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DISCOVER: Study to Evaluate the Safety and Efficacy of Emtricitabine and Tenofovir Alafenamide (F/TAF) Fixed-Dose Combination Once Daily for Pre-Exposure Prophylaxis in Men and Transgender Women Who Have Sex With Men and Are At Risk of HIV-1 Infection

Sponsor
Gilead Sciences (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02842086
Collaborator
(none)
5,399
Enrollment
93
Locations
4
Arms
131.9
Anticipated Duration (Months)
58.1
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to assess the rates of HIV-1 infection in Men (MSM) and transgender women (TGW) who have sex with men and who are administered daily emtricitabine/tenofovir alafenamide (F/TAF) or emtricitabine/tenofovir disoproxil fumarate (F/TDF) with a minimum follow-up of 48 weeks and at least 50% of participants have 96 weeks of follow-up after randomization.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
5399 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Double-blind Study to Evaluate the Safety and Efficacy of Emtricitabine and Tenofovir Alafenamide (F/TAF) Fixed-Dose Combination Once Daily for Pre-Exposure Prophylaxis in Men and Transgender Women Who Have Sex With Men and Are At Risk of HIV-1 Infection
Actual Study Start Date :
Sep 2, 2016
Actual Primary Completion Date :
Jan 31, 2019
Anticipated Study Completion Date :
Sep 1, 2027

Arms and Interventions

Arm Intervention/Treatment
Experimental: F/TAF

F/TAF+ F/TDF placebo for at least 96 weeks

Drug: F/TAF
200/25 mg tablet administered orally once daily
Other Names:
  • Descovy®

    • Drug: F/TDF Placebo
    Tablet administered orally once daily
    Experimental: F/TDF

    F/TDF+ F/TAF placebo for at least 96 weeks

    Drug: F/TDF
    200/300 mg tablet administered orally once daily
    Other Names:
  • Truvada®

    • Drug: F/TAF Placebo
    Tablet administered orally once daily
    Experimental: Open-label

    Once all participants have been on blinded treatment for at least 96 weeks, the study will be unblinded and participants will be offered the option to continue on open-label F/TAF treatment for 96 weeks.

    Drug: F/TAF
    200/25 mg tablet administered orally once daily
    Other Names:
  • Descovy®

    		•
    Experimental: Open-Label Extension

    Participants who remain on study at Open-label Week 96 will have the option to continue on open-label F/TAF treatment in the Open-label extension phase for 408 weeks.

    Drug: F/TAF
    200/25 mg tablet administered orally once daily
    Other Names:
  • Descovy®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of HIV-1 Infection Per 100 Person Years (PY) [When all participants completed minimum follow-up of 48 weeks and at least 50% of the participants completed 96 weeks of follow-up after randomization or permanently discontinued from the study (maximum 125 weeks)]

      The incidence of HIV-1 infection rate per 100 PY was calculated as the number of participants who became HIV infected during the study after the first dose of study drug divided by the sum of all participants' years (where a year is 365.25 days) of follow-up while at risk of HIV infection during the study. HIV-1 infection is defined by one or more of the following criteria of contributing HIV tests performed via central lab or local lab: Serologic evidence of seroconversion (reactive screening HIV Antigen/Antibody or Antibody test, confirmed by reactive HIV-1/HIV-2 differentiation assay), excluding HIV vaccinated participants, or Virologic evidence of HIV-1 infection (positive qualitative HIV-1 RNA test or any detectable quantitative HIV-1 RNA test), or Evidence of acute HIV-1 infection (reactive p24 Antigen or positive qualitative or quantitative RNA, in the absence of reactive HIV-1 Antibody results)

    Secondary Outcome Measures

    1. Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 in the Blinded Phase [Baseline, Week 48]

      Percent Change = Change from baseline at Week 48 visit/value at baseline * 100%.

    2. Percent Change From Baseline in Spine BMD at Week 48 in the Blinded Phase [Baseline, Week 48]

      Percent Change = Change from baseline at Week 48 visit/value at baseline * 100%.

    3. Percent Change From Baseline in Urine Beta-2-Microglobulin to Creatinine Ratio at Week 48 in the Blinded Phase [Baseline, Week 48]

      Percent Change = Change from baseline at Week 48 visit/value at baseline * 100%. For urine creatinine, value of < 1 was handled as a missing value in its summary and the calculation of related ratios.

    4. Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48 in the Blinded Phase [Baseline, Week 48]

      Percent Change = Change from baseline at Week 48 visit/value at baseline * 100%. For urine creatinine, value of < 1 was handled as a missing value in its summary and the calculation of related ratios.

    5. Number of Participants by Urine Protein (UP) and Urine Protein to Creatinine Ratio (UPCR) Categories at Week 48 in the Blinded Phase [Baseline, Week 48]

      The UPCR was only calculated when corresponding UP ≥ 4.0 mg/dL. The UPCR "≤ 200 mg/g" category includes both participants with UP < 4.0 mg/dL and participants with UPCR ≤ 200 mg/g.

    6. Change From Baseline in Serum Creatinine at Week 48 in the Blinded Phase [Baseline, Week 48]

    7. Incidence of HIV-1 Infection Per 100 PY [When all participants have 96 weeks of follow-up after randomization or permanently discontinued from the study (maximum 157 weeks)]

      The incidence of HIV-1 infection rate per 100 PY was calculated as the number of participants who became HIV infected during the study after the first dose of study drug divided by the sum of all participants' years (where a year is 365.25 days) of follow-up while at risk of HIV infection during the study. HIV-1 infection is defined by one or more of the following criteria of contributing HIV tests performed via central lab or local lab: Serologic evidence of seroconversion (reactive screening HIV Antigen/Antibody or Antibody test, confirmed by reactive HIV-1/HIV-2 differentiation assay), excluding HIV vaccinated participants, or Virologic evidence of HIV-1 infection (positive qualitative HIV-1 RNA test or any detectable quantitative HIV-1 RNA test), or Evidence of acute HIV-1 infection (reactive p24 Antigen or positive qualitative or quantitative RNA, in the absence of reactive HIV-1 Antibody results)

    8. Percent Change From Baseline in Hip BMD at Week 96 in the Blinded Phase [Baseline, Week 96]

      Percent Change = Change from baseline at Week 96 visit/value at baseline * 100%.

    9. Percent Change From Baseline in Spine BMD at Week 96 in the Blinded Phase [Baseline, Week 96]

      Percent Change = Change from baseline at Week 96 visit/value at baseline * 100%.

    10. Percent Change From Baseline in Urine Beta-2-Microglobulin to Creatinine Ratio at Week 96 in the Blinded Phase [Baseline, Week 96]

      Percent Change = Change from baseline at Week 96 visit/value at baseline * 100%. For urine creatinine, value of < 1 was handled as a missing value in its summary and the calculation of related ratios.

    11. Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96 in the Blinded Phase [Baseline, Week 96]

      Percent Change = Change from baseline at Week 96 visit/value at baseline * 100%. For urine creatinine, value of < 1 was handled as a missing value in its summary and the calculation of related ratios.

    12. Number of Participants by UP and UPCR Categories at Week 96 in the Blinded Phase [Baseline, Week 96]

      The UPCR was only calculated when corresponding UP ≥ 4.0 mg/dL. The UPCR "≤ 200 mg/g" category includes both participants with UP < 4.0 mg/dL and participants with UPCR ≤ 200 mg/g.

