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    Clinical Trial Results:
    A Phase 1b, Open-label study to Evaluate the PK, Safety and Efficacy of B/F/TAF in HIV-1 infected, Virologically Suppressed, Pregnant Women in their Second and Third Trimesters

    Summary
    EudraCT number
    		 2021-001073-23
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    18 Aug 2022

    Results information
    Results version number
    		 v2(current)
    This version publication date
    29 Dec 2023
    First version publication date
    02 Mar 2023
    Other versions
    		 v1
    Version creation reason
    • New data added to full data set
    Added neonates arm group in adverse events section.

    Trial information

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    Trial identification
    Sponsor protocol code
    GS-US-380-5310
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03960645
    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
    Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
    Scientific contact
    Gilead Clinical Study Information Center, Gilead Sciences, GileadClinicalTrials@gilead.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    18 Aug 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    21 Jul 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Aug 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to evaluate the steady state pharmacokinetics (PK) of bictegravir (BIC) and confirm the dose of BIC/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg fixed dose combination (FDC) in human immunodeficiency virus 1 (HIV-1) infected, virologically suppressed pregnant women in their second and third trimesters.
    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
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 Jun 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Dominican Republic: 6
    Country: Number of subjects enrolled
    Thailand: 49
    Country: Number of subjects enrolled
    United States: 7
    Worldwide total number of subjects
    62
    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)
    29
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    33
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants were enrolled at study sites in the Dominican Republic, Thailand, and the United States.

    Pre-assignment
    Screening details
    		 33 pregnant women were enrolled in the B/F/TAF group. Neonates born to these women were also enrolled in the study for follow up. A total of 29 neonate participants were enrolled.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 B/F/TAF
    Arm description
    		 Pregnant women participants received fixed dose combination (FDC) tablet of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily for up to 38 weeks (from the second or third trimesters of pregnancy, depending on enrollment, through 12 weeks post-partum).
    Arm type
    		 Experimental

    Investigational medicinal product name
    B/F/TAF
    Investigational medicinal product code
    Other name
    GS-9883/F/TAF, Biktarvy®, BVY
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    50/200/25 mg FDC administered as a single dose.

    Arm title
    		 Neonates
    Arm description
    		 Neonates born to women participants in the study were followed from birth up to 8 weeks of age after obtaining consent from the parent or legal guardian. None of the neonates participating in the study were treated with the study drug.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		B/F/TAF Neonates
    Started
    33
    29
    Completed
    32
    29
    Not completed
    1
    0
         Protocol Violation
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    B/F/TAF
    Reporting group description
    		 Pregnant women participants received fixed dose combination (FDC) tablet of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily for up to 38 weeks (from the second or third trimesters of pregnancy, depending on enrollment, through 12 weeks post-partum).

    Reporting group title
    Neonates
    Reporting group description
    		 Neonates born to women participants in the study were followed from birth up to 8 weeks of age after obtaining consent from the parent or legal guardian. None of the neonates participating in the study were treated with the study drug.

    Reporting group values
    		 B/F/TAF Neonates Total
    Number of subjects
    		 33 29 62
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 30 ( 5.0 ) 0 ( 0.0 ) -
    Gender categorical
    Units: Subjects
        Female
    		 33 10 43
        Male
    		 0 19 19
    Race
    Units: Subjects
        Asian
    		 25 24 49
        Black
    		 6 4 10
        Other
    		 1 1 2
        White
    		 1 0 1
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 4 4 8
        Not Hispanic or Latino
    		 29 25 54

    End points

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    End points reporting groups
    Reporting group title
    B/F/TAF
    Reporting group description
    		 Pregnant women participants received fixed dose combination (FDC) tablet of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg, orally, once daily for up to 38 weeks (from the second or third trimesters of pregnancy, depending on enrollment, through 12 weeks post-partum).

    Reporting group title
    Neonates
    Reporting group description
    		 Neonates born to women participants in the study were followed from birth up to 8 weeks of age after obtaining consent from the parent or legal guardian. None of the neonates participating in the study were treated with the study drug.

