Vaccine Therapy in Preventing Human Papillomavirus Infection in Young HIV-Positive Male Patients Who Have Sex With Males

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from a gene-modified virus may help the body build an effective immune response to prevent viral infection. PURPOSE: This phase II trial is studying how well vaccine therapy works in preventing human papillomavirus (HPV) infection in young HIV-positive male patients who have sex with males.

Detailed Description
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OBJECTIVES: Primary To determine the protective effect of the HPV-6, -11, -16, -18 vaccine in preventing penile/scrotal condyloma and HPV-6, -11, -16, -18- associated perianal/anal disease in HIV-positive males who have sex with males (MSM) age 13-26 years by comparing the incidence of these lesions among those naïve to the relevant HPV type(s) at baseline to those who are not naïve at baseline. To determine the protective effect of the HPV-6, -11, -16, -18 vaccine in preventing persistent anogenital infection with HPV-6, -11, -16, or 18 in HIV-positive MSM age 13-26 years by comparing the incidence of persistent infection among those naïve to the relevant HPV type(s) at baseline to those who are not naïve at baseline. To determine the protective effect of the HPV-6, -11, -16, -18 vaccine in preventing anogenital lesions associated with HPV 6,-11,-16, -18 and persistent infection with these types, in HIV-positive MSM age 13-26 years by comparing the incidence of lesions and persistent infection among those naïve to the relevant types at baseline to incident lesions and infection among MSM naïve to these HPV types who participated in the Merck 020 protocol and who received placebo as part of the protocol. Secondary To define the safety of the HPV-6, -11, -16, -18 vaccine in HIV-positive MSM age 13-26 years. To evaluate the levels and persistence of HPV 6, 11, 16 and 18 Ab titers after the vaccination series among subjects who are seropositive and seronegative at baseline. To examine whether the protective effect and antibody titers vary as a function of the following at the time of initial vaccination: subject age, HAART treatment status, HIV viral load, CD4 + T-cell count, and nadir CD4 level. Tertiary To quantify anogenital HPV DNA viral load prior to and after receipt of the quadrivalent HPV vaccine. To identify and quantify HPV types in the oral cavity of HIV-positive MSM prior to and after receipt of the quadrivalent HPV vaccine. To identify HPV strain variants among HIV-positive participants prior to and after receipt of the quadrivalent HPV vaccine. Assess the prevalence and incidence of urinary and gonorrhea and Chlamydia trachomatis infection at baseline and their relationship with prevalent and incident anogenital HPV infection and anal condyloma or AIN. To characterize young men's risk perceptions, sexual behaviors, and STI diagnosis after HPV vaccination. OUTLINE: This is a multicenter study. Patients receive quadrivalent human papillomavirus (types 6, 11, 16, and 18) recombinant vaccine intramuscularly on day 1 and in weeks 8 and 24. Blood and tissue samples may be collected periodically for laboratory studies. After completion of study treatment, patients are followed up for 2 years.

Official Title
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AMC-072: Protective Effect of Quadrivalent Vaccine in Young HIV-Positive Males Who Have Sex With Males

Conditions
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Penile Cancer, Precancerous Condition, Anal Cancer, Nonneoplastic Condition

