Pre-Exposure Prophylaxis of HIV-1 Infection
Conditions
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.
Interventions
DRUGF/TAF
200/25 mg tablet administered orally once daily
DRUGF/TDF
200/300 mg tablet administered orally once daily
DRUGF/TAF Placebo
Tablet administered orally once daily
DRUGF/TDF Placebo
Tablet administered orally once daily
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
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/mm\^3; platelets ≥ 75,000/mm\^3; 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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%. |
| 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%. |
| 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. |
| 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. |
| 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. |
| Change From Baseline in Serum Creatinine at Week 48 in the Blinded Phase | Baseline, Week 48 | — |
| 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) |
| 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%. |
| 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%. |
| 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. |
| 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. |
| 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. |
| Change From Baseline in Serum Creatinine at Week 96 in the Blinded Phase | Baseline, Week 96 | — |
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events | First dose date up to the data cut for end of blinded treatment (maximum: 157 weeks) | — |
| 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) | — |
Countries
Austria, Canada, Denmark, France, Germany, Ireland, Italy, Netherlands, Spain, United Kingdom, United States
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 details
5857 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| Descovy (DVY) 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. | 2,694 |
| Truvada (TVD) 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. | 2,693 |
| Total | 5,387 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 18 | 20 |
| Overall Study | Death | 3 | 3 |
| Overall Study | HIV-1 Infection | 5 | 6 |
| Overall Study | Investigator's Discretion | 9 | 13 |
| Overall Study | Lost to Follow-up | 274 | 236 |
| Overall Study | Non-Compliance with Study Drug | 9 | 8 |
| Overall Study | Protocol Violation | 8 | 4 |
| Overall Study | Randomized but Never Treated | 6 | 6 |
| Overall Study | Still in Double-Blind Phase | 7 | 3 |
| Overall Study | Withdrew Consent | 205 | 194 |
Baseline characteristics
| Characteristic | Descovy (DVY) | Total | Truvada (TVD) |
|---|---|---|---|
| Age, Continuous | 36 years STANDARD_DEVIATION 10.6 | 36 years STANDARD_DEVIATION 10.6 | 36 years STANDARD_DEVIATION 10.7 |
| Hip Bone Mineral Density (BMD) | 1.030 g/cm^2 STANDARD_DEVIATION 0.1553 | 1.025 g/cm^2 STANDARD_DEVIATION 0.1443 | 1.021 g/cm^2 STANDARD_DEVIATION 0.1322 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 635 Participants | 1318 Participants | 683 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 2058 Participants | 4066 Participants | 2008 Participants |
| Race/Ethnicity, Customized Ethnicity Not Permitted | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 12 Participants | 26 Participants | 14 Participants |
| Race/Ethnicity, Customized Race Asian | 113 Participants | 233 Participants | 120 Participants |
| Race/Ethnicity, Customized Race Black/Mixed Black | 240 Participants | 474 Participants | 234 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Pacific Islander | 17 Participants | 40 Participants | 23 Participants |
| Race/Ethnicity, Customized Race Not Permitted | 3 Participants | 8 Participants | 5 Participants |
| Race/Ethnicity, Customized Race Other (Nonblack) | 45 Participants | 95 Participants | 50 Participants |
| Race/Ethnicity, Customized Race White | 2264 Participants | 4511 Participants | 2247 Participants |
| Region of Enrollment Austria | 35 Participants | 77 Participants | 42 Participants |
| Region of Enrollment Canada | 191 Participants | 353 Participants | 162 Participants |
| Region of Enrollment Denmark | 98 Participants | 202 Participants | 104 Participants |
| Region of Enrollment France | 18 Participants | 32 Participants | 14 Participants |
| Region of Enrollment Germany | 187 Participants | 370 Participants | 183 Participants |
| Region of Enrollment Ireland | 40 Participants | 78 Participants | 38 Participants |
| Region of Enrollment Italy | 37 Participants | 58 Participants | 21 Participants |
| Region of Enrollment Netherlands | 31 Participants | 71 Participants | 40 Participants |
| Region of Enrollment Spain | 219 Participants | 414 Participants | 195 Participants |
| Region of Enrollment United Kingdom | 247 Participants | 512 Participants | 265 Participants |
| Region of Enrollment United States | 1591 Participants | 3220 Participants | 1629 Participants |