    Primary: Pharmacokinetic (PK) Parameter: AUCtau of Bictegravir (BIC)

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    End point title
    		 Pharmacokinetic (PK) Parameter: AUCtau of Bictegravir (BIC) [1] [2]
    End point description
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). PK analysis set included all enrolled adult participants who took at least 1 dose of study drug (B/F/TAF), and had at least 1 non-missing concentration value reported by the PK laboratory for the corresponding analytes (BIC, FTC, TAF, and tenofovir diphosphate [TFV-DP]). Participants in the PK analysis set with available data were analysed.
    End point type
    Primary
    End point timeframe
    Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The statistical analysis of this primary endpoint is provided in the attachment.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The neonates did not receive the study drug so they were not analyzed for the primary endpoint.
    End point values
    		 B/F/TAF
    Number of subjects analysed
    32
    Units: hours*nanograms per milliliter (h*ng/mL)
    arithmetic mean (standard deviation)
        Second Trimester (n=20)
    62772.2 ( 20242.18 )
        Third Trimester (n=30)
    60163.4 ( 17482.06 )
        Week 6 Post-partum (n=31)
    134820.3 ( 36217.30 )
        Week 12 Post-partum (n=32)
    148251.6 ( 42189.17 )
    Attachments
    		 Statistical Analysis
    No statistical analyses for this end point

    Secondary: PK Parameter: AUCtau of Emtricitabine (FTC) and Tenofovir Alafenamide (TAF)

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    End point title
    		 PK Parameter: AUCtau of Emtricitabine (FTC) and Tenofovir Alafenamide (TAF) [3]
    End point description
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). Participants in the PK analysis set with available data were analysed.
    End point type
    Secondary
    End point timeframe
    Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
    Notes
    [3] - 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: The neonates did not receive the study drug so they were not analyzed for the secondary endpoint.
    End point values
    		 B/F/TAF
    Number of subjects analysed
    32
    Units: h*ng/mL
    arithmetic mean (standard deviation)
        FTC: Second Trimester (n=21)
    10263.8 ( 2054.35 )
        FTC: Third Trimester (n=30)
    10435.2 ( 2121.87 )
        FTC: Week 6 Post-partum (n=31)
    16277.5 ( 4023.42 )
        FTC: Week 12 Post-partum (n=32)
    15308.5 ( 3359.83 )
        TAF: Second Trimester (n=15)
    235.5 ( 107.36 )
        TAF: Third Trimester (n=17)
    212.1 ( 95.38 )
        TAF: Week 6 Post-partum (n=27)
    374.3 ( 153.54 )
        TAF: Week 12 Post-partum (n=30)
    296.4 ( 94.37 )
    Attachments
    		 Statistical Analysis
    No statistical analyses for this end point

    Secondary: PK Parameter: AUClast of BIC, FTC, and TAF

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    End point title
    		 PK Parameter: AUClast of BIC, FTC, and TAF [4]
    End point description
    AUClast is defined as the concentration of drug from time zero to the last observable concentration. Participants in the PK analysis set with available data were analysed.
    End point type
    Secondary
    End point timeframe
    Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The neonates did not receive the study drug so they were not analyzed for the secondary endpoint.
    End point values
    		 B/F/TAF
    Number of subjects analysed
    32
    Units: h*ng/mL
    arithmetic mean (standard deviation)
        BIC: Second Trimester (n=21)
    63187.5 ( 19814.99 )
        BIC: Third Trimester (n=30)
    60145.3 ( 17484.52 )
        BIC: Week 6 Post-partum (n=31)
    135058.9 ( 36348.21 )
        BIC: Week 12 Post-partum (n=32)
    148265.3 ( 42201.47 )
        FTC: Second Trimester (n=21)
    10258.5 ( 2049.53 )
        FTC: Third Trimester (n=30)
    10434.2 ( 2121.13 )
        FTC: Week 6 Post-partum (n=31)
    16329.7 ( 4095.44 )
        FTC: Week 12 Post-partum (n=32)
    15308.5 ( 3359.79 )
        TAF: Second Trimester (n=21)
    220.4 ( 98.98 )
        TAF: Third Trimester (n=30)
    202.2 ( 84.98 )
        TAF: Week 6 Post-partum (n=31)
    356.7 ( 151.27 )
        TAF: Week 12 Post-partum (n=32)
    294.3 ( 97.88 )
    No statistical analyses for this end point

