      • Centre de maternal et infantile sur le sida, CHU Sainte Justine
    • Montréal, Quebec, Canada, H4A 3J1
      • Chronic Viral Illness Service, Hopital Royal Victoria (McGill University)
    • Québec City, Quebec, Canada, G1V 4G2
      • CHUL and Mother-Child Center Soleil, Centre de Recherche en Infectiologie CHU de Quebec, (Universite Laval)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

HIV positive girls and women (greater than, or equal to, age 11) attending the HIV treatment clinics in each of the 13 sites across Canada and who have enrolled in the original study, "A Study of an HPV VLP Vaccine in a Cohort of HIV Positive Girls and Women (CTN 236)" and received at least one dose of the quadrivalent HPV vaccine, will be offered participation in the study.

Description

Inclusion Criteria:

• Enrolled in CTN 236 study, phase 1
• Able to give fully informed consent or assent

Exclusion Criteria:

• Did not receive at least one vaccination via CTN 236, phase 1
• Cannot provide fully informed consent or assent

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Study Population; HIV positive girls and women (greater than, or equal to, age 11) attending the HIV treatment clinics in each of the 13 sites across Canada and who have enrolled in the original study, "A Study of an HPV VLP Vaccine in a Cohort of HIV Positive Girls and Women (CTN 236)" and received at least one dose of quadrivalent HPV vaccine, will be offered participation on this study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Objective	To measure the antibody response to each genotype contained in the qHPV vaccine to 96 months post-vaccination regimen.	96 month post-vaccination regimen

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Objective #1	To determine the incidence rate and nature of 'breakthrough' HPV incidence and persistent (2 sequential positive HPV DNA in > 6 months) infections of vaccine - non-vaccine-containing high-risk types.	96 month post-vaccination regimen
Secondary Objective #2	To determine the incidence rate of cervical dysplasia (LSIL or greater) and/or vulvar and vaginal dysplasia associated HPV genotypes (both with and without vaccine types	96 month post-vaccination regimen
Secondary Objective #3	To determine the incidence rate of external genital warts.	96 month post-vaccination regimen

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Objective #1	To examine the relationship between HSV-2 serostatus and peak HPV antibody response as well as HPV incidence and persistent infections	96 month post-vaccination regimen
Exploratory Objective #2	To relate vaginal microbiome profiles to HPV acquisition/persistence and cervical dysplasia.	96 month post-vaccination regimen

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: University Health Network, Toronto; McGill University; Canadian Institutes of Health Research (CIHR); British Columbia Cancer Agency; CIHR Canadian HIV Trials Network; British Columbia Centre for Disease Control; BC Women's Hospital & Health Centre; Women's Health Research Institute of British Columbia; Merck Canada Inc.; Vaccine Evaluation Center, Canada; University of Saskatoon
• Investigators: Principal Investigator: Deborah M Money, MD, FRCSC, Dept. OB/GYN, University of British Columbia

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): March 30, 2021
• Study Completion (Actual): March 30, 2021

Study Registration Dates

• First Submitted: March 31, 2025
• First Submitted That Met QC Criteria: March 31, 2025
• First Posted (Actual): April 8, 2025

Study Record Updates

• Last Update Posted (Actual): April 8, 2025
• Last Update Submitted That Met QC Criteria: March 31, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: HIV; Women; Cervical Cancer; HPV; Genital Warts; HPV Vaccine
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Uterine Diseases; Genital Diseases, Female; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; DNA Virus Infections; Genital Neoplasms, Female; Skin Diseases; Slow Virus Diseases; Precancerous Conditions; Uterine Cervical Diseases; Skin Diseases, Infectious; Uterine Neoplasms; Tumor Virus Infections; Skin Diseases, Viral; Warts; HIV Infections; Acquired Immunodeficiency Syndrome; Uterine Cervical Neoplasms; Papillomavirus Infections; Uterine Cervical Dysplasia; Condylomata Acuminata
• Other Study ID Numbers: H14-02364

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No