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    Clinical Trial Results:
    A Phase 3, Randomized, Active-Controlled, Double-blind Clinical Study to Evaluate the Efficacy and Safety of Oral Islatravir Once-Monthly as Preexposure Prophylaxis in Cisgender Women at High Risk for HIV-1 Infection

    Summary
    EudraCT number
    		 2021-001289-39
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    11 Jun 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    22 Dec 2024
    First version publication date
    22 Dec 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MK-8591-022
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04644029
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme LLC
    Sponsor organisation address
    126 East Lincoln Avenue, P.O. Box 2000, Rahway, NJ, United States, 07065
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme LLC, ClinicalTrialsDisclosure@merck.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-002938-PIP01-20
    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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    11 Jun 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    18 Jul 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Jun 2024
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    This study evaluated whether oral islatravir (ISL) is effective in preventing Human Immunodeficiency Virus Type 1 (HIV-1) infection in women at high-risk for HIV-1 infection. The study compared oral ISL taken once a month versus standard-of-care medication for prevention of HIV-1 infection, emtricitabine/tenofovir disoproxil (FTC/TDF) taken once per day. The primary hypothesis is that oral ISL is more effective than FTC/TDF at reducing the incidence rate per year of confirmed HIV-1 infections.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research. The following additional measure defined for this individual study was in place for the protection of trial subjects: Based on laboratory findings of decreased lymphocyte and CD4+ T-cell counts across the islatravir program, dosing of blinded study intervention was halted on 13-Dec-2021 and screening and randomization of new participants was ended. Blinded assessments conducted prior to this date are designated as Study Part 1. During Study Part 2, participants from Part 1 have the option to receive daily open-label FTC/TDF while continuing in the study for safety monitoring. Study Part 3 was added to unblind each participant's Part 1 study intervention assignment, continue participants on FTC/TDF, and monitor safety.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    24 Feb 2021
    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
    South Africa: 656
    Country: Number of subjects enrolled
    United States: 74
    Worldwide total number of subjects
    730
    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)
    0
    Adults (18-64 years)
    730
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 One person mistakenly received study drug without being randomized. They are not included in Participant Flow or Baseline Characteristics because they were not enrolled in the study, but their adverse events are reported in the Adverse Events module because they received study drug.

    Period 1
    Period 1 title
    Randomization
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ISL QM
    Arm description
    		 ISL (islatravir) once monthly AND placebo to FTC/TDF (emtricitabine/tenofovir disoproxil) once daily. Following study-wide cessation of ISL administration, participants had the option to receive open-label FTC/TDF. Placebo was no longer administered once open label treatment began.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo to FTC/TDF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    0 mg tablet administered once daily during Part 1.

    Investigational medicinal product name
    Islatravir
    Investigational medicinal product code
    Other name
    MK-8591
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral 60 mg tablet administered once monthly during Part 1.

    Arm title
    		 FTC/TDF QD
    Arm description
    		 FTC/TDF (TRUVADA™ or generic product emtricitabine/tenofovir disoproxil) administered once daily. Placebo to ISL (islatravir) administered once monthly. Following study-wide cessation of ISL administration, participants had the option to continue on open-label FTC/TDF. Placebo was no longer administered once open label treatment began.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Placebo to ISL
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    0 mg tablet administered orally once monthly in Part 1.

    Investigational medicinal product name
    FTC/TDF
    Investigational medicinal product code
    Other name
    TRUVADA™ Emtricitabine/Tenofovir disoproxil Emtricitabine/Tenofovir disoproxil fumarate
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Each tablet contains 200 mg emtricitabine and 245 mg of tenofovir disoproxil (equivalent to 300 mg tenofovir disoproxil fumarate or 201.22 mg tenofovir disoproxil phosphate), administered orally once daily in Parts 1, 2, and 3.

    Number of subjects in period 1
    		ISL QM FTC/TDF QD
    Started
    364
    366
    Completed
    362
    365
    Not completed
    2
    1
         Randomized in error: not treated
    2
    1
    Period 2
    Period 2 title
    Treatment
    Is this the baseline period?
    		 Yes [1]
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Data analyst, Assessor
    Blinding implementation details
    Part 1: A double-blinding technique with in-house blinding was used. Participants, investigators, and Sponsor personnel or delegates involved in study intervention administration or clinical evaluation were blinded. Part 2: Sponsor personnel not directly involved with blinded safety monitoring were unblinded to participants' Part 1 study intervention. Part 3: Participants, investigators, and all Sponsor personnel were unblinded to participants' original study intervention group.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ISL QM
    Arm description
    		 ISL (islatravir) once monthly AND placebo to FTC/TDF (emtricitabine/tenofovir disoproxil) once daily. Following study-wide cessation of ISL administration, participants had the option to receive open-label FTC/TDF. Placebo was no longer administered once open label treatment began.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo to FTC/TDF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    0 mg tablet administered once daily during Part 1.