    13. Change From Baseline in Serum Creatinine at Week 96 in the Blinded Phase [Baseline, Week 96]

    14. Percentage of Participants Experiencing Treatment-Emergent Adverse Events [First dose date up to the data cut for end of blinded treatment (maximum: 157 weeks)]

    15. Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality [First dose date up to the data cut for end of blinded treatment (maximum: 157 weeks)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Key Inclusion Criteria:

    • Must be at high risk of sexual acquisition of HIV

    • HIV-1 negative status

    • MSM and TGW (male at birth) who have at least one of the following:

    • condomless anal intercourse with at least two unique male partners in the past 12 weeks (partners must be either HIV-infected or of unknown HIV status)

    • documented history of syphilis in the past 24 weeks

    • documented history of rectal gonorrhea or chlamydia in the past 24 weeks

    • Adequate renal function: estimated glomerular filtration rate ≥ 60 mL/min according to the Cockcroft-Gault formula

    • Adequate liver and hematologic function:

    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN) and total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin

    • Absolute neutrophil count ≥ 1000/mm3; platelets ≥ 75,000/mm3; hemoglobin ≥ 10 g/dL

    Key Exclusion Criteria

    • Grade 3 or Grade 4 proteinuria or glycosuria that is unexplained or not clinically manageable.

    NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Beverly Hills California United States 90211
    2 Los Angeles California United States 90036
    3 Los Angeles California United States 90069
    4 Newport Beach California United States 92663
    5 Oakland California United States 94609
    6 Sacramento California United States 95817
    7 Sacramento California United States 95825
    8 San Diego California United States 92103
    9 San Francisco California United States 94102
    10 San Francisco California United States 94103
    11 San Francisco California United States 94118
    12 Torrance California United States 90502
    13 Aurora Colorado United States 80045
    14 Denver Colorado United States 80209
    15 New Haven Connecticut United States 06510
    16 Washington District of Columbia United States 20009
    17 Washington District of Columbia United States 20036
    18 Fort Lauderdale Florida United States 33308
    19 Fort Lauderdale Florida United States 33316
    20 Fort Pierce Florida United States 34982
    21 Miami Florida United States 33136
    22 Orlando Florida United States 32803
    23 Pensacola Florida United States 32504
    24 West Palm Beach Florida United States 33407
    25 Atlanta Georgia United States 30308
    26 Atlanta Georgia United States 30309
    27 Atlanta Georgia United States 30312
    28 Macon Georgia United States 31201
    29 Chicago Illinois United States 60612
    30 Chicago Illinois United States 60613
    31 New Orleans Louisiana United States 70119
    32 Boston Massachusetts United States 02215
    33 Springfield Massachusetts United States 01105
    34 Berkley Michigan United States 48072
    35 Detroit Michigan United States 48202
    36 Minneapolis Minnesota United States 55415
    37 Las Vegas Nevada United States 89104
    38 Somers Point New Jersey United States 08244
    39 Santa Fe New Mexico United States 87505
    40 Bronx New York United States 10467
    41 New York New York United States 10029
    42 New York New York United States 10032
    43 New York New York United States 10037
    44 Chapel Hill North Carolina United States 27599-7215
    45 Huntersville North Carolina United States 28078
    46 Cleveland Ohio United States 44109
    47 Philadelphia Pennsylvania United States 19107
    48 Austin Texas United States 78705
    49 Dallas Texas United States 75208
    50 Dallas Texas United States 75246
    51 Houston Texas United States 77098
    52 Seattle Washington United States 98101
    53 Seattle Washington United States 98104
    54 Milwaukee Wisconsin United States 53226
    55 Graz Austria 8051
    56 Vienna Austria 1090
    57 Vancouver British Columbia Canada V6Z 2T1
    58 Toronto Ontario Canada M5G 1K2
    59 Montreal Quebec Canada H2l 4P9
    60 Montreal Quebec Canada H2L5B1
    61 Montréal Quebec Canada H2W 1T8
    62 Hvidovre Region Hovedstaden Denmark 2650
    63 Aarhus N Region Midtjylland Denmark 8200
    64 Copenhagen RegionH Denmark 2100
    65 Odense Denmark 5000
    66 Nice Alpe Maritimes France 6202
    67 Marseille Provence France 13006
    68 Paris Provence France 75020
    69 Paris cedex 10 France 75475
    70 Munich Bavaria Germany 81675
    71 Berlin Germany 10439
    72 Berlin Germany 10777
    73 Frankfurt Germany 60596
    74 Dublin 7 Dublin Ireland D07 A8NN
    75 Dublin Ireland 8
    76 Milan Italy 20127
    77 Roma Italy 00149
    78 Amsterdam Netherlands
    79 Badalona Barcelona Spain 08907
    80 Barcelona Spain 08015
    81 Madrid Spain 28010
    82 Vigo Spain 36312
    83 Soho London United Kingdom W1D 6AQ
    84 Whitechapel London United Kingdom E1 1BB
    85 Edinburgh Scotland United Kingdom EH3 9HA
    86 Brighton Sussex United Kingdom BN2 1ES
    87 Birmingham United Kingdom B9 5SS
    88 London United Kingdom E9 6SR
    89 London United Kingdom SE18 4QH
    90 London United Kingdom SE5 9RJ
    91 London United Kingdom W2 1NY
    92 London United Kingdom WC1E 6JB
    93 Manchester United Kingdom M13 0FH

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT02842086
    Other Study ID Numbers:
    • GS-US-412-2055
    • 2016-001399-31
    First Posted:
    Jul 22, 2016
    Last Update Posted:
    Jul 15, 2022
    Last Verified:
    Jun 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Infections
    Communicable Diseases
    HIV Infections
    Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
    Emtricitabine tenofovir alafenamide

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at study sites in the United States, Canada, and the European Union. The first participant was screened on 02 September 2016. The data cut date for the end of blinded treatment phase was 12 December 2019.
    Pre-assignment Detail 5857 participants were screened.
    Arm/Group Title Descovy (DVY) Truvada (TVD)
    Arm/Group Description Blinded Phase: Descovy (DVY; emtricitabine/tenofovir alafenamide [F/TAF] 200/25 mg) fixed-dose combination (FDC) tablet plus placebo-to-match Truvada (TVD) (emtricitabine/tenofovir disoproxil fumarate [F/TDF] 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. Blinded Phase: TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks.
    Period Title: Overall Study
    STARTED 2700 2699
    COMPLETED 2156 2206
    NOT COMPLETED 544 493

    Baseline Characteristics

    Arm/Group Title Descovy (DVY) Truvada (TVD) Total
    Arm/Group Description Blinded Phase: DVY (F/TAF 200/25 mg) FDC tablet plus placebo-to-match TVD (F/TDF 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. Blinded Phase: TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks. Total of all reporting groups
    Overall Participants 2694 2693 5387
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    36
    (10.6)
    36
    (10.7)
    36
    (10.6)
    Sex/Gender, Customized (Count of Participants)
    Transgender Women
    45
    1.7%
    29
    1.1%
    74
    1.4%
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    Male
    2694
    100%
    2693
    100%
    5387
    100%
    Race/Ethnicity, Customized (Count of Participants)
    American Indian or Alaska Native
    12
    0.4%
    14
    0.5%
    26
    0.5%
    Asian
    113
    4.2%
    120
    4.5%
    233
    4.3%
    Black/Mixed Black
    240
    8.9%
    234
    8.7%
    474
    8.8%
    Native Hawaiian or Pacific Islander
    17
    0.6%
    23
    0.9%
    40
    0.7%
    White
    2264
    84%
    2247
    83.4%
    4511
    83.7%
    Other (Nonblack)
    45
    1.7%
    50
    1.9%
    95
    1.8%
    Not Permitted
    3
    0.1%
    5
    0.2%
    8
    0.1%
    Race/Ethnicity, Customized (Count of Participants)
    Hispanic or Latino
    635
    23.6%
    683
    25.4%
    1318
    24.5%
    Not Hispanic or Latino
    2058
    76.4%
    2008
    74.6%
    4066
    75.5%
    Not Permitted
    1
    0%
    2
    0.1%
    3
    0.1%
    Region of Enrollment (Count of Participants)
    Canada
    191
    7.1%
    162
    6%
    353
    6.6%
    Austria
    35
    1.3%
    42
    1.6%
    77
    1.4%
    Denmark
    98
    3.6%
    104
    3.9%
    202
    3.7%
    France
    18
    0.7%
    14
    0.5%
    32
    0.6%
    Germany
    187
    6.9%
    183
    6.8%
    370
    6.9%
    Ireland
    40
    1.5%
    38
    1.4%
    78
    1.4%
    Italy
    37
    1.4%
    21
    0.8%
    58
    1.1%
    Netherlands
    31
    1.2%
    40
    1.5%
    71
    1.3%
    Spain
    219
    8.1%
    195
    7.2%
    414
    7.7%
    United Kingdom
    247
    9.2%
    265
    9.8%
    512
    9.5%
    United States
    1591
    59.1%
    1629
    60.5%
    3220
    59.8%
    Hip Bone Mineral Density (BMD) (g/cm^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [g/cm^2]
    1.030
    (0.1553)
    1.021
    (0.1322)
    1.025
    (0.1443)
    Spine BMD (g/cm^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [g/cm^2]
    1.134
    (0.1646)
    1.131
    (0.1381)
    1.132
    (0.1518)
    Urine Beta-2 Microglobulin to Creatinine Ratio (µg/g) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [µg/g]
    204.3
    (951.77)
    188.5
    (1010.19)
    196.4
    (981.35)
    Urine Retinol Binding Protein (RBP) to Creatinine Ratio (µg/g) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [µg/g]
    148.8
    (553.54)
    142.8
    (256.64)
    145.8
    (431.41)
    Urine Protein (UP) and Urine Protein to Creatinine Ratio (UPCR) Categories (Count of Participants)
    ≤ 200 mg/g
    2662
    98.8%
    2657
    98.7%
    5319
    98.7%
    > 200 mg/g
    25
    0.9%
    25
    0.9%
    50
    0.9%
    Serum Creatinine (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    0.96
    (0.146)
    0.96
    (0.148)
    0.96
    (0.147)