Intervention / Treatment
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* Biological: quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Men with a history of at least one male sexual partner Men is defined as those documented male at birth (including male-to-female transgendered persons) HIV-1 infection as documented by any federally approved, licensed HIV test performed in conjunction with screening (ELISA, western blot, or other approved test) Alternatively, this documentation may include a record that another physician has documented that the patient has HIV based on prior ELISA and western blot, or other approved diagnostic tests Meets one of the following sets of criteria: Patients receiving antiretroviral therapy: Receipt of antiretroviral therapy for at least 3 months prior to entry No change in antiretroviral therapy within 30 days prior to entry Patients 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, LSIL/condyloma, or ASCUS result within 90 days prior to entry, and no HGAIN on biopsy No current or history of anal or peri-anal carcinoma No anal cytological result of HSIL, atypical squamous cells suggestive of HSIL (ASC-H), or suggestive of invasive carcinoma at screening; or history of these results No presence of penile or scrotal condyloma, LGAIN (condyloma or AIN 1), HGAIN (e.g., AIN 2 or 3, or perianal intraepithelial neoplasia grade 2 or 3), or invasive carcinoma at pre-entry on biopsy No history of HGAIN PATIENT CHARACTERISTICS: Karnofsky performance score ≥ 70 within 45 days prior to entry Absolute neutrophil count (ANC) > 750 cells/mm^3 Hemoglobin ≥ 9.0 g/dL Platelet count ≥ 100,000/mm^3 AST (SGOT), ALT (SGPT) ≤ 3 times upper limit of normal (ULN) Total or conjugated (direct) bilirubin ≤ 2.5 times ULN within 45 days before study entry, with the exception of isolated hyperbilirubinemia that is considered due to atazanavir Calculated creatinine clearance ≥ 60 mL/min No hemophilia No active drug or alcohol use or dependence that, in the opinion of the site Investigator, would interfere with adherence to study requirements No serious illness requiring systemic treatment and/or hospitalization within 45 days prior to entry No serious medical or psychiatric illness that, in the opinion of the site Investigator, will interfere with the ability of the subject to give informed consent or adhere to the protocol No allergy to yeast or any of the components of Gardasil PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior splenectomy No prior receipt of Gardasil or other HPV vaccine No use of any systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids for greater than 14 days, investigational vaccines, interleukins, interferons, growth factors, or IVIG within 45 days prior to study entry No expected use of any systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids used for greater than 14 days, investigational vaccines, interleukins, interferons, growth factors, or IVIG during study followup No patients with hepatitis C who expect to initiate treatment for hepatitis C (e.g., interferons) during this trial Not currently receiving anticoagulation therapy other than acetylsalicylic acid