    Investigational medicinal product name
    Islatravir
    Investigational medicinal product code
    Other name
    MK-8591
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral 60 mg tablet administered once monthly during Part 1.

    Arm title
    		 FTC/TDF QD
    Arm description
    		 FTC/TDF (TRUVADA™ or generic product emtricitabine/tenofovir disoproxil) administered once daily. Placebo to ISL (islatravir) administered once monthly. Following study-wide cessation of ISL administration, participants had the option to continue on open-label FTC/TDF. Placebo was no longer administered once open label treatment began.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Placebo to ISL
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    0 mg tablet administered orally once monthly in Part 1.

    Investigational medicinal product name
    FTC/TDF
    Investigational medicinal product code
    Other name
    TRUVADA™ Emtricitabine/Tenofovir disoproxil Emtricitabine/Tenofovir disoproxil fumarate
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Each tablet contains 200 mg emtricitabine and 245 mg of tenofovir disoproxil (equivalent to 300 mg tenofovir disoproxil fumarate or 201.22 mg tenofovir disoproxil phosphate), administered orally once daily in Parts 1, 2, and 3.

    Notes
    [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
    Justification: The All Patients as Treated population was used as the baseline population.
    Number of subjects in period 2 [2]
    		ISL QM FTC/TDF QD
    Started
    362
    365
    Received Open-Label FTC/TDF
    343
    345
    Completed
    0
    0
    Not completed
    362
    365
         Adverse event, serious fatal
    1
    -
         Physician decision
    1
    2
         Consent withdrawn by subject
    21
    19
         Unknown
    -
    1
         Study Terminated by Sponsor
    308
    309
         Lost to follow-up
    31
    34
    Notes
    [2] - 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: Baseline characteristics were calculated on the number of participants treated instead of the number randomized (worldwide total). 3 participants randomized in error and were not treated, so this "Treated" period is a more accurate representation of the population assessed throughout the study.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    ISL QM
    Reporting group description
    		 ISL (islatravir) once monthly AND placebo to FTC/TDF (emtricitabine/tenofovir disoproxil) once daily. Following study-wide cessation of ISL administration, participants had the option to receive open-label FTC/TDF. Placebo was no longer administered once open label treatment began.

    Reporting group title
    FTC/TDF QD
    Reporting group description
    		 FTC/TDF (TRUVADA™ or generic product emtricitabine/tenofovir disoproxil) administered once daily. Placebo to ISL (islatravir) administered once monthly. Following study-wide cessation of ISL administration, participants had the option to continue on open-label FTC/TDF. Placebo was no longer administered once open label treatment began.

    Reporting group values
    		 ISL QM FTC/TDF QD Total
    Number of subjects
    		 362 365 727
    Age categorical
    The baseline characteristics population includes all randomized participants who received study drug.
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 362 365 727
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age Continuous
    The baseline characteristics population includes all randomized participants who received study drug.
    Units: years
        arithmetic mean (standard deviation)
    		 26.0 ( 6.1 ) 26.1 ( 6.3 ) -
    Sex: Female, Male
    The baseline characteristics population includes all randomized participants who received study drug.
    Units: Participants
        Female
    		 362 365 727
        Male
    		 0 0 0
    Race (NIH/OMB)
    The baseline characteristics population includes all randomized participants who received study drug.
    Units: Subjects
        American Indian or Alaska Native
    		 1 1 2
        Asian
    		 5 6 11
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 334 338 672
        White
    		 19 15 34
        More than one race
    		 3 4 7
        Unknown or Not Reported
    		 0 1 1
    Ethnicity (NIH/OMB)
    The baseline characteristics population includes all randomized participants who received study drug.
    Units: Subjects
        Hispanic or Latino
    		 11 13 24
        Not Hispanic or Latino
    		 329 330 659
        Unknown or Not Reported
    		 22 22 44

    End points

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    End points reporting groups
    Reporting group title
    ISL QM
    Reporting group description
    		 ISL (islatravir) once monthly AND placebo to FTC/TDF (emtricitabine/tenofovir disoproxil) once daily. Following study-wide cessation of ISL administration, participants had the option to receive open-label FTC/TDF. Placebo was no longer administered once open label treatment began.

