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    Clinical Trial Results:
    A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Tenofovir DF as Part of an Optimized Antiretroviral Regimen in HIV-1-Infected Adolescents

    Summary
    EudraCT number
    		 2015-000727-85
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    19 Dec 2013

    Results information
    Results version number
    		 v1(current)
    This version publication date
    22 Mar 2016
    First version publication date
    05 Aug 2015
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GS-US-104-0321
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00352053
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Gilead Sciences
    Sponsor organisation address
    333 Lakeside Drive, Foster City, CA, United States, 94404
    Public contact
    Clinical Trial Mailbox, Gilead Sciences International Ltd , ClinicalTrialDisclosures@gilead.com
    Scientific contact
    Clinical Trial Mailbox, Gilead Sciences International Ltd , ClinicalTrialDisclosures@gilead.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000533-PIP01-08
    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 Dec 2013
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Dec 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study is to assess the safety and efficacy of tenofovir disoproxil fumarate (tenofovir DF; TDF) plus a genotype-guided optimized background regimen (OBR) compared to placebo plus OBR in the treatment of human immunodeficiency virus type 1 (HIV-1) infected antiretroviral treatment-experienced adolescents with plasma HIV-1 ribonucleic acid (RNA) levels greater than or equal to 1000 copies/mL.
    Protection of trial subjects
    The protocol and consent/assent forms were submitted by each investigator to a duly constituted Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for review and approval before study initiation. All revisions to the consent/assent forms (if applicable) after initial IEC/IRB approval were submitted by the investigator to the IEC/IRB for review and approval before implementation in accordance with regulatory requirements. This study was conducted in accordance with recognized international scientific and ethical standards, including but not limited to the International Conference on Harmonization guideline for Good Clinical Practice (ICH GCP) and the original principles embodied in the Declaration of Helsinki.
    Background therapy
    		 All participants received a genotype-guided optimized background regimen (OBR) consisting of a minimum of 3 and a maximum of 5 antiretroviral agents (ARV) for the duration of the study.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Jun 2006
    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: 86
    Country: Number of subjects enrolled
    Panama: 4
    Worldwide total number of subjects
    90
    EEA total number of subjects
    0
    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)
    90
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 There were 17 sites in Brazil and 1 site in Panama. First participant was screened on 13 June 2006. The last study visit occurred on 19 December 2013.

    Pre-assignment
    Screening details
    		 123 participants were screened.

    Period 1
    Period 1 title
    Randomized Phase (Through Week 48)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    Participants were randomized to either TDF or placebo, plus a genotype-guided optimized background regimen (OBR) consisting of 3 minimum (min.) to 5 maximum (max.) antiretroviral (ARV) agents. Participants in the TDF group who experienced virologic failure (VF) during the randomized phase discontinued the study. Participants in the placebo group who experienced VF discontinued the randomized phase, and were eligible to enroll early in the first open-label TDF extension phase.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Tenofovir DF
    Arm description
    		 TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tenofovir DF
    Investigational medicinal product code
    Other name
    Viread®, TDF
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tenofovir DF 300 mg tablet administered orally once daily

    Arm title
    		 Placebo
    Arm description
    		 Placebo to match TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tenofovir DF Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo to match tenofovir DF 300 administered orally once daily

    Number of subjects in period 1 [1]
    		Tenofovir DF Placebo
    Started
    45
    42
    Switched to open-label TDF after VF
    0 [2]
    10 [3]
    Completed
    27
    36
    Not completed
    18
    6
         Physician decision
    2
    4
         Virologic failure
    14
    -
         Adverse event, non-fatal
    1
    -
         Intolerance to Antiretroviral Regimen
    1
    -
         Withdrawal by subject
    -
    2
    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: 3 participants who were enrolled but not treated are not included in the subject disposition table.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: No participants randomized to TDF who discontinued the double-blind phase due to VF were enrolled in the 1st open-label extension phase.
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: 10 participants randomized to placebo experienced VF, discontinued the double-blind phase, and enrolled early in the 1st open-label TDF extension phase.
    Period 2
    Period 2 title
    First Extension Phase (Weeks 48-144)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Tenofovir DF
    Arm description
    		 TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tenofovir DF
    Investigational medicinal product code
    Other name
    Viread®, TDF
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tenofovir DF 300 mg tablet administered orally once daily

    Arm title
    		 Placebo
    Arm description
    		 Placebo to match TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tenofovir DF
    Investigational medicinal product code
    Other name
    Viread®, TDF
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tenofovir DF 300 mg tablet administered orally once daily

    Number of subjects in period 2 [4]
    		Tenofovir DF Placebo
    Started
    24
    36
    Completed
    12
    19
    Not completed
    12
    17
         Physician decision
    9
    13
         Pregnancy
    1
    -
         Lost to follow-up
    1
    -
         Lack of efficacy
    1
    4
    Notes
    [4] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: 3 participants in the Tenofovir DF Group who completed the Randomized Phase did not continue in the First Extension Phase.
    Period 3
    Period 3 title
    Second Extension Phase (Weeks 144-240)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Tenofovir DF
    Arm description
    		 TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tenofovir DF
    Investigational medicinal product code
    Other name
    Viread®, TDF
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tenofovir DF 300 mg tablet administered orally once daily

    Arm title
    		 Placebo
    Arm description
    		 Placebo to match TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tenofovir DF
    Investigational medicinal product code
    Other name
    Viread®, TDF
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tenofovir DF 300 mg tablet administered orally once daily

    Number of subjects in period 3 [5]
    		Tenofovir DF Placebo
    Started
    9
    14
    Completed
    4
    9
    Not completed
    5
    5
         Physician decision
    4
    4
         Withdrawal by subject
    1
    1
    Notes
    [5] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: 3 participants in the Tenofovir DF Group and 5 participants in the Placebo Group who completed the First Extension Phase did not continue in the Second Extension Phase.
    Period 4
    Period 4 title
    Third Extension Phase (Weeks 240-294)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Tenofovir DF
    Arm description
    		 TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tenofovir DF
    Investigational medicinal product code
    Other name
    Viread®, TDF
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tenofovir DF 300 mg tablet administered orally once daily

    Arm title
    		 Placebo
    Arm description
    		 Placebo to match TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tenofovir DF
    Investigational medicinal product code
    Other name
    Viread®, TDF
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Tenofovir DF 300 mg tablet administered orally once daily

    Number of subjects in period 4 [6]
    		Tenofovir DF Placebo
    Started
    1
    4
    Completed
    0
    2
    Not completed
    1
    2
         Lack of efficacy
    1
    1
         Withdrawal by subject
    -
    1
    Notes
    [6] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: 3 participants in the Tenofovir DF Group and 5 participants in the Placebo Group who completed the Second Extension Phase did not continue in the Third Extension Phase.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Tenofovir DF
    Reporting group description
    		 TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo to match TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.