    Outcome Measures

    1. Primary Outcome
    Title Incidence of HIV-1 Infection Per 100 Person Years (PY)
    Description The incidence of HIV-1 infection rate per 100 PY was calculated as the number of participants who became HIV infected during the study after the first dose of study drug divided by the sum of all participants' years (where a year is 365.25 days) of follow-up while at risk of HIV infection during the study. HIV-1 infection is defined by one or more of the following criteria of contributing HIV tests performed via central lab or local lab: Serologic evidence of seroconversion (reactive screening HIV Antigen/Antibody or Antibody test, confirmed by reactive HIV-1/HIV-2 differentiation assay), excluding HIV vaccinated participants, or Virologic evidence of HIV-1 infection (positive qualitative HIV-1 RNA test or any detectable quantitative HIV-1 RNA test), or Evidence of acute HIV-1 infection (reactive p24 Antigen or positive qualitative or quantitative RNA, in the absence of reactive HIV-1 Antibody results)
    Time Frame When all participants completed minimum follow-up of 48 weeks and at least 50% of the participants completed 96 weeks of follow-up after randomization or permanently discontinued from the study (maximum 125 weeks)

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set included all participants who were randomized into the study, received at least 1 dose of study drug, were not HIV positive on Day 1, and had at least 1 postbaseline HIV laboratory assessment.
    Arm/Group Title Descovy (DVY) Truvada (TVD)
    Arm/Group Description Blinded Phase: DVY (F/TAF 200/25 mg) FDC tablet plus placebo-to-match TVD (F/TDF 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. Blinded Phase: TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks.
    Measure Participants 2670 2665
    Number (95% Confidence Interval) [HIV-1 infections per 100 PY]
    0.160
    0.342
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Descovy (DVY), Truvada (TVD)
    Comments Noninferiority was assessed using a 95.003% confidence interval (CI) constructed using a generalized model associated with a Poisson distribution and logarithmic link with the treatment group being the main effect and with a noninferiority margin of 1.62.
    Type of Statistical Test Non-Inferiority
    Comments Noninferiority of DVY to TVD was to be concluded if the upper bound of the 2-sided 95.003% CI of the rate ratio (DVY group over TVD group) in the HIV infection incidence rate was less than 1.62.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Rate Ratio
    Estimated Value 0.468
    Confidence Interval (2-Sided) 95.003%
    0.191 to 1.149
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 in the Blinded Phase
    Description Percent Change = Change from baseline at Week 48 visit/value at baseline * 100%.
    Time Frame Baseline, Week 48

    Outcome Measure Data

    Analysis Population Description
    Hip Dual-Energy X-ray Absorptiometry (DXA) Analysis Set included all DXA substudy participants who were randomized and received at least one dose of study drug, and had nonmissing hip BMD value for the baseline visit. Participants were grouped according to the treatment they actually received. Participants with available data were analyzed.
    Arm/Group Title Descovy (DVY) Truvada (TVD)
    Arm/Group Description Blinded Phase: DVY (F/TAF 200/25 mg) FDC tablet plus placebo-to-match TVD (F/TDF 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. Blinded Phase: TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks.
    Measure Participants 159 157
    Mean (Standard Deviation) [Percent Change]
    0.218
    (2.3668)
    -0.968
    (2.4343)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Descovy (DVY), Truvada (TVD)
    Comments Hip BMD results were compared between the 2 treatment groups using analysis of variance (ANOVA), which included baseline TVD for pre-exposure prophylaxis (PrEP) and treatment as fixed effects.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Difference in least squares mean (LSM)
    Estimated Value 1.142
    Confidence Interval (2-Sided) 95%
    0.628 to 1.655
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Percent Change From Baseline in Spine BMD at Week 48 in the Blinded Phase
    Description Percent Change = Change from baseline at Week 48 visit/value at baseline * 100%.
    Time Frame Baseline, Week 48

    Outcome Measure Data

    Analysis Population Description
    Spine DXA Analysis Set included all DXA substudy participants who were randomized and received at least one dose of study drug, and had nonmissing spine BMD value for the baseline visit. Participants were grouped according to the treatment they actually received. Participants with available data were analyzed.
    Arm/Group Title Descovy (DVY) Truvada (TVD)
    Arm/Group Description Blinded Phase: DVY (F/TAF 200/25 mg) FDC tablet plus placebo-to-match TVD (F/TDF 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. Blinded Phase: TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks.
    Measure Participants 160 159
    Mean (Standard Deviation) [Percent Change]
    0.512
    (2.9854)
    -1.061
    (2.9382)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Descovy (DVY), Truvada (TVD)
    Comments Spine BMD results were compared between the 2 treatment groups using ANOVA, which included baseline TVD for PrEP and treatment as fixed effects.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LSM
    Estimated Value 1.567
    Confidence Interval (2-Sided) 95%
    0.913 to 2.220
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Percent Change From Baseline in Urine Beta-2-Microglobulin to Creatinine Ratio at Week 48 in the Blinded Phase
    Description Percent Change = Change from baseline at Week 48 visit/value at baseline * 100%. For urine creatinine, value of < 1 was handled as a missing value in its summary and the calculation of related ratios.
    Time Frame Baseline, Week 48

    Outcome Measure Data

    Analysis Population Description
    The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug. Participants were grouped according to the treatment they actually received. Participants with available data were analyzed.
    Arm/Group Title Descovy (DVY) Truvada (TVD)
    Arm/Group Description Blinded Phase: DVY (F/TAF 200/25 mg) FDC tablet plus placebo-to-match TVD (F/TDF 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. Blinded Phase: TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks.
    Measure Participants 2346 2337
    Median (Inter-Quartile Range) [Percent Change]
    -10.6
    15.4
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Descovy (DVY), Truvada (TVD)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-values were from the Van Elteren test stratified by baseline TVD for PrEP.
    Method Van Elteren test
    Comments
    5. Secondary Outcome
    Title Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48 in the Blinded Phase
    Description Percent Change = Change from baseline at Week 48 visit/value at baseline * 100%. For urine creatinine, value of < 1 was handled as a missing value in its summary and the calculation of related ratios.
    Time Frame Baseline, Week 48

