HIV InfectionsPhase 2NCT00604175
Safety of and Immune Response to the Human Papillomavirus (HPV) Vaccine in HIV-Infected Women
A Phase 2 study testing Quadrivalent HPV vaccine in people with HIV Infections and Sexually Transmitted Diseases, run by National Institute of Allergy and Infectious Diseases (NIAID) at 61 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 13 to 45 years, women only
- Conditions the study is for
- HIV Infections, Sexually Transmitted Diseases
- What is being tested?
- Quadrivalent HPV vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 319 participants
- Where
- 61 sitesin 4 countries
- Study dates
- Feb 2008to Nov 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 45 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
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- 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.)
Who cannot join
- 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
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- 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
Trial locations and contacts
61 sites in 4 countries.
61 sites in 4 countries
United States56 sites
Usc La Nichd Crs
Alhambra, California, 90033
The Ponce de Leon Center CRS
Atlanta, Georgia, 30308
University of Colorado Hospital CRS
Aurora, Colorado, 80045
IHV Baltimore Treatment CRS
Baltimore, Maryland, 21201
Johns Hopkins University CRS
Baltimore, Maryland, 21205
Alabama Therapeutics CRS
Birmingham, Alabama, 35294-2050
Massachusetts General Hospital CRS (MGH CRS)
Boston, Massachusetts, 02114
Bmc Actg Crs
Boston, Massachusetts, 02118
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, 02215
Cooper Univ. Hosp. CRS
Camden, New Jersey, 08103
Chapel Hill CRS
Chapel Hill, North Carolina, 27599
Mt. Sinai Hosp. Med. Ctr. - Chicago, Womens & Childrens HIV Program
Chicago, Illinois, 60608
Northwestern University CRS
Chicago, Illinois, 60611
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, 60612
Rush University CRS
Chicago, Illinois, 60612
Cincinnati CRS
Cincinnati, Ohio, 45219
Case CRS
Cleveland, Ohio, 44106
MetroHealth CRS
Cleveland, Ohio, 44109
Ohio State University CRS
Columbus, Ohio, 43210
Trinity Health and Wellness Center CRS
Dallas, Texas, 75208
Denver Public Health CRS
Denver, Colorado, 80204
Henry Ford Hosp. CRS
Detroit, Michigan, 48202
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, 27710
South Florida CDTC Ft Lauderdale NICHD CRS
Fort Lauderdale, Florida, 33316
Greensboro CRS
Greensboro, North Carolina, 27401
Texas Children's Hospital CRS
Houston, Texas, 77030-2399
Houston AIDS Research Team CRS
Houston, Texas, 77030
Univ. of Florida Jacksonville NICHD CRS
Jacksonville, Florida, 32209
University of California, UC San Diego CRS
La Jolla, California, 92093-0672
Miller Children's Hosp. Long Beach CA NICHD CRS
Long Beach, California, 90806
University of Southern California CRS
Los Angeles, California, 90033-1079
UCLA CARE Center CRS
Los Angeles, California, 90035
Pediatric Perinatal HIV Clinical Trials Unit CRS
Miami, Florida, 33136
The University of Miami AIDS Clinical Research Unit (ACRU) CRS
Miami, Florida, 33136
Vanderbilt Therapeutics (VT) CRS
Nashville, Tennessee, 37204
Tulane Univ. New Orleans NICHD CRS
New Orleans, Louisiana, 70112
Weill Cornell Chelsea CRS
New York, New York, 10011
NY Univ. HIV/AIDS CRS
New York, New York, 10016
Columbia P&S CRS
New York, New York, 10032-3732
Columbia IMPAACT CRS
New York, New York, 10032
New Jersey Medical School- Adult Clinical Research Ctr. CRS
Newark, New Jersey, 07103
Stanford AIDS Clinical Trials Unit CRS
Palo Alto, California, 94304-5350
Penn Therapeutics, CRS
Philadelphia, Pennsylvania, 19104
Thomas Jefferson Univ. Med. Ctr. CRS
Philadelphia, Pennsylvania, 19107
University of Pittsburgh CRS
Pittsburgh, Pennsylvania, 15213
The Research & Education Group-Portland CRS
Portland, Oregon, 97210
The Miriam Hospital Clinical Research Site (TMH CRS) CRS
Providence, Rhode Island, 02906
Virginia Commonwealth Univ. Medical Ctr. CRS
Richmond, Virginia, 23298
Trillium Health ACTG CRS
Rochester, New York, 14607
Univ. of Rochester ACTG CRS
