Safety and Immunogenicity of GlaxoSmithKline Biologicals' HPV Vaccine 580299 (Cervarix) in HIV Infected Females
Condition: Infections, Papillomavirus
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Intervention: Cervarix; Placebo Control
Intervention description: Intramuscular injection, 3 doses; Intramuscular injection, 3 doses
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 150.0
Sex: Female
Minimum age: 18 Years
Maximum age: 25 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: HPV; Human papillomavirus (HPV) vaccine; Human Immunodeficiency Virus (HIV); Cervical cancer; Papillomavirus

Summary:

      Infection with human papillomavirus (HPV) has been clearly established as the central cause
      of cervical cancer. The current study is designed to evaluate the safety and immunogenicity
      of GlaxoSmithKline Biologicals' HPV vaccine 580299 in HIV infected adult females living in
      the Republic of South Africa. The study is double blinded, randomized for HIV positive
      subjects and open for HIV negative subjects. The Protocol Posting has been updated in order
      to comply with the FDA Amendment Act, Sep 2007.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects who the investigator believes that they can and will comply with the
             requirements of the protocol

          -  A female between, and including, 18 and 25 years of age at the time of the first
             vaccination.

          -  Written, signed or thumb-printed informed consent obtained from the subject prior to
             enrolment.

          -  Subjects willing to undergo HIV Voluntary Counseling and Testing (VCT) and willing to
             be informed of their HIV status.

          -  Subjects willing to provide place of residence and be visited at home.

          -  HIV seropositive subjects:

               1. Subjects must be HIV seropositive according to WHO case definition

               2. Subjects with WHO Clinical Stage 1 HIV-associated disease

               3. Subjects currently on antiretroviral therapy (ART) must be compliant to ART and
                  have undetectable viral load

          -  HIV seronegative subjects: Subjects confirmed as HIV seronegative at the screening
             visit are eligible to participate in the HIV-/HPV group of the study.

          -  Non-virgin subjects must have a normal colposcopy at the screening visit.

          -  Non-virgin subjects must have a normal cervical cytology (Pap smear) or no greater
             than atypical squamous cells of undetermined significance (ASC-US) at the screening
             visit.

          -  All subjects must have a negative urine pregnancy test at the screening visit and at
             visit 1 (Day 0).

          -  Subjects must be of non-childbearing potential or, if of childbearing potential, must
             be abstinent or have used adequate contraceptive precautions for 30 days prior to
             vaccination, have a negative pregnancy test and must agree to continue such
             precautions for two months after completion of the vaccination series.

          -  Subjects must have had no more than 6 life-time sexual partners prior to enrolment.

          -  Subjects must have one single intact cervix

        Exclusion Criteria:

          -  Active tuberculosis (TB)

          -  Current TB prophylaxis or therapy.

          -  Anemia at the screening visit.

          -  increased creatinine at the screening visit.

          -  Increased hepatic enzym (ALT) at the screening visit

          -  Use of any investigational or non-registered product (drug or vaccine) other than the
             study vaccine within 30 days preceding the first dose of study vaccine/control, or
             planned use during the entire study period (up to Month 12).

          -  Chronic administration of immunosuppressants or other immune-modifying drugs within 6
             months prior to the first vaccine dose.

          -  Administration of a vaccine not foreseen by the study protocol within 30 days before
             the first dose of study vaccine/control. Enrolment will be postponed until the subject
             is outside the specified window.

          -  Planned administration of a vaccine not foreseen by the study protocol within 30 days
             before or 30 days after (i.e., Days 0-29) any dose of study vaccine.

          -  Previous vaccination against HPV, or planned administration of any HPV vaccine other
             than that foreseen by the study protocol during the study period (Month 0 to Month
             12).

          -  previous administration of components of the investigational vaccine

          -  Cancer or autoimmune disease under treatment.

          -  Hypersensitivity to latex.

          -  History of allergic disease or reactions likely to be exacerbated by any component of
             the vaccine/control.

          -  Acute disease at the time of enrolment.

          -  Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal
             functional abnormality, as determined by physical examination or laboratory testing
             performed at the screening visit.

          -  History of any neurological disorders or seizures.

          -  Pregnant or breastfeeding female.

          -  A subject planning to become pregnant, likely to become pregnant (as determined by the
             investigator) or planning to discontinue contraceptive precautions during the study
             period, up to two months after the last vaccine dose.

          -  Concurrently participating in another clinical study, at any time during the study
             period (up to Month 12), in which the subject has been or will be exposed to an
             investigational or a non-investigational product (pharmaceutical product or device).

          -  Any medically diagnosed or suspected immunodeficient condition (other than HIV for HIV
             seropositive subjects), based on medical history, physical examination and/or
             laboratory tests results.

          -  Administration of immunoglobulins and/or any blood products within the three months
             preceding the first dose of study vaccine/control or planned administration during the
             study period. Enrolment will be postponed until the subject is outside the specified
             window.

          -  Administration of trimethoprim/sulphamethoxazole within 7 days before the first dose
             of study vaccine/control, or planned administration of trimethoprim/sulphamethoxazole
             within 7 days after the first dose of study vaccine/control.

          -  Current drugs or alcohol abuse.