    Outcome Measure Data

    Analysis Population Description
    Participants in Safety Analysis Set with available data were analyzed.
    Arm/Group Title Descovy (DVY) Truvada (TVD)
    Arm/Group Description Blinded Phase: DVY (F/TAF 200/25 mg) FDC tablet plus placebo-to-match TVD (F/TDF 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. Blinded Phase: TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks.
    Measure Participants 2360 2354
    Median (Inter-Quartile Range) [Percent Change]
    0.1
    20.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Descovy (DVY), Truvada (TVD)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-values were from the Van Elteren test stratified by baseline TVD for PrEP.
    Method Van Elteren test
    Comments
    6. Secondary Outcome
    Title Number of Participants by Urine Protein (UP) and Urine Protein to Creatinine Ratio (UPCR) Categories at Week 48 in the Blinded Phase
    Description The UPCR was only calculated when corresponding UP ≥ 4.0 mg/dL. The UPCR "≤ 200 mg/g" category includes both participants with UP < 4.0 mg/dL and participants with UPCR ≤ 200 mg/g.
    Time Frame Baseline, Week 48

    Outcome Measure Data

    Analysis Population Description
    Participants in Safety Analysis Set with available data were analyzed.
    Arm/Group Title Descovy (DVY) Truvada (TVD)
    Arm/Group Description Blinded Phase: DVY (F/TAF 200/25 mg) FDC tablet plus placebo-to-match TVD (F/TDF 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. Blinded Phase: TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks.
    Measure Participants 2355 2348
    ≤ 200 mg/g at Baseline; ≤ 200 mg/g at Week 48
    2318
    86%
    2295
    85.2%
    ≤ 200 mg/g at Baseline; > 200 mg/g at Week 48
    16
    0.6%
    35
    1.3%
    > 200 mg/g at Baseline; ≤ 200 mg/g at Week 48
    12
    0.4%
    8
    0.3%
    > 200 mg/g at Baseline; > 200 mg/g at Week 48
    9
    0.3%
    10
    0.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Descovy (DVY), Truvada (TVD)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0048
    Comments P-value for difference between treatment groups in distributions of UPCR ≤ 200 mg/g versus > 200 mg/g was from the rank analysis of covariance adjusting for baseline category and baseline TVD for PrEP.
    Method Rank analysis of covariance
    Comments
    7. Secondary Outcome
    Title Change From Baseline in Serum Creatinine at Week 48 in the Blinded Phase
    Description
    Time Frame Baseline, Week 48

    Outcome Measure Data

    Analysis Population Description
    Participants in Safety Analysis Set with available data were analyzed.
    Arm/Group Title Descovy (DVY) Truvada (TVD)
    Arm/Group Description Blinded Phase: DVY (F/TAF 200/25 mg) FDC tablet plus placebo-to-match TVD (F/TDF 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. Blinded Phase: TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks.
    Measure Participants 2370 2368
    Mean (Standard Deviation) [mg/dL]
    -0.01
    (0.107)
    0.01
    (0.111)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Descovy (DVY), Truvada (TVD)
    Comments Results were compared between the 2 treatment groups using the analysis of covariance (ANCOVA) model including baseline TVD for PrEP and treatment as fixed effects and baseline serum creatinine as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LSM
    Estimated Value -0.02
    Confidence Interval (2-Sided) 95%
    -0.02 to -0.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Incidence of HIV-1 Infection Per 100 PY
    Description The incidence of HIV-1 infection rate per 100 PY was calculated as the number of participants who became HIV infected during the study after the first dose of study drug divided by the sum of all participants' years (where a year is 365.25 days) of follow-up while at risk of HIV infection during the study. HIV-1 infection is defined by one or more of the following criteria of contributing HIV tests performed via central lab or local lab: Serologic evidence of seroconversion (reactive screening HIV Antigen/Antibody or Antibody test, confirmed by reactive HIV-1/HIV-2 differentiation assay), excluding HIV vaccinated participants, or Virologic evidence of HIV-1 infection (positive qualitative HIV-1 RNA test or any detectable quantitative HIV-1 RNA test), or Evidence of acute HIV-1 infection (reactive p24 Antigen or positive qualitative or quantitative RNA, in the absence of reactive HIV-1 Antibody results)
    Time Frame When all participants have 96 weeks of follow-up after randomization or permanently discontinued from the study (maximum 157 weeks)

    Outcome Measure Data

    Analysis Population Description
    Participants in Full Analysis Set were analyzed.
    Arm/Group Title Descovy (DVY) Truvada (TVD)
    Arm/Group Description Blinded Phase: DVY (F/TAF 200/25 mg) FDC tablet plus placebo-to-match TVD (F/TDF 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. Blinded Phase: TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks.
    Measure Participants 2670 2665
    Number (95% Confidence Interval) [HIV-1 infections per 100 PY]
    0.159
    0.297
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Descovy (DVY), Truvada (TVD)
    Comments Noninferiority was assessed using a 95.003% CI constructed using a generalized model associated with a Poisson distribution and logarithmic link with the treatment group being the main effect and with a noninferiority margin of 1.62.
    Type of Statistical Test Non-Inferiority
    Comments Noninferiority of DVY to TVD was to be concluded if the upper bound of the 2-sided 95.003% CI of the rate ratio (DVY group over TVD group) in the HIV infection incidence rate was less than 1.62.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Rate Ratio
    Estimated Value 0.536
    Confidence Interval (2-Sided) 95.003%
    0.227 to 1.264
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Percent Change From Baseline in Hip BMD at Week 96 in the Blinded Phase
    Description Percent Change = Change from baseline at Week 96 visit/value at baseline * 100%.
    Time Frame Baseline, Week 96

    Outcome Measure Data

    Analysis Population Description
    Participants in Hip DXA Analysis Set with available data were analyzed.
    Arm/Group Title Descovy (DVY) Truvada (TVD)
    Arm/Group Description Blinded Phase: DVY (F/TAF 200/25 mg) FDC tablet plus placebo-to-match TVD (F/TDF 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. Blinded Phase: TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks.
    Measure Participants 144 138
    Mean (Standard Deviation) [Percent Change]
    0.565
    (2.9379)
    -1.048
    (2.9277)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Descovy (DVY), Truvada (TVD)
    Comments Hip BMD results were compared between the 2 treatment groups using ANOVA, which included baseline TVD for PrEP and treatment as fixed effects.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LSM
    Estimated Value 1.567
    Confidence Interval (2-Sided) 95%
    0.896 to 2.237
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title Percent Change From Baseline in Spine BMD at Week 96 in the Blinded Phase
    Description Percent Change = Change from baseline at Week 96 visit/value at baseline * 100%.
    Time Frame Baseline, Week 96

    Outcome Measure Data

    Analysis Population Description
    Participants in Spine DXA Analysis Set with available data were analyzed.
    Arm/Group Title Descovy (DVY) Truvada (TVD)
    Arm/Group Description Blinded Phase: DVY (F/TAF 200/25 mg) FDC tablet plus placebo-to-match TVD (F/TDF 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. Blinded Phase: TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks.
    Measure Participants 145 142
    Mean (Standard Deviation) [Percent Change]
    0.831
    (3.4608)
    -1.426
    (3.5508)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Descovy (DVY), Truvada (TVD)
    Comments Spine BMD results were compared between the 2 treatment groups using ANOVA, which included baseline TVD for PrEP and treatment as fixed effects.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LSM
    Estimated Value 2.253
    Confidence Interval (2-Sided) 95%
    1.437 to 3.069
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title Percent Change From Baseline in Urine Beta-2-Microglobulin to Creatinine Ratio at Week 96 in the Blinded Phase
    Description Percent Change = Change from baseline at Week 96 visit/value at baseline * 100%. For urine creatinine, value of < 1 was handled as a missing value in its summary and the calculation of related ratios.
    Time Frame Baseline, Week 96