Rochester, New York, 14642
UCSD Antiviral Research Center CRS
San Diego, California, 92103
Ucsf Hiv/Aids Crs
San Francisco, California, 94110
University of Washington AIDS CRS
Seattle, Washington, 98104-9929
Washington University Therapeutics (WT) CRS
St Louis, Missouri, 63110-1010
Georgetown University CRS (GU CRS)
Washington D.C., District of Columbia, 20007
Howard Univ. Washington DC NICHD CRS
Washington D.C., District of Columbia, 20060
Puerto Rico3 sites
Puerto Rico AIDS Clinical Trials Unit CRS
San Juan, 00935
University of Puerto Rico Pediatric HIV/AIDS Research Program CRS
San Juan, 00935
San Juan City Hosp. PR NICHD CRS
San Juan, 00936
Brazil1 site
Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
Rio de Janeiro, 21040-900
South Africa1 site
Wits Helen Joseph Hospital CRS (Wits HJH CRS)
Johannesburg, Gauteng, 2092
About this study
Official title: A Phase II Study to Evaluate the Immunogenicity and Safety of a Quadrivalent Human Papillomavirus Vaccine in HIV-1-Infected Females
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.
Read the 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
- Being tested
- Quadrivalent HPV vaccine
- Keywords
- HIV, HPV 6, HPV 11, HPV 16, HPV 18, Vaccine
- Medical subject headings
- HIV Infections, Sexually Transmitted Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Quadrivalent HPV vaccineBiological
Also called GARDASIL
Quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine. All participants received the vaccine via intramuscular injection at baseline, Week 8 and Week 24.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Biological: Quadrivalent HPV vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Week 28
Secondary outcomes (12)
HPV6 Antibody Titers Among Those Seronegative for HPV6 at Baseline
HPV antibody titers to type 6 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (7 mMU/mL, and after assay change in December 2012, 11 mMU/mL for HPV6). Geometric mean HPV6 titers with 95% CIs were calculated among the subset of participants who were seronegative for HPV6 (<20 mMU/mL) at baseline.
Measured: Weeks 28, 72
HPV11 Antibody Titers Among Those Seronegative for HPV11 at Baseline
HPV antibody titers to type 11 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (8 mMU/mL for HPV11). Geometric mean HPV11 titers with 95% CIs were calculated among the subset of participants who were seronegative for HPV11 (<16 mMU/mL) at baseline.
Measured: Weeks 28, 72
HPV16 Antibody Titers Among Those Seronegative for HPV16 at Baseline
HPV antibody titers to type 16 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (11 mMU/mL for HPV16). Geometric mean HPV16 titers with 95% CIs were calculated among the subset of participants who were seronegative for HPV16 (<20 mMU/mL) at baseline.
Measured: Weeks 28, 72
HPV18 Antibody Titers Among Those Seronegative for HPV18 at Baseline
HPV antibody titers to type 18 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (10 mMU/mL for HPV18). Geometric mean HPV18 titers with 95% CIs were calculated among the subset of participants who were seronegative for HPV18 (<24 mMU/mL) at baseline.
Measured: Weeks 28, 72
Change in Log10 HPV6 Antibody Titers From Baseline Among Those Seropositive for HPV6 at Baseline
Change in log10 HPV6 antibody titers was calculated as log10 HPV6 antibody titers at a later timepoint (Week 28, Week 72) minus log10 HPV6 antibody titers at baseline among those seropositive for HPV6 (>=20 mMU/mL) at baseline. HPV antibody titers to type 6 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (7 mMU/mL, and after assay change in December 2012, 11 mMU/mL for HPV6).
Measured: Weeks 0, 28, 72
Change in Log10 HPV11 Antibody Titers From Baseline Among Those Seropositive for HPV11 at Baseline
Change in log10 HPV11 antibody titers was calculated as log10 HPV11 antibody titers at a later timepoint (Week 28, Week 72) minus log10 HPV11 antibody titers at baseline among those seropositive for HPV11 (>=16 mMU/mL) at baseline. HPV antibody titers to type 11 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (8 mMU/mL for HPV11).
