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

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

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.

Study Overview

• Status: Completed
• Conditions: Infection; Precancerous Condition
• Intervention / Treatment: Biological: Gardasil

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-1793
      • UCLA Clinical AIDS Research and Education (CARE) Center
    • San Francisco, California, United States, 94143
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • Colorado
    • Denver, Colorado, United States, 80204-4507
      • Denver Health Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Cancer Research Center
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
    • New York, New York, United States, 10021
      • New York Weill Cornell Cancer Center at Cornell University
    • New York, New York, United States, 10010
      • Laser Surgery Care
  • Washington
    • Seattle, Washington, United States, 98101
      • Benaroya Research Institute at Virginia Mason Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

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
Evaluate Oral Levels of Serum IgA Before and After the Vaccination Series		Weeks 0, 28 and 76
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

Collaborators and Investigators

• Sponsor: AIDS Malignancy Consortium
• Collaborators: National Cancer Institute (NCI); The Emmes Company, LLC
• Investigators: Study Chair: Timothy J. Wilkin, MD, MPH, Weill Medical College of Cornell University; Principal Investigator: Joel Palefsky, MD, University of California, San Francisco

Publications and helpful links

General Publications

• Kang M, Umbleja T, Ellsworth G, Aberg J, Wilkin T. Effects of Sex, Existing Antibodies, and HIV-1-Related and Other Baseline Factors on Antibody Responses to Quadrivalent HPV Vaccine in Persons With HIV. J Acquir Immune Defic Syndr. 2022 Apr 1;89(4):414-422. doi: 10.1097/QAI.0000000000002891.
• Wilkin T, Lee JY, Lensing SY, Stier EA, Goldstone SE, Berry JM, Jay N, Aboulafia D, Cohn DL, Einstein MH, Saah A, Mitsuyasu RT, Palefsky JM. Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in HIV-1-infected men. J Infect Dis. 2010 Oct 15;202(8):1246-53. doi: 10.1086/656320.

Helpful Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: August 6, 2007
• First Submitted That Met QC Criteria: August 6, 2007
• First Posted (Estimated): August 8, 2007

Study Record Updates

• Last Update Posted (Estimated): November 14, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: infection; low-grade squamous intraepithelial lesion; atypical squamous cells of undetermined significance
• Additional Relevant MeSH Terms: Neoplasms; Infections; Precancerous Conditions; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: AMC-052; U01CA121947 (U.S. NIH Grant/Contract); CDR0000559149 (Other Identifier: NCI)