    Outcome Measure Data

    Analysis Population Description
    Participants in Safety Analysis Set with available data were analyzed.
    Arm/Group Title Descovy (DVY) Truvada (TVD)
    Arm/Group Description Blinded Phase: DVY (F/TAF 200/25 mg) FDC tablet plus placebo-to-match TVD (F/TDF 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. Blinded Phase: TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks.
    Measure Participants 2169 2195
    Median (Inter-Quartile Range) [Percent Change]
    -14.5
    14.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Descovy (DVY), Truvada (TVD)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-values were from the Van Elteren test stratified by baseline TVD for PrEP.
    Method Van Elteren test
    Comments
    12. Secondary Outcome
    Title Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96 in the Blinded Phase
    Description Percent Change = Change from baseline at Week 96 visit/value at baseline * 100%. For urine creatinine, value of < 1 was handled as a missing value in its summary and the calculation of related ratios.
    Time Frame Baseline, Week 96

    Outcome Measure Data

    Analysis Population Description
    Participants in Safety Analysis Set with available data were analyzed.
    Arm/Group Title Descovy (DVY) Truvada (TVD)
    Arm/Group Description Blinded Phase: DVY (F/TAF 200/25 mg) FDC tablet plus placebo-to-match TVD (F/TDF 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. Blinded Phase: TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks.
    Measure Participants 2188 2211
    Median (Inter-Quartile Range) [Percent Change]
    0.3
    21.4
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Descovy (DVY), Truvada (TVD)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments P-values were from the Van Elteren test stratified by baseline TVD for PrEP.
    Method Van Elteren test
    Comments
    13. Secondary Outcome
    Title Number of Participants by UP and UPCR Categories at Week 96 in the Blinded Phase
    Description The UPCR was only calculated when corresponding UP ≥ 4.0 mg/dL. The UPCR "≤ 200 mg/g" category includes both participants with UP < 4.0 mg/dL and participants with UPCR ≤ 200 mg/g.
    Time Frame Baseline, Week 96

    Outcome Measure Data

    Analysis Population Description
    Participants in Safety Analysis Set with available data were analyzed.
    Arm/Group Title Descovy (DVY) Truvada (TVD)
    Arm/Group Description Blinded Phase: DVY (F/TAF 200/25 mg) FDC tablet plus placebo-to-match TVD (F/TDF 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. Blinded Phase: TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks.
    Measure Participants 2175 2199
    ≤ 200 mg/g at Baseline; ≤ 200 mg/g at Week 96
    2134
    79.2%
    2153
    79.9%
    ≤ 200 mg/g at Baseline; > 200 mg/g at Week 96
    21
    0.8%
    28
    1%
    > 200 mg/g at Baseline; ≤ 200 mg/g at Week 96
    14
    0.5%
    10
    0.4%
    > 200 mg/g at Baseline; > 200 mg/g at Week 96
    6
    0.2%
    8
    0.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Descovy (DVY), Truvada (TVD)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2163
    Comments P-value for difference between treatment groups in distributions of UPCR ≤ 200 mg/g versus > 200 mg/g was from the rank analysis of covariance adjusting for baseline category and baseline TVD for PrEP.
    Method Rank analysis of covariance
    Comments
    14. Secondary Outcome
    Title Change From Baseline in Serum Creatinine at Week 96 in the Blinded Phase
    Description
    Time Frame Baseline, Week 96

    Outcome Measure Data

    Analysis Population Description
    Participants in Safety Analysis Set with available data were analyzed.
    Arm/Group Title Descovy (DVY) Truvada (TVD)
    Arm/Group Description Blinded Phase: DVY (F/TAF 200/25 mg) FDC tablet plus placebo-to-match TVD (F/TDF 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. Blinded Phase: TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks.
    Measure Participants 2194 2218
    Mean (Standard Deviation) [mg/dL]
    0.01
    (0.114)
    0.03
    (0.117)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Descovy (DVY), Truvada (TVD)
    Comments Results were compared between the 2 treatment groups using the ANCOVA model including baseline TVD for PrEP and treatment as fixed effects and baseline serum creatinine as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LSM
    Estimated Value -0.02
    Confidence Interval (2-Sided) 95%
    -0.02 to -0.01
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    15. Secondary Outcome
    Title Percentage of Participants Experiencing Treatment-Emergent Adverse Events
    Description
    Time Frame First dose date up to the data cut for end of blinded treatment (maximum: 157 weeks)

    Outcome Measure Data

    Analysis Population Description
    Participants in Safety Analysis Set were analyzed.
    Arm/Group Title Descovy (DVY) Truvada (TVD)
    Arm/Group Description Blinded Phase: DVY (F/TAF 200/25 mg) FDC tablet plus placebo-to-match TVD (F/TDF 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. Blinded Phase: TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks.
    Measure Participants 2694 2693
    Number [percentage of participants]
    93.7
    3.5%
    93.6
    3.5%
    16. Secondary Outcome
    Title Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality
    Description
    Time Frame First dose date up to the data cut for end of blinded treatment (maximum: 157 weeks)

    Outcome Measure Data

    Analysis Population Description
    Participants in Safety Analysis Set with available data were analyzed.
    Arm/Group Title Descovy (DVY) Truvada (TVD)
    Arm/Group Description Blinded Phase: DVY (F/TAF 200/25 mg) FDC tablet plus placebo-to-match TVD (F/TDF 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. Blinded Phase: TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks.
    Measure Participants 2672 2665
    Number [percentage of participants]
    76.1
    2.8%
    79.1
    2.9%

