Effectiveness of the Q-HPV Vaccine 9-years Post Vaccination Among HIV Positive Adolescents

A Longitudinal Cohort Study to Assess Effectiveness and B-memory Response to the Quadrivalent HPV Vaccine 9 Years Post-vaccination Among HIV-Infected Boys and Girls Ages 9-14 Years in Kenya

The risk for Human Papillomavirus (HPV) infection persists through an individual sexual life and duration of protection is critical to vaccine effectiveness in protection from oncogenic hrHPV infection. HIV-infected individuals have an increased risk for HPV infection, and persistent infection.

Most vaccine efficacy data among HIV-infected adolescents is represented by immunogenicity data, and there is little published literature on vaccine effectiveness as assessed by persistent incident genital HPV infection.

Investigators shall re-enroll a cohort of previously vaccinated HIV-infected girls and boys for assessment of genital HPV infection 9-years post initial 3 doses of vaccination with quadrivalent HPV vaccine at ages 9 to 14 years.

Study Overview

• Status: Completed
• Conditions: HPV Infection; HPV Vaccination
• Intervention / Treatment: Drug: Quadrivalent Human Papillomavirus (Types 6,11,16,18) Recombinant Vaccine

Detailed Description

Background: Genital Human Papilloma Virus (HPV) infections occur rapidly after sexual debut, and immunosuppressed individuals are at greater risk for incident and persistent infection. HPV vaccine contains virus-like particles (VLP), which are highly immunogenic and induce a robust humoral response that has been demonstrated to confer long term protection from HPV infection and associated disease among HIV-uninfected individuals. The magnitude of type-specific vaccine induced neutralizing HPV antibody responses are diminished among HIV-infected compared to uninfected individuals.

There is no established minimum level of antibody that predicts protection against HPV infection or associated disease, the impact of lower antibody titers among HIV infected individuals on vaccine efficacy is unknown. The risk of HPV exposure persists throughout a person's sexual life and the duration of protection, especially when the vaccine is given in the early adolescent period is critical to vaccine effectiveness. Long lasting memory is characterized by memory B cells and long-lived plasma cells and a QHPV booster dose has demonstrated an anamnestic response among HIV-infected adolescents.

HPV efficacy and effectiveness data for HIV-uninfected individuals has informed the current World Health Organization (WHO) two-dose vaccine schedule. The field lacks data on effectiveness of three dose or two-dose for the HIV-infected adolescents. The current on-going research for single dose schedules gives urgency to the determination of long-term efficacy of three HPV vaccine 231 doses for the HIV-infected adolescent.

Investigators shall recall HIV-infected girls and boys who were previously vaccinated at ages 9-14 years with three doses of the quadrivalent vaccine (QHPV) in 2014 and evaluated for vaccine immunogenicity.

Method: The participants will be assessed for genital warts and genital HPV infection. Type specific HPV DNA will be assessed using genital swabs and genital warts assessed through physical examination among sexually active participants at enrollment, month 6 &12.

Among those that have not become sexually active, or that decline a genital exam, a self-collected swab will be requested. A sub-set of approximately 30 participants, will receive a booster dose of QHPV, from this subset, Peripheral Blood Mononuclear Cells (PBMC) and plasma samples will be collected at enrollment, at month 1 and month 12 to evaluate for memory B and T cell responses.

The total duration of study follow up will be 12 months.

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 4

Contacts and Locations

Study Locations

• Kenya
  • Kiambu
    • Thika, Kiambu, Kenya
      • Phrd-Ccr-Kemri

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• HIV-infected
• enrolled previously and received received three doses of quadrivalent HPV- vaccine in 2014

Exclusion Criteria:

• Decline re-enrollment
• unable to provide informed consent
• minor without parent or guardian consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Quadrivalent HPV Vaccine; Gardasil® 0.5 mL administered intramuscularly in the deltoid or anterolateral area of the thigh	Drug: Quadrivalent Human Papillomavirus (Types 6,11,16,18) Recombinant Vaccine; Gardasil; Other Names: Gardasil-4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistent Genital HPV infection	Number of participants with incident persistent genital infection with the QHPV specific serotypes: -6, -11, -16 and -18 and additional 13 oncogenic HPV serotypes (31,33,35,39,45,51,52,56,58,59,66, 68,73)	Nine years after primary vaccination
Sustained QHPV vaccine specific antibody titers	Concentration of QHPV specific antibody titers (HPV -6, -11, -16 & -18) nine years after primary vaccination	Nine years after primary vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune memory following three doses of QHPV	B cell marker concentration following a booster 4th dose of QHPV	One month after booster vaccine

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Nelly Mugo, MD, University of Washington

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2022
• Primary Completion (Actual): October 31, 2023
• Study Completion (Actual): October 31, 2023

Study Registration Dates

• First Submitted: June 10, 2022
• First Submitted That Met QC Criteria: June 22, 2022
• First Posted (Actual): June 28, 2022

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 23, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: adolescents; Genital HPV infection; quadrivalent HPV vaccination; HIV-infected
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Disease Attributes; DNA Virus Infections; Tumor Virus Infections; Urogenital Diseases; Genital Diseases; Papillomavirus Infections
• Other Study ID Numbers: STUDY00013326

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes