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

NCT00604175 | Completed Phase 2 Results DMC

• 3 other identifiers: A524010393ACTG A5240
• Study Type: interventional
• Target: 319
• Locations: 4 countries
• Sites: 61

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.

Conditions

HIV Infections; Sexually Transmitted Diseases

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants With HPV6 Antibody Development From Seronegative Status at Baseline to Seropositive Status a Month After Completion of HPV Vaccination Series

  Percentage of participants with HPV6 antibody development from seronegative status (HPV6 antibody titers \<20 mMU/mL) at baseline to seropositive (HPV6 antibody titers \>=20 mMU/mL) status a month after the completion of HPV vaccination series. HPV serotyping was performed centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum.

  Week 28

• Percentage of Participants With HPV11 Antibody Development From Seronegative Status at Baseline to Seropositive Status a Month After Completion of HPV Vaccination Series

  Percentage of participants with HPV11 antibody development from seronegative status (HPV11 antibody titers \<16 mMU/mL) at baseline to seropositive (HPV11 antibody titers \>=16 mMU/mL) status a month after the completion of HPV vaccination series. HPV serotyping was performed centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum.

  Week 28

• Percentage of Participants With HPV16 Antibody Development From Seronegative Status at Baseline to Seropositive Status a Month After Completion of HPV Vaccination Series

  Percentage of participants with HPV16 antibody development from seronegative status (HPV16 antibody titers \<20 mMU/mL) at baseline to seropositive (HPV16 antibody titers \>=20 mMU/mL) status a month after the completion of HPV vaccination series. HPV serotyping was performed centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum.

  Week 28

• Percentage of Participants With HPV18 Antibody Development From the Seronegative Status at Baseline to Seropositive Status a Month After Completion of HPV Vaccination Series

  Percentage of participants with HPV18 antibody development from seronegative status (HPV18 antibody titers \<24 mMU/mL) at baseline to seropositive (HPV18 antibody titers \>=24 mMU/mL) status a month after the completion of HPV vaccination series. HPV serotyping was performed centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum.

  Week 28

Secondary Outcomes (12)

• HPV6 Antibody Titers Among Those Seronegative for HPV6 at Baseline

  Weeks 28, 72

• HPV11 Antibody Titers Among Those Seronegative for HPV11 at Baseline

  Weeks 28, 72

• HPV16 Antibody Titers Among Those Seronegative for HPV16 at Baseline

  Weeks 28, 72

• HPV18 Antibody Titers Among Those Seronegative for HPV18 at Baseline

  Weeks 28, 72

• Change in Log10 HPV6 Antibody Titers From Baseline Among Those Seropositive for HPV6 at Baseline

  Weeks 0, 28, 72

Study Arms (3)

Stratum A

EXPERIMENTAL

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

Biological: Quadrivalent HPV vaccine

Stratum B

EXPERIMENTAL

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.

Biological: Quadrivalent HPV vaccine

Stratum C

EXPERIMENTAL

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

Biological: Quadrivalent HPV vaccine

Interventions

Quadrivalent HPV vaccine 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.

Also known as: GARDASIL

Stratum A; Stratum B; Stratum C

Eligibility Criteria

• Age: 13 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.)

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• National Institute of Dental and Craniofacial Research (NIDCR): collaborator

Study Sites (61)

Alabama Therapeutics CRS

Birmingham, Alabama, 35294-2050, United States

Location

Usc La Nichd Crs

Alhambra, California, 90033, United States

Location

University of California, UC San Diego CRS

La Jolla, California, 92093-0672, United States

Location

Miller Children's Hosp. Long Beach CA NICHD CRS

Long Beach, California, 90806, United States

Location

University of Southern California CRS

Los Angeles, California, 90033-1079, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

Stanford AIDS Clinical Trials Unit CRS

Palo Alto, California, 94304-5350, United States

Location

UCSD Antiviral Research Center CRS

San Diego, California, 92103, United States

Location

Ucsf Hiv/Aids Crs

San Francisco, California, 94110, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

Location

Denver Public Health CRS

Denver, Colorado, 80204, United States

Location

Georgetown University CRS (GU CRS)

