Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A phase IV, observer-blind, randomized, controlled, multicentric study to assess the safety and immunogenicity of GSK Biologicals’ HPV-16/18 L1 VLP AS04 vaccine (Cervarix) administered intramuscularly according to a three-dose schedule (Day 0, Week 6, Month 6) in human immunodeficiency virus-infected (HIV+) female subjects aged 15 - 25 years, as compared to Merck’s HPV-6/11/16/18 vaccine (Gardasil)

    Summary
    EudraCT number
    		 2013-003429-28
    Trial protocol
    		 EE  
    Global end of trial date
    19 Apr 2017

    Results information
    Results version number
    		 v3(current)
    This version publication date
    05 Jun 2019
    First version publication date
    30 Apr 2017
    Other versions
    		 v1 , v2
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    109823
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01031069
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline Biologicals
    Sponsor organisation address
    Rue de l’Institut 89, Rixensart, Belgium, B-1330
    Public contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    19 Mar 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    13 Jan 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Apr 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the safety of both vaccines in HIV+ subjects for up to 1 month after the third dose of vaccine. To demonstrate non-inferiority of Cervarix versus (vs.) Gardasil in terms of geometric mean titres (GMTs) against HPV-16 and HPV-18 measured by Pseudovirion-based neutralization assay (PBNA) 1 month after administration of the third dose of vaccine in HIV+ subjects. If the first primary objective for immunogenicity was demonstrated, superiority of Cervarix over Gardasil in terms of GMTs against HPV-16 and HPV-18 measured by PBNA in HIV+ subjects was assessed following a sequential approach.
    Protection of trial subjects
    All subjects were supervised after vaccination/product administration with appropriate medical treatment readily available. Vaccines were administered by qualified and trained personnel. Vaccines were administered only to eligible subjects that had no contraindications to any components of the vaccines.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    26 Oct 2010
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Brazil: 431
    Country: Number of subjects enrolled
    Estonia: 37
    Country: Number of subjects enrolled
    India: 224
    Country: Number of subjects enrolled
    Thailand: 181
    Worldwide total number of subjects
    873
    EEA total number of subjects
    37
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    265
    Adults (18-64 years)
    608
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 A number of 873 subjects were enrolled, out of which 173 subjects were excluded from all statistical analyses. 154 subjects were not administered any vaccine dose (146 screen failures subjects and 8 subjects that did not participate from Visit 1).

    Pre-assignment
    Screening details
    		 Screening involved: checking of inclusion/exclusion criteria, demographic data, history and physical examination, AF B sputum test and/or chest X-ray, blood sampling for HIV testing and safety, urine pregnancy testing, birth control and HIV, STI, STD counselling, checking records for concomitant medication/vaccination, subject card distribution.

    Pre-assignment period milestones
    Number of subjects started
    		 873
    Number of subjects completed
    		 546

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Excluded from all statistical analyses: 173
    Reason: Number of subjects
    		 No vaccination received: 154
    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Assessor
    Blinding implementation details
    Data collected in an observer-blind manner. The vaccine recipient and those responsible for the evaluation of any study endpoint were unaware of which vaccine was administered during the entire study period.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 HIV+/Cervarix Group
    Arm description
    		 HIV seropositive female subjects, between and including 15 and 25 years of age, who received 3 doses of Cervarix vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cervarix
    Investigational medicinal product code
    Other name
    HPV vaccine, GSK Biologicals’ HPV vaccine 580299
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received three doses of the study vaccine administered intramuscularly according to a Day 0, Week 6, and Month 6 vaccination schedule.

    Arm title
    		 HIV+/Gardasil Group
    Arm description
    		 HIV seropositive female subjects, between and including 15 and 25 years of age, who received 3 doses of Gardasil vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Gardasil
    Investigational medicinal product code
    Other name
    Merck’s Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) vaccine
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received three doses of the study vaccine administered intramuscularly according to a Day 0, Week 6, and Month 6 vaccination schedule.

    Arm title
    		 HIV-/Cervarix Group
    Arm description
    		 HIV seronegative female subjects, between and including 15 and 25 years of age, who received 3 doses of Cervarix vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Cervarix
    Investigational medicinal product code
    Other name
    HPV vaccine, GSK Biologicals’ HPV vaccine 580299
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received three doses of the study vaccine administered intramuscularly according to a Day 0, Week 6, and Month 6 vaccination schedule.

    Arm title
    		 HIV-/Gardasil Group
    Arm description
    		 HIV seronegative female subjects, between and including 15 and 25 years of age, who received 3 doses of Gardasil vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Gardasil
    Investigational medicinal product code
    Other name
    Merck’s Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) vaccine
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received three doses of the study vaccine administered intramuscularly according to a Day 0, Week 6, and Month 6 vaccination schedule.

    Number of subjects in period 1 [1]
    		HIV+/Cervarix Group HIV+/Gardasil Group HIV-/Cervarix Group HIV-/Gardasil Group
    Started
    129
    128
    144
    145
    Completed
    117
    117
    103
    111
    Not completed
    12
    11
    41
    34
         Consent withdrawn by subject
    2
    3
    18
    18
         Migrated/moved from study area
    1
    2
    1
    1
         Unspecified
    -
    -
    1
    -
         Lost to follow-up
    9
    5
    21
    15
         Serious Adverse Event
    -
    1
    -
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: A number of 873 subjects were enrolled, out of which 173 subjects were excluded because of data integrity issues at one center and 154 subjects were not administered any vaccine dose (146 screen failures subjects and 8 subjects that did not participate from Visit 1).

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    HIV+/Cervarix Group
    Reporting group description
    		 HIV seropositive female subjects, between and including 15 and 25 years of age, who received 3 doses of Cervarix vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6.

    Reporting group title
    HIV+/Gardasil Group
    Reporting group description
    		 HIV seropositive female subjects, between and including 15 and 25 years of age, who received 3 doses of Gardasil vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6.

    Reporting group title
    HIV-/Cervarix Group
    Reporting group description
    		 HIV seronegative female subjects, between and including 15 and 25 years of age, who received 3 doses of Cervarix vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6.

    Reporting group title
    HIV-/Gardasil Group
    Reporting group description
    		 HIV seronegative female subjects, between and including 15 and 25 years of age, who received 3 doses of Gardasil vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6.

    Reporting group values
    		 HIV+/Cervarix Group HIV+/Gardasil Group HIV-/Cervarix Group HIV-/Gardasil Group Total
    Number of subjects
    		 129 128 144 145 546
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 37 36 47 47 167
        Adults (18-64 years)
    		 92 92 97 98 379
        From 65-84 years
    		 0 0 0 0 0
        85 years and over
    		 0 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 20.4 ± 3.4 20.1 ± 3.5 19.3 ± 3.0 19.6 ± 3.0 -
    Gender categorical
    Units: Subjects
        Female
    		 129 128 144 145 546
        Male
    		 0 0 0 0 0
    Race/Ethnicity, Customized
    Units: Subjects
        African Heritage/African American
    		 10 6 4 4 24
        Asian - Central/South Asian Heritage
    		 20 18 67 68 173
        Asian - East Asian Heritage
    		 3 2 1 0 6
        Asian - Japanese Heritage
    		 0 0 1 2 3
        Asian - South East Asian Heritage
    		 40 44 39 42 165
        White - Arabic/North African Heritage
    		 17 12 7 6 42
        White - Caucasian/European Heritage
    		 33 37 24 19 113
        Unspecified
    		 6 9 1 4 20

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    HIV+/Cervarix Group
    Reporting group description
    		 HIV seropositive female subjects, between and including 15 and 25 years of age, who received 3 doses of Cervarix vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6.

    Reporting group title
    HIV+/Gardasil Group
    Reporting group description
    		 HIV seropositive female subjects, between and including 15 and 25 years of age, who received 3 doses of Gardasil vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6.

    Reporting group title
    HIV-/Cervarix Group
    Reporting group description
    		 HIV seronegative female subjects, between and including 15 and 25 years of age, who received 3 doses of Cervarix vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6.

    Reporting group title
    HIV-/Gardasil Group
    Reporting group description
    		 HIV seronegative female subjects, between and including 15 and 25 years of age, who received 3 doses of Gardasil vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6.

    Primary: Number of human immunodeficiency virus positive subjects (HIV+) with any and Grade 3 solicited local symptoms

    		 Close Top of page
    End point title
    		 Number of human immunodeficiency virus positive subjects (HIV+) with any and Grade 3 solicited local symptoms [1] [2]
    End point description
    Assessed solicited local symptoms were pain, redness, swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest, pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling with a maximum diameter greater than 50 millimeters (mm).
    End point type
    Primary
    End point timeframe
    During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical analyses were available.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV positive subjects.
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group
    Number of subjects analysed
    128
    127
    Units: Participants
        Any Pain, Dose 1 (N=128;125)
    115
    58
        Grade 3 Pain, Dose 1 (N=128;125)
    4
    0
        Any Redness, Dose 1 (N=128;125)
    24
    19
        Grade 3 Redness, Dose 1 (N=128;125)
    0
    0
        Any Swelling, Dose 1 (N=128;125)
    25
    6
        Grade 3 Swelling, Dose 1 (N=128;125)
    2
    0
        Any Pain, Dose 2 (N=127;125)
    98
    56
        Grade 3 Pain, Dose 2 (N=127;125)
    5
    6
        Any Redness, Dose 2 (N=127;125)
    18
    13
        Grade 3 Redness, Dose 2 (N=127;125)
    1
    0
        Any Swelling, Dose 2 (N=127;125)
    16
    11
        Grade 3 Swelling, Dose 2 (N=127;125)
    0
    0
        Any Pain, Dose 3 (N=117;117)
    87
    60
        Grade 3 Pain, Dose 3 (N=117;117)
    5
    2
        Any Redness, Dose 3 (N=117;117)
    17
    18
        Grade 3 Redness, Dose 3 (N=117;117)
    0
    0
        Any Swelling, Dose 3 (N=117;117)
    19
    10
        Grade 3 Swelling, Dose 3 (N=117;117)
    1
    0
        Any Pain, Across Doses (N=128;127)
    120
    85
        Grade 3 Pain, Across Doses (N=128;127)
    11
    6
        Any Redness, Across Doses (N=128;127)
    41
    34
        Grade 3 Redness, Across Doses (N=128;127)
    1
    0
        Any Swelling, Across Doses (N=128;127)
    38
    20
        Grade 3 Swelling, Across Doses (N=128;127)
    2
    0
    No statistical analyses for this end point

    Primary: Number of HIV+ subjects with any, Grade 3 and related solicited general symptoms

    		 Close Top of page
    End point title
    		 Number of HIV+ subjects with any, Grade 3 and related solicited general symptoms [3] [4]
    End point description
    Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal [nausea, vomiting, diarrhoea and/or abdominal pain], headache, myalgia, rash, temperature [defined as axillary temperature higher than (>) 37.5 degrees Celsius (°C)] and urticaria. Any = occurrence of the symptom regardless of intensity grade and relationship. Grade 3 symptom = symptom that prevented normal activity. Grade 3 temperature = temperature > 39.0 °C. Grade 3 urticaria = urticaria distributed on at least 4 body areas. Related = symptom assessed by the investigator as related to the vaccination.
    End point type
    Primary
    End point timeframe
    During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical analyses were available.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV positive subjects.
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group
    Number of subjects analysed
    128
    127
    Units: Participants
        Any Arthralgia, Dose 1 (N=128;125)
    29
    20
        Grade 3 Arthralgia, Dose 1 (N=128;125)
    1
    1
        Related Arthralgia, Dose 1 (N=128;125)
    19
    13
        Any Fatigue, Dose 1 (N=128;125)
    50
    47
        Grade 3 Fatigue, Dose 1 (N=128;125)
    4
    0
        Related Fatigue, Dose 1 (N=128;125)
    30
    29
        Any Gastrointestinal, Dose 1 (N=128;125)
    30
    21
        Grade 3 Gastrointestinal, Dose 1 (N=128;125)
    2
    0
        Related Gastrointestinal, Dose 1 (N=128;125)
    19
    15
        Any Headache, Dose 1 (N=128;125)
    61
    48
        Grade 3 Headache, Dose 1 (N=128;125)
    4
    1
        Related Headache, Dose 1 (N=128;125)
    39
    27
        Any Myalgia, Dose 1 (N=128;125)
    49
    34
        Grade 3 Myalgia, Dose 1 (N=128;125)
    2
    1
        Related Myalgia, Dose 1 (N=128;125)
    35
    25
        Any Rash, Dose 1 (N=128;125)
    7
    4
        Grade 3 Rash, Dose 1 (N=128;125)
    1
    0
        Related Rash, Dose 1 (N=128;125)
    4
    0
        Any Temperature, Dose 1 (N=128;125)
    9
    5
        Grade 3 Temperature, Dose 1 (N=128;125)
    0
    0
        Related Temperature, Dose 1 (N=128;125)
    7
    4
        Any Urticaria, Dose 1 (N=128;125)
    8
    3
        Grade 3 Urticaria, Dose 1 (N=128;125)
    0
    0
        Related Urticaria, Dose 1 (N=128;125)
    6
    3
        Any Arthralgia, Dose 2 (N=127;125)
    18
    21
        Grade 3 Arthralgia, Dose 2 (N=127;125)
    0
    3
        Related Arthralgia, Dose 2 (N=127;125)
    11
    14
        Any Fatigue, Dose 2 (N=127;125)
    38
    40
        Grade 3 Fatigue, Dose 2 (N=127;125)
    2
    1
        Related Fatigue, Dose 2 (N=127;125)
    20
    25
        Any Gastrointestinal, Dose 2 (N=127;125)
    15
    17
        Grade 3 Gastrointestinal, Dose 2 (N=127;125)
    0
    0
        Related Gastrointestinal, Dose 2 (N=127;125)
    11
    11
        Any Headache, Dose 2 (N=127;125)
    48
    37
        Grade 3 Headache, Dose 2 (N=127;125)
    5
    3
        Related Headache, Dose 2 (N=127;125)
    30
    20
        Any Myalgia, Dose 2 (N=127;125)
    36
    26
        Grade 3 Myalgia, Dose 2 (N=127;125)
    2
    4
        Related Myalgia, Dose 2 (N=127;125)
    25
    19
        Any Rash, Dose 2 (N=127;125)
    2
    1
        Grade 3 Rash, Dose 2 (N=127;125)
    0
    0
        Related Rash, Dose 2 (N=127;125)
    0
    0
        Any Temperature, Dose 2 (N=127;125)
    11
    4
        Grade 3 Temperature, Dose 2 (N=127;125)
    0
    0
        Related Temperature, Dose 2 (N=127;125)
    9
    2
        Any Urticaria, Dose 2 (N=127;125)
    5
    4
        Grade 3 Urticaria, Dose 2 (N=127;125)
    1
    0
        Related Urticaria, Dose 2 (N=127;125)
    4
    4
        Any Arthralgia, Dose 3 (N=117;117)
    17
    15
        Grade 3 Arthralgia, Dose 3 (N=117;117)
    2
    1
        Related Arthralgia, Dose 3 (N=117;117)
    13
    12
        Any Fatigue, Dose 3 (N=117;117)
    40
    31
        Grade 3 Fatigue, Dose 3 (N=117;117)
    1
    1
        Related Fatigue, Dose 3 (N=117;117)
    30
    22
        Any Gastrointestinal, Dose 3 (N=117;117)
    13
    17
        Grade 3 Gastrointestinal, Dose 3 (N=117;117)
    1
    1
        Related Gastrointestinal, Dose 3 (N=117;117)
    9
    13
        Any Headache, Dose 3 (N=117;117)
    48
    27
        Grade 3 Headache, Dose 3 (N=117;117)
    2
    2
        Related Headache, Dose 3 (N=117;117)
    39
    16
        Any Myalgia, Dose 3 (N=117;117)
    30
    21
        Grade 3 Myalgia, Dose 3 (N=117;117)
    4
    1
        Related Myalgia, Dose 3 (N=117;117)
    26
    17
        Any Rash, Dose 3 (N=117;117)
    2
    1
        Grade 3 Rash, Dose 3 (N=117;117)
    0
    0
        Related Rash, Dose 3 (N=117;117)
    1
    0
        Any Temperature, Dose 3 (N=117;117)
    10
    12
        Grade 3 Temperature, Dose 3 (N=117;117)
    1
    1
        Related Temperature, Dose 3 (N=117;117)
    7
    6
        Any Urticaria, Dose 3 (N=117;117)
    2
    4
        Grade 3 Urticaria, Dose 3 (N=117;117)
    0
    0
        Related Urticaria, Dose 3 (N=117;117)
    2
    2
        Any Arthralgia, Across Doses (N=128;127)
    41
    38
        Grade 3 Arthralgia, Across Doses (N=128;127)
    3
    4
        Related Arthralgia, Across Doses (N=128;127)
    31
    28
        Any Fatigue, Across Doses (N=128;127)
    73
    59
        Grade 3 Fatigue, Across Doses (N=128;127)
    6
    2
        Related Fatigue, Across Doses (N=128;127)
    50
    39
        Any Gastrointestinal, Across Doses (N=128;127)
    41
    35
        Grade 3 Gastrointestinal, Across Doses (N=128;127)
    3
    1
        Related Gastrointestinal, Across Doses (N=128;127)
    27
    23
        Any Headache, Across Doses (N=128;127)
    88
    63
        Grade 3 Headache, Across Doses (N=128;127)
    11
    4
        Related Headache, Across Doses (N=128;127)
    65
    39
        Any Myalgia, Across Doses (N=128;127)
    68
    51
        Grade 3 Myalgia, Across Doses (N=128;127)
    7
    4
        Related Myalgia, Across Doses (N=128;127)
    52
    37
        Any Rash, Across Doses (N=128;127)
    11
    5
        Grade 3 Rash, Across Doses (N=128;127)
    1
    0
        Related Rash, Across Doses (N=128;127)
    5
    0
        Any Temperature, Across Doses (N=128;127)
    23
    19
        Grade 3 Temperature, Across Doses (N=128;127)
    1
    1
        Related Temperature, Across Doses (N=128;127)
    18
    10
        Any Urticaria, Across Doses (N=128;127)
    13
    9
        Grade 3 Urticaria, Across Doses (N=128;127)
    1
    0
        Related Urticaria, Across Doses (N=128;127)
    10
    8
    No statistical analyses for this end point

    Primary: Number of HIV+ subjects with any, Grade 3 and related unsolicited adverse events (AEs)