Measured: Weeks 0, 28, 72
Change in Log10 HPV16 Antibody Titers From Baseline Among Those Seropositive for HPV16 at Baseline
Change in log10 HPV16 antibody titers was calculated as log10 HPV16 antibody titers at a later timepoint (Week 28, Week 72) minus log10 HPV16 antibody titers at baseline among those seropositive for HPV16 (>=20 mMU/mL) at baseline. HPV antibody titers to type 16 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (11 mMU/mL for HPV16).
Measured: Weeks 0, 28, 72
Change in Log10 HPV18 Antibody Titers From Baseline Among Those Seropositive for HPV18 at Baseline
Change in log10 HPV18 antibody titers was calculated as log10 HPV18 antibody titers at a later timepoint (Week 28, Week 72) minus log10 HPV18 antibody titers at baseline among those seropositive for HPV18 (>=24 mMU/mL) at baseline. HPV antibody titers to type 18 were measured centrally using the competitive Luminex ImmunoAssay (HPV-4, cLIA) on stored serum. The results below the lower limit of detection (LLD) were assigned the values of half the LLD (10 mMU/mL for HPV18).
Measured: Weeks 0, 28, 72
Number of Participants With Signs and Symptoms of Grade 3 or Higher
Number of participants who experienced a sign or symptom of Grade 3 or higher at any time after baseline while on study. Grading of signs and symptoms was according to Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004.
Measured: From baseline to up to Week 72
Number of Participants With Laboratory Abnormalities of Grade 3 or Higher
Number of participants who experienced a laboratory abnormality of Grade 3 or higher at any time after baseline while on study. Grading of laboratory abnormalities was according to Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004.
Measured: From baseline to up to Week 72
Change in Log10 HIV Viral Load (VL) From Baseline
A blood sample was drawn for local testing to determine the HIV VL. Change in log10 HIV VL was calculated as log10 HIV VL at a later time point (Weeks 4, 12, 28, 52 and 72) minus log10 HIV VL at baseline.
Measured: Weeks 0, 4, 12, 28, 52, and 72
Change in CD4 Cell Count From Baseline
A blood sample was drawn for local testing to determine the CD4 cell count. Change in CD4 cell count was calculated as CD4 cell count at a later time point (Weeks 4, 8, 12, 24, 28, 52 and 72) minus CD4 cell count at baseline.
Measured: Weeks 0, 4, 8, 12, 24, 28, 52 and 72
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2008 (estimated)
- Study startFeb 2008
- Primary completionJan 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 319 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Institute of Dental and Craniofacial Research (NIDCR)
- Responsible party
- Sponsor
- Investigators
- Erna Milunka Kojic, MD, Study chair, Department of Immunology/Infectious Disease, The Miriam Hospital, Brown UniversitySusan Cu-Uvin, MD, Study chair, Obstetrics-Gynecology and Medicine, The Miriam Hospital, Brown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00604175
- Sponsor's protocol ID
- A5240
- Other IDs
- 10393, ACTG A5240
- Status last verified
- Aug 2015
- First submitted
- 17 Jan 2008
- Last updated
- 4 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 17672042Chaturvedi 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.
PubMed 17117025De 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.
PubMed 17762573Kojic 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.
PubMed 17762572Palefsky J. Human papillomavirus infection in HIV-infected persons. Top HIV Med. 2007 Aug-Sep;15(4):130-3.
PubMed 17720998Kojic 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.
PubMed 24723284Kang 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.
PubMed 34907980Cespedes 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.