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 26 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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaccination<br>Gardasil (quadrivalent HPV types 6, 11, 16, 18) vaccination at weeks 0, 8, 24. | Biological: quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine<br> <br> Other: laboratory biomarker analysis<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of AIN or Anal/Perianal Condyloma Associated With HPV 6 DNA | Incident events are defined as having AIN (e.g., AIN or anal/perianal condyloma) with HPV 6 positive DNA in participants without HPV-6 related AIN at baseline. | Post Month 7 through Month 24 | 
| Incidence of AIN or Anal/Perianal Condyloma Associated With HPV 11 DNA | Incident events are defined as having AIN (e.g., AIN or anal/perianal condyloma) with HPV 11 positive DNA in participants without HPV-11 related AIN at baseline. | Post Month 7 through Month 24 | 
| Incidence of AIN or Anal/Perianal Condyloma Associated With HPV 16 DNA | Incident events are defined as having AIN (e.g., AIN or anal/perianal condyloma) with HPV 16 positive DNA in participants without HPV-16 related AIN at baseline. | Post Month 7 through Month 24 | 
| Incidence of AIN or Anal/Perianal Condyloma Associated With HPV 18 DNA | Incident events are defined as having AIN (e.g., AIN or anal/perianal condyloma) with HPV 18 positive DNA in participants without HPV-18 related AIN at baseline. | Post Month 7 through Month 24 | 
| Incidence of Persistent Anogenital Infection With HPV 6 DNA | Incident events are defined as having HPV 6 positive PCR results at 2 or more consecutive visits in those who were DNA negative for HPV 6. Persistence was defined based on being persistent in the same anatomical site. | Post Month 7 through Month 24 | 
| Incidence of Persistent Anogenital Infection With HPV 11 DNA | Incident events are defined as having positive PCR results with HPV 11 at 2 or more consecutive visits in those who were DNA negative for HPV 11 at baseline. Persistence was defined based on being persistent in the same anatomical site. | Post Month 7 through Month 24 | 
| Incidence of Persistent Anogenital Infection With HPV 16 DNA | Incident events are defined as having positive PCR results with HPV 16 at 2 or more consecutive visits in those who were DNA negative for HPV 16 at baseline. Persistence was defined based on being persistent in the same anatomical site. | Post Month 7 through Month 24 | 
| Incidence of Persistent Anogenital Infection With HPV 18 DNA | Incident events are defined as having positive PCR results with HPV 18 at 2 or more consecutive visits in those who were DNA negative for HPV 18. Persistence was defined based on being persistent in the same anatomical site. | Post Month 7 through Month 24 | 
| Incidence of HGAIN Associated With HPV 6 | Incident events are defined as having HGAIN (e.g., AIN 2 or 3, or perianal intraepithelial neoplasia grade 2 or 3) with HPV 6 positive DNA in participants without HPV 6 related HGAIN at baseline. | Post month 7 through month 24 | 
| Incidence of HGAIN Associated With HPV 11 | Incident events are defined as having HGAIN (e.g., AIN 2 or 3, or perianal intraepithelial neoplasia grade 2 or 3) with HPV 11 positive DNA in participants without HPV 11 related HGAIN at baseline. | Post month 7 through month 24 | 
| Incidence of HGAIN Associated With HPV 16 | Incident events are defined as having HGAIN (e.g., AIN 2 or 3, or perianal intraepithelial neoplasia grade 2 or 3) with HPV 16 positive DNA in participants without HPV 16 related HGAIN at baseline. | Post month 7 through month 24 | 
| Incidence of HGAIN Associated With HPV 18 | Incident events are defined as having HGAIN (e.g., AIN 2 or 3, or perianal intraepithelial neoplasia grade 2 or 3) with HPV 18 positive DNA in participants without HPV 18 related HGAIN at baseline. | Post month 7 through month 24 | 
| Incidence of Penile/Scrotal Condyloma in HPV 6 Naive and Prior Exposed Participants | Incident events are defined as having penile/scrotal warts reported clinically in participants penile/scrotal condyloma at baseline. | Post month 7 through month 24 | 
| Incidence of Penile/Scrotal Condyloma in HPV 11 Naive and Prior Exposed Participants | Incident events are defined as having penile/scrotal warts reported clinically in participants penile/scrotal condyloma at baseline. | Post month 7 through month 24 | 
| Incidence of Penile/Scrotal Condyloma in HPV 16 Naive and Prior Exposed Participants | Incident events are defined as having penile/scrotal warts reported clinically in participants penile/scrotal condyloma at baseline. | Post month 7 through month 24 | 
| Incidence of Penile/Scrotal Condyloma in HPV 18 Naive and Prior Exposed Participants | Incident events are defined as having penile/scrotal warts reported clinically in participants penile/scrotal condyloma at baseline. | Post month 7 through month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Grade ≥ 3 Adverse Events (AEs) That Were Possibly, Probably, or Definitely Related to the Vaccine | Number of participants who experienced grade 3 and higher AEs that were possibly, probably or definitely related to the vaccine. | Through Month 24 | 
| Geometric Mean Titers for HPV 6 | Geometric mean concentration of antibodies for HPV 6 at each visit | Baseline through month 24 | 
| Geometric Mean Titers for HPV 11 | Geometric mean concentration of antibodies for HPV 11 at each visit | Baseline through month 24 | 
| Geometric Mean Titers for HPV 16 | Geometric mean concentration of antibodies for HPV 16 at each visit | Baseline through 24 months | 
| Geometric Mean Titers for HPV 18 | Geometric mean concentration of antibodies for HPV 18 at each visit | Baseline through 24 months | 
| Geometric Mean Titers for HPV 6 According to Participant Age, HIV Viral Load, CD4+ T Cell Count, and Nadir CD4 Level | Geometric mean concentration of antibodies for HPV 6 at 7 and 24 months | at 7 and 24 Months | 
| Geometric Mean Titers for HPV 11 According to Participant Age, HIV Viral Load, CD4+ T Cell Count, and Nadir CD4 Level | Geometric mean concentration of antibodies for HPV 11 at 7 and 24 months | at 7 and 24 Months | 
| Geometric Mean Titers for HPV 16 According to Participant Age, HIV Viral Load, CD4+ T Cell Count, and Nadir CD4 Level | Geometric mean concentration of antibodies for HPV 16 at 7 and 24 months | at 7 and 24 Months | 
| Geometric Mean Titers for HPV 18 According to Participant Age, HIV Viral Load, CD4+ T Cell Count, and Nadir CD4 Level | Geometric mean concentration of antibodies for HPV 18 at 7 and 24 months | at 7 and 24 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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human papilloma virus infection, anal cancer, penile cancer, HIV infection