| Serum Creatinine | 0.96 mg/dL STANDARD_DEVIATION 0.146 | 0.96 mg/dL STANDARD_DEVIATION 0.147 | 0.96 mg/dL STANDARD_DEVIATION 0.148 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 2694 Participants | 5387 Participants | 2693 Participants |
| Sex/Gender, Customized Transgender Women | 45 Participants | 74 Participants | 29 Participants |
| Spine BMD | 1.134 g/cm^2 STANDARD_DEVIATION 0.1646 | 1.132 g/cm^2 STANDARD_DEVIATION 0.1518 | 1.131 g/cm^2 STANDARD_DEVIATION 0.1381 |
| Urine Beta-2 Microglobulin to Creatinine Ratio | 204.3 µg/g STANDARD_DEVIATION 951.77 | 196.4 µg/g STANDARD_DEVIATION 981.35 | 188.5 µg/g STANDARD_DEVIATION 1010.19 |
| Urine Protein (UP) and Urine Protein to Creatinine Ratio (UPCR) Categories ≤ 200 mg/g | 2662 Participants | 5319 Participants | 2657 Participants |
| Urine Protein (UP) and Urine Protein to Creatinine Ratio (UPCR) Categories > 200 mg/g | 25 Participants | 50 Participants | 25 Participants |
| Urine Retinol Binding Protein (RBP) to Creatinine Ratio | 148.8 µg/g STANDARD_DEVIATION 553.54 | 145.8 µg/g STANDARD_DEVIATION 431.41 | 142.8 µg/g STANDARD_DEVIATION 256.64 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 2,694 | 3 / 2,693 |
| other Total, other adverse events | 2,258 / 2,694 | 2,229 / 2,693 |
| serious Total, serious adverse events | 202 / 2,694 | 186 / 2,693 |
Outcome results
Primary
Incidence of HIV-1 Infection Per 100 Person Years (PY)
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)
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Descovy (DVY) | Incidence of HIV-1 Infection Per 100 Person Years (PY) | 0.160 HIV-1 infections per 100 PY |
| Truvada (TVD) | Incidence of HIV-1 Infection Per 100 Person Years (PY) | 0.342 HIV-1 infections per 100 PY |
Comparison: 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 1.62.95.003% CI: [0.191, 1.149]
Secondary
Change From Baseline in Serum Creatinine at Week 48 in the Blinded Phase
Time frame: Baseline, Week 48
Population: Participants in Safety Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Descovy (DVY) | Change From Baseline in Serum Creatinine at Week 48 in the Blinded Phase | -0.01 mg/dL | Standard Deviation 0.107 |
| Truvada (TVD) | Change From Baseline in Serum Creatinine at Week 48 in the Blinded Phase | 0.01 mg/dL | Standard Deviation 0.111 |
Comparison: 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.p-value: <0.000195% CI: [-0.02, -0.01]ANCOVA
Secondary
Change From Baseline in Serum Creatinine at Week 96 in the Blinded Phase
Time frame: Baseline, Week 96
Population: Participants in Safety Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Descovy (DVY) | Change From Baseline in Serum Creatinine at Week 96 in the Blinded Phase | 0.01 mg/dL | Standard Deviation 0.114 |
| Truvada (TVD) | Change From Baseline in Serum Creatinine at Week 96 in the Blinded Phase | 0.03 mg/dL | Standard Deviation 0.117 |
Comparison: 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.p-value: <0.000195% CI: [-0.02, -0.01]ANCOVA
Secondary
Incidence of HIV-1 Infection Per 100 PY
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)
Population: Participants in Full Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Descovy (DVY) | Incidence of HIV-1 Infection Per 100 PY | 0.159 HIV-1 infections per 100 PY |
| Truvada (TVD) | Incidence of HIV-1 Infection Per 100 PY | 0.297 HIV-1 infections per 100 PY |
Comparison: 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 1.62.95.003% CI: [0.227, 1.264]
Secondary
Number of Participants by UP and UPCR Categories at Week 96 in the Blinded Phase
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
Population: Participants in Safety Analysis Set with available data were analyzed.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Descovy (DVY) | Number of Participants by UP and UPCR Categories at Week 96 in the Blinded Phase | ≤ 200 mg/g at Baseline; ≤ 200 mg/g at Week 96 | 2134 Participants |
| Descovy (DVY) | Number of Participants by UP and UPCR Categories at Week 96 in the Blinded Phase | ≤ 200 mg/g at Baseline; > 200 mg/g at Week 96 | 21 Participants |
| Descovy (DVY) | Number of Participants by UP and UPCR Categories at Week 96 in the Blinded Phase | > 200 mg/g at Baseline; ≤ 200 mg/g at Week 96 | 14 Participants |
| Descovy (DVY) | Number of Participants by UP and UPCR Categories at Week 96 in the Blinded Phase | > 200 mg/g at Baseline; > 200 mg/g at Week 96 | 6 Participants |
| Truvada (TVD) | Number of Participants by UP and UPCR Categories at Week 96 in the Blinded Phase | > 200 mg/g at Baseline; > 200 mg/g at Week 96 | 8 Participants |
| Truvada (TVD) | Number of Participants by UP and UPCR Categories at Week 96 in the Blinded Phase | ≤ 200 mg/g at Baseline; ≤ 200 mg/g at Week 96 | 2153 Participants |
| Truvada (TVD) | Number of Participants by UP and UPCR Categories at Week 96 in the Blinded Phase | > 200 mg/g at Baseline; ≤ 200 mg/g at Week 96 | 10 Participants |
| Truvada (TVD) | Number of Participants by UP and UPCR Categories at Week 96 in the Blinded Phase | ≤ 200 mg/g at Baseline; > 200 mg/g at Week 96 | 28 Participants |
