Vaccine Therapy in Preventing HPV in HIV-Positive Women in India

Study Overview
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Brief Summary
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RATIONALE: 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.

Detailed Description
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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.

Official Title
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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

Conditions
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Cervical Cancer, Nonneoplastic Condition, Precancerous Condition

Intervention / Treatment
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* Biological: quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine
* Genetic: DNA analysis
* Genetic: polymerase chain reaction
* Other: cytology specimen collection procedure
* Procedure: colposcopic biopsy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gardasil Vaccination<br>Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24. | Biological: quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine<br>* Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24.<br>Genetic: DNA analysis<br>* Weeks 0, 2, 10, 26, and 52.<br>* Other names: HIV viral load test and HPV neutralization assays.;Genetic: polymerase chain reaction<br>* Screening, week 36, and week 52.<br>Other: cytology specimen collection procedure<br>* Screening, week 36, and week 52.<br>Procedure: colposcopic biopsy<br>* Screening, week 36, and week 52.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, in Terms of Grade 3 or 4 Adverse Events Attributed to the Vaccine, According to NCI CTCAE v3.0 | Number of grade 3 or 4 adverse events attributed to vaccine per 100 patients | 52 weeks from study entry | 
| Number of Patients With Significant Decrease (at the 0.05 Significance Level) in CD4+ Cell Count | Significant decrease (at the 0.05 significance level) in CD4+ cell count to 75% of the baseline level on two or more consecutive tests | Screening/Week 0, Weeks 2, 10, 26, and 52. | 
| Number of Patients With Detectable HPV Antibodies to HPV 16 at Week 28 | Number of participants with detectable HPV antibody to HPV 16 among those with undetectable antibodies to HPV 16 at baseline | Week 28 | 
| Number of Patients With a Significant Increase in HIV Viral Load | 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 | Screening/week 0, weeks, 2, 10, 26 and 52 | 
| Number of Patients With Detectable Antibodies to HPV-6 | Detectable antibodies to HPV-6 among participant who had undetectable antibodies to HPV-6 at baseline | 28 weeks | 
| Number of Patients With Detectable Antibodies to HPV-11 | Detectable antibodies to HPV-11 among those who had undetectable antibodies to HPV-11 at baseline | 28 weeks | 
| Number of Patients With Detectable Antibodies to HPV-18 | Detectable antibodies to HPV-18 among participants with undetectable antibodies to HPV-18 at baseline | 28 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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human papilloma virus infection, cervical cancer, cervical intraepithelial neoplasia, HIV infection