    Secondary: PK Parameter: Cmax of BIC, FTC, and TAF

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    End point title
    		 PK Parameter: Cmax of BIC, FTC, and TAF [5]
    End point description
    Cmax is defined as the maximum observed concentration of drug during the dosing interval. Participants in the PK analysis set with available data were analysed.
    End point type
    Secondary
    End point timeframe
    Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
    Notes
    [5] - 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: The neonates did not receive the study drug so they were not analyzed for the secondary endpoint.
    End point values
    		 B/F/TAF
    Number of subjects analysed
    32
    Units: ng/mL
    arithmetic mean (standard deviation)
        BIC: Second Trimester (n=21)
    5819.0 ( 1752.29 )
        BIC: Third Trimester (n=30)
    5374.7 ( 1393.86 )
        BIC: Week 6 Post-partum (n=31)
    9765.5 ( 2274.93 )
        BIC: Week 12 Post-partum (n=32)
    11025.3 ( 2747.42 )
        FTC: Second Trimester (n=21)
    2639.1 ( 965.60 )
        FTC: Third Trimester (n=30)
    2586.0 ( 686.42 )
        FTC: Week 6 Post-partum (n=31)
    3394.8 ( 951.83 )
        FTC: Week 12 Post-partum (n=32)
    3360.0 ( 902.47 )
        TAF: Second Trimester (n=21)
    332.4 ( 173.29 )
        TAF: Third Trimester (n=30)
    270.9 ( 113.93 )
        TAF: Week 6 Post-partum (n=31)
    506.4 ( 249.33 )
        TAF: Week 12 Post-partum (n=32)
    494.6 ( 259.51 )
    Attachments
    		 Statistical Analysis
    No statistical analyses for this end point

    Secondary: PK Parameter: Ctau of BIC and FTC

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    End point title
    		 PK Parameter: Ctau of BIC and FTC [6]
    End point description
    Ctau is defined as the observed drug concentration at the end of the dosing interval. Participants in the PK analysis set with available data were analysed.
    End point type
    Secondary
    End point timeframe
    Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The neonates did not receive the study drug so they were not analyzed for the secondary endpoint.
    End point values
    		 B/F/TAF
    Number of subjects analysed
    32
    Units: ng/mL
    arithmetic mean (standard deviation)
        BIC: Second Trimester (n=20)
    1046.4 ( 472.68 )
        BIC: Third Trimester (n=30)
    1072.4 ( 447.03 )
        BIC: Week 6 Post-partum (n=31)
    3530.3 ( 1354.20 )
        BIC: Week 12 Post-partum (n=32)
    3641.9 ( 1241.64 )
        FTC: Second Trimester (n=21)
    59.8 ( 62.17 )
        FTC: Third Trimester (n=30)
    51.4 ( 13.98 )
        FTC: Week 6 Post-partum (n=31)
    152.1 ( 271.50 )
        FTC: Week 12 Post-partum (n=32)
    81.1 ( 27.34 )
    Attachments
    		 Statistical Analysis
    No statistical analyses for this end point

    Secondary: PK Parameter: Clast of BIC, FTC, and TAF

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    End point title
    		 PK Parameter: Clast of BIC, FTC, and TAF [7]
    End point description
    Clast is defined as the last observable concentration of drug. Participants in the PK analysis set with available data were analysed.
    End point type
    Secondary
    End point timeframe
    Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
    Notes
    [7] - 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: The neonates did not receive the study drug so they were not analyzed for the secondary endpoint.
    End point values
    		 B/F/TAF
    Number of subjects analysed
    32
    Units: ng/mL
    arithmetic mean (standard deviation)
        BIC: Second Trimester (n=21)
    1141.10 ( 631.431 )
        BIC: Third Trimester (n=30)
    1075.13 ( 447.847 )
        BIC: Week 6 Post-partum (n=31)
    3535.48 ( 1371.162 )
        BIC: Week 12 Post-partum (n=32)
    3641.88 ( 1240.605 )
        FTC: Second Trimester (n=21)
    75.08 ( 130.792 )
        FTC: Third Trimester (n=30)
    51.65 ( 14.182 )
        FTC: Week 6 Post-partum (n=31)
    156.16 ( 292.579 )
        FTC: Week 12 Post-partum (n=32)
    81.18 ( 27.334 )
        TAF: Second Trimester (n=21)
    4.49 ( 5.130 )
        TAF: Third Trimester (n=30)
    4.80 ( 4.048 )
        TAF: Week 6 Post-partum (n=31)
    3.13 ( 1.849 )
        TAF: Week 12 Post-partum (n=32)
    3.36 ( 1.999 )
    No statistical analyses for this end point

