Effectiveness of the Q-HPV Vaccine 9-years Post Vaccination Among HIV Positive Adolescents
Condition: HPV Infection; HPV Vaccination
MeSH terms: Papillomavirus Infections
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

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.
    

Intervention name(s): Quadrivalent Human Papillomavirus (Types 6,11,16,18) Recombinant Vaccine
Intervention type(s): Drug
Intervention description(s): Gardasil
Other intervention name(s): Gardasil-4
Intervention model: Single Group Assignment
Intervention model description: Quadrivalent HPV vaccine
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Genital HPV infection; quadrivalent HPV vaccination; HIV-infected; adolescents