Safety of and Immune Response to the Human Papillomavirus (HPV) Vaccine in HIV-Infected Women

NCT ID: NCT00604175

Last Updated: 2021-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 319 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2012-11-30

Brief Summary

Human papillomavirus (HPV) is the most common sexually transmitted disease in the world. HPV infection can cause genital warts and certain cervical problems, including cervical cancer. HPV infection may be more severe and harder to treat in HIV-infected people. The purpose of this study was to determine whether the quadrivalent HPV vaccine is safe, tolerable, and effective in producing antibodies to HPV in HIV-infected women.

Detailed Description

HPV is a DNA virus that affects both men and women. Approximately 90 types of HPV have been identified, 30 of which are sexually transmitted. The most common forms of HPV are types 6, 11, 16, and 18. The quadrivalent HPV vaccine that was tested in this study had been shown in previous studies to be effective in preventing infection with HPV 6, 11, 16, and 18 in healthy young women. According to a report by the Centers for Disease Control and Prevention (CDC), 80% of women will have acquired HPV by the age of 50. HIV infected women have been reported to have a higher prevalence and persistence of HPV infection, as well as an increased risk for abnormal Pap smears and cervical cancer. HPV types 16 and 18 cause the majority of cervical cancers worldwide, and types 6 and 11 are responsible for the majority of cases of genital warts. Vaccinations for preventable infections are particularly important among HIV infected people because people with HIV have compromised immune systems; therefore, any infection is very serious and can potentially be fatal. However, standard vaccination series have not been very successful because a compromised immune system may not produce the desired immune response to a vaccine. The HPV vaccine is designed to protect against infection with HPV types 6, 11, 16, and 18 and has been approved by the FDA for use in women between the ages of 9 and 26. The purpose of this study was to determine whether the quadrivalent HPV vaccine is safe, tolerable, and effective in producing antibodies to HPV in HIV infected females.

The study consisted of single arm evaluations of HPV vaccine immunogenicity and safety in 3 groups based on the study screening CD4 cell count as follows:

• Stratum A: CD4 cell count >350 cells/mm^3
• Stratum B: CD4 cell count >200 to <=350 cells/mm^3
• Stratum C: CD4 cell count <=200 cells/mm^3

In Version 1.0 of the protocol, the target accrual was n=67 participants with screening HIV viral load <=10,000 copies/mL and n=67 participants with HIV viral load >10,000 copies/mL within each CD4 stratum, yielding n=134 in each CD4 stratum. In light of subsequent findings from completed HPV vaccine studies, the sample size was changed to n=94 participants per CD4 stratum in Version 2.0 of the protocol, and stratification by screening HIV viral load was removed. All Stratum A and Stratum B participants were enrolled under protocol Version 1.0.

The study duration was 72 weeks. All participants received HPV vaccine administered by intramuscular injection at baseline, and at Weeks 8 and 24. Following each injection, participants remained at the clinic for 30 minutes of observation for adverse events. A telephone follow-up or a home visit by study staff was performed within 2 days following each injection.

Participants returned to the clinic for visits at Weeks 4, 8, 12, 24, 28, 52, and 72. Most study visits included a physical exam, medication review, blood and urine collection, and answering questions about signs and symptoms since previous visit. Some visits included measurement of HIV viral load and CD4 cell count; collection of endocervical wick, cervical cytobrush and anal swab; and an oral exam. A subset of participants were asked to provide additional blood samples and oral cytobrush specimens.

Conditions

HIV Infections; Sexually Transmitted Diseases

Keywords

HIV; HPV 6; HPV 11; HPV 16; HPV 18; Vaccine

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Stratum A

Participants with screening CD4 count \>350 cells/mm\^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.

Group Type: EXPERIMENTAL

Quadrivalent HPV vaccine

Intervention Type: BIOLOGICAL

Quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine. All participants received the vaccine via intramuscular injection at baseline, Week 8 and Week 24.

Stratum B

Participants with screening CD4 count \>200 to \<=350 cells/mm\^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.

Group Type: EXPERIMENTAL

Quadrivalent HPV vaccine

Intervention Type: BIOLOGICAL

Quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine. All participants received the vaccine via intramuscular injection at baseline, Week 8 and Week 24.

Stratum C

Participants with screening CD4 count \<=200 cells/mm\^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24.

Group Type: EXPERIMENTAL

Quadrivalent HPV vaccine

Intervention Type: BIOLOGICAL

Quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine. All participants received the vaccine via intramuscular injection at baseline, Week 8 and Week 24.

Interventions

Quadrivalent HPV vaccine

Quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine. All participants received the vaccine via intramuscular injection at baseline, Week 8 and Week 24.

