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

AIDS Malignancy Consortium

Status and phase

Completed

Phase 2

Conditions

Anal Cancer

Penile Cancer

Nonneoplastic Condition

Precancerous Condition

Treatments

Biological: quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine

Other: laboratory biomarker analysis

Study type

Interventional

Funder types

Other

NETWORK

Industry

NIH

Identifiers

NCT01209325

U01CA121947 (U.S. NIH Grant/Contract)

AMC-072 (Other Identifier)

CDR0000685816 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

149 patients

Sex

Male

Ages

13 to 26 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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