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

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.

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