Intervention Type: BIOLOGICAL

Other Intervention Names

GARDASIL

Eligibility Criteria

Inclusion Criteria

• HIV infection
• CD4 count obtained within 45 days prior to study entry
• Karnofsky performance score >=70 on at least one occasion within 45 days prior to study entry
• The following labs within 45 days prior to study entry:

• hemoglobin >8.0 g/dL
• direct bilirubin <2.5 x upper limit of normal (ULN)
• alanine aminotransferase, ALT (SGPT) <3 xULN
• aspartate aminotransferase, AST (SGOT) <3 xULN
• platelet count >=100,000 /mm^3
• Willing to use acceptable forms of contraception for the duration of the study
• Written informed consent from participant or from parent or guardian, if applicable
• If on HAART, then the same regimen for at least 12 weeks prior to study entry with no change within 30 days prior to study entry. (This criterion was removed in Version 2.0 of the protocol.)
• HIV viral load obtained within 45 days prior to study entry (This criterion was removed in Version 2.0 of the protocol.)

Exclusion Criteria

• Abnormal Pap test with confirmed biopsy results of cervical intraepithelial neoplasia (CIN) II or III or cervical cancer within 180 days prior to study entry
• Vulval intraepithelial neoplasia (VIN) II or III or cancer confirmed by biopsy results within 180 days prior to study entry
• Physician-diagnosed genital warts within 180 days prior to study entry
• Previous cervical dysplasia treatment, including loop electrosurgical excision procedure (LEEP), cervical cryotherapy, cone biopsy, and cervical laser vaporization within 180 days prior to study entry
• Use of any systemic antineoplastic or immunomodulatory treatment, systemic corticosteroids, investigational vaccines, interleukins, interferons, growth factors, or intravenous immunoglobulin (IVIG) within 45 days prior to study entry. Participants who had received standard of care (e.g., hepatitis B, influenza, and tetanus) vaccines were not excluded.
• Known allergy or hypersensitivity to yeast or any components of the vaccine or its formulation
• Current drug or alcohol use or dependence or any other condition that may interfere with study participation
• Serious illness requiring systemic treatment and/or hospitalization within 45 days prior to study entry
• Total hysterectomy. Participants who had undergone partial hysterectomy and had a cervix were not excluded.
• Hemophilia
• Currently on anticoagulation therapy other than acetylsalicylic acid
• Prior vaccination with an HPV vaccine
• Pregnant or breastfeeding

• Minimum Eligible Age: 13 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Dental and Craniofacial Research (NIDCR)

NIH

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Erna Milunka Kojic, MD

Role: STUDY_CHAIR

Department of Immunology/Infectious Disease, The Miriam Hospital, Brown University

Susan Cu-Uvin, MD

Role: STUDY_CHAIR

Obstetrics-Gynecology and Medicine, The Miriam Hospital, Brown University

Locations

Alabama Therapeutics CRS

Birmingham, Alabama, United States

Usc La Nichd Crs

Alhambra, California, United States

University of California, UC San Diego CRS

La Jolla, California, United States

Miller Children's Hosp. Long Beach CA NICHD CRS

Long Beach, California, United States

University of Southern California CRS

Los Angeles, California, United States

UCLA CARE Center CRS

Los Angeles, California, United States

Stanford AIDS Clinical Trials Unit CRS

Palo Alto, California, United States

UCSD Antiviral Research Center CRS

San Diego, California, United States

Ucsf Hiv/Aids Crs

San Francisco, California, United States

University of Colorado Hospital CRS

Aurora, Colorado, United States

Denver Public Health CRS

Denver, Colorado, United States

Georgetown University CRS (GU CRS)