    		 Close Top of page
    End point title
    		 Number of HIV+ subjects with any, Grade 3 and related unsolicited adverse events (AEs) [5] [6]
    End point description
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 symptom = symptom that prevented normal activity. Related = symptom assessed by the investigator as related to the vaccination.
    End point type
    Primary
    End point timeframe
    During the 30-day follow-up period (from the day of vaccination up to 29 subsequent days) after any vaccination
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical analyses were available.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV positive subjects.
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group
    Number of subjects analysed
    129
    128
    Units: Participants
        Any AE(s)
    41
    41
        Grade 3 AE(s)
    7
    4
        Related AE(s)
    9
    8
    No statistical analyses for this end point

    Primary: Number of HIV+ subjects with serious adverse events (SAEs)

    		 Close Top of page
    End point title
    		 Number of HIV+ subjects with serious adverse events (SAEs) [7] [8]
    End point description
    SAEs assessed include any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or represented a congenital anomaly/birth defect in the offspring of a study subject.
    End point type
    Primary
    End point timeframe
    From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical analyses were available.
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV positive subjects.
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group
    Number of subjects analysed
    129
    128
    Units: Participants
        SAE(s)
    6
    6
    No statistical analyses for this end point

    Primary: Number of HIV+ subjects with medically significant conditions (MSCs)

    		 Close Top of page
    End point title
    		 Number of HIV+ subjects with medically significant conditions (MSCs) [9] [10]
    End point description
    Medically significant conditions (MSCs) are defined as AEs prompting emergency room or physician visits that were not related to common diseases, or not related to routine visits for physical examination or vaccination, SAEs that were not related to common diseases.
    End point type
    Primary
    End point timeframe
    From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical analyses were available.
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV positive subjects.
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group
    Number of subjects analysed
    129
    128
    Units: Participants
        MSC(s)
    17
    27
    No statistical analyses for this end point

    Primary: Number of HIV+ subjects with potential immune-mediated diseases (pIMDs)

    		 Close Top of page
    End point title
    		 Number of HIV+ subjects with potential immune-mediated diseases (pIMDs) [11] [12]
    End point description
    Potential immune-mediated diseases are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
    End point type
    Primary
    End point timeframe
    From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical analyses were available.
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV positive subjects.
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group
    Number of subjects analysed
    129
    128
    Units: Participants
        pIMD(s)
    1
    0
    No statistical analyses for this end point

    Primary: Number of HIV+ subjects reporting pregnancies and outcomes of reported pregnancies

    		 Close Top of page
    End point title
    		 Number of HIV+ subjects reporting pregnancies and outcomes of reported pregnancies [13] [14]
    End point description
    Pregnancy related outcomes were: live infant no apparent congenital anomaly, live infant congenital anomaly, elective termination (termin.) no apparent congenital anomaly, elective termination (termin.) congenital anomaly, ectopic pregnancy, spontaneous abortion no apparent congenital (congen.) anomaly, stillbirth no apparent congenital anomaly, stillbirth congenital anomaly, lost to follow-up, pregnancy ongoing, missing.
    End point type
    Primary
    End point timeframe
    From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical analyses were available.
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV positive subjects.
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group
    Number of subjects analysed
    4
    2
    Units: Participants
        Live infant NO apparent congenital anomaly
    3
    1
        Live infant congenital anomaly
    0
    0
        Elective termin. NO apparent congenital anomaly
    0
    0
        Elective termin. congenital anomaly
    0
    0
        Ectopic pregnancy
    0
    0
        Spontaneous abortion NO apparent congen. anomaly
    1
    1
        Stillbirth NO apparent congenital anomaly
    0
    0
        Stillbirth congenital anomaly
    0
    0
        Lost to follow-up
    0
    0
        Pregnancy ongoing
    0
    0
        Missing
    0
    0
    No statistical analyses for this end point

    Primary: Number of HIV+ subjects with haematological and biochemical parameter abnormalities

    		 Close Top of page
    End point title
    		 Number of HIV+ subjects with haematological and biochemical parameter abnormalities [15] [16]
    End point description
    Among assessed haematological and biochemical parameters were: alanine aminotransferase [ALAT], basophilis [BSPH], creatinine [CRT], eosinophils [ESPH], haematocrit [HTCR], haemoglobin [HGB], lymphocytes [LYMP], monocytes [MONO], neutrophils [NTPH], platelets [PLAT], red blood cells [RBC] and white blood cells [WBC]. Unknown = value unknown for the specified visit and laboratory parameter; Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
    End point type
    Primary
    End point timeframe
    At Month 7 (30 days after the last vaccination dose at Month 6)
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical analyses were available.
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV positive subjects.
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group
    Number of subjects analysed
    121
    121
    Units: Participants
        ALAT, Unknown (N=121;121)
    0
    0
        ALAT, Below (N=121;121)
    4
    3
        ALAT, Within (N=121;121)
    110
    105
        ALAT, Above (N=121;121)
    7
    13
        BSPH, Unknown (N=121;121)
    0
    0
        BSPH, Below (N=121;121)
    0
    0
        BSPH, Within (N=121;121)
    120
    121
        BSPH, Above (N=121;121)
    1
    0
        CRT, Unknown (N=121;120)
    0
    0
        CRT, Below (N=121;120)
    29
    36
        CRT, Within (N=121;120)
    91
    84
        CRT, Above (N=121;120)
    1
    0
        ESPH, Unknown (N=121;121)
    0
    0
        ESPH, Below (N=121;121)
    9
    10
        ESPH, Within (N=121;121)
    108
    106
        ESPH, Above (N=121;121)
    4
    5
        HTCR, Unknown (N=121;121)
    0
    0
        HTCR, Below (N=121;121)
    19
    27
        HTCR, Within (N=121;121)
    101
    92
        HTCR, Above (N=121;121)
    1
    2
        HGB, Unknown (N=121;121)
    0
    0
        HGB, Below (N=121;121)
    28
    37
        HGB, Within (N=121;121)
    92
    83
        HGB, Above (N=121;121)
    1
    1
        LYMP, Unknown (N=121;121)
    0
    0
        LYMP, Below (N=121;121)
    12
    11
        LYMP, Within (N=121;121)
    96
    97
        LYMP, Above (N=121;121)
    13
    13
        MONO, Unknown (N=121;121)
    0
    0
        MONO, Below (N=121;121)
    4
    7
        MONO, Within (N=121;121)
    106
    97
        MONO, Above (N=121;121)
    11
    17
        NTPH, Unknown (N=121;121)
    0
    0
        NTPH, Below (N=121;121)
    16
    17
        NTPH, Within (N=121;121)
    97
    93
        NTPH, Above (N=121;121)
    8
    11
        PLAT, Unknown (N=121;121)
    0
    0
        PLAT, Below (N=121;121)
    1
    3
        PLAT, Within (N=121;121)
    118
    114
        PLAT, Above (N=121;121)
    2
    4
        RBC, Unknown (N=121;121)
    0
    0
        RBC, Below (N=121;121)
    36
    34
        RBC, Within (N=121;121)
    82
    84
        RBC, Above (N=121;121)
    3
    3
        WBC, Unknown (N=121;121)
    0
    0
        WBC, Below (N=121;121)
    10
    9
        WBC, Within (N=121;121)
    106
    108
        WBC, Above (N=121;121)
    5
    4
    No statistical analyses for this end point

    Primary: Cluster of differentiation 4 (CD4+) cell count in HIV+ subjects at Month 7

    		 Close Top of page
    End point title
    		 Cluster of differentiation 4 (CD4+) cell count in HIV+ subjects at Month 7 [17] [18]
    End point description
    CD4+ cell count, expressed in cells/cubic millimeter (mm3), was assessed for HIV+ subjects.
    End point type
    Primary
    End point timeframe
    At Month 7 (30 days after the last vaccination dose at Month 6)
    Notes
    [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint is only reporting values for HIV positive subjects.
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV positive subjects.
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group
    Number of subjects analysed
    121
    121
    Units: cells/mm3
    median (inter-quartile range (Q1-Q3))
        CD4+ cell count
    554.0 (440.0 to 799.0)
    568.0 (457.0 to 773.4)
    No statistical analyses for this end point

    Primary: HIV viral load (VL) in HIV+ subjects at Month 7

    		 Close Top of page
    End point title
    		 HIV viral load (VL) in HIV+ subjects at Month 7 [19] [20]
    End point description
    HIV VL, expressed in HIV copies/milliliter (mL), was assessed for HIV+ subjects.
    End point type
    Primary
    End point timeframe
    At Month 7 (30 days after the last vaccination dose at Month 6)
    Notes
    [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical analyses were available.
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV positive subjects.
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group
    Number of subjects analysed
    96
    95
    Units: HIV copies/mL
    median (inter-quartile range (Q1-Q3))
        HIV viral load
    1.9 (1.3 to 3.8)
    2.5 (1.3 to 3.8)
    No statistical analyses for this end point

    Primary: Number of HIV+ subjects by World Health Organization (WHO) HIV clinical staging

    		 Close Top of page
    End point title
    		 Number of HIV+ subjects by World Health Organization (WHO) HIV clinical staging [21] [22]
    End point description
    HIV+ subjects were categorised into clinical stages 1 through 4, as per the WHO classification [WHO, 2009].
    End point type
    Primary
    End point timeframe
    At Month 7 (30 days after the last vaccination dose at Month 6)
    Notes
    [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical analyses were available.
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV positive subjects.
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group
    Number of subjects analysed
    129
    128
    Units: Participants
        Clinical Stage 1
    113
    114
        Clinical Stage 2
    6
    2
        Clinical Stage 3
    1
    1
        Clinical Stage 4
    1
    4
    No statistical analyses for this end point

    Primary: Pseudovirion-Based Neutralization Assay (PBNA) Titers of anti-HPV-16/18 antibodies in HIV+ subjects, based on Adapted According-to-Protocol (ATP) cohort for immunogenicity

    		 Close Top of page
    End point title
    		 Pseudovirion-Based Neutralization Assay (PBNA) Titers of anti-HPV-16/18 antibodies in HIV+ subjects, based on Adapted According-to-Protocol (ATP) cohort for immunogenicity [23]
    End point description
    Titers of anti-HPV-16/18 antibodies, expressed as Geometric Mean Titers (GMTs), with cut-offs greater than or equal to (≥) 40 estimated dose giving 50% signal reduction when compared to a control without serum (ED50), as assessed by the Pseudovirion-Based Neutralization Assay [PBNA], in HIV+ subjects. Between-group comparisons to assess non-inferiority were performed on the ATP cohort for immunogenicity (by PBNA, regardless of HPV serostatus at baseline).
    End point type
    Primary
    End point timeframe
    At Month 7 (30 days after the last vaccination dose at Month 6)
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV positive subjects.
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group
    Number of subjects analysed
    79
    83
    Units: Titers
    geometric mean (confidence interval 95%)
        Anti-HPV-16 (N=79;83)
    23436.1 (18186.4 to 30201.1)
    7507.0 (5378.1 to 10478.6)
        Anti-HPV-18 (N=79;82)
    12490.9 (9681.7 to 16115.2)
    1459.6 (965.4 to 2206.7)
    Statistical analysis title
    		 Anti-HPV-16 Adjusted GMT ratios - non-inferiority
    Statistical analysis description
    Adjusted GMT ratios for anti-HPV-16 neutra antibody (ED50): To demonstrate that the immunogenicity of Cervarix vaccine (HIV+/Cervarix Group) was non-inferior to that of Gardasil vaccine (HIV+/Gardasil Group), in terms of geometric mean titers (GMTs) against HPV-16, measured by Pseudovirion-based neutralization assay (PBNA) one month after the administration of the third dose of vaccine in HIV+ subjects.
    Comparison groups
    HIV+/Gardasil Group v HIV+/Cervarix Group
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [24]
    Method
    Parameter type
    		 Adjusted GMT ratio
    Point estimate
    2.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.92
         upper limit
    		 4.52
    Notes
    [24] - Non-inferiority was defined as the lower limit of the 95% confidence interval (CI) for the ratio of GMTs (Cervarix over Gardasil) being above (>) 0.5 for HPV-16 type. Note: Primary objectives were to be assessed sequentially: firstly, non-inferiority for both HPV-16 and HPV-18, and then, superiority for HPV-18 followed by superiority for HPV-16.
    Statistical analysis title
    		 Anti-HPV-18 Adjusted GMT ratios - non-inferiority
    Statistical analysis description
    Adjusted GMT ratios for anti-HPV-18 neutra antibody (ED50): To demonstrate that the immunogenicity of Cervarix vaccine (HIV+/Cervarix Group) was non-inferior to that of Gardasil vaccine (HIV+/Gardasil Group), in terms of geometric mean titers (GMTs) against HPV-18, measured by Pseudovirion-based neutralization assay (PBNA) one month after the administration of the third dose of vaccine in HIV+ subjects.
    Comparison groups
    HIV+/Gardasil Group v HIV+/Cervarix Group
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [25]
    Method
    Parameter type
    		 Adjusted GMT ratio
    Point estimate
    7.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.84
         upper limit
    		 12.66
    Notes
    [25] - Non-inferiority was defined as the lower limit of the 95% confidence interval (CI) for the ratio of GMTs (Cervarix over Gardasil) being above (>) 0.5 for HPV-18 type. Note: Primary objectives were to be assessed sequentially: firstly, non-inferiority for both HPV-16 and HPV-18, and then, superiority for HPV-18 followed by superiority for HPV-16.

    Primary: Pseudovirion-Based Neutralization Assay (PBNA) Titers of anti-HPV-16/18 antibodies in HIV+ subjects, based on Total Vaccinated Cohort (TVC)

    		 Close Top of page
    End point title
    		 Pseudovirion-Based Neutralization Assay (PBNA) Titers of anti-HPV-16/18 antibodies in HIV+ subjects, based on Total Vaccinated Cohort (TVC) [26]
    End point description
    Titers of anti-HPV-16/18 antibodies, expressed as Geometric Mean Titers (GMTs), with cut-offs greater than or equal to (≥) 40 estimated dose giving 50% signal reduction when compared to a control without serum (ED50), as assessed by the Pseudovirion-Based Neutralization Assay [PBNA], in HIV+ subjects. Between-group comparisons to assess superiority were performed on the TVC (by PBNA, regardless of HPV serostatus at baseline).
    End point type
    Primary
    End point timeframe
    At Month 7 (30 days after the last vaccination dose at Month 6)
    Notes
    [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV positive subjects.
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group
    Number of subjects analysed
    108
    109
    Units: Titers
    geometric mean (confidence interval 95%)
        Anti-HPV-16
    21106.6 (15961.3 to 27910.6)
    7533.7 (5616.7 to 10105.0)
        Anti-HPV-18
    11580.5 (8851.5 to 15150.9)
    1451.9 (1009.0 to 2089.2)
    Statistical analysis title
    		 Anti-HPV-18 Adjusted GMT ratios - superiority
    Statistical analysis description
    Adjusted GMT ratios for anti-HPV-18 neutra antibody (ED50): To demonstrate that the immunogenicity of Cervarix vaccine (HIV+/Cervarix Group) was superior to that of Gardasil vaccine (HIV+/Gardasil Group), in terms of geometric mean titers (GMTs) against HPV-18, measured by Pseudovirion-based neutralization assay (PBNA) in HIV+ subjects, assessed following a sequential approach.
    Comparison groups
    HIV+/Cervarix Group v HIV+/Gardasil Group
    Number of subjects included in analysis
    217
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [27]
    P-value
    		 < 0.0001 [28]
    Method
    		 ANOVA
    Parameter type
    		 Adjusted GMT ratio
    Point estimate
    7.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.79
         upper limit
    		 11.54
    Notes
    [27] - Superiority was defined as the lower limit of the 95% CI for the ratio of GMTs (Cervarix over Gardasil) being above 1 for HPV-18 type, with a statistically significant p-value. Note: Primary objectives were to be assessed sequentially: firstly, non-inferiority for both HPV-16 and HPV-18, and then, superiority for HPV-18 followed by superiority for HPV-16.
    [28] - ANOVA model on the log10 transformation of the titers for HIV+ subjects and including the vaccine group as fixed effect.
    Statistical analysis title
    		 Anti-HPV-16 Adjusted GMT ratio - superiority
    Statistical analysis description
    Adjusted GMT ratios for anti-HPV-16 neutra antibody (ED50): To demonstrate that the immunogenicity of Cervarix vaccine (HIV+/Cervarix Group) was superior to that of Gardasil vaccine (HIV+/Gardasil Group), in terms of geometric mean titers (GMTs) against HPV-16, measured by Pseudovirion-based neutralization assay (PBNA) in HIV+ subjects, following a sequential approach.
    Comparison groups
    HIV+/Cervarix Group v HIV+/Gardasil Group
    Number of subjects included in analysis
    217
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [29]
    P-value
    		 < 0.0001 [30]
    Method
    		 ANOVA
    Parameter type
    		 Adjusted GMT ratio
    Point estimate
    2.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.83
         upper limit
    		 4.11
    Notes
    [29] - Superiority was defined as the lower limit of the 95% CI for the ratio of GMTs (Cervarix over Gardasil) being above 1 for HPV-16 type, with a statistically significant p-value. Note: Primary objectives were to be assessed sequentially: firstly, non-inferiority for both HPV-16 and HPV-18, and then, superiority for HPV-18 followed by superiority for HPV-16.
    [30] - ANOVA model on the log10 transformation of the titers for HIV+ subjects and including the vaccine group as fixed effect.

