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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Infection, Precancerous Condition

Intervention / Treatment
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* Biological: Gardasil


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gardasil<br>Quadrivalent HPV Vaccine (types 6, 11, 16, 18) for intramuscular injection at study entry, week 8, week 24, and week 128. | Biological: Gardasil<br>* week 0, 8, 24, 128<br>* Other names: quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of ≥ Grade 3 Adverse Events Probably or Definitely Related to the Vaccine | Occurrence of grade 3+ adverse events that are at least probably and definitely related to the vaccine | All study visits | 
| Detectable Human Papillomavirus (HPV) Antibody to Type 6 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 6 at Baseline |  | Week 28 | 
| Detectable Human Papillomavirus (HPV) Antibody to Type 11 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 11 at Baseline |  | Week 28 | 
| Detectable Human Papillomavirus (HPV) Antibody to Type 16 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 16 at Baseline |  | Week 28 | 
| Detectable Human Papillomavirus (HPV) Antibody to Type 18 a Month After the Completion of HPV Vaccination Series (Week 28) Among Patients Seronegative for Type 18 at Baseline |  | Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Longitudinal Changes in CD4+ Cell Count From Baseline | CD4+ cell count at week 0 was subtracted from CD4+ cell counts at each of weeks 4, 12, and 28. | Week 0, 4, 12, 28 | 
| Longitudinal Changes in Plasma HIV-1 RNA From Baseline | Plasma HIV-1 RNA at week 0 was subtracted from plasma HIV-1 RNA at each of weeks 4, 12, and 28. | Week 0, 4, 12, 28 | 
| HPV Antibody Titers to Type 6 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | HPV antibody titers to type 6 at baseline and weeks 28 and 76 according to baseline seropositive status will measured in Milli-Merck units per milliliters | weeks 0, 28, and 76 | 
| HPV Antibody Titers to Type 11 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | HPV antibody titers to type 11 at baseline and weeks 28 and 76 according to baseline seropositive status will measured in Milli-Merck units per milliliters | weeks 0, 28, and 76 | 
| HPV Antibody Titers to Type 16 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | HPV antibody titers to type 16 at baseline and weeks 28 and 76 according to baseline seropositive status will measured in Milli-Merck units per milliliters | weeks 0, 28, and 76 | 
| HPV Antibody Titers to Type 18 at Baseline and Weeks 28 and 76 According to Baseline Seropositive Status | HPV antibody titers to type 18 at baseline and weeks 28 and 76 according to baseline seropositive status will measured in Milli-Merck units per milliliters | weeks 0, 28, and 76 | 
| Evaluate Oral Levels of Serum IgA Before and After the Vaccination Series |  | Weeks 0, 28 and 76 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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infection, low-grade squamous intraepithelial lesion, atypical squamous cells of undetermined significance