    Reporting group values
    		 Tenofovir DF Placebo Total
    Number of subjects
    		 45 42 87
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 14 ± 1.5 14 ± 1.5 -
    Gender categorical
    Units: Subjects
        Female
    		 24 25 49
        Male
    		 21 17 38
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 45 42 87
        Not Hispanic or Latino
    		 0 0 0
        Unknown or Not Reported
    		 0 0 0
    Race
    Units: Subjects
        White
    		 23 22 45
        Black or African Heritage
    		 14 11 25
        Mulatto
    		 4 4 8
        Mixed Race
    		 1 2 3
        Indian Descendant
    		 1 1 2
        Mestizo
    		 0 2 2
        Black and White Race
    		 1 0 1
        South American Indian
    		 1 0 1
    Body Mass Index
    Units: kg/m^2
        arithmetic mean (standard deviation)
    		 18.72 ± 2.304 19.99 ± 3.238 -
    CD4 Cell Count
    Units: cells/mm^3
        arithmetic mean (standard deviation)
    		 390 ± 244 357 ± 200.8 -
    CD4 Percentage
    CD4 percentage is the percentage of total lymphocytes that are CD4 cells.
    Units: Percentage of CD4 lymphocytes
        arithmetic mean (standard deviation)
    		 17.8 ± 9.7 17.6 ± 8.31 -
    Height
    Units: cm
        arithmetic mean (standard deviation)
    		 155.84 ± 10.071 156.05 ± 8.569 -
    Human Immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA)
    Units: log10 copies/mL
        arithmetic mean (standard deviation)
    		 4.71 ± 0.723 4.56 ± 0.746 -
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    		 45.84 ± 9.639 49.09 ± 11.342 -

    End points

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    End points reporting groups
    Reporting group title
    Tenofovir DF
    Reporting group description
    		 TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo to match TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.
    Reporting group title
    Tenofovir DF
    Reporting group description
    		 TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo to match TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.
    Reporting group title
    Tenofovir DF
    Reporting group description
    		 TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo to match TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.
    Reporting group title
    Tenofovir DF
    Reporting group description
    		 TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo to match TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.

    Subject analysis set title
    Placebo/TDF, HIV-1 RNA < 1000 Copies/mL
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA < 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.

    Subject analysis set title
    Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Participants who were randomized to placebo and switched to open-label TDF 300 mg tablets (plus OBR) with HIV-1 RNA ≥ 1000 copies/mL at the time of the switch when a new baseline was established. The analysis time point is calculated as the number of weeks after the switch.

    Primary: Time-weighted average change from baseline through Week 24 (DAVG24) in plasma HIV-1 RNA

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    End point title
    		 Time-weighted average change from baseline through Week 24 (DAVG24) in plasma HIV-1 RNA
    End point description
    DAVG24 was defined as the time-weighted average between the first postbaseline value through the last value up to Week 24 minus the baseline value. DAVG24 was calculated using the trapezoidal rule with all available postbaseline data minus the baseline value. Data for participants who discontinued the randomized (double-blind) phase of the study early were included up until the point of study discontinuation (missing data not imputed). For the TDF and Placebo groups, only data collected during the double-blind phase are included. Intent-to-treat (ITT) Analysis Set: participants who were randomized and received at least 1 dose of study drug, with baseline HIV-1 RNA ≥ 1000 copies/mL and who had no major eligibility criteria violations.
    End point type
    Primary
    End point timeframe
    Baseline to 24 Weeks
    End point values
    		 Tenofovir DF Placebo
    Number of subjects analysed
    44
    41
    Units: log10 copies/mL
        median (inter-quartile range (Q1-Q3))
    -1.58 (-2.15 to -0.27)
    -1.549 (-2.36 to -0.34)
    Statistical analysis title
    		 Difference in change from baseline
    Statistical analysis description
    Null hypothesis: Time-weighted average changes from baseline through Week 24 in plasma HIV-1 RNA for the tenofovir DF and placebo groups are equal. Alternative hypothesis: Time-weighted average changes from baseline through Week 24 in plasma HIV-1 RNA for the tenofovir DF and placebo groups are different (two-sided).
    Comparison groups
    Tenofovir DF v Placebo
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 other [1]
    P-value
    		 = 0.55 [2]
    Method
    		 Van Elteren test
    Confidence interval
    Notes
    [1] - Intergroup analysis
    [2] - No adjustments for multiple comparisons were made. P-value is from a Van Elteren test stratified by baseline genotypic sensitivity score (GSS) (without tenofovir DF) <= or > median (median GSS is 2).

    Secondary: Time-weighted average change from baseline through Week 48 (DAVG48) in plasma HIV-1 RNA

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    End point title
    		 Time-weighted average change from baseline through Week 48 (DAVG48) in plasma HIV-1 RNA
    End point description
    DAVG48 was defined as the time-weighted average between the first postbaseline value through the last value up to Week 48 minus the baseline value. DAVG48 was calculated using the trapezoidal rule with all available postbaseline data minus the baseline value. Data for participants who discontinued the double-blind phase of the study early were included up until the point of discontinuation from the study (ie, missing data were not imputed). For the TDF and Placebo groups, only data collected during the double-blind phase are included. ITT Analysis Set
    End point type
    Secondary
    End point timeframe
    Baseline to 48 weeks
    End point values
    		 Tenofovir DF Placebo
    Number of subjects analysed
    44
    41
    Units: log10 copies/mL
        median (inter-quartile range (Q1-Q3))
    -1.423 (-2.25 to -0.25)
    -1.352 (-2.72 to -0.53)
    Statistical analysis title
    		 Difference in change from baseline
    Statistical analysis description
    Null hypothesis: Time-weighted average changes from baseline through Week 48 in plasma HIV-1 RNA for the tenofovir DF and placebo groups are equal. Alternative hypothesis: Time-weighted average changes from baseline through Week 48 in plasma HIV-1 RNA for the tenofovir DF and placebo groups are different (two-sided).
    Comparison groups
    Tenofovir DF v Placebo
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 other [3]
    P-value
    		 = 0.4 [4]
    Method
    		 Van Elteren test
    Confidence interval
    Notes
    [3] - Intergroup analysis
    [4] - No adjustments for multiple comparisons were made. P-value is from a Van Elteren test stratified by baseline GSS (without tenofovir DF) <= or > median (median GSS is 2).

    Secondary: Change from baseline to Week 24 in HIV-1 RNA

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    End point title
    		 Change from baseline to Week 24 in HIV-1 RNA
    End point description
    ITT Analysis Set. The Tenofovir DF and Placebo groups were analyzed using the last observation carried forward (LOCF) method (includes the participant's last available postbaseline value for missing data). The Placebo/TDF groups were analyzed using the missing = excluded method (participants with missing data were excluded from the analysis). For the TDF and Placebo groups, only data collected during the double-blind phase are included.
    End point type
    Secondary
    End point timeframe
    Baseline to 24 weeks
    End point values
    		 Tenofovir DF Placebo Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    44
    41
    18
    16
    Units: log10 copies/mL
        median (inter-quartile range (Q1-Q3))
    -1.23 (-2.3 to -0.1)
    -1.27 (-2.8 to -0.1)
    0 (0 to 0)
    -0.1 (-0.6 to 0.3)
    Statistical analysis title
    		 Difference in change from baseline
    Statistical analysis description
    Null hypothesis: Changes from baseline through Week 24 in plasma HIV-1 RNA for the tenofovir DF and placebo groups are equal. Alternative hypothesis: Changes from baseline through Week 24 in plasma HIV-1 RNA for the tenofovir DF and placebo groups are different (two-sided).
    Comparison groups
    Tenofovir DF v Placebo
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 other [5]
    P-value
    		 = 0.58 [6]
    Method
    		 Van Elteren test
    Confidence interval
    Notes
    [5] - Intergroup analysis
    [6] - No adjustments for multiple comparisons were made. P-value is from a Van Elteren test stratified by baseline GSS (without tenofovir DF) <= or > median (median GSS is 2).