    Reporting group title
    FTC/TDF QD
    Reporting group description
    		 FTC/TDF (TRUVADA™ or generic product emtricitabine/tenofovir disoproxil) administered once daily. Placebo to ISL (islatravir) administered once monthly. Following study-wide cessation of ISL administration, participants had the option to continue on open-label FTC/TDF. Placebo was no longer administered once open label treatment began.
    Reporting group title
    ISL QM
    Reporting group description
    		 ISL (islatravir) once monthly AND placebo to FTC/TDF (emtricitabine/tenofovir disoproxil) once daily. Following study-wide cessation of ISL administration, participants had the option to receive open-label FTC/TDF. Placebo was no longer administered once open label treatment began.

    Reporting group title
    FTC/TDF QD
    Reporting group description
    		 FTC/TDF (TRUVADA™ or generic product emtricitabine/tenofovir disoproxil) administered once daily. Placebo to ISL (islatravir) administered once monthly. Following study-wide cessation of ISL administration, participants had the option to continue on open-label FTC/TDF. Placebo was no longer administered once open label treatment began.

    Primary: Incidence Rate Per Year of Confirmed HIV-1 infection Among Participants During Blinded Treatment +42 Days Post-Blind

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    End point title
    		 Incidence Rate Per Year of Confirmed HIV-1 infection Among Participants During Blinded Treatment +42 Days Post-Blind [1]
    End point description
    Incidence rate per year of confirmed HIV-1 infections is the number of participants with confirmed HIV-1 infections during the assessment period divided by the number of person-years in the arm. Data are based on participants with confirmed HIV-1 infection. The originally planned primary statistical analysis was removed via amendment when open-label treatment was initiated. The analysis population includes all participants who were randomized and received at least 1 dose of study intervention and did not have confirmed HIV-1 infections prior to or at randomization.
    End point type
    Primary
    End point timeframe
    Up to approximately 325 days
    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: No statistical analyses were planned for this endpoint.
    End point values
    		 ISL QM FTC/TDF QD
    Number of subjects analysed
    362
    363
    Units: Percentage of Participants/Person-Year
        number (not applicable)
    0.000
    0.000
    No statistical analyses for this end point

    Primary: Number of Participants Who Discontinued Blinded Study Treatment Due to an AE

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    End point title
    		 Number of Participants Who Discontinued Blinded Study Treatment Due to an AE [2]
    End point description
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued blinded study treatment due to an AE will be reported for each treatment arm. The analysis population includes all participants who were randomized and received at least 1 dose of study intervention.
    End point type
    Primary
    End point timeframe
    Up to 283 days
    Notes
    [2] - 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: No statistical analyses were planned for this endpoint.
    End point values
    		 ISL QM FTC/TDF QD
    Number of subjects analysed
    362
    365
    Units: Participants
    2
    4
    No statistical analyses for this end point

    Primary: Number of Participants Who Experienced an Adverse Event (AE) During Blinded Treatment + 42 Days Post-Blind

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    End point title
    		 Number of Participants Who Experienced an Adverse Event (AE) During Blinded Treatment + 42 Days Post-Blind [3]
    End point description
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced an AE will be reported for each treatment arm. The analysis population includes all participants who were randomized and received at least 1 dose of study intervention.
    End point type
    Primary
    End point timeframe
    Up to approximately 325 days
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses were planned for this endpoint.
    End point values
    		 ISL QM FTC/TDF QD
    Number of subjects analysed
    362
    365
    Units: Participants
    198
    255
    No statistical analyses for this end point

    Secondary: Incidence Rate Per Year During Blinded Treatment of Confirmed HIV-1 infection Among ISL-Treated Participants

