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

AIDS Malignancy Consortium

Status and phase

Completed

Phase 2

Conditions

Infection

Precancerous Condition

Treatments

Biological: Gardasil

Study type

Interventional

Funder types

NETWORK

Industry

NIH

Identifiers

NCT00513526

U01CA121947 (U.S. NIH Grant/Contract)

CDR0000559149 (Other Identifier)

AMC-052

Details and patient eligibility

About

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.

Full description

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.

Enrollment

112 patients

Sex

Male

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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