    Secondary: Change from baseline to Week 48 in HIV-1 RNA

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    End point title
    		 Change from baseline to Week 48 in HIV-1 RNA
    End point description
    ITT Analysis Set. The Tenofovir DF and Placebo groups were analyzed using the LOCF method. The Placebo/TDF groups were analyzed using the missing = excluded method. For the TDF and Placebo groups, only data collected during the double-blind phase are included.
    End point type
    Secondary
    End point timeframe
    Baseline to 48 weeks
    End point values
    		 Tenofovir DF Placebo Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    44
    41
    18
    8
    Units: log10 copies/mL
        median (inter-quartile range (Q1-Q3))
    -0.97 (-2.3 to 0)
    -1.53 (-3 to 0)
    0 (0 to 0.6)
    0.2 (-0.1 to 0.5)
    Statistical analysis title
    		 Difference in change from baseline
    Statistical analysis description
    Null hypothesis: Changes from baseline through Week 48 in plasma HIV-1 RNA for the tenofovir DF and placebo groups are equal. Alternative hypothesis: Changes from baseline through Week 48 in plasma HIV-1 RNA for the tenofovir DF and placebo groups are different (two-sided).
    Comparison groups
    Placebo v Tenofovir DF
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 other [7]
    P-value
    		 = 0.37 [8]
    Method
    		 Van Elteren test
    Confidence interval
    Notes
    [7] - Intergroup analysis
    [8] - No adjustments for multiple comparisons were made. P-value is from a Van Elteren test stratified by baseline GSS (without tenofovir DF) <= or > median (median GSS is 2).

    Secondary: Change from Baseline to Week 96 in HIV-1 RNA

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    End point title
    		 Change from Baseline to Week 96 in HIV-1 RNA [9]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Baseline to 96 weeks
    Notes
    [9] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    19
    17
    3
    Units: log10 copies/mL
        median (inter-quartile range (Q1-Q3))
    -2.1 (-2.5 to -0.6)
    0 (0 to 0.9)
    0.1 (-1.4 to 0.8)
    No statistical analyses for this end point

    Secondary: Change from baseline to Week 144 in HIV-1 RNA

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    End point title
    		 Change from baseline to Week 144 in HIV-1 RNA [10]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Baseline to 144 weeks
    Notes
    [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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    10
    11
    2
    Units: log10 copies/mL
        median (inter-quartile range (Q1-Q3))
    -2.5 (-2.7 to -2.2)
    0.2 (0 to 1.6)
    0.7 (0.6 to 0.8)
    No statistical analyses for this end point

    Secondary: Change From Baseline to Week 192 in HIV-1 RNA

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    End point title
    		 Change From Baseline to Week 192 in HIV-1 RNA [11]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Baseline to 192 weeks
    Notes
    [11] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    7
    5
    2
    Units: log10 copies/mL
        median (inter-quartile range (Q1-Q3))
    -2 (-2.5 to -0.7)
    0 (0 to 0.2)
    -0.1 (-1.4 to 1.3)
    No statistical analyses for this end point

    Secondary: Change from baseline to Week 240 in HIV-1 RNA

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    End point title
    		 Change from baseline to Week 240 in HIV-1 RNA [12]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Baseline to 240 weeks
    Notes
    [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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    4
    2
    1
    Units: log10 copies/mL
        median (inter-quartile range (Q1-Q3))
    -2.5 (-2.6 to -2.2)
    -0.4 (-0.8 to 0)
    -1.4 (-1.4 to -1.4)
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 288 in HIV-1 RNA

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    End point title
    		 Change from Baseline to Week 288 in HIV-1 RNA [13]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Baseline to 288 weeks
    Notes
    [13] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    1
    1
    1
    Units: log10 copies/mL
        median (inter-quartile range (Q1-Q3))
    -1.1 (-1.1 to -1.1)
    -0.8 (-0.8 to -0.8)
    0.6 (0.6 to 0.6)
    No statistical analyses for this end point

    Secondary: Change from baseline to Week 336 in HIV-1 RNA

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    End point title
    		 Change from baseline to Week 336 in HIV-1 RNA [14]
    End point description
    ITT Analysis Set, missing = excluded method No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.
    End point type
    Secondary
    End point timeframe
    Baseline to 336 weeks
    Notes
    [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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    0 [15]
    0 [16]
    0 [17]
    Units: log10 copies/mL
        median (inter-quartile range (Q1-Q3))
    ( to )
    ( to )
    ( to )
    Notes
    [15] - No analysis was performed because the study ended early after Week 294.
    [16] - No analysis was performed because the study ended early after Week 294.
    [17] - No analysis was performed because the study ended early after Week 294.
    No statistical analyses for this end point

    Secondary: Change from baseline to Week 24 in Cluster Determinant 4 (CD4) count

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    End point title
    		 Change from baseline to Week 24 in Cluster Determinant 4 (CD4) count
    End point description
    ITT Analysis Set, missing = excluded method For the TDF and Placebo groups, only data collected during the double-blind phase are included.
    End point type
    Secondary
    End point timeframe
    Baseline to 24 weeks
    End point values
    		 Tenofovir DF Placebo Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    42
    41
    18
    16
    Units: cells/mm3
        median (inter-quartile range (Q1-Q3))
    69 (-26 to 172)
    49 (-3 to 156)
    -43 (-181 to 53)
    -12 (-48 to 59)
    Statistical analysis title
    		 Difference in change from baseline
    Statistical analysis description
    Null hypothesis: Changes from baseline through Week 24 in plasma CD4 count for the tenofovir DF and placebo groups are equal. Alternative hypothesis: Changes from baseline through Week 24 in CD4 count for the tenofovir DF and placebo groups are different (two-sided).
    Comparison groups
    Tenofovir DF v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 other [18]
    P-value
    		 = 0.71 [19]
    Method
    		 Van Elteren test
    Confidence interval
    Notes
    [18] - Intergroup analysis
    [19] - No adjustments for multiple comparisons were made. P-value is from a Van Elteren test stratified by baseline GSS (without tenofovir DF) <= or > median (median GSS is 2).

    Secondary: Change from baseline to Week 48 in CD4 count

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    End point title
    		 Change from baseline to Week 48 in CD4 count
    End point description
    ITT Analysis Set, missing = excluded method For the TDF and Placebo groups, only data collected during the double-blind phase are included.
    End point type
    Secondary
    End point timeframe
    Baseline to 48 weeks
    End point values
    		 Tenofovir DF Placebo Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    32
    31
    17
    11
    Units: cells/mm3
        median (inter-quartile range (Q1-Q3))
    152 (-4 to 241)
    148 (42 to 289)
    15 (-69 to 95)
    -47 (-83 to 67)
    Statistical analysis title
    		 Difference in change from baseline
    Statistical analysis description
    Null hypothesis: Changes from baseline through Week 48 in plasma CD4 count for the tenofovir DF and placebo groups are equal. Alternative hypothesis: Changes from baseline through Week 48 in CD4 count for the tenofovir DF and placebo groups are different (two-sided).
    Comparison groups
    Tenofovir DF v Placebo
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 other [20]
    P-value
    		 = 0.47 [21]
    Method
    		 Van Elteren test
    Confidence interval
    Notes
    [20] - Intergroup analysis
    [21] - No adjustments for multiple comparisons were made. P-value is from a Van Elteren test stratified by baseline GSS (without tenofovir DF) <= or > median (median GSS is 2).