    Secondary: Number of HIV- subjects with any and Grade 3 solicited local symptoms

    		 Close Top of page
    End point title
    		 Number of HIV- subjects with any and Grade 3 solicited local symptoms [31]
    End point description
    Assessed solicited local symptoms were pain, redness, swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest, pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling with a maximum diameter greater than 50 millimeters (mm).
    End point type
    Secondary
    End point timeframe
    During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
    Notes
    [31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV negative subjects.
    End point values
    		 HIV-/Cervarix Group HIV-/Gardasil Group
    Number of subjects analysed
    141
    144
    Units: Participants
        Any Pain, Dose 1 (N=141;144)
    127
    91
        Grade 3 Pain, Dose 1 (N=141;144)
    10
    1
        Any Redness, Dose 1 (N=141;144)
    32
    21
        Grade 3 Redness, Dose 1 (N=141;144)
    0
    0
        Any Swelling, Dose 1 (N=141;144)
    23
    14
        Grade 3 Swelling, Dose 1 (N=141;144)
    0
    0
        Any Pain, Dose 2 (N=136;139)
    108
    92
        Grade 3 Pain, Dose 2 (N=136;139)
    6
    2
        Any Redness, Dose 2 (N=136;139)
    29
    29
        Grade 3 Redness, Dose 2 (N=136;139)
    0
    0
        Any Swelling, Dose 2 (N=136;139)
    24
    27
        Grade 3 Swelling, Dose 2 (N=136;139)
    0
    0
        Any Pain, Dose 3 (N=125;129)
    94
    82
        Grade 3 Pain, Dose 3 (N=125;129)
    10
    6
        Any Redness, Dose 3 (N=125;129)
    28
    19
        Grade 3 Redness, Dose 3 (N=125;129)
    0
    0
        Any Swelling, Dose 3 (N=125;129)
    29
    19
        Grade 3 Swelling, Dose 3 (N=125;129)
    0
    0
        Any Pain, Across Doses (N=141;144)
    133
    119
        Grade 3 Pain, Across Doses (N=141;144)
    22
    8
        Any Redness, Across Doses (N=141;144)
    52
    42
        Grade 3 Redness, Across Doses (N=141;144)
    0
    0
        Any Swelling, Across Doses (N=141;144)
    47
    39
        Grade 3 Swelling, Across Doses (N=141;144)
    0
    0
    No statistical analyses for this end point

    Secondary: Number of HIV- subjects with any, Grade 3 and related solicited general symptoms

    		 Close Top of page
    End point title
    		 Number of HIV- subjects with any, Grade 3 and related solicited general symptoms [32]
    End point description
    Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal [nausea, vomiting, diarrhoea and/or abdominal pain], headache, myalgia, rash, temperature [defined as axillary temperature higher than (>) 37.5 degrees Celsius (°C)] and urticaria. Any = occurrence of the symptom regardless of intensity grade and relationship. Grade 3 symptom = symptom that prevented normal activity. Grade 3 temperature = temperature > 39.0 °C. Grade 3 urticaria = urticaria distributed on at least 4 body areas. Related = symptom assessed by the investigator as related to the vaccination.
    End point type
    Secondary
    End point timeframe
    During the 7-day follow-up period (from the day of vaccination up to 6 subsequent days) after each vaccine dose and across doses
    Notes
    [32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV negative subjects.
    End point values
    		 HIV-/Cervarix Group HIV-/Gardasil Group
    Number of subjects analysed
    141
    144
    Units: Participants
        Any Arthralgia, Dose 1 (N=141;144)
    17
    21
        Grade 3 Arthralgia, Dose 1 (N=141;144)
    0
    0
        Related Arthralgia, Dose 1 (N=141;144)
    9
    11
        Any Fatigue, Dose 1 (N=141;144)
    45
    34
        Grade 3 Fatigue, Dose 1 (N=141;144)
    3
    2
        Related Fatigue, Dose 1 (N=141;144)
    29
    17
        Any Gastrointestinal, Dose 1 (N=141;144)
    19
    14
        Grade 3 Gastrointestinal, Dose 1 (N=141;144)
    1
    1
        Related Gastrointestinal, Dose 1 (N=141;144)
    8
    11
        Any Headache, Dose 1 (N=141;144)
    45
    45
        Grade 3 Headache, Dose 1 (N=141;144)
    0
    2
        Related Headache, Dose 1 (N=141;144)
    29
    22
        Any Myalgia, Dose 1 (N=141;144)
    44
    36
        Grade 3 Myalgia, Dose 1 (N=141;144)
    1
    2
        Related Myalgia, Dose 1 (N=141;144)
    28
    21
        Any Rash, Dose 1 (N=141;144)
    2
    6
        Grade 3 Rash, Dose 1 (N=141;144)
    0
    0
        Related Rash, Dose 1 (N=141;144)
    2
    2
        Any Temperature, Dose 1 (N=141;144)
    11
    8
        Grade 3 Temperature, Dose 1 (N=141;144)
    0
    0
        Related Temperature, Dose 1 (N=141;144)
    7
    5
        Any Urticaria, Dose 1 (N=141;144)
    3
    3
        Grade 3 Urticaria, Dose 1 (N=141;144)
    0
    0
        Related Urticaria, Dose 1 (N=141;144)
    3
    3
        Any Arthralgia, Dose 2 (N=136;139)
    14
    12
        Grade 3 Arthralgia, Dose 2 (N=136;139)
    0
    0
        Related Arthralgia, Dose 2 (N=136;139)
    9
    5
        Any Fatigue, Dose 2 (N=136;139)
    34
    34
        Grade 3 Fatigue, Dose 2 (N=136;139)
    2
    0
        Related Fatigue, Dose 2 (N=136;139)
    19
    19
        Any Gastrointestinal, Dose 2 (N=136;139)
    9
    15
        Grade 3 Gastrointestinal, Dose 2 (N=136;139)
    1
    1
        Related Gastrointestinal, Dose 2 (N=136;139)
    7
    6
        Any Headache, Dose 2 (N=136;139)
    35
    31
        Grade 3 Headache, Dose 2 (N=136;139)
    5
    2
        Related Headache, Dose 2 (N=136;139)
    23
    19
        Any Myalgia, Dose 2 (N=136;139)
    36
    26
        Grade 3 Myalgia, Dose 2 (N=136;139)
    1
    0
        Related Myalgia, Dose 2 (N=136;139)
    28
    19
        Any Rash, Dose 2 (N=136;139)
    2
    4
        Grade 3 Rash, Dose 2 (N=136;139)
    0
    0
        Related Rash, Dose 2 (N=136;139)
    1
    1
        Any Temperature, Dose 2 (N=136;139)
    10
    10
        Grade 3 Temperature, Dose 2 (N=136;139)
    1
    0
        Related Temperature, Dose 2 (N=136;139)
    5
    8
        Any Urticaria, Dose 2 (N=136;139)
    1
    1
        Grade 3 Urticaria, Dose 2 (N=136;139)
    0
    0
        Related Urticaria, Dose 2 (N=136;139)
    1
    1
        Any Arthralgia, Dose 3 (N=125;129)
    9
    14
        Grade 3 Arthralgia, Dose 3 (N=125;129)
    0
    2
        Related Arthralgia, Dose 3 (N=125;129)
    9
    11
        Any Fatigue, Dose 3 (N=125;129)
    32
    20
        Grade 3 Fatigue, Dose 3 (N=125;129)
    1
    2
        Related Fatigue, Dose 3 (N=125;129)
    29
    15
        Any Gastrointestinal, Dose 3 (N=125;129)
    7
    9
        Grade 3 Gastrointestinal, Dose 3 (N=125;129)
    1
    0
        Related Gastrointestinal, Dose 3 (N=125;129)
    6
    6
        Any Headache, Dose 3 (N=125;129)
    33
    25
        Grade 3 Headache, Dose 3 (N=125;129)
    3
    2
        Related Headache, Dose 3 (N=125;129)
    26
    17
        Any Myalgia, Dose 3 (N=125;129)
    26
    28
        Grade 3 Myalgia, Dose 3 (N=125;129)
    2
    2
        Related Myalgia, Dose 3 (N=125;129)
    22
    21
        Any Rash, Dose 3 (N=125;129)
    2
    0
        Grade 3 Rash, Dose 3 (N=125;129)
    0
    0
        Related Rash, Dose 3 (N=125;129)
    2
    0
        Any Temperature, Dose 3 (N=125;129)
    9
    10
        Grade 3 Temperature, Dose 3 (N=125;129)
    2
    1
        Related Temperature, Dose 3 (N=125;129)
    7
    6
        Any Urticaria, Dose 3 (N=125;129)
    2
    3
        Grade 3 Urticaria, Dose 3 (N=125;129)
    0
    0
        Related Urticaria, Dose 3 (N=125;129)
    2
    3
        Any Arthralgia, Across Doses (N=141;144)
    31
    34
        Grade 3 Arthralgia, Across Doses (N=141;144)
    0
    2
        Related Arthralgia, Across Doses (N=141;144)
    20
    18
        Any Fatigue, Across Doses (N=141;144)
    65
    56
        Grade 3 Fatigue, Across Doses (N=141;144)
    5
    4
        Related Fatigue, Across Doses (N=141;144)
    45
    33
        Any Gastrointestinal, Across Doses (N=141;144)
    28
    26
        Grade 3 Gastrointestinal, Across Doses (N=141;144)
    2
    1
        Related Gastrointestinal, Across Doses (N=141;144)
    17
    17
        Any Headache, Across Doses (N=141;144)
    69
    67
        Grade 3 Headache, Across Doses (N=141;144)
    7
    5
        Related Headache, Across Doses (N=141;144)
    51
    40
        Any Myalgia, Across Doses (N=141;144)
    64
    53
        Grade 3 Myalgia, Across Doses (N=141;144)
    3
    4
        Related Myalgia, Across Doses (N=141;144)
    44
    40
        Any Rash, Across Doses (N=141;144)
    5
    8
        Grade 3 Rash, Across Doses (N=141;144)
    0
    0
        Related Rash, Across Doses (N=141;144)
    5
    3
        Any Temperature, Across Doses (N=141;144)
    22
    24
        Grade 3 Temperature, Across Doses (N=141;144)
    3
    1
        Related Temperature, Across Doses (N=141;144)
    16
    16
        Any Urticaria, Across Doses (N=141;144)
    4
    6
        Grade 3 Urticaria, Across Doses (N=141;144)
    0
    0
        Related Urticaria, Across Doses (N=141;144)
    4
    6
    No statistical analyses for this end point

    Secondary: Number of HIV- subjects with unsolicited adverse events (AEs)

    		 Close Top of page
    End point title
    		 Number of HIV- subjects with unsolicited adverse events (AEs) [33]
    End point description
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 symptom = symptom that prevented normal activity. Related = symptom assessed by the investigator as related to the vaccination.
    End point type
    Secondary
    End point timeframe
    During the 30-day follow-up period (from the day of vaccination up to 29 subsequent days) after any vaccination
    Notes
    [33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV negative subjects.
    End point values
    		 HIV-/Cervarix Group HIV-/Gardasil Group
    Number of subjects analysed
    144
    145
    Units: Participants
        Any AE(s)
    26
    32
        Grade 3 AE(s)
    1
    3
        Related AE(s)
    4
    2
    No statistical analyses for this end point

    Secondary: Number of HIV- subjects with serious adverse events (SAEs)

    		 Close Top of page
    End point title
    		 Number of HIV- subjects with serious adverse events (SAEs) [34]
    End point description
    SAEs assessed include any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or represented a congenital anomaly/birth defect in the offspring of a study subject.
    End point type
    Secondary
    End point timeframe
    From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
    Notes
    [34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV negative subjects.
    End point values
    		 HIV-/Cervarix Group HIV-/Gardasil Group
    Number of subjects analysed
    144
    145
    Units: Participants
        SAE(s)
    1
    0
    No statistical analyses for this end point

    Secondary: Number of HIV- subjects with medically significant conditions (MSCs)

    		 Close Top of page
    End point title
    		 Number of HIV- subjects with medically significant conditions (MSCs) [35]
    End point description
    Medically significant conditions (MSCs) are defined as AEs prompting emergency room or physician visits that were not related to common diseases, or not related to routine visits for physical examination or vaccination, SAEs that were not related to common diseases.
    End point type
    Secondary
    End point timeframe
    From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
    Notes
    [35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV negative subjects.
    End point values
    		 HIV-/Cervarix Group HIV-/Gardasil Group
    Number of subjects analysed
    144
    145
    Units: Participants
        MSC(s)
    7
    14
    No statistical analyses for this end point

    Secondary: Number of HIV- subjects with potential immune-mediated disease (pIMDs)

    		 Close Top of page
    End point title
    		 Number of HIV- subjects with potential immune-mediated disease (pIMDs) [36]
    End point description
    Potential immune-mediated diseases are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
    End point type
    Secondary
    End point timeframe
    From Day 0 up to Month 7 (from Day 0 up to 30 days after the last vaccination dose at Month 6)
    Notes
    [36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV negative subjects.
    End point values
    		 HIV-/Cervarix Group HIV-/Gardasil Group
    Number of subjects analysed
    144
    145
    Units: Participants
        pIMD(s)
    0
    0
    No statistical analyses for this end point

    Secondary: Number of subjects reporting pregnancies and outcomes of reported pregnancies

    		 Close Top of page
    End point title
    		 Number of subjects reporting pregnancies and outcomes of reported pregnancies
    End point description
    Pregnancy related outcomes were: live infant no apparent congenital anomaly, live infant congenital anomaly, elective termination (termin.) no apparent congenital anomaly, elective termination (termin.) congenital anomaly, ectopic pregnancy, spontaneous abortion no apparent congenital (congen.) anomaly, stillbirth no apparent congenital anomaly, stillbirth congenital anomaly, lost to follow-up, pregnancy ongoing, missing.
    End point type
    Secondary
    End point timeframe
    During the entire study period (from Day 0 up to Month 24)
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group HIV-/Cervarix Group HIV-/Gardasil Group
    Number of subjects analysed
    10
    8
    3
    7
    Units: Participants
        Live infant NO apparent congenital anomaly
    8
    7
    3
    7
        Live infant congenital anomaly
    0
    0
    0
    0
        Elective termin. NO apparent congenital anomaly
    1
    0
    0
    0
        Elective termin. congenital anomaly
    0
    0
    0
    0
        Ectopic pregnancy
    0
    0
    0
    0
        Spontaneous abortion NO apparent congen. anomaly
    1
    1
    0
    0
        Stillbirth NO apparent congenital anomaly
    0
    0
    0
    0
        Stillbirth congenital anomaly
    0
    0
    0
    0
        Lost to follow-up
    0
    0
    0
    0
        Pregnancy ongoing
    0
    0
    0
    0
        Missing
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of subjects with relevant abnormalities in alanine aminotransferase, basophils, creatinine and eosinophils parameters

