Impact of a Human Papilloma Virus (HPV) Vaccine in HIV-Infected Young Women

• ClinicalTrials.gov Identifier: NCT00710593
• Recruitment Status: Completed
• First Posted: July 4, 2008
• Results First Posted: May 22, 2017
• Last Update Posted: July 2, 2017
• Sponsor: University of North Carolina, Chapel Hill
• Information provided by (Responsible Party): University of North Carolina, Chapel Hill

Study Description

Brief Summary:

The purpose of this study is to evaluate the immunogenicity, safety, tolerability, and behavioral impact of an HPV-6, -11, -16, -18 vaccine in HIV-infected young women.

Condition or disease	Intervention/treatment	Phase
HIV Infection	Biological: HPV vaccine for strains -6, -11, -16, and -18	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 99 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Immunogenicity, Safety, Tolerability, and Behavioral Consequences of an HPV-6, -11, -16, -18 Vaccine in HIV-Infected Young Women
• Study Start Date: February 2008
• Actual Primary Completion Date: February 2011
• Actual Study Completion Date: February 2011

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: A: HAART naive or no HAART in past 6 months; Participants who are ART naïve or, if ART-exposed, have not received highly active antiretroviral therapy (HAART) for at least the six months prior to study entry. All subjects will receive three doses of the HPV-6, -11, -16, -18 vaccine at the recommended dose and schedule (Day 0, Week 8, and Week 24).	Biological: HPV vaccine for strains -6, -11, -16, and -18; All subjects will receive three doses of the HPV-6, -11, -16, -18 vaccine at the recommended dose and schedule (Day 0, Week 8, and Week 24).
Active Comparator: B: HAART atleast 6 months/ 2 viral loads <400 in last 6 months; Participants who have been receiving highly active antiretroviral therapy (HAART) for at least six months at the time of study entry, with two HIV-1 RNA plasma viral loads < 400 copies/ml on two previous clinical visits within the 6 months prior to study entry. All subjects will receive three doses of the HPV-6, -11, -16, -18 vaccine at the recommended dose and schedule (Day 0, Week 8, and Week 24).	Biological: HPV vaccine for strains -6, -11, -16, and -18; All subjects will receive three doses of the HPV-6, -11, -16, -18 vaccine at the recommended dose and schedule (Day 0, Week 8, and Week 24).

Outcome Measures

Primary Outcome Measures :

1. HPV-6 Antibody Level (Geometric Mean Titer of HPV-6) [ Time Frame: Week 28 ]
   The outcome measure for the primary objective is immunogenicity as measured by the GMT of HPV-6, -11, -16, -18 vaccine four weeks after the administration of vaccine dose #3, measured as a continuous variable. Vaccine dose # 3 was administered at Week 24.
2. HPV-11 Antibody Level (Geometric Mean Titer of HPV-11) [ Time Frame: Week 28 ]
   The outcome measure for the primary objective is immunogenicity as measured by the GMTs of HPV-6, -11, -16, -18 vaccine four weeks after the administration of vaccine dose #3, measured as a continuous variable. Vaccine Dose #3 was administered at Week 24.
3. HPV-16 Antibody Level (Geometric Mean Titer of HPV-16) [ Time Frame: Week 28 ]
   The outcome measure for the primary objective is immunogenicity as measured by the GMTs of HPV-6, -11, -16, -18 vaccine four weeks after the administration of vaccine dose #3, measured as a continuous variable. Vaccine dose # 3 was administered at Week 24.
4. HPV-18 Antibody Level (Geometric Mean Titer of HPV-18) [ Time Frame: Week 28 ]
   The outcome measure for the primary objective is immunogenicity as measured by the GMTs of HPV-6, -11, -16, -18 vaccine four weeks after the administration of vaccine dose #3, measured as a continuous variable. Vaccine dose #3 was administered at Week 24.

Secondary Outcome Measures :