    Secondary: Change from baseline to Week 96 in CD4 count

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    End point title
    		 Change from baseline to Week 96 in CD4 count [22]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Baseline to 96 weeks
    Notes
    [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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    20
    17
    3
    Units: cells/mm3
        median (inter-quartile range (Q1-Q3))
    152 (52 to 266)
    -6 (-96 to 85)
    -69 (-75 to 278)
    No statistical analyses for this end point

    Secondary: Change from baseline to Week 144 in CD4 count

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    End point title
    		 Change from baseline to Week 144 in CD4 count [23]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Baseline to 144 weeks
    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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    12
    11
    2
    Units: cells/mm^3
        median (inter-quartile range (Q1-Q3))
    188 (53 to 361)
    -88 (-165 to 93)
    33 (-109 to 174)
    No statistical analyses for this end point

    Secondary: Change from baseline to Week 192 in CD4 count

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    End point title
    		 Change from baseline to Week 192 in CD4 count [24]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Baseline to 192 weeks
    Notes
    [24] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    7
    6
    2
    Units: cells/mm^3
        median (inter-quartile range (Q1-Q3))
    166 (-82 to 333)
    -70 (-155 to 220)
    -23 (-46 to 1)
    No statistical analyses for this end point

    Secondary: Change from baseline to Week 240 in CD4 count

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    End point title
    		 Change from baseline to Week 240 in CD4 count [25]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Baseline to 240 weeks
    Notes
    [25] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    5
    2
    1
    Units: cells/mm^3
        median (inter-quartile range (Q1-Q3))
    221 (59 to 368)
    571 (-13 to 1155)
    258 (258 to 258)
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 288 in CD4 Count

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    End point title
    		 Change from Baseline to Week 288 in CD4 Count [26]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Baseline to 288 weeks
    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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    1
    1
    1
    Units: cells/mm^3
        median (inter-quartile range (Q1-Q3))
    310 (310 to 310)
    100 (100 to 100)
    309 (309 to 309)
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 336 in CD4 Count

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    End point title
    		 Change from Baseline to Week 336 in CD4 Count [27]
    End point description
    ITT Analysis Set, missing = excluded method No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.
    End point type
    Secondary
    End point timeframe
    Baseline to 336 weeks
    Notes
    [27] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    0 [28]
    0 [29]
    0 [30]
    Units: cells/mm^3
        median (inter-quartile range (Q1-Q3))
    ( to )
    ( to )
    ( to )
    Notes
    [28] - No analysis was performed because the study ended early after Week 294.
    [29] - No analysis was performed because the study ended early after Week 294.
    [30] - No analysis was performed because the study ended early after Week 294.
    No statistical analyses for this end point

    Secondary: Change from baseline to Week 24 in CD4 Percentage

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    End point title
    		 Change from baseline to Week 24 in CD4 Percentage
    End point description
    ITT Analysis Set, missing = excluded method CD4 percentage is the percentage of total lymphocytes that are CD4 cells. For the TDF and Placebo groups, only data collected during the double-blind phase are included.
    End point type
    Secondary
    End point timeframe
    Baseline to 24 weeks
    End point values
    		 Tenofovir DF Placebo Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    42
    41
    18
    16
    Units: Percentage of CD4 lymphocytes
        median (inter-quartile range (Q1-Q3))
    3 (0 to 6)
    2 (-1 to 4)
    0 (-3 to 3)
    -1 (-3 to 2)
    Statistical analysis title
    		 Difference in change from baseline
    Statistical analysis description
    Null hypothesis: Changes from baseline through Week 24 in plasma CD4% for the tenofovir DF and placebo groups are equal. Alternative hypothesis: Changes from baseline through Week 24 in CD4% for the tenofovir DF and placebo groups are different (two-sided).
    Comparison groups
    Tenofovir DF v Placebo
    Number of subjects included in analysis
    83
    Analysis specification
    Pre-specified
    Analysis type
    		 other [31]
    P-value
    		 = 0.26 [32]
    Method
    		 Van Elteren test
    Confidence interval
    Notes
    [31] - Intergroup analysis
    [32] - No adjustments for multiple comparisons were made. P-value is from a Van Elteren test stratified by baseline GSS (without tenofovir DF) <= or > median (median GSS is 2).

    Secondary: Change from baseline to Week 48 in CD4 Percentage

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    End point title
    		 Change from baseline to Week 48 in CD4 Percentage
    End point description
    ITT Analysis Set, missing = excluded method CD4 percentage is the percentage of total lymphocytes that are CD4 cells. For the TDF and Placebo groups, only data collected during the double-blind phase are included.
    End point type
    Secondary
    End point timeframe
    Baseline to 48 weeks
    End point values
    		 Tenofovir DF Placebo Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    32
    31
    17
    11
    Units: Percentage of CD4 lymphocytes
        median (inter-quartile range (Q1-Q3))
    6 (2.5 to 9)
    5 (2 to 8)
    2 (1 to 4)
    -1 (-4 to 7)
    Statistical analysis title
    		 Difference in change from baseline
    Statistical analysis description
    Null hypothesis: Changes from baseline through Week 48 in plasma CD4% for the tenofovir DF and placebo groups are equal. Alternative hypothesis: Changes from baseline through Week 48 in CD4% for the tenofovir DF and placebo groups are different (two-sided).
    Comparison groups
    Tenofovir DF v Placebo
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 other [33]
    P-value
    		 = 0.63 [34]
    Method
    		 Van Elteren test
    Confidence interval
    Notes
    [33] - Intergroup analysis
    [34] - No adjustments for multiple comparisons were made. P-value is from a Van Elteren test stratified by baseline GSS (without tenofovir DF) <= or > median (median GSS is 2).

    Secondary: Change from baseline to Week 96 in CD4 Percentage

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    End point title
    		 Change from baseline to Week 96 in CD4 Percentage [35]
    End point description
    ITT Analysis Set, missing = excluded method CD4 percentage is the percentage of total lymphocytes that are CD4 cells.
    End point type
    Secondary
    End point timeframe
    Baseline to 96 weeks
    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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    20
    17
    3
    Units: Percentage of CD4 lymphocytes
        median (inter-quartile range (Q1-Q3))
    5 (2 to 8)
    2 (0 to 5)
    9 (2 to 15)
    No statistical analyses for this end point

    Secondary: Change from baseline to Week 144 in CD4 Percentage

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    End point title
    		 Change from baseline to Week 144 in CD4 Percentage [36]
    End point description
    ITT Analysis Set, missing = excluded method CD4 percentage is the percentage of total lymphocytes that are CD4 cells.
    End point type
    Secondary
    End point timeframe
    Baseline to 144 weeks
    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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    12
    11
    2
    Units: Percentage of CD4 lymphocytes
        median (inter-quartile range (Q1-Q3))
    6.5 (-2 to 13)
    0 (-4 to 8)
    5.5 (2 to 9)
    No statistical analyses for this end point