    Adverse Events

    Time Frame First dose date up to the data cut for end of blinded treatment (maximum: 157 weeks)
    Adverse Event Reporting Description The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug. Participants were grouped according to the treatment they actually received.
    Arm/Group Title Descovy (DVY) Truvada (TVD)
    Arm/Group Description DVY (F/TAF 200/25 mg) FDC tablet plus placebo-to-match TVD (F/TDF 200/300 mg) FDC tablet administered orally once daily for at least 96 weeks. TVD (F/TDF 200/300 mg) FDC tablet plus placebo-to-match DVY (F/TAF 200/25 mg) FDC tablet administered orally once daily for at least 96 weeks.
    All Cause Mortality
    Descovy (DVY) Truvada (TVD)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/2694 (0.1%) 3/2693 (0.1%)
    Serious Adverse Events
    Descovy (DVY) Truvada (TVD)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 202/2694 (7.5%) 186/2693 (6.9%)
    Blood and lymphatic system disorders
    Agranulocytosis 1/2694 (0%) 0/2693 (0%)
    Anaemia 1/2694 (0%) 1/2693 (0%)
    Lymphadenitis 0/2694 (0%) 2/2693 (0.1%)
    Lymphadenopathy 0/2694 (0%) 1/2693 (0%)
    Pancytopenia 1/2694 (0%) 0/2693 (0%)
    Sickle cell anaemia with crisis 1/2694 (0%) 0/2693 (0%)
    Splenomegaly 1/2694 (0%) 0/2693 (0%)
    Cardiac disorders
    Acute myocardial infarction 1/2694 (0%) 1/2693 (0%)
    Angina pectoris 1/2694 (0%) 0/2693 (0%)
    Atrial fibrillation 2/2694 (0.1%) 7/2693 (0.3%)
    Cardiac failure 1/2694 (0%) 0/2693 (0%)
    Cardiac failure acute 0/2694 (0%) 1/2693 (0%)
    Cardiac flutter 0/2694 (0%) 1/2693 (0%)
    Left ventricular failure 0/2694 (0%) 1/2693 (0%)
    Mitral valve incompetence 1/2694 (0%) 0/2693 (0%)
    Myocardial infarction 1/2694 (0%) 3/2693 (0.1%)
    Myocarditis 1/2694 (0%) 0/2693 (0%)
    Palpitations 0/2694 (0%) 1/2693 (0%)
    Supraventricular tachycardia 2/2694 (0.1%) 0/2693 (0%)
    Congenital, familial and genetic disorders
    Pectus excavatum 0/2694 (0%) 1/2693 (0%)
    Sickle cell disease 1/2694 (0%) 0/2693 (0%)
    Ear and labyrinth disorders
    Sudden hearing loss 2/2694 (0.1%) 0/2693 (0%)
    Endocrine disorders
    Hyperparathyroidism primary 1/2694 (0%) 0/2693 (0%)
    Eye disorders
    Ocular myasthenia 1/2694 (0%) 0/2693 (0%)
    Gastrointestinal disorders
    Abdominal pain 1/2694 (0%) 2/2693 (0.1%)
    Abdominal pain upper 1/2694 (0%) 0/2693 (0%)
    Anal fissure 0/2694 (0%) 1/2693 (0%)
    Anal fistula 0/2694 (0%) 2/2693 (0.1%)
    Colitis 1/2694 (0%) 1/2693 (0%)
    Constipation 2/2694 (0.1%) 0/2693 (0%)
    Cyclic vomiting syndrome 1/2694 (0%) 0/2693 (0%)
    Diarrhoea 1/2694 (0%) 3/2693 (0.1%)
    Diverticular perforation 0/2694 (0%) 1/2693 (0%)
    Duodenitis 1/2694 (0%) 0/2693 (0%)
    Enlarged uvula 0/2694 (0%) 1/2693 (0%)
    Enteritis 1/2694 (0%) 0/2693 (0%)
    Gastrointestinal haemorrhage 0/2694 (0%) 1/2693 (0%)
    Gastrooesophageal reflux disease 0/2694 (0%) 1/2693 (0%)
    Haemorrhoids 1/2694 (0%) 0/2693 (0%)
    Hiatus hernia 0/2694 (0%) 1/2693 (0%)
    Inguinal hernia 1/2694 (0%) 0/2693 (0%)
    Intestinal fistula 2/2694 (0.1%) 0/2693 (0%)
    Intestinal obstruction 1/2694 (0%) 0/2693 (0%)
    Mesenteric vein thrombosis 0/2694 (0%) 2/2693 (0.1%)
    Mesenteritis 1/2694 (0%) 0/2693 (0%)
    Nausea 1/2694 (0%) 0/2693 (0%)
    Obstructive pancreatitis 0/2694 (0%) 1/2693 (0%)
    Oesophageal perforation 1/2694 (0%) 0/2693 (0%)
    Oesophageal rupture 1/2694 (0%) 0/2693 (0%)
    Pancreatitis 0/2694 (0%) 2/2693 (0.1%)
    Proctitis 1/2694 (0%) 1/2693 (0%)
    Rectal lesion 1/2694 (0%) 0/2693 (0%)
    Small intestinal obstruction 1/2694 (0%) 0/2693 (0%)
    Volvulus 1/2694 (0%) 0/2693 (0%)
    Vomiting 1/2694 (0%) 1/2693 (0%)
    General disorders
    Chest pain 2/2694 (0.1%) 4/2693 (0.1%)
    Death 0/2694 (0%) 1/2693 (0%)
    Non-cardiac chest pain 2/2694 (0.1%) 1/2693 (0%)
    Oedema peripheral 0/2694 (0%) 1/2693 (0%)
    Pyrexia 2/2694 (0.1%) 0/2693 (0%)
    Sudden death 0/2694 (0%) 1/2693 (0%)
    Systemic inflammatory response syndrome 1/2694 (0%) 0/2693 (0%)
    Treatment failure 1/2694 (0%) 0/2693 (0%)
    Hepatobiliary disorders
    Biliary colic 0/2694 (0%) 1/2693 (0%)
    Cholecystitis 2/2694 (0.1%) 2/2693 (0.1%)
    Cholecystitis acute 0/2694 (0%) 1/2693 (0%)
    Cholelithiasis 0/2694 (0%) 1/2693 (0%)
    Hepatitis acute 0/2694 (0%) 1/2693 (0%)
    Immune system disorders
    Amyloidosis 0/2694 (0%) 1/2693 (0%)
    Anaphylactic reaction 0/2694 (0%) 1/2693 (0%)
    Infections and infestations
    Abdominal abscess 1/2694 (0%) 0/2693 (0%)
    Abscess limb 2/2694 (0.1%) 0/2693 (0%)
    Abscess oral 0/2694 (0%) 1/2693 (0%)
    Anal abscess 2/2694 (0.1%) 3/2693 (0.1%)
    Appendicitis 9/2694 (0.3%) 10/2693 (0.4%)
    Appendicitis perforated 0/2694 (0%) 1/2693 (0%)
    Brain abscess 0/2694 (0%) 1/2693 (0%)
    Breast abscess 0/2694 (0%) 1/2693 (0%)
    Campylobacter gastroenteritis 1/2694 (0%) 0/2693 (0%)
    Cellulitis 7/2694 (0.3%) 5/2693 (0.2%)
    Cellulitis of male external genital organ 1/2694 (0%) 0/2693 (0%)
    Cholecystitis infective 1/2694 (0%) 1/2693 (0%)
    Chronic tonsillitis 1/2694 (0%) 0/2693 (0%)
    Device related infection 0/2694 (0%) 1/2693 (0%)
    Diverticulitis 3/2694 (0.1%) 3/2693 (0.1%)
    Endocarditis 0/2694 (0%) 1/2693 (0%)
    Epididymitis 1/2694 (0%) 0/2693 (0%)
    Erysipelas 0/2694 (0%) 1/2693 (0%)
    Eye infection gonococcal 0/2694 (0%) 1/2693 (0%)
    Gastroenteritis 2/2694 (0.1%) 4/2693 (0.1%)
    Gastroenteritis Escherichia coli 1/2694 (0%) 0/2693 (0%)
    Gastroenteritis bacterial 1/2694 (0%) 0/2693 (0%)
    Gastroenteritis shigella 2/2694 (0.1%) 0/2693 (0%)
    Gastrointestinal viral infection 0/2694 (0%) 1/2693 (0%)
    Giardiasis 1/2694 (0%) 0/2693 (0%)
    Gonorrhoea 0/2694 (0%) 1/2693 (0%)
    Groin abscess 0/2694 (0%) 2/2693 (0.1%)