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    End point title
    		 Incidence Rate Per Year During Blinded Treatment of Confirmed HIV-1 infection Among ISL-Treated Participants [4]
    End point description
    Incidence rate per year of confirmed HIV-1 infections is the number of participants with confirmed HIV-1 infections during the assessment period divided by the number of person-years in the arm. Data are based on participants with confirmed HIV-1 infection. The originally planned secondary statistical analysis was removed via amendment when open-label treatment was initiated. The analysis population includes all participants who were randomized and received at least 1 dose of ISL and did not have confirmed HIV-1 infections prior to or at randomization.
    End point type
    Secondary
    End point timeframe
    Up to approximately 237 days
    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: Per protocol, data are only presented for the ISL-treated arm.
    End point values
    		 ISL QM
    Number of subjects analysed
    362
    Units: Percentage of Participants/Person-Year
        number (not applicable)
    0.000
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Blinded arms and mistaken treatment arm: Up to approximately 325 days Open-label arms: Up to approximately 866 days (starting 42 days after last blinded treatment; includes the time leading up to first open-label treatment)
    Adverse event reporting additional description
    Following sponsor decision to stop dosing blinded study treatment, participants were offered the option to receive open-label FTC/TDF. Open-label arms include all events occurring >42 days after a participant's final blinded treatment. All-Cause Mortality includes all randomized participants starting from the time of randomization.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    FTC/TDF QD
    Reporting group description
    		 FTC/TDF (TRUVADA™ or generic product emtricitabine/tenofovir disoproxil) administered once daily. Placebo to ISL (islatravir) administered once monthly. Following study-wide cessation of ISL administration, participants had the option to continue on open-label FTC/TDF. Placebo was no longer administered once open label treatment began. Adverse events during the open-label period are not counted in this arm.

    Reporting group title
    ISL QM
    Reporting group description
    		 ISL (islatravir) once monthly AND placebo to FTC/TDF (emtricitabine/tenofovir disoproxil) once daily. Following study-wide cessation of ISL administration, participants had the option to receive open-label FTC/TDF administered once daily. Adverse events during the open-label period are not counted in this arm.

    Reporting group title
    FTC/TDF > Open-Label FTC/TDF Second Course
    Reporting group description
    		 This arm represents participants who received open-label FTC/TDF (TRUVADA™ or generic product emtricitabine/tenofovir disoproxil) administered once daily, after previously receiving FTC/TDF QD during the blinded portion of the study.

    Reporting group title
    FTC/TDF-Treated Without Randomization
    Reporting group description
    		 The participant in this arm was mistakenly given daily FTC/TDF plus monthly placebo to ISL without completing enrollment and randomization. Following study unblinding, participant continued to receive open-label daily FTC/TDF. Adverse events were collected for this participant during blinded and open-label treatment due to receiving study drug, but zero participants are reported as affected and zero adverse event instances are reported due to the risk of identification of a person.

    Reporting group title
    ISL QM > Open-Label FTC/TDF
    Reporting group description
    		 This arm represents participants who received open-label FTC/TDF (TRUVADA™ or generic product emtricitabine/tenofovir disoproxil) administered once daily, after previously receiving ISL QM during the blinded portion of the study.

