Effectiveness and B-memory Cell Response to QHPV Vaccine 9-years Post-vaccination Among HIV-infected Boys and Girls

In 2013, the Investigators enrolled a cohort of 180 HIV-1 infected adolescent girls and boys ages 9-14 years and administered three doses of the QHPV vaccine (NCT04711265). For this study, the Investigators shall evaluate vaccine effectiveness 9 years post first vaccination.

Participants will be evaluated for HPV type specific antibody, genital HPV infection, genital warts and a subset of 30 participants will be evaluated for memory B and T cell responses.

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 participles (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 doses for the HIV-infected adolescent.

The 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.

A sub-set of study participants will receive a booster dose of QHPV and evaluated for memory B and T cell responses.

The total duration of study follow up will be 12 months

Eligibility Criteria:
Inclusion Criteria:

1. received three doses of the quadrivalent HPV vaccine and enrolled in the quadrivalent HPV vaccine safety and immunogenicity study (MISP 38406)
2. participant consent or parental/guardian consent and participant assent for participants still \<18 years of age
3. participants and guardians who consented to be contacted for further evaluation and participation in research and
4. are willing to continue longer-term follow up.

Exclusion Criteria:

1. Did not participate in the quadrivalent HPV vaccine safety and immunogenicity study (MISP 38406)
2. Not willing or able to provide written informed consent/assent to participate in the study