    Hepatitis A 6/2694 (0.2%) 2/2693 (0.1%)
    Infected bite 1/2694 (0%) 1/2693 (0%)
    Infective tenosynovitis 1/2694 (0%) 0/2693 (0%)
    Influenza 2/2694 (0.1%) 1/2693 (0%)
    Large intestine infection 1/2694 (0%) 0/2693 (0%)
    Localised infection 0/2694 (0%) 1/2693 (0%)
    Lower respiratory tract infection 1/2694 (0%) 1/2693 (0%)
    Lymphogranuloma venereum 1/2694 (0%) 1/2693 (0%)
    Malaria 0/2694 (0%) 1/2693 (0%)
    Measles 0/2694 (0%) 1/2693 (0%)
    Meningitis streptococcal 1/2694 (0%) 0/2693 (0%)
    Neurosyphilis 1/2694 (0%) 0/2693 (0%)
    Orchitis 2/2694 (0.1%) 0/2693 (0%)
    Osteomyelitis 1/2694 (0%) 1/2693 (0%)
    Parotid abscess 1/2694 (0%) 0/2693 (0%)
    Perineal abscess 1/2694 (0%) 1/2693 (0%)
    Periorbital cellulitis 0/2694 (0%) 1/2693 (0%)
    Perirectal abscess 1/2694 (0%) 0/2693 (0%)
    Peritonitis 0/2694 (0%) 1/2693 (0%)
    Peritonsillar abscess 1/2694 (0%) 0/2693 (0%)
    Pharyngeal abscess 1/2694 (0%) 0/2693 (0%)
    Plasmodium falciparum infection 0/2694 (0%) 1/2693 (0%)
    Pneumonia 5/2694 (0.2%) 4/2693 (0.1%)
    Pneumonia pneumococcal 1/2694 (0%) 0/2693 (0%)
    Pneumonia staphylococcal 0/2694 (0%) 1/2693 (0%)
    Postoperative wound infection 0/2694 (0%) 1/2693 (0%)
    Proctitis chlamydial 1/2694 (0%) 0/2693 (0%)
    Pyelonephritis 1/2694 (0%) 1/2693 (0%)
    Rectal abscess 1/2694 (0%) 0/2693 (0%)
    Scrotal abscess 2/2694 (0.1%) 0/2693 (0%)
    Sepsis 3/2694 (0.1%) 1/2693 (0%)
    Septic shock 1/2694 (0%) 1/2693 (0%)
    Shigella infection 0/2694 (0%) 1/2693 (0%)
    Staphylococcal sepsis 0/2694 (0%) 1/2693 (0%)
    Streptococcal sepsis 1/2694 (0%) 0/2693 (0%)
    Tonsillitis 1/2694 (0%) 2/2693 (0.1%)
    Tooth infection 0/2694 (0%) 1/2693 (0%)
    Urinary tract infection 0/2694 (0%) 3/2693 (0.1%)
    Viral pericarditis 0/2694 (0%) 1/2693 (0%)
    Viral rash 1/2694 (0%) 0/2693 (0%)
    Wound infection 1/2694 (0%) 0/2693 (0%)
    Injury, poisoning and procedural complications
    Accidental overdose 0/2694 (0%) 1/2693 (0%)
    Alcohol poisoning 1/2694 (0%) 0/2693 (0%)
    Ankle fracture 2/2694 (0.1%) 0/2693 (0%)
    Cervical vertebral fracture 0/2694 (0%) 1/2693 (0%)
    Concussion 0/2694 (0%) 3/2693 (0.1%)
    Contusion 1/2694 (0%) 0/2693 (0%)
    Craniocerebral injury 1/2694 (0%) 0/2693 (0%)
    Deep vein thrombosis postoperative 1/2694 (0%) 0/2693 (0%)
    Facial bones fracture 0/2694 (0%) 1/2693 (0%)
    Fall 1/2694 (0%) 1/2693 (0%)
    Femur fracture 1/2694 (0%) 0/2693 (0%)
    Foot fracture 1/2694 (0%) 2/2693 (0.1%)
    Gun shot wound 0/2694 (0%) 1/2693 (0%)
    Head injury 1/2694 (0%) 0/2693 (0%)
    Heat stroke 0/2694 (0%) 1/2693 (0%)
    Intentional overdose 0/2694 (0%) 1/2693 (0%)
    Joint dislocation 1/2694 (0%) 0/2693 (0%)
    Ligament injury 1/2694 (0%) 0/2693 (0%)
    Ligament rupture 1/2694 (0%) 0/2693 (0%)
    Limb injury 1/2694 (0%) 0/2693 (0%)
    Lower limb fracture 1/2694 (0%) 0/2693 (0%)
    Neck injury 1/2694 (0%) 0/2693 (0%)
    Overdose 4/2694 (0.1%) 1/2693 (0%)
    Pelvic fracture 0/2694 (0%) 1/2693 (0%)
    Post procedural complication 0/2694 (0%) 1/2693 (0%)
    Post procedural haemorrhage 3/2694 (0.1%) 1/2693 (0%)
    Radius fracture 0/2694 (0%) 2/2693 (0.1%)
    Reactive gastropathy 1/2694 (0%) 0/2693 (0%)
    Rib fracture 0/2694 (0%) 1/2693 (0%)
    Road traffic accident 4/2694 (0.1%) 1/2693 (0%)
    Scrotal haematoma 0/2694 (0%) 1/2693 (0%)
    Seroma 1/2694 (0%) 0/2693 (0%)
    Skull fracture 0/2694 (0%) 1/2693 (0%)
    Splenic rupture 0/2694 (0%) 1/2693 (0%)
    Subdural haematoma 1/2694 (0%) 1/2693 (0%)
    Tendon injury 0/2694 (0%) 1/2693 (0%)
    Tendon rupture 2/2694 (0.1%) 0/2693 (0%)
    Thoracic vertebral fracture 0/2694 (0%) 1/2693 (0%)
    Toxicity to various agents 2/2694 (0.1%) 2/2693 (0.1%)
    Traumatic intracranial haemorrhage 1/2694 (0%) 0/2693 (0%)
    Ulna fracture 0/2694 (0%) 1/2693 (0%)
    Upper limb fracture 1/2694 (0%) 0/2693 (0%)
    Investigations
    Aspartate aminotransferase increased 0/2694 (0%) 1/2693 (0%)
    Scan myocardial perfusion abnormal 0/2694 (0%) 1/2693 (0%)
    Metabolism and nutrition disorders
    Dehydration 1/2694 (0%) 0/2693 (0%)
    Diabetic ketoacidosis 1/2694 (0%) 1/2693 (0%)
    Hyperglycaemia 1/2694 (0%) 0/2693 (0%)
    Hypoglycaemia 1/2694 (0%) 0/2693 (0%)
    Metabolic acidosis 1/2694 (0%) 0/2693 (0%)
    Obesity 0/2694 (0%) 1/2693 (0%)
    Type 1 diabetes mellitus 0/2694 (0%) 1/2693 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 1/2694 (0%) 0/2693 (0%)
    Bursitis 0/2694 (0%) 1/2693 (0%)
    Cervical spinal stenosis 0/2694 (0%) 1/2693 (0%)
    Intervertebral disc degeneration 1/2694 (0%) 1/2693 (0%)
    Intervertebral disc protrusion 2/2694 (0.1%) 0/2693 (0%)
    Limb mass 0/2694 (0%) 1/2693 (0%)
    Osteoarthritis 0/2694 (0%) 2/2693 (0.1%)
    Rhabdomyolysis 2/2694 (0.1%) 0/2693 (0%)
    Rotator cuff syndrome 1/2694 (0%) 0/2693 (0%)
    Scoliosis 1/2694 (0%) 0/2693 (0%)
    Spinal osteoarthritis 0/2694 (0%) 1/2693 (0%)
    Spinal stenosis 0/2694 (0%) 1/2693 (0%)
    Synovial cyst 0/2694 (0%) 1/2693 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Anogenital warts 0/2694 (0%) 1/2693 (0%)
    Astrocytoma 1/2694 (0%) 0/2693 (0%)
    Carcinoid tumour 0/2694 (0%) 1/2693 (0%)
    Gastrointestinal carcinoma 1/2694 (0%) 0/2693 (0%)
    Gastrointestinal stromal tumour 0/2694 (0%) 1/2693 (0%)
    Hodgkin's disease 1/2694 (0%) 0/2693 (0%)
    Melanocytic naevus 1/2694 (0%) 0/2693 (0%)
    Metastases to lymph nodes 1/2694 (0%) 0/2693 (0%)
    Metastatic squamous cell carcinoma 0/2694 (0%) 1/2693 (0%)
    Oesophageal cancer metastatic 1/2694 (0%) 0/2693 (0%)
    Pituitary tumour 0/2694 (0%) 1/2693 (0%)
    Prostate cancer 3/2694 (0.1%) 0/2693 (0%)
    Renal cell carcinoma 1/2694 (0%) 0/2693 (0%)
    Testicular seminoma (pure) 1/2694 (0%) 0/2693 (0%)
