Human Papillomavirus Vaccine Therapy in Treating Men With HIV-1 Infection

A Single-Arm, Open-Label Pilot Trial of the Safety and Immunogenicity of a Quadrivalent Human Papillomavirus Vaccine in HIV-1-Infected Men

RATIONALE: Vaccines made from human papillomavirus may help the body build an effective immune response to kill HIV cells.

PURPOSE: This phase II trial is studying the side effects and how well human papillomavirus vaccine therapy works in treating men with HIV-1 infection.

OBJECTIVES:

Primary

• To assess the safety and tolerability of quadrivalent human papillomavirus (HPV) (types 6, 11, 16, 18) recombinant vaccine in HIV-infected men.
• To assess the immunogenicity of the quadrivalent HPV vaccine for types 6, 11, 16 and 18 in subjects who are antibody-negative at baseline.

Secondary

• To evaluate the changes in plasma HIV-1 RNA and CD4+ count after the vaccination series.
• To describe the associations of CD4+ count, nadir CD4+ count, and age on antibody response.
• To evaluate the levels and persistence of HPV 6, 11, 16, and 18 antibody titers after the vaccination series among subjects according to serostatus at baseline.
• To evaluate the oral levels of serum IgA before and after the vaccination series.

Tertiary

• To evaluate prevalent and incident HPV infections in the anal canal.
• To evaluate cytological and histological abnormalities in the anal canal.
• To evaluate prevalent and incident HPV infections in the oral cavity.
• To compare oral and anal compartmental shedding of HPV before and after vaccination.

OUTLINE: This is a multicenter study.

Patients receive quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine intramuscularly on day 0 and weeks 8 and 24.

After completion of protocol therapy, patients are followed at 7, 12, and 18 months.

DISEASE CHARACTERISTICS:

Inclusion criteria:

• HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by western blot prior to 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

• Anal human papilloma virus DNA PCR-negative for either type 16 and/or type 18 within 90 days prior to entry

• If receiving antiretroviral therapy:

  • Receipt of antiretroviral therapy for at least 6 months prior to entry
  • No change in antiretroviral therapy within 30 days prior to entry
  • CD4 cell count > 200 cells/mm³ within 90 days prior to study entry
  • HIV-1 RNA < 200 copies/mL within 90 days prior to entry

• If not receiving antiretroviral therapy:

  • CD4 cell count ≥ 350 cells/mm³ within 90 days prior to study entry
  • No plans to start antiretroviral therapy prior to week 28

• Normal anal cytological result, or atypical squamous cell of undetermined significance or low-grade squamous intraepithelial lesions (SIL) result within 90 days prior to entry

Exclusion criteria:

• Current or history of anal or perianal carcinoma

• Anal cytological result of high-grade SIL (HSIL), atypical squamous cells suggestive of HSIL, or suggestive of invasive carcinoma at screening or a history of these results

• Presence of high-grade anal intraepithelial neoplasm (HGAIN) (e.g., AIN 2 or 3, or perianal intraepithelial neoplasia grade 2 or 3), or invasive carcinoma at pre-entry, or history of HGAIN

  • Current or history of anal or peri-anal condyloma is allowed

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Karnofsky performance status 70-100%
• Absolute neutrophil count > 750 cells/mm³
• Hemoglobin ≥ 9.0 g/dL
• Platelet count ≥ 100,000/mm³
• Creatinine clearance ≥ 60 mL/min
• AST and ALT ≤ 3 times ULN
• Total or conjugated (direct) bilirubin ≤ 2.5 times ULN

Exclusion criteria:

• Serious medical or psychiatric illness, active drug or alcohol use, or dependence that, in the opinion of the site Investigator, would interfere with adherence to study requirements
• Serious illness requiring systemic treatment and/or hospitalization within the past 45 days
• Allergy to yeast or any of the components of quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine
• Hemophilia

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• See Disease Characteristics

Exclusion criteria:

• Prior splenectomy

• Currently receiving anticoagulation therapy other than acetylsalicylic acid

• Use of any systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids, investigational vaccines, interleukins, interferons, growth factors, or IVIG within 45 days prior to study entry

  • Routine standard of care, including hepatitis A or B, influenza, or pneumococcal and tetanus vaccines are not excluded
  • Hepatitis C co-infected patients are eligible provided no concurrent initiation of treatment for hepatitis C

• Prior receipt of quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine or other HPV vaccine