    Secondary: PK Parameter: Tmax of BIC, FTC, and TAF

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    End point title
    		 PK Parameter: Tmax of BIC, FTC, and TAF [8]
    End point description
    Tmax is defined as the time (observed time point) of Cmax. Participants in the PK analysis set with available data were analysed.
    End point type
    Secondary
    End point timeframe
    Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The neonates did not receive the study drug so they were not analyzed for the secondary endpoint.
    End point values
    		 B/F/TAF
    Number of subjects analysed
    32
    Units: hours
    median (full range (min-max))
        BIC: Second Trimester (n=21)
    2.00 (1.00 to 12.00)
        BIC: Third Trimester (n=30)
    2.00 (1.00 to 6.00)
        BIC: Week 6 Post-partum (n=31)
    1.50 (0.50 to 12.00)
        BIC: Week 12 Post-partum (n=32)
    1.50 (0.50 to 4.00)
        FTC: Second Trimester (n=21)
    1.50 (0.50 to 4.00)
        FTC: Third Trimester (n=30)
    1.50 (0.50 to 4.00)
        FTC: Week 6 Post-partum (n=31)
    1.50 (0.50 to 4.00)
        FTC: Week 12 Post-partum (n=32)
    1.00 (0.50 to 3.00)
        TAF: Second Trimester (n=21)
    0.75 (0.25 to 4.00)
        TAF: Third Trimester (n=30)
    1.00 (0.25 to 3.00)
        TAF: Week 6 Post-partum (n=31)
    0.75 (0.25 to 3.00)
        TAF: Week 12 Post-partum (n=32)
    0.75 (0.25 to 3.00)
    No statistical analyses for this end point

    Secondary: PK Parameter: t1/2 of BIC, FTC, and TAF

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    End point title
    		 PK Parameter: t1/2 of BIC, FTC, and TAF [9]
    End point description
    t1/2 is defined as the estimate of the terminal elimination half-life of the drug. Participants in the PK analysis set with available data were analysed.
    End point type
    Secondary
    End point timeframe
    Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
    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: The neonates did not receive the study drug so they were not analyzed for the secondary endpoint.
    End point values
    		 B/F/TAF
    Number of subjects analysed
    32
    Units: hours
    median (full range (min-max))
        BIC: Second Trimester (n=19)
    9.09 (4.75 to 16.04)
        BIC: Third Trimester (n=30)
    9.91 (7.53 to 16.24)
        BIC: Week 6 Post-partum (n=29)
    18.24 (12.18 to 29.59)
        BIC: Week 12 Post-partum (n=30)
    17.27 (4.534 to 26.3)
        FTC: Second Trimester (n=20)
    6.43 (4.76 to 7.36)
        FTC: Third Trimester (n=30)
    6.41 (4.49 to 7.91)
        FTC: Week 6 Post-partum (n=28)
    6.27 (4.47 to 7.80)
        FTC: Week 12 Post-partum (n=32)
    5.76 (3.83 to 8.19)
        TAF: Second Trimester (n=14)
    0.30 (0.22 to 0.66)
        TAF: Third Trimester (n=16)
    0.28 (0.19 to 0.62)
        TAF: Week 6 Post-partum (n=26)
    0.40 (0.25 to 0.60)
        TAF: Week 12 Post-partum (n=30)
    0.35 (0.25 to 0.60)
    No statistical analyses for this end point

    Secondary: PK Parameter: CLss/F of BIC, FTC, and TAF

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    End point title
    		 PK Parameter: CLss/F of BIC, FTC, and TAF [10]
    End point description
    CLss/F is defined as the apparent steady-state oral clearance following administration of the drug. Participants in the PK analysis set with available data were analysed.
    End point type
    Secondary
    End point timeframe
    Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
    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: The neonates did not receive the study drug so they were not analyzed for the secondary endpoint.
    End point values
    		 B/F/TAF
    Number of subjects analysed
    32
    Units: mL/h
    arithmetic mean (standard deviation)
        BIC: Second Trimester (n=20)
    911.78 ( 433.301 )
        BIC: Third Trimester (n=30)
    902.47 ( 287.285 )
        BIC: Week 6 Post-partum (n=31)
    399.02 ( 113.214 )
        BIC: Week 12 Post-partum (n=32)
    362.40 ( 95.856 )
        FTC: Second Trimester (n=21)
    20228.02 ( 3981.186 )
        FTC: Third Trimester (n=30)
    19975.85 ( 4223.365 )
        FTC: Week 6 Post-partum (n=31)
    12991.62 ( 3111.349 )
        FTC: Week 12 Post-partum (n=32)
    13645.71 ( 2830.897 )
        TAF: Second Trimester (n=15)
    122677.74 ( 44270.041 )
        TAF: Third Trimester (n=17)
    135061.19 ( 44876.970 )
        TAF: Week 6 Post-partum (n=27)
    76939.32 ( 29189.555 )
        TAF: Week 12 Post-partum (n=30)
    92888.59 ( 29461.550 )
    No statistical analyses for this end point

