Title
Vaccine Therapy in Preventing HPV in HIV-Positive Women in India
A Single-Arm, Open-Label Pilot Study of the Safety and Immunogenicity of the Merck Quadrivalent Human Papillomavirus Vaccine Among HIV-Positive Women in India
Phase
Phase 1Lead Sponsor
AIDS Malignancy ConsortiumStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
Cervical Cancer Nonneoplastic Condition Precancerous ConditionIntervention/Treatment
human papillomavirus quadrivalent (types 6, 11, 16 and 18) vaccine, recombinant ...Study Participants
150RATIONALE: Vaccines made from virus proteins may help the body build an effective immune response to prevent cervical cancer.
PURPOSE: This pilot study is looking at the side effects of a human papillomavirus vaccine and how well it works in preventing cervical cancer in women in India with HIV-1 infection.
OBJECTIVES:
Primary
Assess the safety of the Gardasil® quadrivalent human papillomavirus (HPV) (types 6, 11, 16,18) virus-like-particle vaccine with vs without prior exposure to one or more of the HPV types in the vaccine in HIV-positive women in Chennai, India.
Determine the effect of the vaccine on HIV viral load and CD4+/CD8+ levels in these patients.
Determine the proportion of these patients who respond serologically to the HPV vaccine and the kinetics of their response.
Secondary
Determine the prevalence and incidence of cervical intraepithelial neoplasia in these patients.
Determine the spectrum of cervical HPV types in these patients at baseline, 9 months, and 1 year after vaccination.
OUTLINE: This is a multicenter study.
Patients receive quadrivalent human papillomavirus (HPV) (types 6, 11, 16, 18) recombinant vaccine intramuscularly on day 0 and once in weeks 8 and 24.
Patients undergo cervical cell, buccal cell, and blood sample collection at baseline and periodically after vaccination for immunologic and virologic studies. Cervical cytology specimens are examined by polymerase chain reaction to detect HPV 6, 11, 16, or 18 DNA, as well as 35 other HPV types. Blood samples are analyzed for CD4+/CD8+ cell count, plasma HIV-1 RNA levels, and serum HPV antibody titers for HPV types 6, 11, 16, and 18. Some plasma samples will be stored for future HPV pseudovirion neutralization assays.
After completion of study therapy, patients are followed periodically for up to 12 months.
Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24.
Weeks 0, 2, 10, 26, and 52.
Screening, week 36, and week 52.
Screening, week 36, and week 52.
Screening, week 36, and week 52.
Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24.
DISEASE CHARACTERISTICS: HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by western blot before study entry HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test Meets 1 of the following criteria: Nadir CD4 level of ≤ 350 cells/mm³ and receiving highly active antiretroviral therapy (HAART) for at least 6 months before study entry Nadir CD4 level of > 350 cells/mm³ and not receiving HAART at the time of study entry No known history of high-grade CIN or cervical cancer PATIENT CHARACTERISTICS: Karnofsky performance status 70-100% ANC > 750 cells/mm³ Hemoglobin ≥ 9.0 g/dL Platelet count ≥ 100,000/mm³ Serum creatinine ≤ 3 times upper limit of normal (ULN) AST and ALT ≤ 3.0 times ULN Conjugated (direct) bilirubin ≤ 2.5 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active drug or alcohol use or dependence that would interfere with adherence to study requirements, in the opinion of the site Investigator No serious illness requiring systemic treatment and/or hospitalization within the past 45 days No allergy to yeast or any of the components of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 45 days since prior systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids, investigational vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin Routine standard of care, including hepatitis B, influenza, and tetanus vaccines are allowed
| Event Type | Organ System | Event Term | Gardasil Vaccination |
|---|
Number of grade 3 or 4 adverse events attributed to vaccine per 100 patients
Significant decrease (at the 0.05 significance level) in CD4+ cell count to 75% of the baseline level on two or more consecutive tests
Number of participants with detectable HPV antibody to HPV 16 among those with undetectable antibodies to HPV 16 at baseline
Number of patients with a significant increase in HIV viral load defined as > 1 log increase in HIV load from baseline on 2 consecutive occasions
Detectable antibodies to HPV-6 among participant who had undetectable antibodies to HPV-6 at baseline
Detectable antibodies to HPV-11 among those who had undetectable antibodies to HPV-11 at baseline
Detectable antibodies to HPV-18 among participants with undetectable antibodies to HPV-18 at baseline
