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

Study Overview
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Brief Summary
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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.

Official Title
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Immunogenicity, Safety, Tolerability, and Behavioral Consequences of an HPV-6, -11, -16, -18 Vaccine in HIV-Infected Young Women

Conditions
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HIV Infection

Intervention / Treatment
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* Biological: HPV vaccine for strains -6, -11, -16, and -18


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 23 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A: HAART naive or no HAART in past 6 months<br>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<br>* 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).<br>|
| Active Comparator: B: HAART atleast 6 months/ 2 viral loads <400 in last 6 months<br>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<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HPV-6 Antibody Level (Geometric Mean Titer of HPV-6) | 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. | Week 28 | 
| HPV-11 Antibody Level (Geometric Mean Titer of HPV-11) | 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. | Week 28 | 
| HPV-16 Antibody Level (Geometric Mean Titer of HPV-16) | 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. | Week 28 | 
| HPV-18 Antibody Level (Geometric Mean Titer of HPV-18) | 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. | Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Week 28 | 
| 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 | 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. | Week 28 | 
| 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 | 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. | Week 28 | 
| 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 | 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. | Week 28 | 
| Number of Participants With At Least One Adverse Event Possibly, Probably, or Definitely Related to Vaccine | 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. | Entry, Week 8, and Week 24 | 
| 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. | 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. | Week 48 | 
| 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. | 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 | Week 48 | 
| 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. | 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 | Week 48 | 
| 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. | 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 | Week 48 | 
| Acquisition of HPV-6 DNA by Study Group and Study Visit (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. | Week 24 | 
| Acquisition of HPV-11 DNA by Study Group and Study Visit (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. | Week 24 | 
| Acquisition of HPV-16 DNA by Study Group and Study Visit (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. | Week 24 | 
| Acquisition of HPV-18 DNA by Study Group and Study Visit (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. | Week 24 | 
| Acquisition of HPV-6 DNA by Study Group and Study Visit (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. | Week 48 | 
| Acquisition of HPV-11 DNA by Study Group and Study Visit (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. | Week 48 | 
| Acquisition of HPV-16 DNA by Study Group and Study Visit (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. | Week 48 | 
| Acquisition of HPV-18 DNA by Study Group and Study Visit (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. | Week 48 | 
| 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 | 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 … You feel that condom use during sex is less necessary. You feel it is still just as important to have as few sexual partners as possible. You feel that it is less important to talk to your sex partners about safe sex. You think it is still just as important to use a condom every time you have sex. 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. | Week 48 | 
| Need for Safer Sexual Behaviors (NSSB) (Evaluated by Using the 12-item Knowledge About HPV and HPV Vaccine Measure) | 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. | Week 48 | 
| Visit Compliance Via the Telephone Response System (TRS) Versus the Vaccine Report Card. | 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%. | Day 1 through Week 24 | 
| Adverse Events (AE) Reported Among Participants Who Were Randomized to the Telephone Response System (TRS) or Vaccine Report Card (VRC). | 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. | Day 1 through Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Highly-active antiretroviral therapy, Human papillomavirus, HPV vaccine