Washington D.C., District of Columbia, United States

Howard Univ. Washington DC NICHD CRS

Washington D.C., District of Columbia, United States

South Florida CDTC Ft Lauderdale NICHD CRS

Fort Lauderdale, Florida, United States

Univ. of Florida Jacksonville NICHD CRS

Jacksonville, Florida, United States

Pediatric Perinatal HIV Clinical Trials Unit CRS

Miami, Florida, United States

The University of Miami AIDS Clinical Research Unit (ACRU) CRS

Miami, Florida, United States

The Ponce de Leon Center CRS

Atlanta, Georgia, United States

Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program

Chicago, Illinois, United States

Northwestern University CRS

Chicago, Illinois, United States

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, United States

Rush University CRS

Chicago, Illinois, United States

Tulane Univ. New Orleans NICHD CRS

New Orleans, Louisiana, United States

IHV Baltimore Treatment CRS

Baltimore, Maryland, United States

Johns Hopkins University CRS

Baltimore, Maryland, United States

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, United States

Bmc Actg Crs

Boston, Massachusetts, United States

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, United States

Henry Ford Hosp. CRS

Detroit, Michigan, United States

Washington University Therapeutics (WT) CRS

St Louis, Missouri, United States

Cooper Univ. Hosp. CRS

Camden, New Jersey, United States

New Jersey Medical School- Adult Clinical Research Ctr. CRS

Newark, New Jersey, United States

Weill Cornell Chelsea CRS

New York, New York, United States

NY Univ. HIV/AIDS CRS

New York, New York, United States

Columbia P&S CRS

New York, New York, United States

Columbia IMPAACT CRS

New York, New York, United States

Trillium Health ACTG CRS

Rochester, New York, United States

Univ. of Rochester ACTG CRS

Rochester, New York, United States

Chapel Hill CRS

Chapel Hill, North Carolina, United States

Duke Univ. Med. Ctr. Adult CRS

Durham, North Carolina, United States

Greensboro CRS

Greensboro, North Carolina, United States

Cincinnati CRS

Cincinnati, Ohio, United States

Case CRS

Cleveland, Ohio, United States

MetroHealth CRS

Cleveland, Ohio, United States

Ohio State University CRS

Columbus, Ohio, United States

The Research & Education Group-Portland CRS

Portland, Oregon, United States

Penn Therapeutics, CRS

Philadelphia, Pennsylvania, United States

Thomas Jefferson Univ. Med. Ctr. CRS

Philadelphia, Pennsylvania, United States

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, United States

The Miriam Hospital Clinical Research Site (TMH CRS) CRS

Providence, Rhode Island, United States

Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, United States

Trinity Health and Wellness Center CRS

Dallas, Texas, United States

Texas Children's Hospital CRS

Houston, Texas, United States

Houston AIDS Research Team CRS

Houston, Texas, United States

Virginia Commonwealth Univ. Medical Ctr. CRS

Richmond, Virginia, United States

University of Washington AIDS CRS

Seattle, Washington, United States

Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

Rio de Janeiro, , Brazil

Puerto Rico AIDS Clinical Trials Unit CRS

San Juan, , Puerto Rico

University of Puerto Rico Pediatric HIV/AIDS Research Program CRS

San Juan, , Puerto Rico

San Juan City Hosp. PR NICHD CRS

San Juan, , Puerto Rico

Wits Helen Joseph Hospital CRS (Wits HJH CRS)

Johannesburg, Gauteng, South Africa

Countries

United States; Brazil; Puerto Rico; South Africa

References

Cameron JE, Hagensee ME. Human papillomavirus infection and disease in the HIV+ individual. Cancer Treat Res. 2007;133:185-213. doi: 10.1007/978-0-387-46816-7_7.

Reference Type: BACKGROUND

PMID: 17672042 (View on PubMed)

Chaturvedi AK, Goedert JJ. Human papillomavirus genotypes among women with HIV: implications for research and prevention. AIDS. 2006 Nov 28;20(18):2381-3. doi: 10.1097/01.aids.0000253366.94072.b4. No abstract available.

Reference Type: BACKGROUND

PMID: 17117025 (View on PubMed)

De Vuyst H, Franceschi S. Human papillomavirus vaccines in HIV-positive men and women. Curr Opin Oncol. 2007 Sep;19(5):470-5. doi: 10.1097/CCO.0b013e3282c8c8fc.

Reference Type: BACKGROUND

PMID: 17762573 (View on PubMed)

Kojic EM, Cu-Uvin S. Update: human papillomavirus infection remains highly prevalent and persistent among HIV-infected individuals. Curr Opin Oncol. 2007 Sep;19(5):464-9. doi: 10.1097/CCO.0b013e3282c8c84c.

Reference Type: BACKGROUND

PMID: 17762572 (View on PubMed)

Palefsky J. Human papillomavirus infection in HIV-infected persons. Top HIV Med. 2007 Aug-Sep;15(4):130-3.

Reference Type: BACKGROUND

PMID: 17720998 (View on PubMed)

Kojic EM, Kang M, Cespedes MS, Umbleja T, Godfrey C, Allen RT, Firnhaber C, Grinsztejn B, Palefsky JM, Webster-Cyriaque JY, Saah A, Aberg JA, Cu-Uvin S. Immunogenicity and safety of the quadrivalent human papillomavirus vaccine in HIV-1-infected women. Clin Infect Dis. 2014 Jul 1;59(1):127-35. doi: 10.1093/cid/ciu238. Epub 2014 Apr 9.

Reference Type: RESULT

PMID: 24723284 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34907980 (View on PubMed)

Cespedes MS, Kang M, Kojic EM, Umbleja T, Godfrey C, Webster-Cyriaque JY, Masih R, Firnhaber C, Grinsztejn B, Saah A, Cu-Uvin S, Aberg JA. Anogenital human papillomavirus virus DNA and sustained response to the quadrivalent HPV vaccine in women living with HIV-1. Papillomavirus Res. 2018 Dec;6:15-21. doi: 10.1016/j.pvr.2018.08.002. Epub 2018 Aug 16.

Reference Type: DERIVED

PMID: 30118852 (View on PubMed)

Other Identifiers

10393

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG A5240

Identifier Type: -

Identifier Source: secondary_id

A5240

Identifier Type: -

Identifier Source: org_study_id