1. Immunogenicity of the HPV-6, -11, -16, -18 Vaccine Four Weeks After Vaccine Dose #3 as Measured as a Binary Variable (Responder vs. Non-responder) for HPV-6 [ Time Frame: Week 28 ]
   Subjects who had a greater than or equal to (>=) 20 Milli-Merck units (mMU)/milliliter (mL) response were classified as responders; subjects who had a less than (<) 20 mMU/mL response were classified as non-responders.
2. Immunogenicity of the HPV-6, -11, -16, -18 Vaccine Four Weeks After Vaccine Dose #3 as Measured as a Binary Variable (Responder vs. Non-responder) for HPV-11 [ Time Frame: Week 28 ]
   Subjects who had a >= 16 mMU/mL were classified as responders; subjects who had a less than < 16 mMU/mL response were classified as non-responders.
3. Immunogenicity of the HPV-6, -11, -16, -18 Vaccine Four Weeks After Vaccine Dose #3 as Measured as a Binary Variable (Responder vs. Non-responder) for HPV-16 [ Time Frame: Week 28 ]
   Subjects who had a >= 20 mMU/mL were classified as responders; subjects who had a less than < 20 mMU/mL response were classified as non-responders.
4. Immunogenicity of the HPV-6, -11, -16, -18 Vaccine Four Weeks After Vaccine Dose #3 as Measured as a Binary Variable (Responder vs. Non-responder) for HPV-18 [ Time Frame: Week 28 ]
   Subjects who had a >= 24 mMU/mL were classified as responders; subjects who had a less than < 24 mMU/mL response were classified as non-responders.
5. Number of Participants With At Least One Adverse Event Possibly, Probably, or Definitely Related to Vaccine [ Time Frame: Entry, Week 8, and Week 24 ]
   When a subject had at least one adverse event or sign/symptom during the study after doses 1, 2 or 3, and the event was possibly, probably, or definitely related to vaccine, this subject was considered to have had a vaccine-associated adverse event, sign and/or symptom.
6. Persistence of Immunogenicity of the HPV-6, -11, -16, and -18 Vaccine 24 Weeks Post Vaccine Dose #3 as Measured by the Geometric Mean Titers (GMT) of HPV-6. [ Time Frame: Week 48 ]
   Persistence of immunogenicity as measured by geometric mean titers (GMT) to HPV-6, -11, -16, -18 vaccine 24 weeks after the administration of vaccine dose #3, measured as a continuous variable. Vaccine dose #3 was administered at Week 24.
7. Persistence of Immunogenicity of the HPV-6, -11, -16, and -18 Vaccine 24 Weeks Post Vaccine Dose #3 as Measured by the Geometric Mean Titers (GMT) of HPV-11. [ Time Frame: Week 48 ]
   Persistence of immunogenicity as measured by geometric mean titers (GMT) to HPV-6, -11, -16, -18 vaccine 24 weeks after the administration of vaccine dose #3, measured as a continuous variable. Vaccine dose # 3 was administered at Week 24
8. Persistence of Immunogenicity of the HPV-6, -11, -16, and -18 Vaccine 24 Weeks Post Vaccine Dose #3 as Measured by the Geometric Mean Titers (GMT) of HPV-16. [ Time Frame: Week 48 ]
   Persistence of immunogenicity as measured by geometric mean titers (GMT) to HPV-6, -11, -16, -18 vaccine 24 weeks after the administration of vaccine dose #3, measured as a continuous variable. Vaccine dose # 3 was administered at Week 24
9. Persistence of Immunogenicity of the HPV-6, -11, -16, and -18 Vaccine 24 Weeks Post Vaccine Dose #3 as Measured by the Geometric Mean Titers (GMT) of HPV-18. [ Time Frame: Week 48 ]
   Persistence of immunogenicity as measured by geometric mean titers (GMT) to HPV-6, -11, -16, -18 vaccine 24 weeks after the administration of vaccine dose #3, measured as a continuous variable. Vaccine dose # 3 was administered at Week 24
10. Acquisition of HPV-6 DNA by Study Group and Study Visit (Week 24). [ Time Frame: Week 24 ]
    Type-specific HPV DNA among subjects who were both HPV DNA negative and HPV-6 sero-negative by study group and study visit at Week 24.
11. Acquisition of HPV-11 DNA by Study Group and Study Visit (Week 24). [ Time Frame: Week 24 ]
    Type-specific HPV DNA among subjects who were both HPV DNA negative and HPV-11 sero-negative by study group and study visit at Week 24.
12. Acquisition of HPV-16 DNA by Study Group and Study Visit (Week 24). [ Time Frame: Week 24 ]
    Type-specific HPV DNA among subjects who were both HPV DNA negative and HPV-16 sero-negative by study group and study visit at Week 24.
13. Acquisition of HPV-18 DNA by Study Group and Study Visit (Week 24). [ Time Frame: Week 24 ]
    Type-specific HPV DNA among subjects who were both HPV DNA negative and HPV-18 sero-negative by study group and study visit at Week 24.
14. Acquisition of HPV-6 DNA by Study Group and Study Visit (Week 48). [ Time Frame: Week 48 ]
    Type-specific HPV DNA among subjects who were both HPV DNA negative and HPV sero-negative by study group and study visit at Week 48.
15. Acquisition of HPV-11 DNA by Study Group and Study Visit (Week 48). [ Time Frame: Week 48 ]
    Type-specific HPV DNA among subjects who were both HPV DNA negative and HPV sero-negative by study group and study visit at Week 48.
16. Acquisition of HPV-16 DNA by Study Group and Study Visit (Week 48). [ Time Frame: Week 48 ]
    Type-specific HPV DNA among subjects who were both HPV DNA negative and HPV sero-negative by study group and study visit at Week 48.
17. Acquisition of HPV-18 DNA by Study Group and Study Visit (Week 48). [ Time Frame: Week 48 ]
    Type-specific HPV DNA among subjects who were both HPV DNA negative and HPV sero-negative by study group and study visit at Week 48.
18. Percentage of Participants Who Reported a Lower Need to Practice Safe Sex Following HPV Vaccination and the Percentage of Participants That Reported a Higher Need to Practice Safe Sex Following HPV Vaccination [ Time Frame: Week 48 ]