    Secondary: Change from baseline to Week 192 in CD4 Percentage

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    End point title
    		 Change from baseline to Week 192 in CD4 Percentage [37]
    End point description
    ITT Analysis Set, missing = excluded method CD4 percentage is the percentage of total lymphocytes that are CD4 cells.
    End point type
    Secondary
    End point timeframe
    Baseline to 192 weeks
    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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    7
    6
    2
    Units: Percentage of CD4 lymphocytes
        median (inter-quartile range (Q1-Q3))
    5 (-2 to 11.6)
    1.9 (-1 to 10)
    4.8 (1.5 to 8)
    No statistical analyses for this end point

    Secondary: Change from baseline to Week 240 in CD4 Percentage

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    End point title
    		 Change from baseline to Week 240 in CD4 Percentage [38]
    End point description
    ITT Analysis Set, missing = excluded method CD4 percentage is the percentage of total lymphocytes that are CD4 cells.
    End point type
    Secondary
    End point timeframe
    Baseline to 240 weeks
    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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    5
    2
    1
    Units: Percentage of CD4 lymphocytes
        median (inter-quartile range (Q1-Q3))
    10 (-2 to 13.3)
    8.9 (8.2 to 9.6)
    18.9 (18.9 to 18.9)
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 288 in CD4 Percentage

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    End point title
    		 Change from Baseline to Week 288 in CD4 Percentage [39]
    End point description
    ITT Analysis Set, missing = excluded method CD4 percentage is the percentage of total lymphocytes that are CD4 cells.
    End point type
    Secondary
    End point timeframe
    Baseline to 288 weeks
    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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    1
    1
    1
    Units: Percentage of CD4 lymphocytes
        median (inter-quartile range (Q1-Q3))
    7.4 (7.4 to 7.4)
    4 (4 to 4)
    11.9 (11.9 to 11.9)
    No statistical analyses for this end point

    Secondary: Change from baseline to Week 336 in CD4 Percentage

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    End point title
    		 Change from baseline to Week 336 in CD4 Percentage [40]
    End point description
    ITT Analysis Set, missing = excluded method No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.
    End point type
    Secondary
    End point timeframe
    Baseline to 336 weeks
    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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    0 [41]
    0 [42]
    0 [43]
    Units: Percentage of CD4 lymphocytes
        median (inter-quartile range (Q1-Q3))
    ( to )
    ( to )
    ( to )
    Notes
    [41] - No analysis was performed because the study ended early after Week 294.
    [42] - No analysis was performed because the study ended early after Week 294.
    [43] - No analysis was performed because the study ended early after Week 294.
    No statistical analyses for this end point

    Secondary: Percentage of participants with an HIV-1 RNA decrease of ≥ 1.0 log10 copies/mL from baseline to Week 24

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    End point title
    		 Percentage of participants with an HIV-1 RNA decrease of ≥ 1.0 log10 copies/mL from baseline to Week 24
    End point description
    ITT Analysis Set The Tenofovir DF and Placebo groups were analyzed using the LOCF method. The Placebo/TDF groups were analyzed using the missing = excluded method. For the TDF and Placebo groups, only data collected during the double-blind phase are included.
    End point type
    Secondary
    End point timeframe
    Baseline to 24 weeks
    End point values
    		 Tenofovir DF Placebo Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    44
    41
    18
    16
    Units: Percentage of participants
        number (not applicable)
    56.8
    51.2
    0
    12.5
    Statistical analysis title
    		 Difference in percentage
    Statistical analysis description
    Null hypothesis: Percentage of participants who had at least a 1.0 log10 copies/mL decrease from baseline to Week 24 in HIV-1 RNA for the tenofovir DF and placebo groups is equal. Alternative hypothesis: Percentage of participants who had at least a 1.0 log10 copies/mL decrease from baseline to Week 24 in HIV-1 RNA for the tenofovir DF and placebo groups is different (two-sided).
    Comparison groups
    Tenofovir DF v Placebo
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 other [44]
    P-value
    		 = 0.67 [45]
    Method
    		 Fisher exact
    Confidence interval
    Notes
    [44] - Intergroup analysis
    [45] - No adjustments for multiple comparisons were made.

    Secondary: Percentage of participants with an HIV-1 RNA decrease of ≥ 1.0 log10 copies/mL from baseline to Week 48

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    End point title
    		 Percentage of participants with an HIV-1 RNA decrease of ≥ 1.0 log10 copies/mL from baseline to Week 48
    End point description
    ITT Analysis Set. The Tenofovir DF and Placebo groups were analyzed using the LOCF method. The Placebo/TDF groups were analyzed using the missing = excluded method. For the TDF and Placebo groups, only data collected during the double-blind phase are included.
    End point type
    Secondary
    End point timeframe
    Baseline to 48 weeks
    End point values
    		 Tenofovir DF Placebo Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    44
    41
    18
    8
    Units: Percentage of participants
        number (not applicable)
    47.7
    53.7
    0
    0
    Statistical analysis title
    		 Difference in percentage
    Statistical analysis description
    Null hypothesis: Percentage of participants who had at least a 1.0 log10 copies/mL decrease from baseline to Week 48 in HIV-1 RNA for the tenofovir DF and placebo groups is equal. Alternative hypothesis: Percentage of participants who had at least a 1.0 log10 copies/mL decrease from baseline to Week 48 in HIV-1 RNA for the tenofovir DF and placebo groups is different (two-sided).
    Comparison groups
    Tenofovir DF v Placebo
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 other [46]
    P-value
    		 = 0.67 [47]
    Method
    		 Fisher exact
    Confidence interval
    Notes
    [46] - Intergroup analysis
    [47] - No adjustments for multiple comparisons were made.

    Secondary: Percentage of participants with an HIV-1 RNA decrease of ≥ 1.0 log10 copies/mL from baseline to Week 96

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    End point title
    		 Percentage of participants with an HIV-1 RNA decrease of ≥ 1.0 log10 copies/mL from baseline to Week 96 [48]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Baseline to 96 weeks
    Notes
    [48] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    19
    17
    3
    Units: Percentage of participants
        number (not applicable)
    73.7
    5.9
    33.3
    No statistical analyses for this end point

    Secondary: Percentage of participants with an HIV-1 RNA decrease of ≥ 1.0 log10 copies/mL from baseline to Week 144

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    End point title
    		 Percentage of participants with an HIV-1 RNA decrease of ≥ 1.0 log10 copies/mL from baseline to Week 144 [49]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Baseline to 144 weeks
    Notes
    [49] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    10
    11
    2
    Units: Percentage of participants
        number (not applicable)
    90
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of participants with an HIV-1 RNA decrease of ≥ 1.0 log10 copies/mL from baseline to Week 192

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    End point title
    		 Percentage of participants with an HIV-1 RNA decrease of ≥ 1.0 log10 copies/mL from baseline to Week 192 [50]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Baseline to 192 weeks
    Notes
    [50] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    7
    5
    2
    Units: Percentage of participants
        number (not applicable)
    71.4
    0
    50
    No statistical analyses for this end point

    Secondary: Percentage of participants with an HIV-1 RNA decrease of ≥ 1.0 log10 copies/mL from baseline to Week 240

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    End point title
    		 Percentage of participants with an HIV-1 RNA decrease of ≥ 1.0 log10 copies/mL from baseline to Week 240 [51]
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline to 240 weeks
    Notes
    [51] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    4
    2
    1
    Units: Percentage of participants
        number (not applicable)
    100
    0
    100
    No statistical analyses for this end point