    		 Close Top of page
    End point title
    		 Number of subjects with relevant abnormalities in alanine aminotransferase, basophils, creatinine and eosinophils parameters
    End point description
    Among assessed haematological and biochemical parameters were: alanine aminotransferase [ALAT], basophils [BSPH], creatinine [CRT], eosinophils [ESPH]. Unknown = value unknown for the specified visit and laboratory parameter; Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. Note: Month 7 data for HIV+/Cervarix and HIV+/Gardasil groups are also reported in the Primary outcome measure.
    End point type
    Secondary
    End point timeframe
    At Day 0, Week 6, Week 10, Month 6, Month 7, Month 12, Month 18 and Month 24
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group HIV-/Cervarix Group HIV-/Gardasil Group
    Number of subjects analysed
    129
    128
    144
    145
    Units: Participants
        ALAT, Day 0, Unknown (N=129;128;144;145)
    0
    0
    0
    0
        ALAT, Week 6, Unknown (N=128;126;137;142)
    0
    0
    0
    0
        ALAT, Week 10, Unknown (N=128;127;135;136)
    1
    0
    0
    0
        ALAT, Month 6, Unknown (N=123;123;128;134)
    0
    0
    0
    0
        ALAT, Month 7, Unknown (N=121;121;115;125)
    0
    0
    0
    0
        ALAT, Month 12, Unknown (N=122;119;108;118)
    0
    0
    0
    1
        ALAT, Month 18, Unknown (N=121;117;110;117)
    0
    0
    0
    0
        ALAT, Month 24, Unknown (N=116;117;103;111)
    0
    0
    0
    0
        ALAT, Day 0, Below (N=129;128;144;145)
    9
    4
    33
    35
        ALAT, Week 6, Below (N=128;126;137;142)
    4
    5
    35
    32
        ALAT, Week 10, Below (N=128;127;135;136)
    2
    8
    27
    26
        ALAT, Month 6, Below (N=123;123;128;134)
    3
    4
    25
    27
        ALAT, Month 7, Below (N=121;121;115;125)
    4
    3
    20
    23
        ALAT, Month 12, Below (N=122;119;108;118)
    6
    1
    20
    22
        ALAT, Month 18, Below (N=121;117;110;117)
    2
    2
    23
    17
        ALAT, Month 24, Below (N=116;117;103;111)
    0
    1
    14
    14
        ALAT, Day 0, Within (N=129;128;144;145)
    109
    118
    109
    106
        ALAT, Week 6, Within (N=128;126;137;142)
    119
    115
    97
    106
        ALAT, Week 10, Within (N=128;127;135;136)
    117
    110
    104
    109
        ALAT, Month 6, Within (N=123;123;128;134)
    112
    110
    101
    102
        ALAT, Month 7, Within (N=121;121;115;125)
    110
    105
    94
    98
        ALAT, Month 12, Within (N=122;119;108;118)
    104
    112
    86
    95
        ALAT, Month 18, Within (N=121;117;110;117)
    115
    109
    85
    98
        ALAT, Month 24, Within (N=116;117;103;111)
    112
    110
    87
    95
        ALAT, Day 0, Above (N=129;128;144;145)
    11
    6
    2
    4
        ALAT, Week 6, Above (N=128;126;137;142)
    5
    6
    5
    4
        ALAT, Week 10, Above (N=128;127;135;136)
    8
    9
    4
    1
        ALAT, Month 6, Above (N=123;123;128;134)
    8
    9
    2
    5
        ALAT, Month 7, Above (N=121;121;115;125)
    7
    13
    1
    4
        ALAT, Month 12, Above (N=122;119;108;118)
    12
    6
    2
    0
        ALAT, Month 18, Above (N=121;117;110;117)
    4
    6
    2
    2
        ALAT, Month 24, Above (N=116;117;103;111)
    4
    6
    2
    2
        BSPH, Day 0, Unknown (N=129;128;144;145)
    0
    0
    0
    0
        BSPH, Week 6, Unknown (N=128;126;137;142)
    0
    0
    2
    3
        BSPH, Week 10, Unknown (N=128;127;135;136)
    0
    0
    0
    0
        BSPH, Month 6, Unknown (N=123;123;128;134)
    0
    0
    0
    0
        BSPH, Month 7, Unknown (N=121;121;115;125)
    0
    0
    0
    0
        BSPH, Month 12, Unknown (N=122;119;108;118)
    1
    0
    0
    0
        BSPH, Month 18, Unknown (N=121;117;110;117)
    0
    0
    0
    0
        BSPH, Month 24, Unknown (N=116;117;103;111)
    1
    0
    0
    0
        BSPH, Day 0, Below (N=129;128;144;145)
    0
    1
    21
    20
        BSPH, Week 6, Below (N=128;126;137;142)
    0
    1
    8
    7
        BSPH, Week 10, Below (N=128;127;135;136)
    0
    0
    15
    17
        BSPH, Month 6, Below (N=123;123;128;134)
    0
    0
    12
    13
        BSPH, Month 7, Below (N=121;121;115;125)
    0
    0
    6
    8
        BSPH, Month 12, Below (N=122;119;108;118)
    0
    0
    6
    7
        BSPH, Month 18, Below (N=121;117;110;117)
    0
    0
    10
    12
        BSPH, Month 24, Below (N=116;117;103;111)
    0
    0
    7
    8
        BSPH, Day 0, Within (N=129;128;144;145)
    129
    127
    123
    125
        BSPH, Week 6, Within (N=128;126;137;142)
    128
    125
    127
    131
        BSPH, Week 10, Within (N=128;127;135;136)
    127
    124
    119
    119
        BSPH, Month 6, Within (N=123;123;128;134)
    123
    122
    116
    120
        BSPH, Month 7, Within (N=121;121;115;125)
    120
    121
    109
    116
        BSPH, Month 12, Within (N=122;119;108;118)
    121
    119
    102
    111
        BSPH, Month 18, Within (N=121;117;110;117)
    120
    117
    99
    104
        BSPH, Month 24, Within (N=116;117;103;111)
    115
    117
    96
    102
        BSPH, Day 0, Above (N=129;128;144;145)
    0
    0
    0
    0
        BSPH, Week 6, Above (N=128;126;137;142)
    0
    0
    0
    1
        BSPH, Week 10, Above (N=128;127;135;136)
    1
    3
    1
    0
        BSPH, Month 6, Above (N=123;123;128;134)
    0
    1
    0
    1
        BSPH, Month 7, Above (N=121;121;115;125)
    1
    0
    0
    1
        BSPH, Month 12, Above (N=122;119;108;118)
    0
    0
    0
    0
        BSPH, Month 18, Above (N=121;117;110;117)
    1
    0
    1
    1
        BSPH, Month 24, Above (N=116;117;103;111)
    0
    0
    0
    1
        CRT, Day 0, Unknown (N=129;127;144;145)
    0
    0
    0
    0
        CRT, Week 6, Unknown (N=128;125;137;142)
    0
    0
    0
    0
        CRT, Week 10, Unknown (N=128;126;135;136)
    0
    0
    0
    0
        CRT, Month 6, Unknown (N=123;122;128;134)
    0
    0
    0
    0
        CRT, Month 7, Unknown (N=121;120;115;125)
    0
    0
    0
    0
        CRT, Month 12, Unknown (N=122;118;108;118)
    0
    0
    0
    0
        CRT, Month 18, Unknown (N=121;116;110;117)
    0
    0
    0
    0
        CRT, Month 24, Unknown (N=116;116;103;111)
    0
    0
    0
    0
        CRT, Day 0, Below (N=129;127;144;145)
    31
    26
    27
    21
        CRT, Week 6, Below (N=128;125;137;142)
    35
    28
    36
    28
        CRT, Week 10, Below (N=128;126;135;136)
    33
    30
    27
    29
        CRT, Month 6, Below (N=123;122;128;134)
    33
    32
    25
    26
        CRT, Month 7, Below (N=121;120;115;125)
    29
    36
    22
    17
        CRT, Month 12, Below (N=122;118;108;118)
    25
    23
    24
    22
        CRT, Month 18, Below (N=121;116;110;117)
    25
    17
    11
    12
        CRT, Month 24, Below (N=116;116;103;111)
    27
    30
    17
    17
        CRT, Day 0, Within (N=129;127;144;145)
    97
    100
    115
    123
        CRT, Week 6, Within (N=128;125;137;142)
    93
    97
    101
    113
        CRT, Week 10, Within (N=128;126;135;136)
    95
    96
    108
    107
        CRT, Month 6, Within (N=123;122;128;134)
    89
    89
    103
    107
        CRT, Month 7, Within (N=121;120;115;125)
    91
    84
    93
    107
        CRT, Month 12, Within (N=122;118;108;118)
    94
    91
    83
    95
        CRT, Month 18, Within (N=121;116;110;117)
    93
    98
    98
    102
        CRT, Month 24, Within (N=116;116;103;111)
    88
    85
    86
    93
        CRT, Day 0, Above (N=129;127;144;145)
    1
    1
    2
    1
        CRT, Week 6, Above (N=128;125;137;142)
    0
    0
    0
    1
        CRT, Week 10, Above (N=128;126;135;136)
    0
    0
    0
    0
        CRT, Month 6, Above (N=123;122;128;134)
    1
    1
    0
    1
        CRT, Month 7, Above (N=121;120;115;125)
    1
    0
    0
    1
        CRT, Month 12, Above (N=122;118;108;118)
    3
    4
    1
    1
        CRT, Month 18, Above (N=121;116;110;117)
    3
    1
    1
    3
        CRT, Month 24, Above (N=116;116;103;111)
    1
    1
    0
    1
        ESPH, Day 0, Unknown (N=129;128;144;145)
    0
    0
    0
    0
        ESPH, Week 6, Unknown (N=128;126;137;142)
    0
    0
    2
    3
        ESPH, Week 10, Unknown (N=128;127;135;136)
    0
    0
    0
    0
        ESPH, Month 6, Unknown (N=123;123;128;134)
    0
    0
    0
    0
        ESPH, Month 7, Unknown (N=121;121;115;125)
    0
    0
    0
    0
        ESPH, Month 12, Unknown (N=122;119;108;118)
    1
    0
    0
    0
        ESPH, Month 18, Unknown (N=121;117;110;117)
    0
    0
    0
    0
        ESPH, Month 24, Unknown (N=116;117;103;111)
    1
    0
    0
    0
        ESPH, Day 0, Below (N=129;128;144;145)
    15
    18
    3
    4
        ESPH, Week 6, Below (N=128;126;137;142)
    10
    13
    7
    6
        ESPH, Week 10, Below (N=128;127;135;136)
    11
    12
    3
    1
        ESPH, Month 6, Below (N=123;123;128;134)
    9
    13
    4
    4
        ESPH, Month 7, Below (N=121;121;115;125)
    9
    10
    6
    6
        ESPH, Month 12, Below (N=122;119;108;118)
    9
    10
    3
    6
        ESPH, Month 18, Below (N=121;117;110;117)
    4
    9
    6
    4
        ESPH, Month 24, Below (N=116;117;103;111)
    7
    15
    3
    6
        ESPH, Day 0, Within (N=129;128;144;145)
    108
    102
    130
    133
        ESPH, Week 6, Within (N=128;126;137;142)
    109
    102
    115
    126
        ESPH, Week 10, Within (N=128;127;135;136)
    112
    108
    125
    130
        ESPH, Month 6, Within (N=123;123;128;134)
    103
    108
    118
    124
        ESPH, Month 7, Within (N=121;121;115;125)
    108
    106
    103
    112
        ESPH, Month 12, Within (N=122;119;108;118)
    105
    104
    98
    107
        ESPH, Month 18, Within (N=121;117;110;117)
    111
    106
    96
    105
        ESPH, Month 24, Within (N=116;117;103;111)
    103
    99
    99
    99
        ESPH, Day 0, Above (N=129;128;144;145)
    6
    8
    11
    8
        ESPH, Week 6, Above (N=128;126;137;142)
    9
    11
    13
    7
        ESPH, Week 10, Above (N=128;127;135;136)
    5
    7
    7
    5
        ESPH, Month 6, Above (N=123;123;128;134)
    11
    2
    6
    6
        ESPH, Month 7, Above (N=121;121;115;125)
    4
    5
    6
    7
        ESPH, Month 12, Above (N=122;119;108;118)
    7
    5
    7
    5
        ESPH, Month 18, Above (N=121;117;110;117)
    6
    2
    8
    8
        ESPH, Month 24, Above (N=116;117;103;111)
    5
    3
    1
    6
    No statistical analyses for this end point

    Secondary: Number of subjects with relevant abnormalities in haematocrit, haemoglobin, lymphocytes and monocytes parameters

    		 Close Top of page
    End point title
    		 Number of subjects with relevant abnormalities in haematocrit, haemoglobin, lymphocytes and monocytes parameters
    End point description
    Among assessed haematological parameters were: haematocrit [HTCR], haemoglobin [HGB], lymphocytes [LYMP] and monocytes [MONO]. Unknown = value unknown for the specified visit and laboratory parameter; Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. Note: Month 7 data for HIV+/Cervarix and HIV+/Gardasil groups are also reported in the Primary outcome measure.
    End point type
    Secondary
    End point timeframe
    At Day 0, Week 6, Week 10, Month 6, Month 7, Month 12, Month 18 and Month 24
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group HIV-/Cervarix Group HIV-/Gardasil Group
    Number of subjects analysed
    129
    128
    144
    145
    Units: Participants
        HTCR, Day 0, Unknown (N=129;128;144;145)
    0
    0
    0
    0
        HTCR, Week 6, Unknown (N=128;126;137;142)
    0
    1
    0
    0
        HTCR, Week 10, Unknown (N=128;127;135;136)
    0
    0
    0
    0
        HTCR, Month 6, Unknown (N=123;123;128;134)
    0
    0
    0
    0
        HTCR, Month 7, Unknown (N=121;121;115;125)
    0
    0
    0
    1
        HTCR, Month 12, Unknown (N=122;119;108;118)
    1
    0
    0
    0
        HTCR, Month 18, Unknown (N=121;117;110;117)
    0
    0
    0
    0
        HTCR, Month 24, Unknown (N=116;117;103;111)
    1
    0
    0
    0
        HTCR, Day 0, Below (N=129;128;144;145)
    32
    23
    24
    24
        HTCR, Week 6, Below (N=128;126;137;142)
    22
    17
    18
    13
        HTCR, Week 10, Below (N=128;127;135;136)
    30
    22
    11
    7
        HTCR, Month 6, Below (N=123;123;128;134)
    26
    27
    13
    17
        HTCR, Month 7, Below (N=121;121;115;125)
    19
    27
    13
    14
        HTCR, Month 12, Below (N=122;119;108;118)
    24
    25
    15
    17
        HTCR, Month 18, Below (N=121;117;110;117)
    30
    22
    17
    16
        HTCR, Month 24, Below (N=116;117;103;111)
    24
    24
    21
    17
        HTCR, Day 0, Within (N=129;128;144;145)
    96
    102
    120
    118
        HTCR, Week 6, Within (N=128;126;137;142)
    106
    105
    119
    125
        HTCR, Week 10, Within (N=128;127;135;136)
    97
    103
    123
    126
        HTCR, Month 6, Within (N=123;123;128;134)
    97
    95
    115
    117
        HTCR, Month 7, Within (N=121;121;115;125)
    101
    92
    102
    108
        HTCR, Month 12, Within (N=122;119;108;118)
    95
    94
    93
    100
        HTCR, Month 18, Within (N=121;117;110;117)
    91
    92
    90
    101
        HTCR, Month 24, Within (N=116;117;103;111)
    91
    92
    82
    93
        HTCR, Day 0, Above (N=129;128;144;145)
    1
    3
    0
    3
        HTCR, Week 6, Above (N=128;126;137;142)
    0
    3
    0
    4
        HTCR, Week 10, Above (N=128;127;135;136)
    1
    2
    1
    3
        HTCR, Month 6, Above (N=123;123;128;134)
    0
    1
    0
    0
        HTCR, Month 7, Above (N=121;121;115;125)
    1
    2
    0
    2
        HTCR, Month 12, Above (N=122;119;108;118)
    2
    0
    0
    1
        HTCR, Month 18, Above (N=121;117;110;117)
    0
    3
    3
    0
        HTCR, Month 24, Above (N=116;117;103;111)
    0
    1
    0
    1
        HGB, Day 0, Unknown (N=129;128;144;145)
    0
    0
    0
    0
        HGB, Week 6, Unknown (N=128;126;137;142)
    0
    0
    0
    0
        HGB, Week 10, Unknown (N=128;127;135;136)
    0
    0
    0
    0
        HGB, Month 6, Unknown (N=123;123;128;134)
    0
    0
    0
    0
        HGB, Month 7, Unknown (N=121;121;115;125)
    0
    0
    0
    0
        HGB, Month 12, Unknown (N=122;119;108;118)
    1
    0
    0
    0
        HGB, Month 18, Unknown (N=121;117;110;117)
    0
    0
    0
    0
        HGB, Month 24, Unknown (N=116;117;103;111)
    1
    0
    0
    0
        HGB, Day 0, Below (N=129;128;144;145)
    38
    37
    40
    45
        HGB, Week 6, Below (N=128;126;137;142)
    38
    35
    40
    50
        HGB, Week 10, Below (N=128;127;135;136)
    38
    35
    37
    38
        HGB, Month 6, Below (N=123;123;128;134)
    38
    36
    45
    38
        HGB, Month 7, Below (N=121;121;115;125)
    28
    37
    36
    38
        HGB, Month 12, Below (N=122;119;108;118)
    29
    35
    39
    39
        HGB, Month 18, Below (N=121;117;110;117)
    34
    32
    32
    35
        HGB, Month 24, Below (N=116;117;103;111)
    27
    27
    28
    26
        HGB, Day 0, Within (N=129;128;144;145)
    88
    89
    104
    98
        HGB, Week 6, Within (N=128;126;137;142)
    88
    88
    97
    88
        HGB, Week 10, Within (N=128;127;135;136)
    89
    90
    98
    97
        HGB, Month 6, Within (N=123;123;128;134)
    85
    86
    83
    96
        HGB, Month 7, Within (N=121;121;115;125)
    92
    83
    79
    86
        HGB, Month 12, Within (N=122;119;108;118)
    91
    83
    69
    79
        HGB, Month 18, Within (N=121;117;110;117)
    84
    82
    77
    82
        HGB, Month 24, Within (N=116;117;103;111)
    88
    89
    75
    84
        HGB, Day 0, Above (N=129;128;144;145)
    3
    2
    0
    2
        HGB, Week 6, Above (N=128;126;137;142)
    2
    3
    0
    4
        HGB, Week 10, Above (N=128;127;135;136)
    1
    2
    0
    1
        HGB, Month 6, Above (N=123;123;128;134)
    0
    1
    0
    0
        HGB, Month 7, Above (N=121;121;115;125)
    1
    1
    0
    1
        HGB, Month 12, Above (N=122;119;108;118)
    1
    1
    0
    0
        HGB, Month 18, Above (N=121;117;110;117)
    3
    3
    1
    0
        HGB, Month 24, Above (N=116;117;103;111)
    0
    1
    0
    1
        LYMP, Day 0, Unknown (N=129;128;144;145)
    0
    0
    0
    0
        LYMP, Week 6, Unknown (N=128;126;137;142)
    0
    0
    2
    3
        LYMP, Week 10, Unknown (N=128;127;135;136)
    0
    0
    0
    0
        LYMP, Month 6, Unknown (N=123;123;128;134)
    0
    0
    0
    0
        LYMP, Month 7, Unknown (N=121;121;115;125)
    0
    0
    0
    0
        LYMP, Month 12, Unknown (N=122;119;108;118)
    1
    0
    0
    0
        LYMP, Month 18, Unknown (N=121;117;110;117)
    0
    0
    0
    0
        LYMP, Month 24, Unknown (N=116;117;103;111)
    1
    0
    0
    0
        LYMP, Day 0, Below (N=129;128;144;145)
    7
    9
    11
    6
        LYMP, Week 6, Below (N=128;126;137;142)
    6
    11
    12
    6
        LYMP, Week 10, Below (N=128;127;135;136)
    11
    9
    13
    6
        LYMP, Month 6, Below (N=123;123;128;134)
    6
    8
    9
    11
        LYMP, Month 7, Below (N=121;121;115;125)
    12
    11
    6
    6
        LYMP, Month 12, Below (N=122;119;108;118)
    6
    10
    6
    8
        LYMP, Month 18, Below (N=121;117;110;117)
    4
    4
    6
    4
        LYMP, Month 24, Below (N=116;117;103;111)
    8
    9
    6
    7
        LYMP, Day 0, Within (N=129;128;144;145)
    105
    105
    120
    132
        LYMP, Week 6, Within (N=128;126;137;142)
    109
    109
    113
    121
        LYMP, Week 10, Within (N=128;127;135;136)
    101
    102
    110
    124
        LYMP, Month 6, Within (N=123;123;128;134)
    98
    104
    106
    115
        LYMP, Month 7, Within (N=121;121;115;125)
    96
    97
    103
    111
        LYMP, Month 12, Within (N=122;119;108;118)
    104
    95
    92
    98
        LYMP, Month 18, Within (N=121;117;110;117)
    105
    103
    94
    106
        LYMP, Month 24, Within (N=116;117;103;111)
    98
    97
    88
    101
        LYMP, Day 0, Above (N=129;128;144;145)
    17
    14
    13
    7
        LYMP, Week 6, Above (N=128;126;137;142)
    13
    6
    10
    12
        LYMP, Week 10, Above (N=128;127;135;136)
    16
    16
    12
    6
        LYMP, Month 6, Above (N=123;123;128;134)
    19
    11
    13
    8
        LYMP, Month 7, Above (N=121;121;115;125)
    13
    13
    6
    8
        LYMP, Month 12, Above (N=122;119;108;118)
    11
    14
    10
    12
        LYMP, Month 18, Above (N=121;117;110;117)
    12
    10
    10
    7
        LYMP, Month 24, Above (N=116;117;103;111)
    9
    11
    9
    3
        MONO, Day 0, Unknown (N=129;128;144;145)
    0
    0
    0
    0
        MONO, Week 6, Unknown (N=128;126;137;142)
    0
    0
    2
    3
        MONO, Week 10, Unknown (N=128;127;135;136)
    0
    0
    0
    0
        MONO, Month 6, Unknown (N=123;123;128;134)
    0
    0
    0
    0
        MONO, Month 7, Unknown (N=121;121;115;125)
    0
    0
    0
    0
        MONO, Month 12, Unknown (N=122;119;108;118)
    1
    0
    0
    0
        MONO, Month 18, Unknown (N=121;117;110;117)
    0
    0
    0
    0
        MONO, Month 24, Unknown (N=116;117;103;111)
    1
    0
    0
    0
        MONO, Day 0, Below (N=129;128;144;145)
    7
    4
    10
    17
        MONO, Week 6, Below (N=128;126;137;142)
    4
    4
    3
    4
        MONO, Week 10, Below (N=128;127;135;136)
    4
    4
    2
    6
        MONO, Month 6, Below (N=123;123;128;134)
    3
    5
    0
    7
        MONO, Month 7, Below (N=121;121;115;125)
    4
    7
    5
    2
        MONO, Month 12, Below (N=122;119;108;118)
    2
    5
    5
    2
        MONO, Month 18, Below (N=121;117;110;117)
    3
    6
    5
    4
        MONO, Month 24, Below (N=116;117;103;111)
    5
    5
    7
    10
        MONO, Day 0, Within (N=129;128;144;145)
    111
    117
    133
    126
        MONO, Week 6, Within (N=128;126;137;142)
    117
    112
    129
    133
        MONO, Week 10, Within (N=128;127;135;136)
    116
    108
    129
    127
        MONO, Month 6, Within (N=123;123;128;134)
    107
    104
    113
    121
        MONO, Month 7, Within (N=121;121;115;125)
    106
    97
    107
    118
        MONO, Month 12, Within (N=122;119;108;118)
    104
    101
    101
    113
        MONO, Month 18, Within (N=121;117;110;117)
    108
    99
    101
    109
        MONO, Month 24, Within (N=116;117;103;111)
    98
    99
    95
    99
        MONO, Day 0, Above (N=129;128;144;145)
    11
    7
    1
    2
        MONO, Week 6, Above (N=128;126;137;142)
    7
    10
    3
    2
        MONO, Week 10, Above (N=128;127;135;136)
    8
    15
    4
    3
        MONO, Month 6, Above (N=123;123;128;134)
    13
    14
    6
    6
        MONO, Month 7, Above (N=121;121;115;125)
    11
    17
    3
    5
        MONO, Month 12, Above (N=122;119;108;118)
    15
    13
    2
    3
        MONO, Month 18, Above (N=121;117;110;117)
    10
    12
    4
    4
        MONO, Month 24, Above (N=116;117;103;111)
    12
    13
    1
    2
    No statistical analyses for this end point