    Thyroid cancer 1/2694 (0%) 0/2693 (0%)
    Nervous system disorders
    Amyotrophic lateral sclerosis 1/2694 (0%) 0/2693 (0%)
    Cerebral venous sinus thrombosis 1/2694 (0%) 0/2693 (0%)
    Cerebrovascular accident 1/2694 (0%) 1/2693 (0%)
    Facial paralysis 1/2694 (0%) 1/2693 (0%)
    Generalised tonic-clonic seizure 1/2694 (0%) 0/2693 (0%)
    Guillain-Barre syndrome 0/2694 (0%) 1/2693 (0%)
    Haemorrhage intracranial 1/2694 (0%) 0/2693 (0%)
    Headache 0/2694 (0%) 1/2693 (0%)
    Loss of consciousness 1/2694 (0%) 1/2693 (0%)
    Migraine 1/2694 (0%) 1/2693 (0%)
    Myelitis transverse 1/2694 (0%) 0/2693 (0%)
    Nerve compression 1/2694 (0%) 0/2693 (0%)
    Paraesthesia 1/2694 (0%) 0/2693 (0%)
    Partial seizures 0/2694 (0%) 1/2693 (0%)
    Polyneuropathy 0/2694 (0%) 1/2693 (0%)
    Presyncope 0/2694 (0%) 1/2693 (0%)
    Radiculopathy 1/2694 (0%) 1/2693 (0%)
    Sciatica 1/2694 (0%) 0/2693 (0%)
    Seizure 1/2694 (0%) 1/2693 (0%)
    Speech disorder 0/2694 (0%) 1/2693 (0%)
    Syncope 2/2694 (0.1%) 2/2693 (0.1%)
    Transient ischaemic attack 1/2694 (0%) 0/2693 (0%)
    Product Issues
    Device dislocation 1/2694 (0%) 0/2693 (0%)
    Psychiatric disorders
    Acute psychosis 0/2694 (0%) 1/2693 (0%)
    Alcohol use disorder 1/2694 (0%) 0/2693 (0%)
    Alcohol withdrawal syndrome 1/2694 (0%) 0/2693 (0%)
    Alcoholism 0/2694 (0%) 1/2693 (0%)
    Anxiety 1/2694 (0%) 1/2693 (0%)
    Bipolar I disorder 0/2694 (0%) 1/2693 (0%)
    Bipolar disorder 0/2694 (0%) 1/2693 (0%)
    Delirium 1/2694 (0%) 0/2693 (0%)
    Delusion 1/2694 (0%) 1/2693 (0%)
    Depression 5/2694 (0.2%) 3/2693 (0.1%)
    Intentional self-injury 0/2694 (0%) 1/2693 (0%)
    Major depression 0/2694 (0%) 1/2693 (0%)
    Panic attack 2/2694 (0.1%) 0/2693 (0%)
    Personality disorder 0/2694 (0%) 1/2693 (0%)
    Psychotic disorder 2/2694 (0.1%) 3/2693 (0.1%)
    Schizoaffective disorder 0/2694 (0%) 1/2693 (0%)
    Substance abuse 2/2694 (0.1%) 1/2693 (0%)
    Substance-induced psychotic disorder 1/2694 (0%) 1/2693 (0%)
    Suicidal ideation 8/2694 (0.3%) 5/2693 (0.2%)
    Suicide attempt 5/2694 (0.2%) 1/2693 (0%)
    Renal and urinary disorders
    Acute kidney injury 7/2694 (0.3%) 2/2693 (0.1%)
    Calculus urinary 0/2694 (0%) 1/2693 (0%)
    Nephrolithiasis 2/2694 (0.1%) 2/2693 (0.1%)
    Nephrotic syndrome 1/2694 (0%) 0/2693 (0%)
    Renal colic 0/2694 (0%) 1/2693 (0%)
    Renal infarct 0/2694 (0%) 1/2693 (0%)
    Renal tubular necrosis 0/2694 (0%) 1/2693 (0%)
    Ureterolithiasis 0/2694 (0%) 2/2693 (0.1%)
    Urethral stenosis 1/2694 (0%) 0/2693 (0%)
    Reproductive system and breast disorders
    Priapism 1/2694 (0%) 1/2693 (0%)
    Prostatitis 0/2694 (0%) 1/2693 (0%)
    Testicular torsion 2/2694 (0.1%) 1/2693 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 1/2694 (0%) 0/2693 (0%)
    Asthma 1/2694 (0%) 0/2693 (0%)
    Dyspnoea 2/2694 (0.1%) 0/2693 (0%)
    Nasal septum deviation 2/2694 (0.1%) 0/2693 (0%)
    Pneumonia aspiration 1/2694 (0%) 0/2693 (0%)
    Pneumothorax 0/2694 (0%) 1/2693 (0%)
    Pulmonary embolism 1/2694 (0%) 2/2693 (0.1%)
    Pulmonary oedema 0/2694 (0%) 1/2693 (0%)
    Respiratory failure 1/2694 (0%) 0/2693 (0%)
    Vocal cord thickening 0/2694 (0%) 1/2693 (0%)
    Skin and subcutaneous tissue disorders
    Stevens-Johnson syndrome 0/2694 (0%) 1/2693 (0%)
    Social circumstances
    Alcohol use 1/2694 (0%) 0/2693 (0%)
    Surgical and medical procedures
    Ligament operation 0/2694 (0%) 1/2693 (0%)
    Medical device removal 0/2694 (0%) 1/2693 (0%)
    Spinal fusion surgery 0/2694 (0%) 1/2693 (0%)
    Vascular disorders
    Deep vein thrombosis 2/2694 (0.1%) 0/2693 (0%)
    Haematoma 1/2694 (0%) 0/2693 (0%)
    Hypertension 0/2694 (0%) 1/2693 (0%)
    Hypotension 1/2694 (0%) 0/2693 (0%)
    Other (Not Including Serious) Adverse Events
    Descovy (DVY) Truvada (TVD)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2258/2694 (83.8%) 2229/2693 (82.8%)
    Gastrointestinal disorders
    Diarrhoea 479/2694 (17.8%) 451/2693 (16.7%)
    Nausea 209/2694 (7.8%) 204/2693 (7.6%)
    General disorders
    Fatigue 180/2694 (6.7%) 181/2693 (6.7%)
    Infections and infestations
    Anal chlamydia infection 890/2694 (33%) 902/2693 (33.5%)
    Gastroenteritis 171/2694 (6.3%) 141/2693 (5.2%)
    Influenza 145/2694 (5.4%) 143/2693 (5.3%)
    Nasopharyngitis 399/2694 (14.8%) 402/2693 (14.9%)
    Oropharyngeal gonococcal infection 871/2694 (32.3%) 838/2693 (31.1%)
    Pharyngeal chlamydia infection 215/2694 (8%) 186/2693 (6.9%)
    Pharyngitis 166/2694 (6.2%) 108/2693 (4%)
    Proctitis gonococcal 805/2694 (29.9%) 797/2693 (29.6%)
    Syphilis 413/2694 (15.3%) 392/2693 (14.6%)
    Upper respiratory tract infection 402/2694 (14.9%) 346/2693 (12.8%)
    Urethritis 193/2694 (7.2%) 189/2693 (7%)
    Urethritis chlamydial 346/2694 (12.8%) 314/2693 (11.7%)
    Urethritis gonococcal 259/2694 (9.6%) 255/2693 (9.5%)
    Injury, poisoning and procedural complications
    Exposure to communicable disease 554/2694 (20.6%) 548/2693 (20.3%)
    Nervous system disorders
    Headache 206/2694 (7.6%) 209/2693 (7.8%)
    Respiratory, thoracic and mediastinal disorders
    Cough 152/2694 (5.6%) 136/2693 (5.1%)
    Oropharyngeal pain 172/2694 (6.4%) 165/2693 (6.1%)
    Skin and subcutaneous tissue disorders
    Rash 136/2694 (5%) 122/2693 (4.5%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years

    Results Point of Contact

    Name/Title Gilead Clinical Study Information Center
    Organization Gilead Sciences
    Phone 1-833-445-3230 (GILEAD-0)
    Email GileadClinicalTrials@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT02842086
    Other Study ID Numbers:
    • GS-US-412-2055
    • 2016-001399-31
    First Posted:
    Jul 22, 2016
    Last Update Posted:
    Jul 15, 2022
    Last Verified:
    Jun 1, 2022