    Secondary: Percentage of Participants with an HIV-1 RNA Decrease of ≥ 1.0 log10 copies/mL from Baseline to Week 288

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    End point title
    		 Percentage of Participants with an HIV-1 RNA Decrease of ≥ 1.0 log10 copies/mL from Baseline to Week 288 [52]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Baseline to 288 weeks
    Notes
    [52] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    1
    1
    1
    Units: Percentage of participants
        number (not applicable)
    100
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of participants with an HIV-1 RNA decrease of ≥ 1.0 log10 copies/mL from baseline to Week 336

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    End point title
    		 Percentage of participants with an HIV-1 RNA decrease of ≥ 1.0 log10 copies/mL from baseline to Week 336 [53]
    End point description
    ITT Analysis Set, missing = excluded method No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.
    End point type
    Secondary
    End point timeframe
    Baseline to 336 weeks
    Notes
    [53] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    0 [54]
    0 [55]
    0 [56]
    Units: Percentage of participants
        number (not applicable)
    Notes
    [54] - No analysis was performed because the study ended early after Week 294.
    [55] - No analysis was performed because the study ended early after Week 294.
    [56] - No analysis was performed because the study ended early after Week 294.
    No statistical analyses for this end point

    Secondary: Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 24

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    End point title
    		 Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 24
    End point description
    ITT Analysis Set The Tenofovir DF and Placebo groups were analyzed using the missing = failure method in which participants with missing data were considered to have failed to achieve the endpoint. The Placebo/TDF groups were analyzed using the missing = excluded method. For the TDF and Placebo groups, only data collected during the double-blind phase are included.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 Tenofovir DF Placebo Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    44
    41
    18
    16
    Units: Percentage of participants
        number (not applicable)
    40.9
    41.5
    83.3
    6.3
    Statistical analysis title
    		 Difference in percentage
    Statistical analysis description
    Null hypothesis: Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 24 for the tenofovir DF and placebo groups is equal. Alternative hypothesis: Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 24 for the tenofovir DF and placebo groups is different (two-sided).
    Comparison groups
    Tenofovir DF v Placebo
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 other [57]
    P-value
    		 = 1 [58]
    Method
    		 Fisher exact
    Confidence interval
    Notes
    [57] - Intergroup analysis
    [58] - No adjustments for multiple comparisons were made.

    Secondary: Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 48

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    End point title
    		 Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 48
    End point description
    ITT Analysis Set The Tenofovir DF and Placebo groups were analyzed using the missing = failure method. The Placebo/TDF groups were analyzed using the missing = excluded method. For the TDF and Placebo groups, only data collected during the double-blind phase are included.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 Tenofovir DF Placebo Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    44
    41
    18
    8
    Units: Percentage of participants
        number (not applicable)
    34.1
    43.9
    77.8
    0
    Statistical analysis title
    		 Difference in percentage
    Statistical analysis description
    Null hypothesis: Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 48 for the tenofovir DF and placebo groups is equal. Alternative hypothesis: Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 48 for the tenofovir DF and placebo groups is different (two-sided).
    Comparison groups
    Tenofovir DF v Placebo
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 other [59]
    P-value
    		 = 0.38 [60]
    Method
    		 Fisher exact
    Confidence interval
    Notes
    [59] - Intergroup analysis
    [60] - No adjustments for multiple comparisons were made.

    Secondary: Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 96

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    End point title
    		 Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 96 [61]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Week 96
    Notes
    [61] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    19
    17
    3
    Units: Percentage of participants
        number (not applicable)
    63.2
    70.6
    33.3
    No statistical analyses for this end point

    Secondary: Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 144

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    End point title
    		 Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 144 [62]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Week 144
    Notes
    [62] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    10
    11
    2
    Units: Percentage of participants
        number (not applicable)
    70
    72.7
    0
    No statistical analyses for this end point

    Secondary: Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 192

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    End point title
    		 Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 192 [63]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Week 192
    Notes
    [63] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    7
    5
    2
    Units: Percentage of participants
        number (not applicable)
    57.1
    80
    50
    No statistical analyses for this end point

    Secondary: Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 240

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    End point title
    		 Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 240 [64]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Week 240
    Notes
    [64] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    4
    2
    1
    Units: Percentage of participants
        number (not applicable)
    75
    100
    100
    No statistical analyses for this end point

    Secondary: Percentage of Participants with HIV-1 RNA < 400 copies/mL at Week 288

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    End point title
    		 Percentage of Participants with HIV-1 RNA < 400 copies/mL at Week 288 [65]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Week 288
    Notes
    [65] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    1
    1
    1
    Units: Percentage of participants
        number (not applicable)
    0
    100
    0
    No statistical analyses for this end point

    Secondary: Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 336

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    End point title
    		 Percentage of participants with HIV-1 RNA < 400 copies/mL at Week 336 [66]
    End point description
    ITT Analysis Set, missing = excluded method No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.
    End point type
    Secondary
    End point timeframe
    Week 336
    Notes
    [66] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    0 [67]
    0 [68]
    0 [69]
    Units: Percentage of participants
        number (not applicable)
    Notes
    [67] - No analysis was performed because the study ended early after Week 294.
    [68] - No analysis was performed because the study ended early after Week 294.
    [69] - No analysis was performed because the study ended early after Week 294.
    No statistical analyses for this end point

    Secondary: Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24

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    End point title
    		 Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24
    End point description
    ITT Analysis Set The Tenofovir DF and Placebo groups were analyzed using the missing = failure method. The Placebo/TDF groups were analyzed using the missing = excluded method. For the TDF and Placebo groups, only data collected during the double-blind phase are included.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 Tenofovir DF Placebo Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    44
    41
    18
    16
    Units: Percentage of participants
        number (not applicable)
    20.5
    34.1
    77.8
    0
    Statistical analysis title
    		 Difference in percentage
    Statistical analysis description
    Null hypothesis: Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 for the tenofovir DF and placebo groups is equal. Alternative hypothesis: Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 for the tenofovir DF and placebo groups is different (two-sided).
    Comparison groups
    Tenofovir DF v Placebo
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 other [70]
    P-value
    		 = 0.22 [71]
    Method
    		 Fisher exact
    Confidence interval
    Notes
    [70] - Intergroup analysis
    [71] - No adjustments for multiple comparisons were made.

    Secondary: Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48

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    End point title
    		 Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48
    End point description
    ITT Analysis Set The Tenofovir DF and Placebo groups were analyzed using the missing = failure method. The Placebo/TDF groups were analyzed using the missing = excluded method. For the TDF and Placebo groups, only data collected during the double-blind phase are included.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 Tenofovir DF Placebo Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    44
    41
    18
    8
    Units: Percentage of participants
        number (not applicable)
    27.3
    36.6
    61.1
    0
    Statistical analysis title
    		 Difference in percentage
    Statistical analysis description
    Null hypothesis: Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 for the tenofovir DF and placebo groups is equal. Alternative hypothesis: Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 for the tenofovir DF and placebo groups is different (two-sided).
    Comparison groups
    Tenofovir DF v Placebo
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 other [72]
    P-value
    		 = 0.48 [73]
    Method
    		 Fisher exact
    Confidence interval
    Notes
    [72] - Intergroup analysis
    [73] - No adjustments for multiple comparisons were made.