    Secondary: Number of subjects with relevant abnormalities in neutrophils, platelets, red blood cells and white blood cells parameters

    		 Close Top of page
    End point title
    		 Number of subjects with relevant abnormalities in neutrophils, platelets, red blood cells and white blood cells parameters
    End point description
    Among assessed haematological parameters were: neutrophils [NTPH], platelets [PLAT], red blood cells [RBC] and white blood cells [WBC]. Unknown = value unknown for the specified visit and laboratory parameter; Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter. Note: Month 7 data for HIV+/Cervarix and HIV+/Gardasil groups are also reported in the Primary outcome measure.
    End point type
    Secondary
    End point timeframe
    At Day 0, Week 6, Week 10, Month 6, Month 7, Month 12, Month 18 and Month 24
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group HIV-/Cervarix Group HIV-/Gardasil Group
    Number of subjects analysed
    129
    128
    144
    145
    Units: Participants
        NTPH, Day 0, Unknown (N=129;128;144;145)
    0
    0
    0
    0
        NTPH, Week 6, Unknown (N=128;126;137;142)
    0
    0
    2
    3
        NTPH, Week 10, Unknown (N=128;127;135;136)
    0
    0
    0
    0
        NTPH, Month 6, Unknown (N=123;123;128;134)
    0
    0
    0
    0
        NTPH, Month 7, Unknown (N=121;121;115;125)
    0
    0
    0
    0
        NTPH, Month 12, Unknown (N=122;119;108;118)
    1
    0
    0
    0
        NTPH, Month 18, Unknown (N=121;117;110;117)
    0
    0
    0
    0
        NTPH, Month 24, Unknown (N=116;117;103;111)
    1
    0
    0
    0
        NTPH, Day 0, Below (N=129;128;144;145)
    14
    12
    11
    7
        NTPH, Week 6, Below (N=128;126;137;142)
    16
    13
    8
    13
        NTPH, Week 10, Below (N=128;127;135;136)
    18
    17
    12
    10
        NTPH, Month 6, Below (N=123;123;128;134)
    18
    14
    15
    14
        NTPH, Month 7, Below (N=121;121;115;125)
    16
    17
    10
    9
        NTPH, Month 12, Below (N=122;119;108;118)
    19
    16
    12
    11
        NTPH, Month 18, Below (N=121;117;110;117)
    15
    15
    9
    14
        NTPH, Month 24, Below (N=116;117;103;111)
    14
    11
    9
    10
        NTPH, Day 0, Within (N=129;128;144;145)
    106
    99
    117
    122
        NTPH, Week 6, Within (N=128;126;137;142)
    101
    95
    107
    116
        NTPH, Week 10, Within (N=128;127;135;136)
    103
    100
    104
    113
        NTPH, Month 6, Within (N=123;123;128;134)
    100
    98
    98
    104
        NTPH, Month 7, Within (N=121;121;115;125)
    97
    93
    92
    106
        NTPH, Month 12, Within (N=122;119;108;118)
    92
    93
    84
    94
        NTPH, Month 18, Within (N=121;117;110;117)
    98
    89
    86
    92
        NTPH, Month 24, Within (N=116;117;103;111)
    92
    95
    83
    89
        NTPH, Day 0, Above (N=129;128;144;145)
    9
    17
    16
    16
        NTPH, Week 6, Above (N=128;126;137;142)
    11
    18
    20
    10
        NTPH, Week 10, Above (N=128;127;135;136)
    7
    10
    19
    13
        NTPH, Month 6, Above (N=123;123;128;134)
    5
    11
    15
    16
        NTPH, Month 7, Above (N=121;121;115;125)
    8
    11
    13
    10
        NTPH, Month 12, Above (N=122;119;108;118)
    10
    10
    12
    13
        NTPH, Month 18, Above (N=121;117;110;117)
    8
    13
    15
    11
        NTPH, Month 24, Above (N=116;117;103;111)
    9
    11
    11
    12
        PLAT, Day 0, Unknown (N=129;128;144;145)
    0
    0
    0
    0
        PLAT, Week 6, Unknown (N=128;126;137;142)
    0
    0
    1
    1
        PLAT, Week 10, Unknown (N=128;127;135;136)
    0
    0
    1
    0
        PLAT, Month 6, Unknown (N=123;123;128;134)
    0
    0
    0
    0
        PLAT, Month 7, Unknown (N=121;121;115;125)
    0
    0
    1
    0
        PLAT, Month 12, Unknown (N=122;119;108;118)
    1
    0
    1
    0
        PLAT, Month 18, Unknown (N=121;117;110;117)
    0
    0
    0
    0
        PLAT, Month 24, Unknown (N=116;117;103;111)
    1
    0
    0
    0
        PLAT, Day 0, Below (N=129;128;144;145)
    0
    0
    3
    0
        PLAT, Week 6, Below (N=128;126;137;142)
    1
    0
    1
    0
        PLAT, Week 10, Below (N=128;127;135;136)
    1
    1
    0
    0
        PLAT, Month 6, Below (N=123;123;128;134)
    2
    2
    0
    0
        PLAT, Month 7, Below (N=121;121;115;125)
    1
    3
    1
    1
        PLAT, Month 12, Below (N=122;119;108;118)
    3
    1
    0
    2
        PLAT, Month 18, Below (N=121;117;110;117)
    3
    4
    1
    2
        PLAT, Month 24, Below (N=116;117;103;111)
    1
    2
    2
    3
        PLAT, Day 0, Within (N=129;128;144;145)
    123
    122
    133
    138
        PLAT, Week 6, Within (N=128;126;137;142)
    124
    119
    130
    137
        PLAT, Week 10, Within (N=128;127;135;136)
    122
    124
    131
    132
        PLAT, Month 6, Within (N=123;123;128;134)
    116
    118
    127
    131
        PLAT, Month 7, Within (N=121;121;115;125)
    118
    114
    110
    121
        PLAT, Month 12, Within (N=122;119;108;118)
    113
    114
    103
    111
        PLAT, Month 18, Within (N=121;117;110;117)
    117
    110
    106
    111
        PLAT, Month 24, Within (N=116;117;103;111)
    109
    110
    97
    103
        PLAT, Day 0, Above (N=129;128;144;145)
    6
    6
    8
    7
        PLAT, Week 6, Above (N=128;126;137;142)
    3
    7
    5
    4
        PLAT, Week 10, Above (N=128;127;135;136)
    5
    2
    3
    4
        PLAT, Month 6, Above (N=123;123;128;134)
    5
    3
    1
    3
        PLAT, Month 7, Above (N=121;121;115;125)
    2
    4
    3
    3
        PLAT, Month 12, Above (N=122;119;108;118)
    5
    4
    4
    5
        PLAT, Month 18, Above (N=121;117;110;117)
    1
    3
    3
    4
        PLAT, Month 24, Above (N=116;117;103;111)
    5
    5
    4
    5
        RBC, Day 0, Unknown (N=129;128;141;141)
    0
    0
    0
    0
        RBC, Week 6, Unknown (N=128;126;136;139)
    0
    0
    0
    1
        RBC, Week 10, Unknown (N=128;127;134;135)
    0
    0
    0
    0
        RBC, Month 6, Unknown (N=123;123;127;134)
    0
    0
    0
    1
        RBC, Month 7, Unknown (N=121;121;115;125)
    0
    0
    0
    0
        RBC, Month 12, Unknown (N=122;119;108;118)
    1
    0
    0
    1
        RBC, Month 18, Unknown (N=121;117;110;116)
    0
    0
    2
    3
        RBC, Month 24, Unknown (N=116;117;103;111)
    1
    0
    0
    0
        RBC, Day 0, Below (N=129;128;141;141)
    43
    38
    18
    13
        RBC, Week 6, Below (N=128;126;136;139)
    44
    36
    14
    12
        RBC, Week 10, Below (N=128;127;134;135)
    48
    37
    11
    8
        RBC, Month 6, Below (N=123;123;127;134)
    40
    39
    14
    12
        RBC, Month 7, Below (N=121;121;115;125)
    36
    34
    15
    19
        RBC, Month 12, Below (N=122;119;108;118)
    39
    31
    19
    14
        RBC, Month 18, Below (N=121;117;110;116)
    38
    31
    9
    13
        RBC, Month 24, Below (N=116;117;103;111)
    38
    34
    10
    9
        RBC, Day 0, Within (N=129;128;141;141)
    83
    87
    118
    123
        RBC, Week 6, Within (N=128;126;136;139)
    81
    85
    118
    120
        RBC, Week 10, Within (N=128;127;134;135)
    78
    87
    120
    122
        RBC, Month 6, Within (N=123;123;127;134)
    79
    81
    111
    117
        RBC, Month 7, Within (N=121;121;115;125)
    82
    84
    100
    100
        RBC, Month 12, Within (N=122;119;108;118)
    79
    86
    88
    100
        RBC, Month 18, Within (N=121;117;110;116)
    81
    80
    97
    96
        RBC, Month 24, Within (N=116;117;103;111)
    74
    83
    91
    98
        RBC, Day 0, Above (N=129;128;141;141)
    3
    3
    5
    5
        RBC, Week 6, Above (N=128;126;136;139)
    3
    5
    4
    6
        RBC, Week 10, Above (N=128;127;134;135)
    2
    3
    3
    5
        RBC, Month 6, Above (N=123;123;127;134)
    4
    3
    2
    4
        RBC, Month 7, Above (N=121;121;115;125)
    3
    3
    0
    6
        RBC, Month 12, Above (N=122;119;108;118)
    3
    2
    1
    3
        RBC, Month 18, Above (N=121;117;110;116)
    2
    6
    2
    4
        RBC, Month 24, Above (N=116;117;103;111)
    3
    0
    2
    4
        WBC, Day 0, Unknown (N=129;128;143;145)
    0
    0
    0
    0
        WBC, Week 6, Unknown (N=128;126;136;142)
    0
    0
    0
    0
        WBC, Week 10, Unknown (N=128;127;134;136)
    0
    0
    0
    0
        WBC, Month 6, Unknown (N=123;123;127;134)
    0
    0
    0
    0
        WBC, Month 7, Unknown (N=121;121;114;125)
    0
    0
    0
    0
        WBC, Month 12, Unknown (N=122;119;107;118)
    1
    0
    0
    0
        WBC, Month 18, Unknown (N=121;117;109;117)
    0
    0
    0
    0
        WBC, Month 24, Unknown (N=116;117;102;111)
    1
    0
    0
    0
        WBC, Day 0, Below (N=129;128;143;145)
    8
    7
    5
    2
        WBC, Week 6, Below (N=128;126;136;142)
    9
    11
    5
    4
        WBC, Week 10, Below (N=128;127;134;136)
    9
    9
    2
    3
        WBC, Month 6, Below (N=123;123;127;134)
    12
    6
    2
    2
        WBC, Month 7, Below (N=121;121;114;125)
    10
    9
    5
    1
        WBC, Month 12, Below (N=122;119;107;118)
    14
    13
    3
    2
        WBC, Month 18, Below (N=121;117;109;117)
    12
    10
    4
    5
        WBC, Month 24, Below (N=116;117;102;111)
    11
    5
    3
    4
        WBC, Day 0, Within (N=129;128;143;145)
    118
    116
    135
    140
        WBC, Week 6, Within (N=128;126;136;142)
    118
    111
    124
    135
        WBC, Week 10, Within (N=128;127;134;136)
    116
    113
    131
    129
        WBC, Month 6, Within (N=123;123;127;134)
    106
    116
    122
    128
        WBC, Month 7, Within (N=121;121;114;125)
    106
    108
    106
    120
        WBC, Month 12, Within (N=122;119;107;118)
    103
    103
    100
    115
        WBC, Month 18, Within (N=121;117;109;117)
    106
    107
    100
    107
        WBC, Month 24, Within (N=116;117;102;111)
    102
    107
    94
    101
        WBC, Day 0, Above (N=129;128;143;145)
    3
    5
    3
    3
        WBC, Week 6, Above (N=128;126;136;142)
    1
    4
    7
    3
        WBC, Week 10, Above (N=128;127;134;136)
    3
    5
    1
    4
        WBC, Month 6, Above (N=123;123;127;134)
    5
    1
    3
    4
        WBC, Month 7, Above (N=121;121;114;125)
    5
    4
    3
    4
        WBC, Month 12, Above (N=122;119;107;118)
    4
    3
    4
    1
        WBC, Month 18, Above (N=121;117;109;117)
    3
    0
    5
    5
        WBC, Month 24, Above (N=116;117;102;111)
    2
    5
    5
    6
    No statistical analyses for this end point

    Secondary: Number of subjects with SAEs

    		 Close Top of page
    End point title
    		 Number of subjects with SAEs
    End point description
    SAEs assessed include any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or represented a congenital anomaly/birth defect in the offspring of a study subject.
    End point type
    Secondary
    End point timeframe
    During the entire study period (from Day 0 up to Month 24)
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group HIV-/Cervarix Group HIV-/Gardasil Group
    Number of subjects analysed
    129
    128
    144
    145
    Units: Participants
        SAE(s)
    9
    9
    4
    1
    No statistical analyses for this end point

    Secondary: Number of subjects with medically significant conditions (MSCs)

    		 Close Top of page
    End point title
    		 Number of subjects with medically significant conditions (MSCs)
    End point description
    Medically significant conditions (MSCs) are defined as AEs prompting emergency room or physician visits that were not related to common diseases, or not related to routine visits for physical examination or vaccination, SAEs that were not related to common diseases.
    End point type
    Secondary
    End point timeframe
    From Day 0 up to Month 18 (from Day 0 up to 12 months after the last vaccination dose at Month 6)
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group HIV-/Cervarix Group HIV-/Gardasil Group
    Number of subjects analysed
    129
    128
    144
    145
    Units: Participants
        MSC(s)
    25
    37
    10
    17
    No statistical analyses for this end point

    Secondary: Number of subjects with potential immune-mediated diseases (pIMDs)

    		 Close Top of page
    End point title
    		 Number of subjects with potential immune-mediated diseases (pIMDs)
    End point description
    Potential immune-mediated diseases are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
    End point type
    Secondary
    End point timeframe
    From Day 0 up to Month 18 (from Day 0 up to 12 months after the last vaccination dose at Month 6)
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group HIV-/Cervarix Group HIV-/Gardasil Group
    Number of subjects analysed
    129
    128
    144
    145
    Units: Participants
        pIMD(s)
    1
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Cluster of differentiation 4 (CD4+) cell count in HIV+ subjects at Months 12, 18 and 24

    		 Close Top of page
    End point title
    		 Cluster of differentiation 4 (CD4+) cell count in HIV+ subjects at Months 12, 18 and 24 [37]
    End point description
    CD4+ cell count, expressed in cells/cubic millimeter (mm3), was assessed for HIV+ subjects.
    End point type
    Secondary
    End point timeframe
    At Months 12, 18 and 24
    Notes
    [37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV positive subjects.
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group
    Number of subjects analysed
    122
    119
    Units: cells/mm3
    median (inter-quartile range (Q1-Q3))
        CD4+ cell counts, Month 12 (N=122;119)
    584.5 (498.0 to 832.0)
    602.0 (445.0 to 835.0)
        CD4+ cell counts, Month 18 (N=121;117)
    621.0 (472.0 to 789.0)
    572.0 (443.0 to 770.0)
        CD4+ cell counts, Month 24 (N=115;117)
    568.0 (447.0 to 738.0)
    598.0 (441.0 to 834.0)
    No statistical analyses for this end point

    Secondary: HIV viral load (VL) in HIV+ subjects at Months 12, 18 and 24

    		 Close Top of page
    End point title
    		 HIV viral load (VL) in HIV+ subjects at Months 12, 18 and 24 [38]
    End point description
    HIV VL, expressed in HIV copies/milliliter (mL), was assessed for HIV+ subjects.
    End point type
    Secondary
    End point timeframe
    At Months 12, 18 and 24
    Notes
    [38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV positive subjects.
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group
    Number of subjects analysed
    94
    96
    Units: HIV copies/mL
    median (inter-quartile range (Q1-Q3))
        HIV viral load, Month 12 (N=94;96)
    1.6 (1.3 to 3.2)
    2.3 (1.3 to 3.7)
        HIV viral load, Month 18 (N=94;91)
    1.7 (1.3 to 3.2)
    2.2 (1.3 to 3.8)
        HIV viral load, Month 24 (N=93;87)
    1.6 (1.3 to 2.8)
    2.1 (1.3 to 3.8)
    No statistical analyses for this end point

    Secondary: Number of HIV+ subjects by WHO HIV clinical staging

    		 Close Top of page
    End point title
    		 Number of HIV+ subjects by WHO HIV clinical staging [39]
    End point description
    HIV+ subjects were categorised into clinical stages 1 through 4, as per the WHO classification [WHO, 2009].
    End point type
    Secondary
    End point timeframe
    At Months 12, 18 and 24
    Notes
    [39] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV positive subjects.
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group
    Number of subjects analysed
    129
    128
    Units: Participants
        Clinical stage 1, Month 12
    113
    112
        Clinical stage 2, Month 12
    7
    1
        Clinical stage 3, Month 12
    1
    2
        Clinical stage 4, Month 12
    2
    4
        Clinical stage 1, Month 18
    112
    110
        Clinical stage 2, Month 18
    7
    1
        Clinical stage 3, Month 18
    1
    2
        Clinical stage 4, Month 18
    2
    4
        Clinical stage 1, Month 24
    107
    110
        Clinical stage 2, Month 24
    7
    1
        Clinical stage 3, Month 24
    1
    2
        Clinical stage 4, Month 24
    2
    4
    No statistical analyses for this end point