    Serious adverse events
    		 FTC/TDF QD ISL QM FTC/TDF > Open-Label FTC/TDF Second Course FTC/TDF-Treated Without Randomization ISL QM > Open-Label FTC/TDF
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 365 (0.55%)
    4 / 362 (1.10%)
    22 / 345 (6.38%)
    0 / 1 (0.00%)
    13 / 343 (3.79%)
         number of deaths (all causes)
    0
    1
    0
    0
    0
         number of deaths resulting from adverse events
    0
    1
    0
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 365 (0.00%)
    1 / 362 (0.28%)
    0 / 345 (0.00%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    0 / 345 (0.00%)
    0 / 1 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    0 / 345 (0.00%)
    0 / 1 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Crush injury
         subjects affected / exposed
    0 / 365 (0.00%)
    1 / 362 (0.28%)
    0 / 345 (0.00%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skull fracture
         subjects affected / exposed
    0 / 365 (0.00%)
    1 / 362 (0.28%)
    0 / 345 (0.00%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion incomplete
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abortion spontaneous
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 362 (0.00%)
    4 / 345 (1.16%)
    0 / 1 (0.00%)
    2 / 343 (0.58%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 4
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ectopic pregnancy
         subjects affected / exposed
    0 / 365 (0.00%)
    1 / 362 (0.28%)
    0 / 345 (0.00%)
    0 / 1 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Failed trial of labour
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gestational hypertension
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Premature rupture of membranes
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prolonged labour
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    2 / 345 (0.58%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spontaneous rupture of membranes
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    0 / 345 (0.00%)
    0 / 1 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    0 / 345 (0.00%)
    0 / 1 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia of pregnancy
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Faecaloma
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    0 / 345 (0.00%)
    0 / 1 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 362 (0.00%)
    0 / 345 (0.00%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 365 (0.00%)
    1 / 362 (0.28%)
    0 / 345 (0.00%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    0 / 345 (0.00%)
    0 / 1 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicidal ideation
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intentional self-injury
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    0 / 345 (0.00%)
    0 / 1 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic inflammatory disease
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 362 (0.00%)
    0 / 345 (0.00%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 365 (0.00%)
    1 / 362 (0.28%)
    0 / 345 (0.00%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    1 / 345 (0.29%)
    0 / 1 (0.00%)
    0 / 343 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Type 1 diabetes mellitus
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    0 / 345 (0.00%)
    0 / 1 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abnormal loss of weight
         subjects affected / exposed
    0 / 365 (0.00%)
    0 / 362 (0.00%)
    0 / 345 (0.00%)
    0 / 1 (0.00%)
    1 / 343 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 FTC/TDF QD ISL QM FTC/TDF > Open-Label FTC/TDF Second Course FTC/TDF-Treated Without Randomization ISL QM > Open-Label FTC/TDF
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    210 / 365 (57.53%)
    145 / 362 (40.06%)
    284 / 345 (82.32%)
    0 / 1 (0.00%)
    292 / 343 (85.13%)
    Investigations
    CD4 lymphocytes decreased
         subjects affected / exposed
    4 / 365 (1.10%)
    4 / 362 (1.10%)
    14 / 345 (4.06%)
    0 / 1 (0.00%)
    18 / 343 (5.25%)
         occurrences all number
    4
    4
    18
    0
    24
    Blood pressure increased
         subjects affected / exposed
    4 / 365 (1.10%)
    2 / 362 (0.55%)
    18 / 345 (5.22%)
    0 / 1 (0.00%)
    21 / 343 (6.12%)
         occurrences all number
    5
    2
    21
    0
    28
    Blood creatine phosphokinase increased
         subjects affected / exposed
    3 / 365 (0.82%)
    1 / 362 (0.28%)
    10 / 345 (2.90%)
    0 / 1 (0.00%)
    19 / 343 (5.54%)
         occurrences all number
    3
    1
    11
    0
    20
    Blood bicarbonate decreased
         subjects affected / exposed
    1 / 365 (0.27%)
    0 / 362 (0.00%)
    21 / 345 (6.09%)
    0 / 1 (0.00%)
    17 / 343 (4.96%)
         occurrences all number
    1
    0
    25
    0
    22
    Creatinine renal clearance decreased
         subjects affected / exposed
    4 / 365 (1.10%)
    1 / 362 (0.28%)
    20 / 345 (5.80%)
    0 / 1 (0.00%)
    26 / 343 (7.58%)
         occurrences all number
    4
    1
    32
    0
    36
    Nervous system disorders
    Headache
         subjects affected / exposed
    53 / 365 (14.52%)
    43 / 362 (11.88%)
    56 / 345 (16.23%)
    0 / 1 (0.00%)
    61 / 343 (17.78%)
         occurrences all number
    65
    50
    83
    0
    90
    Dizziness