    Secondary: PK Parameter: Vz/F of BIC, FTC, and TAF

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    End point title
    		 PK Parameter: Vz/F of BIC, FTC, and TAF [11]
    End point description
    Vz/F is defined as the apparent volume of distribution of the drug. Participants in the PK analysis set with available data were analysed.
    End point type
    Secondary
    End point timeframe
    Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
    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: The neonates did not receive the study drug so they were not analyzed for the secondary endpoint.
    End point values
    		 B/F/TAF
    Number of subjects analysed
    32
    Units: mL
    arithmetic mean (standard deviation)
        BIC: Second Trimester (n=19)
    11896.24 ( 4417.149 )
        BIC: Third Trimester (n=30)
    13406.77 ( 4349.429 )
        BIC: Week 6 Post-partum (n=29)
    10348.47 ( 3713.380 )
        BIC: Week 12 Post-partum (n=30)
    8692.59 ( 2398.645 )
        FTC: Second Trimester (n=20)
    181767.32 ( 36739.344 )
        FTC: Third Trimester (n=30)
    184791.79 ( 56340.526 )
        FTC: Week 6 Post-partum (n=28)
    117384.90 ( 35385.941 )
        FTC: Week 12 Post-partum (n=32)
    117660.87 ( 33240.095 )
        TAF: Second Trimester (n=14)
    62333.17 ( 37242.307 )
        TAF: Third Trimester (n=16)
    53230.98 ( 16727.325 )
        TAF: Week 6 Post-partum (n=26)
    44440.06 ( 13678.515 )
        TAF: Week 12 Post-partum (n=30)
    49837.70 ( 22019.454 )
    No statistical analyses for this end point

    Secondary: PK Parameter: λz of BIC, FTC, and TAF

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    End point title
    		 PK Parameter: λz of BIC, FTC, and TAF [12]
    End point description
    λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug. Participants in the PK analysis set with available data were analysed.
    End point type
    Secondary
    End point timeframe
    Intensive PK: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours postdose in second trimester (Weeks 20-28), third trimester (Weeks 30-38), Week 6 post-partum, and Week 12 post-partum
    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: The neonates did not receive the study drug so they were not analyzed for the secondary endpoint.
    End point values
    		 B/F/TAF
    Number of subjects analysed
    32
    Units: 1/h
    arithmetic mean (standard deviation)
        BIC: Second Trimester (n=19)
    0.077 ( 0.0231 )
        BIC: Third Trimester (n=30)
    0.068 ( 0.0125 )
        BIC: Week 6 Post-partum (n=29)
    0.040 ( 0.0098 )
        BIC: Week 12 Post-partum (n=30)
    0.043 ( 0.0134 )
        FTC: Second Trimester (n=20)
    0.113 ( 0.0142 )
        FTC: Third Trimester (n=30)
    0.112 ( 0.0173 )
        FTC: Week 6 Post-partum (n=28)
    0.114 ( 0.0151 )
        FTC: Week 12 Post-partum (n=32)
    0.120 ( 0.0209 )
        TAF: Second Trimester (n=14)
    2.227 ( 0.7128 )
        TAF: Third Trimester (n=16)
    2.550 ( 0.7519 )
        TAF: Week 6 Post-partum (n=26)
    1.777 ( 0.4685 )
        TAF: Week 12 Post-partum (n=30)
    1.954 ( 0.4519 )
    No statistical analyses for this end point

    Secondary: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at the Time of Delivery Using the Missing = Excluded Approach in B/F/TAF Group