    Participants' perceptions for the need to practice safe sex following HPV vaccination was measured using a safer sexual behaviors subscale, which was comprised of the following five questions:

    After getting vaccinated against HPV …

    1. You feel that condom use during sex is less necessary.
    2. You feel it is still just as important to have as few sexual partners as possible.
    3. You feel that it is less important to talk to your sex partners about safe sex.
    4. You think it is still just as important to use a condom every time you have sex.
    5. You will be less worried about having unprotected sex. Those who were categorized in the "lower need for safer sexual behaviors (NSSB)" group had a summary score that was less than the median and those in the "higher NSSB" group had a summary score that was equal to or higher than the median.
19. Need for Safer Sexual Behaviors (NSSB) (Evaluated by Using the "12-item Knowledge About HPV and HPV Vaccine" Measure) [ Time Frame: Week 48 ]
    To characterize young women's risk perceptions, sexual behaviors, and sexually transmitted infections (STI) diagnoses over the 48 weeks after initial vaccination, the relationship of baseline "12-item Knowledge About HPV and HPV Vaccine" measure was used to evaluate the need for safer sexual behaviors.
20. Visit Compliance Via the Telephone Response System (TRS) Versus the Vaccine Report Card. [ Time Frame: Day 1 through Week 24 ]
    Visit compliance is the total number of days participants actually called the TRS or completed the VRC divided by the total number of days expected to call the TRS or complete the VRC, multiplied by 100%.
21. Adverse Events (AE) Reported Among Participants Who Were Randomized to the Telephone Response System (TRS) or Vaccine Report Card (VRC). [ Time Frame: Day 1 through Week 24 ]
    Rate of AEs is the total number of AEs divided by the total number of participants. The rate is not a percentage bur rather it could be above 1 or less than 1. This outcome measure looked at number of AEs reported, by grade; number of AEs > Grade 3 identified; and number of AEs > Grade 3 evaluated within 24 or 48 hours.

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 23 Years (Child, Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Young women age 16 years and 0 days to 23 years and 364 days
• HIV-infection after the age of 9 years as documented by a positive result on any of the following licensed tests: any antibody test confirmed by Western blot, HIV-1 culture, HIV-1 DNA polymerase chain reaction (PCR), or plasma HIV-1 RNA > 1,000 copies/ml
• HIV treatment history that falls in one of the following categories:

Group A: ART naïve or if ART-exposed, has not received HAART for at least the six months prior to study entry Group B: Has been receiving HAART for at least six months at the time of study entry, with two HIV-1 RNA plasma viral loads < 400 copies/ml on two previous clinical visits within the 6 months prior to study entry

• Willingness to avoid pregnancy from study entry through the Week 28 visit for subjects of child-bearing potential, i.e., use of at least one barrier or hormonal method; e.g., condoms, Depo-Provera, oral contraceptive pills, etc. Subjects on antiretroviral (ARV) medications must use a barrier contraceptive method because ARV medications can make hormonal birth control less effective.
• Anticipated ability and willingness to complete all study vaccines and evaluations
• Ability and willingness to participate in the study by providing written informed consent

Exclusion Criteria:

• History of any prior vaccination with an HPV vaccine
• Active anogenital warts within three months prior to study entry) or history of cervical intraepithelial neoplasia (CIN) 2/3 (ever, must be documented by colposcopy)
• Previous allergic reaction to any constituents of the HPV vaccine
• Pregnancy
• Active substance use or dependence that, in the opinion of the site personnel, would interfere with adherence to the study
• Active opportunistic infection or current treatment for known or suspected active serious bacterial infection at the time of study entry
• Presence of any known > Grade 3 clinical or laboratory toxicity at the time of study entry (per the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) Toxicity Tables, see ATN MOGO) with the exception of isolated Grade 3 serum total hyperbilirubinemia that is considered due to atazanavir (see Section 9.6 for definition of isolated total hyperbilirubinemia).
• Receipt of any routine vaccine within four weeks prior to study entry
• Receipt of any immune globulin or plasma product within six months prior study entry
• Receipt of any blood product or transfusion, other than immune globulin or plasma as noted above, within four weeks prior to study entry
• Receipt of any restricted medication listed in Section 5.3.2 within the four weeks preceding study entry
• Receipt of any other disallowed medication listed in Section 5.3.3 within the three months preceding study entry
• Thrombocytopenia or coagulation disorder that would contraindicate intramuscular injection
• Anticipation of long-term systemic corticosteroid therapy (more than 10 mg/day of prednisone or equivalent for > 2 consecutive weeks)
• Receipt of corticosteroid therapy at the above dose and duration within 3 months preceding study entry. Use of non-steroidal anti-inflammatory agents and inhaled or topical corticosteroids are not exclusion criteria
• Known or suspected disease of the immune system (other than HIV), i.e., malignancy, current or prior treatment for malignancy
• If other serious, acute or chronic medical or surgical conditions or contraindications are present during screening, the Protocol Team must be consulted to determine whether enrollment may interfere with the evaluation of the protocol objectives and for permission to proceed with the enrollment

Contacts and Locations

Locations

United States, California

Childrens Hospital of Los Angeles

Los Angeles, California, United States, 90027

United States, District of Columbia

Childrens National Medical Center

Washington, D.C., District of Columbia, United States, 20010

United States, Florida

Childrens Diagnostic & Treatment Center

Fort Lauderdale, Florida, United States, 33316

University of Miami School of Medicine

Miami, Florida, United States, 33101

USF College of Medicine

Tampa, Florida, United States, 33606

United States, Illinois

Ruth M Rothstein CORE Center/ John H Stroger Jr Hospital

Chicago, Illinois, United States, 60612

Childrens Memorial Hospital

Chicago, Illinois, United States, 60614

United States, Louisiana

Tulane University Health Sciences Center

New Orleans, Louisiana, United States, 70112

United States, Maryland

University of Maryland

Baltimore, Maryland, United States, 21201

United States, New York

Mount Sinai Medical Center

New York, New York, United States, 10128

Montefiore Medical Center

The Bronx, New York, United States, 10467

United States, Pennsylvania

Childrens Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

United States, Tennessee

St Jude Childrens Research Hospital

Memphis, Tennessee, United States, 38105

Puerto Rico

University of Puerto Rico, Medical Sciences Campus

San Juan, Puerto Rico, 00936-5067

Sponsors and Collaborators

University of North Carolina, Chapel Hill

Investigators

• Study Chair: Jessica A. Kahn, M.D., M.P.H.; Adolescent Trials Network
• Study Chair: Kathleen Squires, M.D.; Adolescent Trials Network

More Information

Additional Information:

Website for the Adolescent Trials Network for HIV/AIDS Interventions 

Publications of Results:

Kahn JA, Xu J, Zimet GD, Liu N, Gonin R, Dillard ME, Squires K; Adolescent Trials Network for HIV/AIDS Interventions. Risk perceptions after human papillomavirus vaccination in HIV-infected adolescents and young adult women. J Adolesc Health. 2012 May;50(5):464-70. doi: 10.1016/j.jadohealth.2011.09.005. Epub 2011 Nov 4.

Kahn JA, Burk RD, Squires KE, Kapogiannis BG, Rudy B, Xu J, Gonin R, Liu N, Worrell C, Wilson CM. Prevalence and risk factors for HPV in HIV-positive young women receiving their first HPV vaccination. J Acquir Immune Defic Syndr. 2012 Nov 1;61(3):390-9. doi: 10.1097/QAI.0b013e3182676fe3.

Kahn JA, Xu J, Kapogiannis BG, Rudy B, Gonin R, Liu N, Wilson CM, Worrell C, Squires KE. Immunogenicity and safety of the human papillomavirus 6, 11, 16, 18 vaccine in HIV-infected young women. Clin Infect Dis. 2013 Sep;57(5):735-44. doi: 10.1093/cid/cit319. Epub 2013 May 10.

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT00710593
• Other Study ID Numbers: ATN 064
• First Posted: July 4, 2008
• Results First Posted: May 22, 2017
• Last Update Posted: July 2, 2017
• Last Verified: April 2017

Keywords provided by University of North Carolina, Chapel Hill:

Highly-active antiretroviral therapy; Human papillomavirus; HPV vaccine

Additional relevant MeSH terms:

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Immunologic Deficiency Syndromes; Immune System Diseases