         subjects affected / exposed
    27 / 365 (7.40%)
    17 / 362 (4.70%)
    3 / 345 (0.87%)
    0 / 1 (0.00%)
    11 / 343 (3.21%)
         occurrences all number
    28
    17
    3
    0
    12
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    19 / 365 (5.21%)
    10 / 362 (2.76%)
    5 / 345 (1.45%)
    0 / 1 (0.00%)
    5 / 343 (1.46%)
         occurrences all number
    19
    12
    5
    0
    8
    Influenza like illness
         subjects affected / exposed
    3 / 365 (0.82%)
    4 / 362 (1.10%)
    41 / 345 (11.88%)
    0 / 1 (0.00%)
    45 / 343 (13.12%)
         occurrences all number
    3
    4
    62
    0
    65
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    41 / 365 (11.23%)
    19 / 362 (5.25%)
    13 / 345 (3.77%)
    0 / 1 (0.00%)
    13 / 343 (3.79%)
         occurrences all number
    43
    21
    15
    0
    16
    Diarrhoea
         subjects affected / exposed
    29 / 365 (7.95%)
    19 / 362 (5.25%)
    21 / 345 (6.09%)
    0 / 1 (0.00%)
    14 / 343 (4.08%)
         occurrences all number
    32
    19
    23
    0
    16
    Vomiting
         subjects affected / exposed
    22 / 365 (6.03%)
    8 / 362 (2.21%)
    12 / 345 (3.48%)
    0 / 1 (0.00%)
    15 / 343 (4.37%)
         occurrences all number
    25
    9
    13
    0
    17
    Reproductive system and breast disorders
    Heavy menstrual bleeding
         subjects affected / exposed
    11 / 365 (3.01%)
    13 / 362 (3.59%)
    39 / 345 (11.30%)
    0 / 1 (0.00%)
    33 / 343 (9.62%)
         occurrences all number
    15
    16
    53
    0
    42
    Vaginal discharge
         subjects affected / exposed
    11 / 365 (3.01%)
    7 / 362 (1.93%)
    30 / 345 (8.70%)
    0 / 1 (0.00%)
    30 / 343 (8.75%)
         occurrences all number
    12
    7
    38
    0
    36
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    8 / 365 (2.19%)
    11 / 362 (3.04%)
    25 / 345 (7.25%)
    0 / 1 (0.00%)
    16 / 343 (4.66%)
         occurrences all number
    8
    11
    28
    0
    19
    Infections and infestations
    Trichomoniasis
         subjects affected / exposed
    11 / 365 (3.01%)
    2 / 362 (0.55%)
    24 / 345 (6.96%)
    0 / 1 (0.00%)
    28 / 343 (8.16%)
         occurrences all number
    12
    2
    28
    0
    36
    Upper respiratory tract infection
         subjects affected / exposed
    12 / 365 (3.29%)
    21 / 362 (5.80%)
    55 / 345 (15.94%)
    0 / 1 (0.00%)
    70 / 343 (20.41%)
         occurrences all number
    13
    24
    74
    0
    89
    Gastroenteritis
         subjects affected / exposed
    6 / 365 (1.64%)
    7 / 362 (1.93%)
    18 / 345 (5.22%)
    0 / 1 (0.00%)
    16 / 343 (4.66%)
         occurrences all number
    6
    7
    18
    0
    18
    Chlamydial infection
         subjects affected / exposed
    17 / 365 (4.66%)
    4 / 362 (1.10%)
    55 / 345 (15.94%)
    0 / 1 (0.00%)
    58 / 343 (16.91%)
         occurrences all number
    17
    4
    71
    0
    78
    Bacterial vaginosis
         subjects affected / exposed
    57 / 365 (15.62%)
    28 / 362 (7.73%)
    143 / 345 (41.45%)
    0 / 1 (0.00%)
    158 / 343 (46.06%)
         occurrences all number
    59
    30
    255
    0
    263
    Urinary tract infection
         subjects affected / exposed
    5 / 365 (1.37%)
    0 / 362 (0.00%)
    34 / 345 (9.86%)
    0 / 1 (0.00%)
    31 / 343 (9.04%)
         occurrences all number
    5
    0
    38
    0
    38
    Vulvovaginal candidiasis
         subjects affected / exposed
    29 / 365 (7.95%)
    13 / 362 (3.59%)
    109 / 345 (31.59%)
    0 / 1 (0.00%)
    114 / 343 (33.24%)
         occurrences all number
    30
    13
    160
    0
    163

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 May 2021
    Amendment 1: Modified the management of participants who become pregnant, modified PK assessments for participants who become pregnant and remain on ISL, and modified breastfeeding options for participants who become pregnant.
    07 Dec 2021
    Amendment 2: Increased frequency of monitoring of lymphocytes, added monitoring of CD4+ T-cells, and added discontinuation criteria in response to findings of decreases in lymphocytes (in studies of participants with or without HIV) and CD4+ T-cell counts (in studies of participants with HIV) in ISL clinical studies.
    01 Mar 2022
    Amendment 3: Defined changes in study design and conduct implemented due to stopping of blinded study intervention, and to describe continued monitoring of participants, as a result of the 13-Dec-2021 discontinuation of blinded study intervention and consequent treatment changes.
    29 Jun 2022
    Amendment 4: Added Part 3 to the study to unblind each participant’s Part 1 study intervention assignment, continue participants on FTC/TDF, and monitor safety.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    11 Jun 2024
    This is date of study termination after adequate follow-up with infants born to participants enrolled in the study.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Based on laboratory findings of decreased lymphocyte and CD4+ T-cell counts across the islatravir program, dosing of blinded study intervention was halted on 13-Dec-2021 and screening and randomization of new participants was ended.
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    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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