    Secondary: Pseudovirion-Based Neutralization Assay (PBNA) Titers of anti-HPV-16/18 antibodies in HIV- subjects, based on TVC

    		 Close Top of page
    End point title
    		 Pseudovirion-Based Neutralization Assay (PBNA) Titers of anti-HPV-16/18 antibodies in HIV- subjects, based on TVC [40]
    End point description
    Titers of anti-HPV-16/18 antibodies, expressed as Geometric Mean Titers (GMTs), with cut-offs greater than or equal to (≥) 40 estimated dose giving 50% signal reduction when compared to a control without serum (ED50), as assessed by the Pseudovirion-Based Neutralization Assay [PBNA], for HIV- subjects. Between-group comparisons to assess superiority were performed on the TVC (by PBNA, regardless of HPV serostatus at baseline).
    End point type
    Secondary
    End point timeframe
    At Month 7 (30 days after the last vaccination dose at Month 6)
    Notes
    [40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for HIV negative subjects.
    End point values
    		 HIV-/Cervarix Group HIV-/Gardasil Group
    Number of subjects analysed
    105
    112
    Units: Titers
    geometric mean (confidence interval 95%)
        Anti-HPV-16 (N=105;112)
    60550.6 (44040.1 to 83250.9)
    19634.8 (14410.8 to 26752.4)
        Anti-HPV-18 (N=105;111)
    32118.1 (23195.8 to 44472.3)
    5773.4 (4205.2 to 7926.4)
    Statistical analysis title
    		 Anti-HPV-18 Adjusted GMT ratio - superiority
    Statistical analysis description
    Adjusted GMT ratio for anti-HPV-18 neutra antibody (ED50): To demonstrate that the immunogenicity of Cervarix vaccine (HIV-/Cervarix Group) was superior to that of Gardasil vaccine (HIV-/Gardasil Group), in terms of geometric mean titers (GMTs) against HPV-18, measured by Pseudovirion-based neutralization assay (PBNA) in HIV- subjects.
    Comparison groups
    HIV-/Gardasil Group v HIV-/Cervarix Group
    Number of subjects included in analysis
    217
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [41]
    P-value
    		 < 0.0001 [42]
    Method
    		 ANOVA
    Parameter type
    		 Adjusted GMT ratio
    Point estimate
    5.38
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 3.2
         upper limit
    		 9.06
    Notes
    [41] - Superiority was defined as the lower limit of the 97.5% CI for the ratio of GMTs (Cervarix over Gardasil) for HPV-18 type being above 1, with a statistically significant p-value.
    [42] - ANOVA model on the log10 transformation of the titers for HIV- subjects and including the vaccine group as fixed effect.
    Statistical analysis title
    		 Anti-HPV-16 Adjusted GMT ratio - superiority
    Statistical analysis description
    Adjusted GMT ratio for anti-HPV-16 neutra antibody (ED50): To demonstrate that the immunogenicity of Cervarix vaccine (HIV-/Cervarix Group) was superior to that of Gardasil vaccine (HIV-/Gardasil Group), in terms of geometric mean titers (GMTs) against HPV-16, measured by Pseudovirion-based neutralization assay (PBNA) in HIV- subjects.
    Comparison groups
    HIV-/Gardasil Group v HIV-/Cervarix Group
    Number of subjects included in analysis
    217
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [43]
    P-value
    		 < 0.0001 [44]
    Method
    		 ANOVA
    Parameter type
    		 Adjusted GMT ratio
    Point estimate
    3.05
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 1.84
         upper limit
    		 5.06
    Notes
    [43] - Superiority was defined as the lower limit of the 97.5% CI for the ratio of GMTs (Cervarix over Gardasil) for HPV-16 type being above 1, with a statistically significant p-value.
    [44] - ANOVA model on the log10 transformation of the titers for HIV- subjects and including the vaccine group as fixed effect.

    Secondary: Anti-HPV-16 and Anti-HPV-18 antibody concentrations by Enzyme-linked immunosorbent assay (ELISA) in serum

    		 Close Top of page
    End point title
    		 Anti-HPV-16 and Anti-HPV-18 antibody concentrations by Enzyme-linked immunosorbent assay (ELISA) in serum
    End point description
    Anti-HPV-16 and anti-HPV-18 antibody concentrations in serum, are presented as Geometric Mean Concentrations (GMCs), with cut-offs greater than or equal to (≥) 19 ELISA units per milliliter (EU/mL) and 18 EU/mL respectively, as assessed by Enzyme-linked immunosorbent assay (ELISA), in all (HIV+ and HIV-) subjects.
    End point type
    Secondary
    End point timeframe
    At Day 0, Week 6, Week 10, Month 7, Month 12, Month 18 and Month 24
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group HIV-/Cervarix Group HIV-/Gardasil Group
    Number of subjects analysed
    81
    84
    77
    80
    Units: EU/mL
    geometric mean (confidence interval 95%)
        anti-HPV-16, Day 0 (N=81;84;77;80)
    17.2 (13.3 to 22.2)
    15.0 (12.0 to 18.9)
    10.2 (9.4 to 11.0)
    10.9 (9.5 to 12.5)
        anti-HPV-16, Week 6 (N=81;84;77;80)
    452.9 (302.3 to 678.5)
    280.2 (182.5 to 430.1)
    390.6 (298.3 to 511.6)
    303.2 (228.0 to 403.3)
        anti-HPV-16, Week 10 (N=81;84;77;80)
    2191.2 (1775.7 to 2704.0)
    1565.5 (1197.5 to 2046.6)
    4512.7 (3771.5 to 5399.7)
    2993.2 (2459.1 to 3643.3)
        anti-HPV-16, Month 7 (N=81;84;77;80)
    4896.0 (4002.2 to 5989.3)
    2145.2 (1647.8 to 2792.7)
    15493.0 (12537.0 to 19146.0)
    5960.9 (5028.9 to 7065.7)
        anti-HPV-16, Month 12 (N=81;81;73;76)
    1392.3 (1077.5 to 1799.0)
    608.8 (445.4 to 832.1)
    4389.3 (3400.5 to 5665.7)
    1772.2 (1473.3 to 2131.7)
        anti-HPV-16, Month 18 (N=77;76;70;72)
    861.3 (662.3 to 1119.9)
    311.4 (226.3 to 428.4)
    2294.1 (1785.0 to 2948.4)
    798.0 (646.6 to 984.8)
        anti-HPV-16, Month 24 (N=71;74;64;69)
    664.6 (499.9 to 883.7)
    243.5 (173.9 to 341.0)
    1893.6 (1443.8 to 2483.7)
    601.9 (481.8 to 752.1)
        anti-HPV-18, Day 0 (N=81;84;77;80)
    13.4 (11.2 to 16.0)
    10.7 (9.3 to 12.3)
    9.3 (8.9 to 9.8)
    9.2 (8.9 to 9.5)
        anti-HPV-18, Week 6 (N=81;84;77;80)
    205.6 (146.3 to 288.7)
    53.2 (36.4 to 77.6)
    277.3 (217.5 to 353.5)
    60.4 (47.5 to 76.8)
        anti-HPV-18, Week 10 (N=81;84;77;80)
    1432.4 (1136.9 to 1804.6)
    277.2 (200.8 to 382.8)
    3174.4 (2596.2 to 3881.4)
    666.1 (549.8 to 806.9)
        anti-HPV-18, Month 7 (N=81;84;77;80)
    2540.8 (2085.9 to 3094.9)
    493.8 (356.6 to 683.8)
    6779.3 (5382.6 to 8538.5)
    1516.5 (1232.9 to 1865.2)
        anti-HPV-18, Month 12 (N=81;81;73;76)
    676.9 (520.1 to 880.9)
    116.2 (82.2 to 164.2)
    1747.7 (1329.4 to 2297.6)
    338.3 (261.2 to 438.1)
        anti-HPV-18, Month 18 (N=77;76;70;72)
    408.7 (310.4 to 538.2)
    55.6 (39.6 to 78.0)
    895.5 (679.6 to 1179.9)
    160.1 (123.7 to 207.1)
        anti-HPV-18, Month 24 (N=71;74;64;69)
    295.2 (216.9 to 401.7)
    52.4 (37.2 to 73.8)
    761.9 (576.6 to 1006.7)
    116.2 (88.8 to 151.9)
    No statistical analyses for this end point

    Secondary: Anti-HPV-16 and anti-HPV-18 antibody concentrations by ELISA in cervicovaginal secretion (CVS)

    		 Close Top of page
    End point title
    		 Anti-HPV-16 and anti-HPV-18 antibody concentrations by ELISA in cervicovaginal secretion (CVS)
    End point description
    Anti-HPV-16 and anti-HPV-18 antibody concentrations in CVS, are presented as Geometric Mean Concentrations (GMCs), with cut-offs greater than or equal to (≥) 0 EU/mL, as assessed by ELISA, in postmenarcheal subjects who volunteered for this procedure. Note: When only 1 subject is analyzed, the lower limit (LL) and the upper limit (UL) are entered equal to the geometric mean concentration (GMC) value as the confidence interval could not be calculated with only 1 subject analyzed.
    End point type
    Secondary
    End point timeframe
    At Day 0, Week 6, Week 10, Month 7, Month 12, Month 18 and Month 24
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group HIV-/Cervarix Group HIV-/Gardasil Group
    Number of subjects analysed
    12
    18
    3
    5
    Units: EU/mL
    geometric mean (confidence interval 95%)
        anti-HPV-16, Day 0 (N=12;18;3;5)
    1.5 (0.8 to 2.6)
    1.4 (0.7 to 2.8)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
        anti-HPV-16, Week 6 (N=7;11;3;5)
    31.5 (4.7 to 211.5)
    3.1 (0.8 to 11.6)
    27.1 (8.7 to 84.2)
    2.7 (0.4 to 16.5)
        anti-HPV-16, Week 10 (N=9;11;0;1)
    38.8 (6.1 to 245.0)
    15.7 (5.4 to 45.2)
    0 (0.0 to 0.0)
    159.8 (159.8 to 159.8)
        anti-HPV-16, Month 7 (N=8;14;3;3)
    23.6 (3.4 to 163.0)
    5.4 (1.6 to 17.6)
    104.2 (40.3 to 269.4)
    53.5 (3.0 to 945.1)
        anti-HPV-16, Month 12 (N=9;15;2;1)
    18.7 (3.2 to 109.0)
    6.8 (2.1 to 22.3)
    107.6 (29.1 to 398.1)
    34.7 (34.7 to 34.7)
        anti-HPV-16, Month 24 (N=7;10;3;1)
    8.1 (1.3 to 50.3)
    4.3 (1.4 to 12.9)
    49.0 (4.5 to 534.2)
    1.0 (1.0 to 1.0)
        anti-HPV-18, Day 0 (N=12;18;3;5)
    1.2 (0.8 to 1.9)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
        anti-HPV-18, Week 6 (N=7;11;3;5)
    16.8 (2.5 to 113.1)
    1.7 (0.5 to 5.2)
    3.0 (0.0 to 312.7)
    1.0 (1.0 to 1.0)
        anti-HPV-18, Week 10 (N=9;11;0;1)
    22.9 (3.4 to 152.2)
    2.3 (0.9 to 5.8)
    0 (0.0 to 0.0)
    21.6 (21.6 to 21.6)
        anti-HPV-18, Month 7 (N=8;14;3;3)
    10.1 (1.8 to 58.2)
    2.2 (1.0 to 4.8)
    44.2 (14.3 to 136.9)
    16.3 (1.0 to 265.0)
        anti-HPV-18, Month 12 (N=9;15;2;1)
    23.9 (8.0 to 72.0)
    2.4 (0.9 to 6.8)
    32.7 (17.2 to 62.1)
    16.3 (16.3 to 16.3)
        anti-HPV-18, Month 24 (N=7;10;3;1)
    8.8 (1.6 to 48.5)
    1.5 (0.8 to 3.0)
    13.8 (1.3 to 149.2)
    1.0 (1.0 to 1.0)
    No statistical analyses for this end point

    Secondary: Frequency of specific B-cells for HPV-16/18 antigens

    		 Close Top of page
    End point title
    		 Frequency of specific B-cells for HPV-16/18 antigens
    End point description
    B cell memory was assessed by Enzyme Linked Immuno Spot (ELISPOT) assay. The assay was performed in a subset of approximately 100 subjects (50 HIV+ and 50 HIV-).
    End point type
    Secondary
    End point timeframe
    At Day 0, Week 6, Week 10, Month 7 and Month 12
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group HIV-/Cervarix Group HIV-/Gardasil Group
    Number of subjects analysed
    16
    12
    20
    20
    Units: B-cells/million cells
    median (inter-quartile range (Q1-Q3))
        HPV-16, Day 0 (N=12;11;18;20)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 61.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
        HPV-18, Day 0 (N=12;11;18;20)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
        HPV-16, Week 6 (N=10;12;15;15)
    91.0 (1.0 to 154.0)
    1.0 (1.0 to 1.0)
    22.0 (1.0 to 154.0)
    1.0 (1.0 to 204.0)
        HPV-18, Week 6 (N=10;12;15;15)
    39.5 (1.0 to 693.0)
    1.0 (1.0 to 45.5)
    155.0 (1.0 to 345.0)
    33.0 (1.0 to 80.0)
        HPV-16, Week 10 (N=12;9;20;20)
    558.0 (95.5 to 989.5)
    198.0 (1.0 to 391.0)
    494.0 (90.5 to 834.0)
    150.5 (33.5 to 726.5)
        HPV-18, Week 10 (N=12;9;20;20)
    150.0 (31.0 to 471.0)
    1.0 (1.0 to 42.0)
    211.0 (84.0 to 656.0)
    29.5 (1.0 to 222.0)
        HPV-16, Month 7 (N=13;9;20;17)
    624.0 (457.0 to 1196.0)
    213.0 (165.0 to 632.0)
    1504.0 (481.0 to 3026.0)
    448.0 (257.0 to 890.0)
        HPV-18, Month 7 (N=13;9;20;17)
    332.0 (153.0 to 494.0)
    1.0 (1.0 to 392.0)
    513.5 (111.5 to 1292.0)
    65.0 (1.0 to 158.0)
        HPV-16, Month 12 (N=16;8;20;17)
    256.5 (75.5 to 891.5)
    121.0 (64.5 to 315.0)
    414.5 (94.5 to 640.5)
    256.0 (218.0 to 449.0)
        HPV-18, Month 12 (N=16;8;20;17)
    101.0 (1.0 to 525.0)
    1.0 (1.0 to 159.0)
    250.5 (1.0 to 481.5)
    58.0 (1.0 to 101.0)
    No statistical analyses for this end point

    Secondary: Frequency of cluster of differentiation 4/8 [CD4+/CD8+] T-cell response

