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

Phase 1

Completed

Conditions: Cervical Cancer
Nonneoplastic Condition
Precancerous Condition

Interventions: 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

Registration Number: NCT00667563

Lead Sponsor: AIDS Malignancy Consortium

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 150

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Gardasil Vaccination	DNA analysis	Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24.
Gardasil Vaccination	cytology specimen collection procedure	Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24.
Gardasil Vaccination	colposcopic biopsy	Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24.
Gardasil Vaccination	quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine	Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24.
Gardasil Vaccination	polymerase chain reaction	Vaccination with the Quadrivalent Human Papillomavirus Recombinant vaccine (0.5 mL Gardasil®) by intramuscular (IM) injection at Day 0, Weeks 8 and 24.

Primary Outcome Measures

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