PubMed 30118852
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study to Evaluate the Immunogenicity and Safety of a Quadrivalent Human Papillomavirus Vaccine in HIV-1-Infected Females
- ClinicalTrials.gov ID
- NCT00604175
- Acronym / sponsor ID
- A5240
- Conditions
- HIV Infections, Sexually Transmitted Diseases
- Keywords
- HIV, HPV 6, HPV 11, HPV 16, HPV 18, Vaccine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 319 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- National Institute of Dental and Craniofacial Research (NIDCR)
- Study start
- Feb 2008
- Primary completion
- Jan 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 30 Jan 2008 (estimated)
- Results
- Posted 17 Oct 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Stratum A | Experimental | Biological: Quadrivalent HPV vaccineParticipants with screening CD4 count >350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24. |
| Stratum B | Experimental | Biological: Quadrivalent HPV vaccineParticipants with screening CD4 count >200 to <=350 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24. |
| Stratum C | Experimental | Biological: Quadrivalent HPV vaccineParticipants with screening CD4 count <=200 cells/mm^3 received 0.5mL of quadrivalent HPV vaccine at baseline and Weeks 8 and 24. |
Who may qualify
- Ages
- 13 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- 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:
- Willing to use acceptable forms of contraception for the duration of the study
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Quadrivalent HPV vaccineAlso: GARDASILQuadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine. All participants received the vaccine via intramuscular injection at baseline, Week 8 and Week 24. | Biological | Stratum A, Stratum B, Stratum C |
Primary outcome
Percentage of Participants With HPV6 Antibody Development From Seronegative Status at Baseline to Seropositive Status a Month After Completion of HPV Vaccination Series
Time frame: Week 28
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.
Percentage of Participants With HPV11 Antibody Development From Seronegative Status at Baseline to Seropositive Status a Month After Completion of HPV Vaccination Series
Time frame: Week 28
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.
Percentage of Participants With HPV16 Antibody Development From Seronegative Status at Baseline to Seropositive Status a Month After Completion of HPV Vaccination Series
Time frame: Week 28
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.
Percentage of Participants With HPV18 Antibody Development From the Seronegative Status at Baseline to Seropositive Status a Month After Completion of HPV Vaccination Series
Time frame: Week 28
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.
12 secondary outcomes
HPV6 Antibody Titers Among Those Seronegative for HPV6 at Baseline
Time frame: Weeks 28, 72
HPV11 Antibody Titers Among Those Seronegative for HPV11 at Baseline
Time frame: Weeks 28, 72
HPV16 Antibody Titers Among Those Seronegative for HPV16 at Baseline
Time frame: Weeks 28, 72
HPV18 Antibody Titers Among Those Seronegative for HPV18 at Baseline
Time frame: Weeks 28, 72
Change in Log10 HPV6 Antibody Titers From Baseline Among Those Seropositive for HPV6 at Baseline
Time frame: Weeks 0, 28, 72
Change in Log10 HPV11 Antibody Titers From Baseline Among Those Seropositive for HPV11 at Baseline
Time frame: Weeks 0, 28, 72
Change in Log10 HPV16 Antibody Titers From Baseline Among Those Seropositive for HPV16 at Baseline
Time frame: Weeks 0, 28, 72
Change in Log10 HPV18 Antibody Titers From Baseline Among Those Seropositive for HPV18 at Baseline
Time frame: Weeks 0, 28, 72
Number of Participants With Signs and Symptoms of Grade 3 or Higher
Time frame: From baseline to up to Week 72
Number of Participants With Laboratory Abnormalities of Grade 3 or Higher
Time frame: From baseline to up to Week 72
Change in Log10 HIV Viral Load (VL) From Baseline
Time frame: Weeks 0, 4, 12, 28, 52, and 72
Change in CD4 Cell Count From Baseline
Time frame: Weeks 0, 4, 8, 12, 24, 28, 52 and 72
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17672042Cameron 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.
- Background: PubMed 17117025Chaturvedi 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.
- Background: PubMed 17762573De 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.
- Background: PubMed 17762572Kojic 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.
- Background: PubMed 17720998Palefsky J. Human papillomavirus infection in HIV-infected persons. Top HIV Med. 2007 Aug-Sep;15(4):130-3.
- Results publication: PubMed 24723284Kojic 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.
- Derived from this study: PubMed 34907980Kang 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.
- Derived from this study: PubMed 30118852Cespedes 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erna Milunka Kojic, MD study chair
Department of Immunology/Infectious Disease, The Miriam Hospital, Brown University
Susan Cu-Uvin, MD study chair
Obstetrics-Gynecology and Medicine, The Miriam Hospital, Brown University
61 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Quadrivalent HPV vaccine in people with HIV Infections and Sexually Transmitted Diseases, run by National Institute of Allergy and Infectious Diseases (NIAID) at 61 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 61 sites in United States, Puerto Rico, Brazil, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Oct 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With HPV6 Antibody Development From Seronegative Status at Baseline to Seropositive Status a Month After Completion of HPV Vaccination Series (time frame: Week 28). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00604175, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2021.