    		 Close Top of page
    End point title
    		 Frequency of cluster of differentiation 4/8 [CD4+/CD8+] T-cell response
    End point description
    The combinations of cytokines expressed were CD4/8-all doubles, CD4/8-d-cluster of differentiation 40 Ligand (CD40L), CD4/8-d-interferon gamma (IFNG), CD4/8-interleukin-2 (IL-2), CD4/8-d-tumour necrosis alpha (TNFA), as assessed by Intracellular cytokine staining (ICS). The assay was performed in a subset of approximately 100 subjects (50 HIV+ and 50 HIV-).
    End point type
    Secondary
    End point timeframe
    At Day 0, Week 6, Week 10, Month 7 and Month 12
    End point values
    		 HIV+/Cervarix Group HIV+/Gardasil Group HIV-/Cervarix Group HIV-/Gardasil Group
    Number of subjects analysed
    17
    15
    21
    19
    Units: CD4 cells/million T-cells
    median (inter-quartile range (Q1-Q3))
        CD4-All doubles,Anti-HPV-16,Day 0 (N=17;15;17;18)
    41.0 (1.0 to 118.0)
    101.0 (43.0 to 215.0)
    1.0 (1.0 to 28.0)
    54.5 (1.0 to 88.0)
        CD4-All doubles,Anti-HPV-18,Day 0 (N=17;15;17;18)
    7.0 (1.0 to 116.0)
    87.0 (18.0 to 184.0)
    1.0 (1.0 to 82.0)
    1.0 (1.0 to 98.0)
        CD4-All doubles,Anti-HPV-16,Week 6 (N=16;14;16;18)
    445.5 (262.0 to 1028.0)
    345.5 (227.0 to 1034.0)
    298.0 (173.0 to 540.5)
    661.0 (234.0 to 982.0)
        CD4-All doubles,Anti-HPV-18,Week 6 (N=16;14;16;18)
    396.0 (163.0 to 832.0)
    309.5 (203.0 to 852.0)
    237.0 (81.0 to 421.5)
    320.5 (117.0 to 524.0)
        CD4-All doubles,Anti-HPV-16,Week 10(N=14;14;19;18)
    2955.5 (1075.0 to 5200.0)
    1449.0 (922.0 to 1778.0)
    1767.0 (916.0 to 4428.0)
    1268.5 (648.0 to 2453.0)
        CD4-All doubles,Anti-HPV-18,Week 10(N=14;14;19;18)
    2036.5 (951.0 to 3123.0)
    602.0 (498.0 to 2079.0)
    1243.0 (587.0 to 3400.0)
    515.5 (414.0 to 1178.0)
        CD4-All doubles,Anti-HPV-16,Month 7(N=13;14;16;17)
    3693.0 (1870.0 to 5153.0)
    1679.5 (1052.0 to 2734.0)
    3414.5 (1424.5 to 4520.0)
    1505.0 (995.0 to 2205.0)
        CD4-All doubles,Anti-HPV-18,Month 7(N=13;14;16;17)
    1866.0 (1267.0 to 2875.0)
    840.5 (518.0 to 1641.0)
    2084.5 (911.0 to 4110.0)
    669.0 (470.0 to 1035.0)
        CD4-All doubles,Anti-HPV-16,Month 12(N=15;14;21;19
    2328.0 (1225.0 to 4614.0)
    1288.0 (976.0 to 2485.0)
    2543.0 (1232.0 to 4264.0)
    830.0 (367.0 to 1386.0)
        CD4-All doubles,Anti-HPV-18,Month 12(N=15;14;21;19
    1654.0 (836.0 to 2634.0)
    808.5 (295.0 to 1932.0)
    1641.0 (985.0 to 2939.0)
    428.0 (162.0 to 938.0)
        CD4-d-CD40L, Anti-HPV-16, Day 0 (N=17;15;17;18)
    22.0 (1.0 to 118.0)
    99.0 (60.0 to 215.0)
    1.0 (1.0 to 58.0)
    46.0 (1.0 to 81.0)
        CD4-d-CD40L, Anti-HPV-18, Day 0 (N=17;15;17;18)
    36.0 (1.0 to 81.0)
    89.0 (1.0 to 176.0)
    1.0 (1.0 to 54.0)
    13.5 (1.0 to 100.0)
        CD4-d-CD40L, Anti-HPV-16, Week 6 (N=16;14;16;18)
    426.0 (258.5 to 999.5)
    326.5 (196.0 to 1034.0)
    298.0 (209.5 to 540.0)
    582.0 (223.0 to 967.0)
        CD4-d-CD40L, Anti-HPV-18, Week 6 (N=16;14;16;18)
    403.5 (144.0 to 835.0)
    296.0 (216.0 to 840.0)
    242.5 (36.5 to 393.0)
    310.0 (95.0 to 521.0)
        CD4-d-CD40L, Anti-HPV-16, Week 10 (N=14;14;19;18)
    2893.5 (988.0 to 5006.0)
    1440.0 (882.0 to 1814.0)
    1678.0 (917.0 to 4306.0)
    1239.0 (562.0 to 2362.0)
        CD4-d-CD40L, Anti-HPV-18, Week 10 (N=14;14;19;18)
    2015.0 (944.0 to 3021.0)
    564.5 (507.0 to 2045.0)
    1051.0 (631.0 to 3317.0)
    474.5 (385.0 to 811.0)
        CD4-d-CD40L, Anti-HPV-16, Month 7 (N=13;14;16;17)
    3658.0 (1804.0 to 5070.0)
    1619.5 (1071.0 to 2600.0)
    3290.0 (1464.5 to 4387.5)
    1389.0 (949.0 to 2133.0)
        CD4-d-CD40L, Anti-HPV-18, Month 7 (N=13;14;16;17)
    1839.0 (1066.0 to 2893.0)
    833.5 (518.0 to 1605.0)
    2014.0 (979.0 to 3878.5)
    647.0 (442.0 to 981.0)
        CD4-d-CD40L, Anti-HPV-16, Month 12 (N=15;14;21;19)
    2266.0 (1178.0 to 4558.0)
    1278.0 (955.0 to 2478.0)
    2519.0 (1232.0 to 4190.0)
    862.0 (353.0 to 1197.0)
        CD4-d-CD40L, Anti-HPV-18, Month 12 (N=15;14;21;19)
    1668.0 (807.0 to 2427.0)
    808.5 (295.0 to 1914.0)
    1641.0 (984.0 to 2767.0)
    394.0 (155.0 to 913.0)
        CD4-d-IFNG, Anti-HPV-16, Day 0 (N=17;15;17;18)
    27.0 (1.0 to 63.0)
    30.0 (1.0 to 51.0)
    1.0 (1.0 to 45.0)
    39.0 (1.0 to 61.0)
        CD4-d-IFNG, Anti-HPV-18, Day 0 (N=17;15;17;18)
    4.0 (1.0 to 42.0)
    51.0 (1.0 to 59.0)
    1.0 (1.0 to 54.0)
    21.0 (1.0 to 46.0)
        CD4-d-IFNG, Anti-HPV-16, Week 6 (N=16;14;16;18)
    222.5 (117.0 to 393.0)
    116.0 (75.0 to 222.0)
    42.5 (1.0 to 127.5)
    241.5 (71.0 to 404.0)
        CD4-d-IFNG, Anti-HPV-18, Week 6 (N=16;14;16;18)
    98.0 (25.0 to 361.0)
    104.5 (35.0 to 211.0)
    1.0 (1.0 to 44.0)
    129.5 (1.0 to 182.0)
        CD4-d-IFNG, Anti-HPV-16, Week 10 (N=14;14;19;18)
    1220.0 (554.0 to 1478.0)
    450.0 (245.0 to 527.0)
    332.0 (282.0 to 1251.0)
    442.0 (160.0 to 935.0)
        CD4-d-IFNG, Anti-HPV-18, Week 10 (N=14;14;19;18)
    694.0 (342.0 to 1207.0)
    326.5 (121.0 to 455.0)
    222.0 (124.0 to 569.0)
    202.0 (122.0 to 279.0)
        CD4-d-IFNG, Anti-HPV-16, Month 7 (N=13;14;16;17)
    1513.0 (891.0 to 1993.0)
    585.5 (190.0 to 846.0)
    731.0 (267.5 to 1245.0)
    495.0 (319.0 to 859.0)
        CD4-d-IFNG, Anti-HPV-18, Month 7 (N=13;14;16;17)
    694.0 (409.0 to 868.0)
    306.0 (171.0 to 382.0)
    414.5 (245.5 to 616.5)
    198.0 (126.0 to 435.0)
        CD4-d-IFNG, Anti-HPV-16, Month 12 (N=15;14;21;19)
    452.0 (368.0 to 1097.0)
    432.0 (202.0 to 835.0)
    621.0 (239.0 to 1042.0)
    302.0 (129.0 to 555.0)
        CD4-d-IFNG, Anti-HPV-18, Month 12 (N=15;14;21;19)
    402.0 (191.0 to 585.0)
    253.5 (92.0 to 415.0)
    273.0 (88.0 to 406.0)
    98.0 (1.0 to 154.0)
        CD4-d-IL-2, Anti-HPV-16, Day 0 (N=17;15;17;18)
    43.0 (1.0 to 81.0)
    30.0 (7.0 to 121.0)
    1.0 (1.0 to 58.0)
    1.0 (1.0 to 21.0)
        CD4-d-IL-2, Anti-HPV-18, Day 0 (N=17;15;17;18)
    46.0 (1.0 to 115.0)
    37.0 (1.0 to 102.0)
    1.0 (1.0 to 31.0)
    13.5 (1.0 to 57.0)
        CD4-d-IL-2, Anti-HPV-16, Week 6 (N=16;14;16;18)
    361.0 (235.5 to 966.0)
    300.0 (234.0 to 827.0)
    245.5 (137.0 to 468.0)
    454.5 (228.0 to 816.0)
        CD4-d-IL-2, Anti-HPV-18, Week 6 (N=16;14;16;18)
    364.5 (161.0 to 858.0)
    193.5 (94.0 to 687.0)
    227.5 (131.5 to 379.5)
    286.0 (129.0 to 413.0)
        CD4-d-IL-2, Anti-HPV-16, Week 10 (N=14;14;19;18)
    2503.0 (938.0 to 4606.0)
    1221.0 (678.0 to 1584.0)
    1542.0 (776.0 to 3499.0)
    929.5 (435.0 to 2128.0)
        CD4-d-IL-2, Anti-HPV-18, Week 10 (N=14;14;19;18)
    1668.5 (635.0 to 2183.0)
    555.5 (349.0 to 1687.0)
    1183.0 (456.0 to 2311.0)
    411.0 (245.0 to 891.0)
        CD4-d-IL-2, Anti-HPV-16, Month 7 (N=13;14;16;17)
    2847.0 (1557.0 to 4064.0)
    1318.5 (672.0 to 2141.0)
    2608.5 (1147.5 to 3875.0)
    1128.0 (697.0 to 1574.0)
        CD4-d-IL-2, Anti-HPV-18, Month 7 (N=13;14;16;17)
    1522.0 (914.0 to 2285.0)
    615.0 (472.0 to 1234.0)
    1442.0 (811.0 to 3471.0)
    537.0 (341.0 to 643.0)
        CD4-d-IL-2, Anti-HPV-16, Month 12 (N=15;14;21;19)
    1792.0 (1076.0 to 4087.0)
    1040.5 (804.0 to 1972.0)
    1861.0 (1861.0 to 3754.0)
    723.0 (330.0 to 1255.0)
        CD4-d-IL-2, Anti-HPV-18, Month 12 (N=15;14;21;19)
    1170.0 (683.0 to 2375.0)
    601.5 (230.0 to 1568.0)
    1342.0 (825.0 to 2794.0)
    337.0 (243.0 to 636.0)
        CD4-d-TNFA, Anti-HPV-16, Day 0 (N=17;15;17;18)
    1.0 (1.0 to 58.0)
    71.0 (1.0 to 252.0)
    32.0 (1.0 to 74.0)
    34.0 (1.0 to 76.0)
        CD4-d-TNFA, Anti-HPV-18, Day 0 (N=17;15;17;18)
    1.0 (1.0 to 52.0)
    35.0 (1.0 to 131.0)
    25.0 (1.0 to 39.0)
    15.5 (1.0 to 83.0)
        CD4-d-TNFA, Anti-HPV-16, Week 6 (N=16;14;16;18)
    326.5 (49.5 to 714.0)
    171.0 (133.0 to 701.0)
    237.0 (89.5 to 325.0)
    337.5 (183.0 to 648.0)
        CD4-d-TNFA, Anti-HPV-18, Week 6 (N=16;14;16;18)
    234.0 (66.0 to 579.0)
    204.0 (94.0 to 539.0)
    162.5 (75.5 to 247.0)
    156.5 (72.0 to 398.0)
        CD4-d-TNFA, Anti-HPV-16, Week 10 (N=14;14;19;18)
    2086.0 (519.0 to 4016.0)
    903.5 (606.0 to 1355.0)
    1260.0 (764.0 to 3094.0)
    865.5 (453.0 to 2100.0)
        CD4-d-TNFA, Anti-HPV-18, Week 10 (N=14;14;19;18)
    1493.5 (592.0 to 2341.0)
    443.0 (248.0 to 1432.0)
    899.0 (415.0 to 2310.0)
    334.5 (203.0 to 958.0)
        CD4-d-TNFA, Anti-HPV-16, Month 7 (N=13;14;16;17)
    2688.0 (1399.0 to 3994.0)
    1109.0 (670.0 to 2066.0)
    2621.0 (1062.0 to 3652.5)
    1215.0 (792.0 to 1665.0)
        CD4-d-TNFA, Anti-HPV-18, Month 7 (N=13;14;16;17)
    1366.0 (1126.0 to 2449.0)
    598.0 (362.0 to 1522.0)
    1614.0 (760.5 to 3463.5)
    505.0 (330.0 to 683.0)
        CD4-d-TNFA, Anti-HPV-16, Month 12 (N=15;14;21;19)
    1937.0 (883.0 to 3961.0)
    1011.5 (681.0 to 2066.0)
    2344.0 (1053.0 to 3741.0)
    646.0 (344.0 to 1219.0)
        CD4-d-TNFA, Anti-HPV-18, Month 12 (N=15;14;21;19)
    1264.0 (707.0 to 2500.0)
    527.0 (174.0 to 1684.0)
    1480.0 (703.0 to 2619.0)
    358.0 (186.0 to 617.0)
        CD8-All doubles,Anti-HPV-16, Day 0 (N=17;15;17;18)
    1.0 (1.0 to 40.0)
    1.0 (1.0 to 43.0)
    1.0 (1.0 to 28.0)
    1.0 (1.0 to 29.0)
        CD8-All doubles,Anti-HPV-18, Day 0 (N=17;15;17;18)
    6.0 (1.0 to 50.0)
    23.0 (1.0 to 60.0)
    21.0 (1.0 to 54.0)
    1.0 (1.0 to 35.0)
        CD8-All doubles,Anti-HPV-16,Week 6 (N=16;14;16;18)
    2.0 (1.0 to 34.5)
    13.0 (1.0 to 70.0)
    1.0 (1.0 to 14.5)
    1.0 (1.0 to 3.0)
        CD8-All doubles,Anti-HPV-18,Week 6 (N=16;14;16;18)
    37.5 (9.0 to 66.5)
    2.0 (1.0 to 42.0)
    1.0 (1.0 to 42.5)
    30.5 (1.0 to 74.0)
        CD8-All doubles,Anti-HPV-16,Week 10(N=14;14;19;18)
    41.0 (1.0 to 75.0)
    3.5 (1.0 to 36.0)
    1.0 (1.0 to 54.0)
    1.0 (1.0 to 29.0)
        CD8-All doubles,Anti-HPV-18,Week 10(N=14;14;19;18)
    11.0 (1.0 to 60.0)
    1.0 (1.0 to 60.0)
    5.0 (1.0 to 84.0)
    1.0 (1.0 to 41.0)
        CD8-All doubles,Anti-HPV-16,Month 7(N=13;14;16;17)
    51.0 (18.0 to 69.0)
    9.5 (1.0 to 33.0)
    1.0 (1.0 to 74.5)
    2.0 (1.0 to 54.0)
        CD8-All doubles,Anti-HPV-18,Month 7(N=13;14;16;17)
    41.0 (1.0 to 159.0)
    30.0 (3.0 to 49.0)
    15.5 (1.0 to 106.5)
    24.0 (1.0 to 54.0)
        CD8-All doubles,Anti-HPV-16,Month 12(N=15;14;21;19
    1.0 (1.0 to 23.0)
    34.0 (1.0 to 79.0)
    23.0 (1.0 to 49.0)
    1.0 (1.0 to 24.0)
        CD8-All doubles,Anti-HPV-18,Month 12(N=15;14;21;19
    25.0 (1.0 to 92.0)
    1.0 (1.0 to 29.0)
    1.0 (1.0 to 37.0)
    1.0 (1.0 to 24.0)
        CD8-d-CD40L, Anti-HPV-16, Day 0 (N=17;15;17;18)
    1.0 (1.0 to 29.0)
    1.0 (1.0 to 6.0)
    1.0 (1.0 to 10.0)
    1.0 (1.0 to 7.0)
        CD8-d-CD40L, Anti-HPV-18, Day 0 (N=17;15;17;18)
    1.0 (1.0 to 29.0)
    1.0 (1.0 to 19.0)
    1.0 (1.0 to 33.0)
    1.0 (1.0 to 16.0)
        CD8-d-CD40L, Anti-HPV-16, Week 6 (N=16;14;16;18)
    1.0 (1.0 to 24.5)
    1.0 (1.0 to 32.0)
    1.0 (1.0 to 18.0)
    1.0 (1.0 to 1.0)
        CD8-d-CD40L, Anti-HPV-18, Week 6 (N=16;14;16;18)
    9.5 (1.0 to 27.5)
    1.0 (1.0 to 17.0)
    1.0 (1.0 to 23.0)
    1.0 (1.0 to 36.0)
        CD8-d-CD40L, Anti-HPV-16, Week 10 (N=14;14;19;18)
    18.5 (1.0 to 73.0)
    1.0 (1.0 to 29.0)
    1.0 (1.0 to 41.0)
    1.0 (1.0 to 27.0)
        CD8-d-CD40L, Anti-HPV-18, Week 10 (N=14;14;19;18)
    10.5 (1.0 to 34.0)
    2.5 (1.0 to 34.0)
    26.0 (1.0 to 72.0)
    1.0 (1.0 to 30.0)
        CD8-d-CD40L, Anti-HPV-16, Month 7 (N=13;14;16;17)
    26.0 (1.0 to 63.0)
    3.0 (1.0 to 20.0)
    2.0 (1.0 to 52.0)
    1.0 (1.0 to 36.0)
        CD8-d-CD40L, Anti-HPV-18, Month 7 (N=13;14;16;17)
    4.0 (1.0 to 42.0)
    15.0 (1.0 to 31.0)
    38.0 (1.0 to 92.0)
    4.0 (1.0 to 33.0)
        CD8-d-CD40L, Anti-HPV-16, Month 12 (N=15;14;21;19)
    1.0 (1.0 to 73.0)
    31.0 (7.0 to 39.0)
    3.0 (1.0 to 30.0)
    1.0 (1.0 to 24.0)
        CD8-d-CD40L, Anti-HPV-18, Month 12 (N=15;14;21;19)
    23.0 (1.0 to 59.0)
    1.0 (1.0 to 8.0)
    1.0 (1.0 to 39.0)
    1.0 (1.0 to 24.0)
        CD8-d-IFNG, Anti-HPV-16, Day 0 (N=17;15;17;18)
    1.0 (1.0 to 29.0)
    1.0 (1.0 to 43.0)
    1.0 (1.0 to 28.0)
    1.0 (1.0 to 2.0)
        CD8-d-IFNG, Anti-HPV-18, Day 0 (N=17;15;17;18)
    6.0 (1.0 to 33.0)
    19.0 (1.0 to 47.0)
    21.0 (1.0 to 54.0)
    4.0 (1.0 to 35.0)
        CD8-d-IFNG, Anti-HPV-16, Week 6 (N=16;14;16;18)
    2.5 (1.0 to 39.5)
    17.5 (1.0 to 78.0)
    1.0 (1.0 to 14.5)
    1.0 (1.0 to 11.0)
        CD8-d-IFNG, Anti-HPV-18, Week 6 (N=16;14;16;18)
    27.5 (1.0 to 55.5)
    1.0 (1.0 to 47.0)
    1.0 (1.0 to 42.5)
    35.5 (1.0 to 84.0)
        CD8-d-IFNG, Anti-HPV-16, Week 10 (N=14;14;19;18)
    34.0 (1.0 to 99.0)
    25.0 (1.0 to 30.0)
    1.0 (1.0 to 38.0)
    1.0 (1.0 to 29.0)
        CD8-d-IFNG, Anti-HPV-18, Week 10 (N=14;14;19;18)
    3.0 (1.0 to 68.0)
    7.5 (1.0 to 34.0)
    24.0 (1.0 to 76.0)
    1.0 (1.0 to 1.0)
        CD8-d-IFNG, Anti-HPV-16, Month 7 (N=13;14;16;17)
    46.0 (1.0 to 68.0)
    1.0 (1.0 to 26.0)
    1.0 (1.0 to 74.5)
    1.0 (1.0 to 50.0)
        CD8-d-IFNG, Anti-HPV-18, Month 7 (N=13;14;16;17)
    41.0 (1.0 to 68.0)
    21.0 (1.0 to 41.0)
    4.0 (1.0 to 90.5)
    3.0 (1.0 to 52.0)
        CD8-d-IFNG, Anti-HPV-16, Month 12 (N=15;14;21;19)
    1.0 (1.0 to 31.0)
    25.0 (1.0 to 57.0)
    1.0 (1.0 to 39.0)
    1.0 (1.0 to 24.0)
        CD8-d-IFNG, Anti-HPV-18, Month 12 (N=15;14;21;19)
    23.0 (1.0 to 92.0)
    1.0 (1.0 to 31.0)
    1.0 (1.0 to 7.0)
    1.0 (1.0 to 4.0)
        CD8-d-IL-2, Anti-HPV-16, Day 0 (N=17;15;17;18)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 16.0)
        CD8-d-IL-2, Anti-HPV-18, Day 0 (N=17;15;17;18)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
        CD8-d-IL-2, Anti-HPV-16, Week 6 (N=16;14;16;18)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
        CD8-d-IL-2, Anti-HPV-18, Week 6 (N=16;14;16;18)
    1.0 (1.0 to 23.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
        CD8-d-IL-2, Anti-HPV-16, Week 10 (N=14;14;19;18)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 32.0)
    1.0 (1.0 to 1.0)
        CD8-d-IL-2, Anti-HPV-18, Week 10 (N=14;14;19;18)
    1.0 (1.0 to 26.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 25.0)
    1.0 (1.0 to 1.0)
        CD8-d-IL-2, Anti-HPV-16, Month 7 (N=13;14;16;17)
    1.0 (1.0 to 23.0)
    1.0 (1.0 to 17.0)
    1.0 (1.0 to 37.5)
    1.0 (1.0 to 1.0)
        CD8-d-IL-2, Anti-HPV-18, Month 7 (N=13;14;16;17)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 29.0)
    1.0 (1.0 to 1.0)
        CD8-d-IL-2, Anti-HPV-16, Month 12 (N=15;14;21;19)
    1.0 (1.0 to 27.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
        CD8-d-IL-2, Anti-HPV-18, Month 12 (N=15;14;21;19)
    1.0 (1.0 to 48.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 19.0)
    1.0 (1.0 to 1.0)
        CD8-d-TNFA, Anti-HPV-16, Day 0 (N=17;15;17;18)
    1.0 (1.0 to 10.0)
    1.0 (1.0 to 35.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 29.0)
        CD8-d-TNFA, Anti-HPV-18, Day 0 (N=17;15;17;18)
    6.0 (1.0 to 50.0)
    7.0 (1.0 to 54.0)
    1.0 (1.0 to 33.0)
    1.0 (1.0 to 34.0)
        CD8-d-TNFA, Anti-HPV-16, Week 6 (N=16;14;16;18)
    1.0 (1.0 to 46.0)
    1.0 (1.0 to 35.0)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 31.0)
        CD8-d-TNFA, Anti-HPV-18, Week 6 (N=16;14;16;18)
    19.0 (1.0 to 50.0)
    1.0 (1.0 to 57.0)
    1.0 (1.0 to 28.0)
    1.0 (1.0 to 26.0)
        CD8-d-TNFA, Anti-HPV-16, Week 10 (N=14;14;19;18)
    1.5 (1.0 to 32.0)
    1.0 (1.0 to 24.0)
    1.0 (1.0 to 31.0)
    1.0 (1.0 to 26.0)
        CD8-d-TNFA, Anti-HPV-18, Week 10 (N=14;14;19;18)
    17.5 (1.0 to 34.0)
    14.0 (1.0 to 61.0)
    5.0 (1.0 to 42.0)
    1.0 (1.0 to 34.0)
        CD8-d-TNFA, Anti-HPV-16, Month 7 (N=13;14;16;17)
    34.0 (1.0 to 41.0)
    13.0 (1.0 to 33.0)
    1.0 (1.0 to 49.0)
    2.0 (1.0 to 33.0)
        CD8-d-TNFA, Anti-HPV-18, Month 7 (N=13;14;16;17)
    41.0 (1.0 to 111.0)
    26.5 (15.0 to 58.0)
    1.0 (1.0 to 58.0)
    1.0 (1.0 to 32.0)
        CD8-d-TNFA, Anti-HPV-16, Month 12 (N=15;14;21;19)
    1.0 (1.0 to 26.0)
    1.0 (1.0 to 54.0)
    28.0 (1.0 to 49.0)
    1.0 (1.0 to 42.0)
        CD8-d-TNFA, Anti-HPV-18, Month 12 (N=15;14;21;19)
    30.0 (24.0 to 62.0)
    1.0 (1.0 to 28.0)
    1.0 (1.0 to 48.0)
    1.0 (1.0 to 40.0)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Solicited local and general symptoms: During the 7-day follow-up period after vaccination; Unsolicited AEs: During the 30-day follow-up period after vaccination; SAEs: during the whole study period (from Day 0 up to Month 24).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    HIV+/Cervarix Group
    Reporting group description
    		 HIV seropositive female subjects, between and including 15 and 25 years of age, who received 3 doses of Cervarix vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6.