    Secondary: Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96

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    End point title
    		 Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 [74]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Week 96
    Notes
    [74] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    19
    17
    3
    Units: Percentage of participants
        number (not applicable)
    47.4
    58.8
    33.3
    No statistical analyses for this end point

    Secondary: Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 144

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    End point title
    		 Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 144 [75]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Week 144
    Notes
    [75] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    10
    11
    2
    Units: Percentage of participants
        number (not applicable)
    70
    45.5
    0
    No statistical analyses for this end point

    Secondary: Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 192

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    End point title
    		 Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 192 [76]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Week 192
    Notes
    [76] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    7
    5
    2
    Units: Percentage of participants
        number (not applicable)
    42.9
    60
    50
    No statistical analyses for this end point

    Secondary: Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 240

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    End point title
    		 Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 240 [77]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Week 240
    Notes
    [77] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    4
    2
    1
    Units: Percentage of participants
        number (not applicable)
    75
    100
    100
    No statistical analyses for this end point

    Secondary: Percentage of Participants with HIV-1 RNA < 50 copies/mL at Week 288

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    End point title
    		 Percentage of Participants with HIV-1 RNA < 50 copies/mL at Week 288 [78]
    End point description
    ITT Analysis Set, missing = excluded method
    End point type
    Secondary
    End point timeframe
    Week 288
    Notes
    [78] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    1
    1
    1
    Units: Percentage of participants
        number (not applicable)
    0
    100
    0
    No statistical analyses for this end point

    Secondary: Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 336

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    End point title
    		 Percentage of participants with HIV-1 RNA < 50 copies/mL at Week 336 [79]
    End point description
    ITT Analysis Set, missing = excluded method No analysis was performed because the last study participant discontinued after Week 294 and the study was closed.
    End point type
    Secondary
    End point timeframe
    Week 336
    Notes
    [79] - 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: For participants randomized to placebo, results after switching to TDF are presented in the Placebo/TDF, HIV-1 RNA < 1000 Copies/mL group, and the Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL group.
    End point values
    		 Tenofovir DF Placebo/TDF, HIV-1 RNA < 1000 Copies/mL Placebo/TDF, HIV-1 RNA ≥ 1000 Copies/mL
    Number of subjects analysed
    0 [80]
    0 [81]
    0 [82]
    Units: Percentage of participants
        number (not applicable)
    Notes
    [80] - No analysis was performed because the study ended early after Week 294.
    [81] - No analysis was performed because the study ended early after Week 294.
    [82] - No analysis was performed because the study ended early after Week 294.
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Virologic Failure through Week 48

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    End point title
    		 Percentage of Participants with Virologic Failure through Week 48
    End point description
    Virologic failure was defined as either nonresponse or viral rebound. - Nonresponse (failure to achieve response). Response was defined as either -- A ≥ 0.5 log10 copies/mL decrease in HIV-1 RNA from baseline at 2 consecutive visits, or -- HIV-1 RNA < 400 copies/mL at 2 consecutive visits. - Viral rebound was defined as either -- Participants who achieved a ≥ 0.5 log10 copies/mL decrease from baseline in plasma HIV-1 RNA at 2 consecutive visits, who then subsequently achieved plasma HIV-1 RNA values ≥ 1.0 log10 copies/mL above their on-study nadir (lowest value) and/or plasma HIV-1 RNA values ≥ the baseline value at 2 consecutive visits, or -- Participants who achieved plasma HIV-1 RNA levels of < 400 copies/mL at 2 consecutive visits, and then subsequently had plasma HIV-1 RNA levels > 1000 copies/mL at 2 consecutive visits. The virologic failure rate was estimated from Kaplan-Meier product limit method by including all HIV-1 RNA data collected during the double-blind phase.
    End point type
    Secondary
    End point timeframe
    Up to 48 weeks. 1 participant without time to respond (6 days of treatment) was excluded. Nonresponders=failures@time 0. Rebounders=failures on study day of first of 2 assessments meeting criteria. Otherwise, censored at last double-blind HIV measurement.
    End point values
    		 Tenofovir DF Placebo
    Number of subjects analysed
    43
    41
    Units: Kaplan-Meier percentage
        number (not applicable)
    51
    39
    Statistical analysis title
    		 Difference in percentage
    Statistical analysis description
    Null hypothesis: The survival functions for the tenofovir DF and placebo groups up to Week 48 are equal. Alternative hypothesis: The survival functions for the tenofovir DF and placebo groups up to Week 48 are different (two-sided).
    Comparison groups
    Tenofovir DF v Placebo
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    		 other [83]
    P-value
    		 = 0.29 [84]
    Method
    		 Logrank
    Confidence interval
    Notes
    [83] - Intergroup analysis
    [84] - No adjustments for multiple comparisons were made.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to Week 294 plus 30 days.
    Adverse event reporting additional description
    Safety Analysis Set: participants were randomized and received at least 1 dose of study medication. MedDRA version 11.1 was used for the Tenofovir DF and Placebo columns; MedDRA version 16.1 was used for the All TDF column. All AEs are reported by system order class and preferred term.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Tenofovir DF
    Reporting group description
    		 Adverse events occurring in the double-blind phase are presented for this reporting group. TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+ OBR for up to an additional 288 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Adverse events occurring in the double-blind phase are presented for this reporting group. Placebo to match TDF+OBR from baseline to Week 48 (double-blind phase), followed by open-label TDF+OBR for up to an additional 288 weeks.

    Reporting group title
    All TDF
    Reporting group description
    		 Adverse events reported for the All TDF group include those reported during the double-blind phase and/or extension phase for subjects who were randomized to TDF group plus adverse events reported during the extension phase only for subjects who switched from placebo to open-label TDF.

    Serious adverse events
    		 Tenofovir DF Placebo All TDF
    Total subjects affected by serious adverse events
         subjects affected / exposed
    10 / 45 (22.22%)
    3 / 42 (7.14%)
    20 / 81 (24.69%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Anogenital warts
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 42 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Overdose
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 42 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Convulsion
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 42 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 42 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Psychotic disorder
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 42 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 42 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 42 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    3 / 45 (6.67%)
    1 / 42 (2.38%)
    5 / 81 (6.17%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 42 (0.00%)
    2 / 81 (2.47%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 42 (0.00%)
    3 / 81 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cryptococcosis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 42 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 42 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jiroveci pneumonia
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 42 (0.00%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 42 (0.00%)
    2 / 81 (2.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 42 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 42 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abscess
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 42 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 42 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 42 (2.38%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mastoiditis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 42 (2.38%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neurocryptococcosis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 42 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 42 (0.00%)
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral toxoplasmosis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 42 (2.38%)
    0 / 81 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Tenofovir DF Placebo All TDF
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    44 / 45 (97.78%)
    35 / 42 (83.33%)
    76 / 81 (93.83%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Skin papilloma
         subjects affected / exposed
    0 / 45 (0.00%)
    3 / 42 (7.14%)
    2 / 81 (2.47%)
         occurrences all number
    0
    4
    2
    Nervous system disorders
    Headache
         subjects affected / exposed
    6 / 45 (13.33%)
    5 / 42 (11.90%)
    16 / 81 (19.75%)
         occurrences all number
    8
    7
    21
    Dizziness
         subjects affected / exposed
    8 / 45 (17.78%)
    5 / 42 (11.90%)
    11 / 81 (13.58%)
         occurrences all number
    9
    8
    13
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    4 / 45 (8.89%)
    1 / 42 (2.38%)
    7 / 81 (8.64%)
         occurrences all number
    10
    1
    16
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    4 / 45 (8.89%)
    5 / 42 (11.90%)
    7 / 81 (8.64%)
         occurrences all number
    4
    8
    9
    Eye disorders
    Conjunctivitis
         subjects affected / exposed
    2 / 45 (4.44%)
    1 / 42 (2.38%)
    5 / 81 (6.17%)
         occurrences all number
    2
    1
    5
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    16 / 45 (35.56%)
    5 / 42 (11.90%)
    21 / 81 (25.93%)
         occurrences all number
    21
    5
    28
    Diarrhoea
         subjects affected / exposed
    10 / 45 (22.22%)
    4 / 42 (9.52%)
    17 / 81 (20.99%)
         occurrences all number
    10
    5
    18
    Nausea
         subjects affected / exposed
    11 / 45 (24.44%)
    3 / 42 (7.14%)
    15 / 81 (18.52%)
         occurrences all number
    14
    6
    18
    Abdominal pain
         subjects affected / exposed
    8 / 45 (17.78%)
    5 / 42 (11.90%)
    9 / 81 (11.11%)
         occurrences all number
    8
    5
    9
    Gastritis
         subjects affected / exposed
    5 / 45 (11.11%)
    1 / 42 (2.38%)
    7 / 81 (8.64%)
         occurrences all number
    5
    1
    9
    Constipation
         subjects affected / exposed
    3 / 45 (6.67%)
    0 / 42 (0.00%)
    4 / 81 (4.94%)
         occurrences all number
    3
    0
    5
    Hepatobiliary disorders
    Jaundice
         subjects affected / exposed
    3 / 45 (6.67%)
    3 / 42 (7.14%)
    4 / 81 (4.94%)
         occurrences all number
    4
    4
    5
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    11 / 45 (24.44%)
    6 / 42 (14.29%)
    24 / 81 (29.63%)
         occurrences all number
    13
    6
    29
    Bronchospasm
         subjects affected / exposed
    3 / 45 (6.67%)
    2 / 42 (4.76%)
    5 / 81 (6.17%)
         occurrences all number
    3
    2
    5
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 42 (0.00%)
    7 / 81 (8.64%)
         occurrences all number
    1
    0
    7
    Musculoskeletal and connective tissue disorders
    Osteopenia
         subjects affected / exposed
    3 / 45 (6.67%)
    2 / 42 (4.76%)
    5 / 81 (6.17%)
         occurrences all number
    3
    2
    5
    Infections and infestations
    Sinusitis
         subjects affected / exposed
    12 / 45 (26.67%)
    6 / 42 (14.29%)
    24 / 81 (29.63%)
         occurrences all number
    14
    6
    31
    Nasopharyngitis
         subjects affected / exposed
    8 / 45 (17.78%)
    7 / 42 (16.67%)
    18 / 81 (22.22%)
         occurrences all number
    10
    10
    34
    Upper respiratory tract infection
         subjects affected / exposed
    8 / 45 (17.78%)
    3 / 42 (7.14%)
    17 / 81 (20.99%)
         occurrences all number
    13
    4
    25
    Tonsillitis
         subjects affected / exposed
    4 / 45 (8.89%)
    3 / 42 (7.14%)
    12 / 81 (14.81%)
         occurrences all number
    4
    4
    13
    Oral herpes
         subjects affected / exposed
    5 / 45 (11.11%)
    3 / 42 (7.14%)
    9 / 81 (11.11%)
         occurrences all number
    7
    3
    12
    Tracheobronchitis
         subjects affected / exposed
    5 / 45 (11.11%)
    1 / 42 (2.38%)
    9 / 81 (11.11%)
         occurrences all number
    6
    1
    11
    Acute sinusitis
         subjects affected / exposed
    3 / 45 (6.67%)
    4 / 42 (9.52%)
    6 / 81 (7.41%)
         occurrences all number
    5
    4
    9
    Rhinitis
         subjects affected / exposed
    3 / 45 (6.67%)
    1 / 42 (2.38%)
    7 / 81 (8.64%)
         occurrences all number
    3
    1
    8
    Pneumonia
         subjects affected / exposed
    2 / 45 (4.44%)
    2 / 42 (4.76%)
    5 / 81 (6.17%)
         occurrences all number
    2
    3
    5
    Body tinea
         subjects affected / exposed
    2 / 45 (4.44%)
    1 / 42 (2.38%)
    5 / 81 (6.17%)
         occurrences all number
    2
    1
    5
    Furuncle
         subjects affected / exposed
    3 / 45 (6.67%)
    1 / 42 (2.38%)
    4 / 81 (4.94%)
         occurrences all number
    4
    1
    5
    Gastroenteritis
         subjects affected / exposed
    2 / 45 (4.44%)
    1 / 42 (2.38%)
    5 / 81 (6.17%)
         occurrences all number
    2
    1
    5
    Bronchopneumonia
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 42 (0.00%)
    5 / 81 (6.17%)
         occurrences all number
    2
    0
    5
    Hordeolum
         subjects affected / exposed
    3 / 45 (6.67%)
    1 / 42 (2.38%)
    3 / 81 (3.70%)
         occurrences all number
    3
    1
    3
    Impetigo
         subjects affected / exposed
    1 / 45 (2.22%)
    3 / 42 (7.14%)
    3 / 81 (3.70%)
         occurrences all number
    1
    3
    3
    Herpes zoster
         subjects affected / exposed
    0 / 45 (0.00%)
    3 / 42 (7.14%)
    3 / 81 (3.70%)
         occurrences all number
    0
    3
    4
    Metabolism and nutrition disorders
    Hypertriglyceridaemia
         subjects affected / exposed
    3 / 45 (6.67%)
    3 / 42 (7.14%)
    6 / 81 (7.41%)
         occurrences all number
    3
    3
    7
    Anorexia
         subjects affected / exposed
    4 / 45 (8.89%)
    1 / 42 (2.38%)
    0 / 81 (0.00%)
         occurrences all number
    4
    1
    0
    Decreased appetite
         subjects affected / exposed
    0 / 45 (0.00%)
    0 / 42 (0.00%)
    5 / 81 (6.17%)
         occurrences all number
    0
    0
    6

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Oct 2006
    An independent data monitoring committee was added to participate in the review of the efficacy and safety profile for the study.
    21 Feb 2007
    The study was extended to 144 weeks with the addition of a 96-week, open-label extension period.
    04 Nov 2008
    The study was extended to 240 weeks with the addition of a second 96-week, open-label extension period.
    03 Sep 2010
    The study was extended for an additional 2 years. After completing the second 96-week study extension with open-label tenofovir DF, currently enrolled subjects at active sites who had not yet reached 18 years of age and who had shown benefit from tenofovir DF were given the option to continue receiving tenofovir DF for an additional 96 weeks. For subjects completing the extension phase, tenofovir DF was provided until the subject reached 18 years of age, until tenofovir DF became commercially available in the country in which the subject was enrolled, or until Gilead was no longer the exclusive seller of tenofovir DF in the country in which the subject was enrolled, whichever occured first.

    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.
    Participants left the study for a number of reasons (eg, turned 18 years old, switched to a different HIV treatment regimen), which led to small numbers of participants analyzed at later time points, and the study was concluded earlier than planned.
    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.

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