A Phase I Study of Quadrivalent Human Papilloma Virus (HPV) (Types 6, 11, 16, 18) Recombinant Vaccine in HIV-Infected and HIV-Negative Pre-Adolescents, Adolescents, and Young Adults
Condition: Human Immunodeficiency Virus; Human Papillomavirus- 6, 11, 16, 18; Adolescent; Papillomavirus Vaccines
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Papilloma
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

        -  Human papilloma virus (HPV) is a common sexually transmitted disease. There are more
           than 100 different HPV types, and both males and females can get HPV infection. Most
           people do not have any symptoms when they become infected and are able to get rid of the
           infection on their own. However, they can still become re-infected with the same or a
           different HPV type, and in some people HPV infection persists.

        -  Persistent HPV infection is associated with the development of precancerous lesions and
           cancer. HPV types are classified as either high risk or low risk based on whether their
           persistence will lead to cancer.

        -  Patients who have suppressed immune systems are at a higher risk for HPV-related
           complications. They are more likely to contract multiple HPV types and have more
           persistent infection that can lead to precancerous lesions or cancer, which are then
           difficult to treat and often recur.

        -  A recently approved vaccine for HPV induces immunity to HPV 6, 11, 16, and 18. It was
           shown to be highly effective in preventing infection with these HPV types, and is
           approved for use in females 9 to 26 years of age. However, much less is known about the
           vaccine s ability to induce immunity in males or individuals with suppressed immune
           systems.

      Objectives:

      - To investigate whether the HPV vaccine is safe to give and able to induce immunity in both
      female and male adolescents and young adults with HIV infection compared to healthy,
      HIV-negative persons of the same age.

      Eligibility:

      - Males and females, 12 to 26 years of age, divided into three groups: (1) Healthy and
      HIV-negative, (2) HIV-positive and on antiretroviral therapy, and (3) HIV-positive and not on
      antiretroviral therapy.

      Design:

        -  Before beginning vaccination, participants will have a complete physical examination and
           blood drawn for routine blood tests, special tests of the immune system, antibody tests,
           and an HIV test.

        -  HPV vaccine will be given by injection into the muscle at 0, 2, and 6 months, according
           to the standard vaccination schedule.

        -  Patients with HIV infection will be monitored for a week following the first injection
           to test the level of HIV in the blood 3 days and 5 days after the first injection.

        -  Participants will also be asked to fill out a 10- to 15-minute Web-based survey about
           awareness, health behaviors, and personal choices related to risk factors for HIV, HPV,
           and other sexually transmitted diseases. Participants are not required to fill out the
           survey to receive the vaccine.

        -  The total duration of the study is 4 years. During the first year of the study,
           participants will return for six additional 1-day visits at months 1, 2, 3, 6, 7, and
           12. Participants will return for 1-day visits every 6 months for the remaining 3 years.
    

Detailed description: 
      Background:

      Human papilloma virus (HPV) is one of the most common sexually transmitted diseases and a
      significant cause of cutaneous genital warts and anogenital cancer.

      Infection with high-risk, oncogenic HPV types, most commonly types 16 and 18, is associated
      with low and high-grade cervical cellular abnormalities that are precursors to invasive
      cervical cancer, as well as vulvar and anal cancer, while HPV types 6 and 11 are associated
      with genital warts.

      Persistence of HPV infection is more common in individuals with or at risk for chronic
      immunosuppression and HIV-infected individuals have a higher prevalence of HPV infection and
      HPV-associated anogential disease compared to age-matched HIV-negative controls.

      Study Objectives:

      To assess the safety and immunogenicity of quadrivalent human papillomavirus (types 6, 11,
      16, 18) recombinant vaccine in HIV-infected preadolescents, adolescents and young adults
      12-26 years of age.

      To determine whether there are differences in HPV vaccine immunogenicity between HIV-infected
      and HIV negative age-matched controls.

      To determine whether there are differences in HPV vaccine immunogenicity between HIV-infected
      patients receiving highly active antiretroviral therapy (HAART) and those not receiving HAART
      with similar CD4 and viral load parameters at entry.

      To determine whether HPV vaccination alters HIV-1 RNA levels.

      To investigate the impact of CD4 count and HIV-1 RNA levels on HPV vaccine immunogenicity.

      To characterize HPV DNA positivity in the study cohort populations through oral/buccal and
      anogenital sampling at baseline.

      To characterize HPV and HIV knowledge and risk and sexual behaviors in the study cohort
      populations.

      Eligibility:

      Individual Cohorts

      Cohort 1: HIV-positive, CD4 cell count greater than or equal to 350 cells/mm3, HIV-1 RNA
      level by RT PCR less than or equal to 20,000 copies/ml, on stable HAART regimen for greater
      than or equal to 6 months.

      Cohort 2: HIV-infected, CD4 cell count greater than or equal to 500 cells/mm3, HIV-1 RNA
      level by RT PCR less than or equal to 20,000 copies/ml, on no antiretroviral treatment.

      Cohort 3: healthy, HIV-negative controls All Cohorts

      Females and males age 12 to 26 years

      Patients must have a hemoglobin greater than or equal to 10.0 gm/dL, neutrophil count (ANC)
      greater than or equal to 1500/mm3, platelet count greater than or equal to 75,000/mm3 and PT
      or PTT less than or equal to 1.5x ULN (with the exception of patients with known clotting
      disorders or lupus anticoagulant); SGPT/SGOT < 2/5x ULN, total bilirubin less than or equal
      to 1.5x ULN unless attributable to protease inhibitor therapy.

      Patients must test negative for hepatitis B virus and hepatitis C virus, unless the result is
      consistent with prior vaccination or prior infection with full recovery.

      No use of investigational agents within 4 weeks of study enrollment or use of
      immunosuppressive or immunomodulating agents within 8 weeks of study entry.

      Study Design:

      This is a non-randomized, prospective, phase I study of quadrivalent human papillomavirus
      (types 6, 11, 16, 18) recombinant vaccine.

      The study includes 3 cohorts of pre-adolescents, adolescents and young adults 12-26 years of
      age as outlined under Eligibility Criteria. Each cohort will enroll 35 patients.

      All study subjects will receive three doses of HPV vaccine at 0, 2 and 6 months administered
      IM.

      Study participants will be monitored at months 0, 1, 2, 3, 6, 7, and 12 (+/- 2 weeks for each
      visit, and every 6 months (+/- 30 days) thereafter for 48 months total.
    

Intervention name(s): Gardasil; Survey
Intervention type(s): Biological; Behavioral
Intervention description(s): .5 mL dose injected IM at 0, 2 and 6 months; Administration of online risk behavior and knowledge survey done at week 0.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: HPV Vaccination; HPV Immunogenicity; HIV Infection; HIV Negative; Adolescents and Young Adults; Healthy Volunteer; HV; Adolescent