Washington D.C., District of Columbia, 20007, United States

Location

Howard Univ. Washington DC NICHD CRS

Washington D.C., District of Columbia, 20060, United States

Location

South Florida CDTC Ft Lauderdale NICHD CRS

Fort Lauderdale, Florida, 33316, United States

Location

Univ. of Florida Jacksonville NICHD CRS

Jacksonville, Florida, 32209, United States

Location

Pediatric Perinatal HIV Clinical Trials Unit CRS

Miami, Florida, 33136, United States

Location

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

Miami, Florida, 33136, United States

Location

The Ponce de Leon Center CRS

Atlanta, Georgia, 30308, United States

Location

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

Chicago, Illinois, 60608, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, 60612, United States

Location

Rush University CRS

Chicago, Illinois, 60612, United States

Location

Tulane Univ. New Orleans NICHD CRS

New Orleans, Louisiana, 70112, United States

Location

IHV Baltimore Treatment CRS

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University CRS

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

Location

Bmc Actg Crs

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hosp. CRS

Detroit, Michigan, 48202, United States

Location

Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110-1010, United States

Location

Cooper Univ. Hosp. CRS

Camden, New Jersey, 08103, United States

Location

New Jersey Medical School- Adult Clinical Research Ctr. CRS

Newark, New Jersey, 07103, United States

Location

Weill Cornell Chelsea CRS

New York, New York, 10011, United States

Location

NY Univ. HIV/AIDS CRS

New York, New York, 10016, United States

Location

Columbia P&S CRS

New York, New York, 10032-3732, United States

Location

Columbia IMPAACT CRS

New York, New York, 10032, United States

Location

Trillium Health ACTG CRS

Rochester, New York, 14607, United States

Location

Univ. of Rochester ACTG CRS

Rochester, New York, 14642, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

Location

Duke Univ. Med. Ctr. Adult CRS

Durham, North Carolina, 27710, United States

Location

Greensboro CRS

Greensboro, North Carolina, 27401, United States

Location

Cincinnati CRS

Cincinnati, Ohio, 45219, United States

Location

Case CRS

Cleveland, Ohio, 44106, United States

Location

MetroHealth CRS

Cleveland, Ohio, 44109, United States

Location

Ohio State University CRS

Columbus, Ohio, 43210, United States

Location

The Research & Education Group-Portland CRS

Portland, Oregon, 97210, United States

Location

Penn Therapeutics, CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson Univ. Med. Ctr. CRS

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

The Miriam Hospital Clinical Research Site (TMH CRS) CRS

Providence, Rhode Island, 02906, United States

Location

Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, 37204, United States

Location

Trinity Health and Wellness Center CRS

Dallas, Texas, 75208, United States

Location

Texas Children's Hospital CRS

Houston, Texas, 77030-2399, United States

Location

Houston AIDS Research Team CRS

Houston, Texas, 77030, United States

Location

Virginia Commonwealth Univ. Medical Ctr. CRS

Richmond, Virginia, 23298, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98104-9929, United States

Location

Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

Rio de Janeiro, 21040-900, Brazil

Location

Puerto Rico AIDS Clinical Trials Unit CRS

San Juan, 00935, Puerto Rico

Location

University of Puerto Rico Pediatric HIV/AIDS Research Program CRS

San Juan, 00935, Puerto Rico

Location

San Juan City Hosp. PR NICHD CRS

San Juan, 00936, Puerto Rico

Location

Wits Helen Joseph Hospital CRS (Wits HJH CRS)

Johannesburg, Gauteng, 2092, South Africa

Location

Related Publications (8)

• 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.

  PMID: 17672042 BACKGROUND

• 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.

  PMID: 17117025 BACKGROUND

• 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.

  PMID: 17762573 BACKGROUND

• 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.

  PMID: 17762572 BACKGROUND

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

  PMID: 17720998 BACKGROUND

• 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.

  PMID: 24723284 RESULT

• 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.

  PMID: 34907980 DERIVED

• 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.

  PMID: 30118852 DERIVED

MeSH Terms

Conditions

HIV Infections; Sexually Transmitted Diseases

Interventions

Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vaccines, Combined; Vaccines; Biological Products; Complex Mixtures; Papillomavirus Vaccines; Viral Vaccines

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301)-628-3313

Study Officials

• Erna Milunka Kojic, MD

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

  STUDY CHAIR

• Susan Cu-Uvin, MD

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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2008
• First Posted: January 30, 2008
• Study Start: February 1, 2008
• Primary Completion: January 1, 2012
• Study Completion: November 1, 2012
• Last Updated: November 4, 2021
• Results First Posted: October 17, 2013

Record last verified: 2015-08

Locations

PR (3); ZA (1); BR (1); US (56)