    Reporting group title
    HIV+/Gardasil Group
    Reporting group description
    		 HIV seropositive female subjects, between and including 15 and 25 years of age, who received 3 doses of Gardasil vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6.

    Reporting group title
    HIV-/Cervarix Group
    Reporting group description
    		 HIV seronegative female subjects, between and including 15 and 25 years of age, who received 3 doses of Cervarix vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6.

    Reporting group title
    HIV-/Gardasil Group
    Reporting group description
    		 HIV seronegative female subjects, between and including 15 and 25 years of age, who received 3 doses of Gardasil vaccine, administered intramuscularly in the deltoid muscle of the non-dominant arm, according to a three-dose schedule: at Day 0, Week 6, Month 6.

    Serious adverse events
    		 HIV+/Cervarix Group HIV+/Gardasil Group HIV-/Cervarix Group HIV-/Gardasil Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 129 (6.98%)
    9 / 128 (7.03%)
    4 / 144 (2.78%)
    1 / 145 (0.69%)
         number of deaths (all causes)
    0
    1
    0
    0
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Head injury
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vaccination complication
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abortion spontaneous complete
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Immune thrombocytopenic purpura
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastritis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Cervical dysplasia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Dissociative disorder
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningitis tuberculous
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Pneumonia mycoplasmal
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vaginitis gardnerella
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 HIV+/Cervarix Group HIV+/Gardasil Group HIV-/Cervarix Group HIV-/Gardasil Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    123 / 129 (95.35%)
    109 / 128 (85.16%)
    136 / 144 (94.44%)
    127 / 145 (87.59%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenoma benign
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    0
    0
    1
    Anogenital warts
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    General disorders and administration site conditions
    Administration site pruritus
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Administration site swelling
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Asthenia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Chest pain
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Discomfort
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Fatigue
         subjects affected / exposed
    73 / 129 (56.59%)
    59 / 128 (46.09%)
    65 / 144 (45.14%)
    56 / 145 (38.62%)
         occurrences all number
    128
    118
    111
    88
    Injection site erythema
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Injection site haematoma
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Injection site pain
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Injection site rash
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Malaise
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pain
         subjects affected / exposed
    121 / 129 (93.80%)
    85 / 128 (66.41%)
    133 / 144 (92.36%)
    119 / 145 (82.07%)
         occurrences all number
    303
    174
    329
    265
    Peripheral swelling
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pyrexia
         subjects affected / exposed
    24 / 129 (18.60%)
    20 / 128 (15.63%)
    23 / 144 (15.97%)
    25 / 145 (17.24%)
         occurrences all number
    32
    22
    31
    29
    Swelling
         subjects affected / exposed
    38 / 129 (29.46%)
    21 / 128 (16.41%)
    47 / 144 (32.64%)
    39 / 145 (26.90%)
         occurrences all number
    60
    28
    76
    60
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Reproductive system and breast disorders
    Breast mass
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dysmenorrhoea
         subjects affected / exposed
    3 / 129 (2.33%)
    1 / 128 (0.78%)
    4 / 144 (2.78%)
    2 / 145 (1.38%)
         occurrences all number
    3
    1
    5
    3
    Metrorrhagia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vaginal discharge
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Vulvovaginal pruritus
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Cough
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Epistaxis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Nasal congestion
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    0
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 128 (1.56%)
    2 / 144 (1.39%)
    0 / 145 (0.00%)
         occurrences all number
    1
    2
    2
    0
    Productive cough
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rhinitis allergic
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    3 / 129 (2.33%)
    1 / 128 (0.78%)
    1 / 144 (0.69%)
    1 / 145 (0.69%)
         occurrences all number
    3
    1
    1
    1
    Sneezing
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    0
    0
    1
    Depression
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    0
    0
    1
    Investigations
    Blood pressure increased
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cd4 lymphocytes decreased
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Viral load increased
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Injury, poisoning and procedural complications
    Burns second degree
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    0
    0
    1
    Ligament sprain
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Muscle strain
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    1
    0
    0
    1
    Nail injury
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    0
    0
    1
    Skin abrasion
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    0
    0
    1
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Tachycardia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    2 / 129 (1.55%)
    2 / 128 (1.56%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    2
    2
    0
    0
    Formication
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Headache
         subjects affected / exposed
    88 / 129 (68.22%)
    63 / 128 (49.22%)
    70 / 144 (48.61%)
    67 / 145 (46.21%)
         occurrences all number
    165
    116
    115
    104
    Hypoaesthesia
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Presyncope
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Somnolence
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Tremor
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 129 (1.55%)
    3 / 128 (2.34%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    2
    3
    0
    1
    Lymphadenopathy
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Polycythaemia
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Ear and labyrinth disorders
    Cerumen impaction
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    0
    0
    1
    Ear pain
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vertigo
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Eye disorders
    Blindness
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dental caries
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 144 (0.69%)
    1 / 145 (0.69%)
         occurrences all number
    0
    1
    1
    2
    Dyspepsia
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 144 (0.69%)
    1 / 145 (0.69%)
         occurrences all number
    0
    0
    1
    1
    Food poisoning
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastritis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    0
    0
    1
    Gastrointestinal disorder
         subjects affected / exposed
    41 / 129 (31.78%)
    35 / 128 (27.34%)
    28 / 144 (19.44%)
    26 / 145 (17.93%)
         occurrences all number
    58
    55
    35
    38
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    0
    0
    1
    Tooth impacted
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Toothache
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    1
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    2
    0
    1
    Eczema
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Erythema
         subjects affected / exposed
    41 / 129 (31.78%)
    34 / 128 (26.56%)
    52 / 144 (36.11%)
    42 / 145 (28.97%)
         occurrences all number
    59
    50
    89
    69
    Miliaria
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pruritus
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Rash
         subjects affected / exposed
    11 / 129 (8.53%)
    5 / 128 (3.91%)
    5 / 144 (3.47%)
    8 / 145 (5.52%)
         occurrences all number
    11
    6
    6
    10
    Rash papular
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Skin discolouration
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin hyperpigmentation
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Urticaria
         subjects affected / exposed
    14 / 129 (10.85%)
    9 / 128 (7.03%)
    4 / 144 (2.78%)
    6 / 145 (4.14%)
         occurrences all number
    17
    11
    6
    7
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    2
    0
    0
    1
    Nephrolithiasis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    0
    0
    1
    Ureterolithiasis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    41 / 129 (31.78%)
    38 / 128 (29.69%)
    31 / 144 (21.53%)
    34 / 145 (23.45%)
         occurrences all number
    64
    56
    40
    47
    Musculoskeletal pain
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Myalgia
         subjects affected / exposed
    68 / 129 (52.71%)
    51 / 128 (39.84%)
    64 / 144 (44.44%)
    54 / 145 (37.24%)
         occurrences all number
    115
    81
    106
    91
    Neck pain
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pain in extremity
         subjects affected / exposed
    0 / 129 (0.00%)
    2 / 128 (1.56%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Tendonitis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    0
    0
    1
    Torticollis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Infections and infestations
    Abscess limb
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    0
    0
    1
    Acarodermatitis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    0
    0
    1
    Bacterial vaginosis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Bartholinitis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    0
    0
    1
    Body tinea
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cervicitis gonococcal
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Conjunctivitis
         subjects affected / exposed
    1 / 129 (0.78%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Cystitis
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    0
    0
    1
    Dermatophytosis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Furuncle
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hepatitis c
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Herpes zoster
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hordeolum
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    0
    0
    1
    Influenza
         subjects affected / exposed
    2 / 129 (1.55%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    2 / 145 (1.38%)
         occurrences all number
    2
    1
    0
    3
    Nasopharyngitis
         subjects affected / exposed
    2 / 129 (1.55%)
    4 / 128 (3.13%)
    2 / 144 (1.39%)
    6 / 145 (4.14%)
         occurrences all number
    4
    5
    3
    7
    Oral herpes
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Otitis media acute
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    1 / 145 (0.69%)
         occurrences all number
    0
    1
    0
    1
    Pharyngitis
         subjects affected / exposed
    1 / 129 (0.78%)
    2 / 128 (1.56%)
    1 / 144 (0.69%)
    2 / 145 (1.38%)
         occurrences all number
    1
    3
    1
    2
    Sinusitis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    1 / 144 (0.69%)
    2 / 145 (1.38%)
         occurrences all number
    1
    0
    1
    3
    Skin infection
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Tonsillitis
         subjects affected / exposed
    2 / 129 (1.55%)
    0 / 128 (0.00%)
    2 / 144 (1.39%)
    0 / 145 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Tooth abscess
         subjects affected / exposed
    0 / 129 (0.00%)
    0 / 128 (0.00%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 129 (2.33%)
    3 / 128 (2.34%)
    2 / 144 (1.39%)
    4 / 145 (2.76%)
         occurrences all number
    3
    3
    2
    5
    Urethritis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vaginal infection
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Varicella
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 144 (0.69%)
    1 / 145 (0.69%)
         occurrences all number
    0
    1
    1
    1
    Viral pharyngitis
         subjects affected / exposed
    0 / 129 (0.00%)
    1 / 128 (0.78%)
    1 / 144 (0.69%)
    0 / 145 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Vulvovaginal candidiasis
         subjects affected / exposed
    1 / 129 (0.78%)
    0 / 128 (0.00%)
    0 / 144 (0.00%)
    0 / 145 (0.00%)
         occurrences all number
    1
    0
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Apr 2010
    The main reason for amending this protocol was that, since the last revision of the WHO guidelines in 2006, new and compelling evidence has become available concerning the start of antiretroviral therapy (ART) in HIV-infected adults and adolescents. Subjects who have a CD4 count ≤ 350 cells/mm3 should be treated irrespective of their clinical stage [WHO, 2009]. - Some clarifications have been made to the flowchart, weight and ARV therapy (if applicable) would be recorded at each visit. Also, a history-directed physical examination will be performed at each visit. - Section 6.2 (Storage and handling of study vaccines) has been modified in order to align the wording with the new version of SOP-BIO-CLIN-7055 v04 entitled “Management of the Cold Chain for GlaxoSmithKline Biologicals investigational human subject research” effective since 31 March 2010. - Facsimile numbers for prompting SAEs to GSK Biologicals have been updated as well as the phone numbers in case of emergency unblinding. - Minor corrections such as inconsistencies, formatting and typos have been made.
    23 Dec 2010
    Protocol Amendment 2 was developed to: - Implement reporting of potential immune-mediated diseases (pIMDs). Due to their potent immune stimulating effect, there are theoretical concerns that modern adjuvants like GSK Biologicals' novel adjuvant systems might result in undesirable effects on the body's immune system, which could include onset of new or exacerbation of underlying autoimmune diseases in particular. Accordingly, a heightened surveillance on the occurrence of any such conditions in recipients of novel adjuvant containing vaccines in clinical trials has been put in place by GSK. - Add two additional HIV tests at Month 7 and Month 24 for HIV negative subjects. - Update the formulation of the HPV-16/18 L1 VLP AS04 vaccine. - Update the list of contributing authors. - Make minor modifications/ clarifications to the protocol.
    23 May 2011
    This amendment was issued to clarify that for HIV+ subjects whose HIV status is documented, the HIV Rapid test does not need to be repeated. - As recommended by the study IDMC, exploratory analyses have been included to evaluate the immunogenicity of the study vaccines in HIV+ subjects stratified by HIV mode of transmission and by nadir CD4 cell count category. - The introduction has been updated with the current licensure status and indication of Cervarix and Gardasil. - Minor corrections such as formatting and typos have been made.
    04 Oct 2011
    Per protocol, assessment of primary objectives for non-inferiority/superiority were planned to be performed on the ATP cohort for immunogenicity in initially seronegative (S-) subjects. In the HPV-020 study, there was a high baseline seropositivity (S+) rate in both HIV + and HIV – subjects (50-80%). As this can also be expected in the HPV-019 study, many subjects will be eliminated from the primary endpoint analysis and this objective might not be met due to a low sample size. Therefore, the HPV-019 protocol was amended to analyse the primary endpoints regardless of initial HPV serostatus. The text in Section 10.3 (sample size estimation) was reworded accordingly.
    20 Mar 2012
    Amendment 5 for the HPV-019 PRI protocol was developed in order to: - Revise the length of interval between the study visits 4 and 5, by allowing subjects to be considered for ATP analyses even if the first four visits occur at the maximum permissible interval for each visit. - Furthermore, since the primary endpoint is evaluated 1 month after administration of the third dose of vaccine, the recommended interval between Visit 4 and Visit 5 has been modified to 30 days. - Update the list of contributing authors.
    06 Jun 2012
    The protocol was amended for the following reason: At the European Medicines Agency’s (EMA) request, GSK Biologicals has updated its procedure for emergency unblinding during the conduct of a clinical study. According to the revised procedure, the responsibility and the decision to break the treatment code in emergency situations resides solely with the investigator and consequently, the investigator would have full authority to break the treatment code.
    19 Dec 2013
    The HPV-019 protocol was amended for the following reasons: - Due to high rate of non evaluable subjects, (data integrity issue at one site; protocol non compliance; high drop out rate) additional subjects would be enrolled in this study, in order to maintain the statistical power for analysis. - The IgG ELISA assay will be replaced by IgG nephelometry assay to measure total IgG in the serum matrix, because the assay output of nephelometry was proven less variable than that of ELISA. This change in the assay will be implemented for the testing of serum samples for all time points. - The assay used to measure anti-HPV-16/-18 antibody concentrations at the designated laboratory was improved to increase the assay precision by changing the assay cut-off value from 8 EL.U/mL to 19 EL.U/mL for HPV-16 and from 7 EL.U/mL to 18 EL.U/mL for HPV-18. This change in the assay would be implemented for the testing of samples for all time points. - Other small changes were made in order to accommodate the recruitment of subjects from another country, to clarify that some activities in the protocol are mandatory only for HIV+ subjects (this reflects what is actually done in the study procedures and is in line with the study procedures manual) and to clarify the blinding strategy for analysis.
    26 Apr 2016
    The protocol was amended to align the section of the protocol on management of HIV+ subjects with the recently revised WHO guidelines on when to start antiretroviral therapy (ART) in HIV+ subjects. The revision of the WHO guidelines presented evidence that earlier use of ART results in better long-term clinical outcomes for people living with HIV compared with delayed treatment, including pregnant and breastfeeding women. This guideline advises to start ART in all adults with HIV regardless of their clinical stage and at any CD4 cell count. At the time of implementation of the protocol amendment, the vaccination phase had already completed, and therefore the exclusion criterion for subsequent vaccination after initiation of ART during the course of the study was not revised.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Thu Apr 25 03:11:55 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA