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

• Safety, in terms of grade 3 or 4 adverse events attributed to the vaccine, according to NCI CTCAE v3.0 [ Time Frame: 52 weeks from study entry ] [ Designated as safety issue: Yes ]
• Significant decrease (at the 0.05 significance level) in CD4+ cell count or HIV RNA rise from baseline of ≥ 1.0 log10 in the level of quantification (or > 200 copies/mL in patients < 50 years old at study entry) [ Time Frame: Screening/Week 0, Weeks 2, 10, 26, and 52. ] [ Designated as safety issue: No ]
• Detectable HPV antibody to HPV 16, 18, 6 or 11 at 1 month after the completion of HPV vaccination series (week 28) [ Time Frame: Week 28 ] [ Designated as safety issue: No ]

• Safety, in terms of grade 3 or 4 adverse events attributed to the vaccine, according to NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
• Significant decrease (at the 0.05 significance level) in CD4+ cell count or HIV RNA rise from baseline of ≥ 1.0 log10 in the level of quantification (or > 200 copies/mL in patients < 50 years old at study entry) [ Designated as safety issue: No ]
• Detectable HPV antibody to HPV 16, 18, 6 or 11 at 1 month after the completion of HPV vaccination series (week 28) [ Designated as safety issue: No ]

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.

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.

• Cervical Cancer
• Nonneoplastic Condition
• Precancerous Condition

• Biological: 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.
• Genetic: DNA analysis
  Weeks 0, 2, 10, 26, and 52.
  Other Name: HIV viral load test and HPV neutralization assays.
• Genetic: polymerase chain reaction
  Screening, week 36, and week 52.
• Other: cytology specimen collection procedure
  Screening, week 36, and week 52.
• Procedure: colposcopic biopsy
  Screening, week 36, and week 52.

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