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    End point title
    		 Percentage of Participants With HIV-1 RNA < 50 Copies/mL at the Time of Delivery Using the Missing = Excluded Approach in B/F/TAF Group [13]
    End point description
    The percentage of participants with HIV-1 RNA < 50 copies/mL at the time of delivery was analysed in B/F/TAF group using missing = excluded approach. In this approach, all missing data were excluded in the computation of the percentages (ie, missing data points were excluded from both the numerator and denominator in the computation). Full analysis set included all adult participants who enrolled into the study and took at least 1 dose of study drug (B/F/TAF). Participants in the full analysis set with available data were analysed.
    End point type
    Secondary
    End point timeframe
    At time of delivery
    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: This secondary endpoint was planned and analyzed only for the B/F/TAF group.
    End point values
    		 B/F/TAF
    Number of subjects analysed
    32
    Units: percentage of participants
        number (confidence interval 95%)
    100.0 (89.1 to 100.0)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Birth Using the Missing = Excluded Approach in Neonates

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    End point title
    		 Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Birth Using the Missing = Excluded Approach in Neonates [14]
    End point description
    The percentage of participants with HIV-1 RNA < 50 copies/mL at the time of birth was analysed in neonates using missing = excluded approach. In this approach, all missing data were excluded in the computation of the percentages (ie, missing data points were excluded from both the numerator and denominator in the computation). Neonate full analysis set included neonates who were born to women participating in the study and had been enrolled into the study as well. Participants in the neonate full analysis set with available data were analysed.
    End point type
    Secondary
    End point timeframe
    At birth
    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: This secondary endpoint was planned and analyzed only for the Neonates group.
    End point values
    		 Neonates
    Number of subjects analysed
    2
    Units: percentage of participants
        number (confidence interval 95%)
    100.0 (15.8 to 100.0)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All-Cause Mortality: From birth up to 8 weeks of age for neonates; From enrollment up to 38 weeks + 30 days for B/F/TAF group. Adverse Events: First dose date up to 38 weeks + 30 days for B/F/TAF group
    Adverse event reporting additional description
    B/F/TAF & Neonates:Safety analysis set. None of neonates participating in study were treated. Adverse events (AE) reported for that group are not treatment emergent (TE). TEAE: any AE with onset on/after start of study drug & no later than 30 days after permanent study drug discontinuation, or any AE leading to premature study drug discontinuation.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    B/F/TAF
    Reporting group description
    		 Pregnant women participants received FDC tablet of B/F/TAF 50/200/25 mg, orally, once daily for up to 38 weeks (from the second or third trimesters of pregnancy, depending on enrollment, through 12 weeks post-partum).

    Reporting group title
    Neonates
    Reporting group description
    		 Neonates born to women participants in the study were followed from birth up to 8 weeks of age after obtaining consent from the parent or legal guardian. None of the neonates participating in the study were treated with the study drug.

    Serious adverse events
    		 B/F/TAF Neonates
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 33 (18.18%)
    5 / 29 (17.24%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Congenital, familial and genetic disorders
    Accessory auricle
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial septal defect
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Nonreassuring foetal heart rate pattern
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    False labour
         subjects affected / exposed
    3 / 33 (9.09%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pre-eclampsia
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Preterm premature rupture of membranes
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Jaundice neonatal
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Neonatal asphyxia
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient tachypnoea of the newborn
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Covid-19
         subjects affected / exposed
    1 / 33 (3.03%)
    0 / 29 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis neonatal
         subjects affected / exposed
    0 / 33 (0.00%)
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 B/F/TAF Neonates
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    19 / 33 (57.58%)
    4 / 29 (13.79%)
    Cardiac disorders
    Foetal heart rate deceleration abnormality
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    Headache
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    Pregnancy, puerperium and perinatal conditions
    Gestational diabetes
         subjects affected / exposed
    4 / 33 (12.12%)
    0 / 29 (0.00%)
         occurrences all number
    4
    0
    Oligohydramnios
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    Postpartum haemorrhage
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    Pre-eclampsia
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    Jaundice neonatal
         subjects affected / exposed
    0 / 33 (0.00%)
    2 / 29 (6.90%)
         occurrences all number
    0
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 33 (9.09%)
    0 / 29 (0.00%)
         occurrences all number
    3
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    Haemorrhoids
         subjects affected / exposed
    2 / 33 (6.06%)
    0 / 29 (0.00%)
         occurrences all number
    2
    0
    Respiratory, thoracic and mediastinal disorders
    Respiratory distress
         subjects affected / exposed
    0 / 33 (0.00%)
    3 / 29 (10.34%)
         occurrences all number
    0
    3
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    4 / 33 (12.12%)
    0 / 29 (0.00%)
         occurrences all number
    4
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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