human papillomavirus vaccine therapy in treating men with hiv-1 infection

Conditions: Infection; Precancerous Condition

Summary: 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.

Eligibility criteria:
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

Keywords: infection low-grade squamous intraepithelial lesion atypical squamous cells of undetermined significance