p-value: 0.2163Rank analysis of covariance
Secondary
Number of Participants by Urine Protein (UP) and Urine Protein to Creatinine Ratio (UPCR) Categories at Week 48 in the Blinded Phase
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
Population: Participants in Safety Analysis Set with available data were analyzed.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Descovy (DVY) | Number of Participants by Urine Protein (UP) and Urine Protein to Creatinine Ratio (UPCR) Categories at Week 48 in the Blinded Phase | ≤ 200 mg/g at Baseline; ≤ 200 mg/g at Week 48 | 2318 Participants |
| Descovy (DVY) | Number of Participants by Urine Protein (UP) and Urine Protein to Creatinine Ratio (UPCR) Categories at Week 48 in the Blinded Phase | ≤ 200 mg/g at Baseline; > 200 mg/g at Week 48 | 16 Participants |
| Descovy (DVY) | Number of Participants by Urine Protein (UP) and Urine Protein to Creatinine Ratio (UPCR) Categories at Week 48 in the Blinded Phase | > 200 mg/g at Baseline; ≤ 200 mg/g at Week 48 | 12 Participants |
| Descovy (DVY) | Number of Participants by Urine Protein (UP) and Urine Protein to Creatinine Ratio (UPCR) Categories at Week 48 in the Blinded Phase | > 200 mg/g at Baseline; > 200 mg/g at Week 48 | 9 Participants |
| Truvada (TVD) | Number of Participants by Urine Protein (UP) and Urine Protein to Creatinine Ratio (UPCR) Categories at Week 48 in the Blinded Phase | > 200 mg/g at Baseline; > 200 mg/g at Week 48 | 10 Participants |
| Truvada (TVD) | Number of Participants by Urine Protein (UP) and Urine Protein to Creatinine Ratio (UPCR) Categories at Week 48 in the Blinded Phase | ≤ 200 mg/g at Baseline; ≤ 200 mg/g at Week 48 | 2295 Participants |
| Truvada (TVD) | Number of Participants by Urine Protein (UP) and Urine Protein to Creatinine Ratio (UPCR) Categories at Week 48 in the Blinded Phase | > 200 mg/g at Baseline; ≤ 200 mg/g at Week 48 | 8 Participants |
| Truvada (TVD) | Number of Participants by Urine Protein (UP) and Urine Protein to Creatinine Ratio (UPCR) Categories at Week 48 in the Blinded Phase | ≤ 200 mg/g at Baseline; > 200 mg/g at Week 48 | 35 Participants |
p-value: 0.0048Rank analysis of covariance
Secondary
Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality
Time frame: First dose date up to the data cut for end of blinded treatment (maximum: 157 weeks)
Population: Participants in Safety Analysis Set with available data were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Descovy (DVY) | Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality | 76.1 percentage of participants |
| Truvada (TVD) | Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality | 79.1 percentage of participants |
Secondary
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time frame: First dose date up to the data cut for end of blinded treatment (maximum: 157 weeks)
Population: Participants in Safety Analysis Set were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Descovy (DVY) | Percentage of Participants Experiencing Treatment-Emergent Adverse Events | 93.7 percentage of participants |
| Truvada (TVD) | Percentage of Participants Experiencing Treatment-Emergent Adverse Events | 93.6 percentage of participants |
Secondary
Percent Change From Baseline in Hip BMD at Week 96 in the Blinded Phase
Percent Change = Change from baseline at Week 96 visit/value at baseline \* 100%.
Time frame: Baseline, Week 96
Population: Participants in Hip DXA Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Descovy (DVY) | Percent Change From Baseline in Hip BMD at Week 96 in the Blinded Phase | 0.565 Percent Change | Standard Deviation 2.9379 |
| Truvada (TVD) | Percent Change From Baseline in Hip BMD at Week 96 in the Blinded Phase | -1.048 Percent Change | Standard Deviation 2.9277 |
Comparison: Hip BMD results were compared between the 2 treatment groups using ANOVA, which included baseline TVD for PrEP and treatment as fixed effects.p-value: <0.000195% CI: [0.896, 2.237]ANOVA
Secondary
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 in the Blinded Phase
Percent Change = Change from baseline at Week 48 visit/value at baseline \* 100%.
Time frame: Baseline, Week 48
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Descovy (DVY) | Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 in the Blinded Phase | 0.218 Percent Change | Standard Deviation 2.3668 |
| Truvada (TVD) | Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 in the Blinded Phase | -0.968 Percent Change | Standard Deviation 2.4343 |
Comparison: 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.p-value: <0.000195% CI: [0.628, 1.655]ANOVA
Secondary
Percent Change From Baseline in Spine BMD at Week 48 in the Blinded Phase
Percent Change = Change from baseline at Week 48 visit/value at baseline \* 100%.
Time frame: Baseline, Week 48
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Descovy (DVY) | Percent Change From Baseline in Spine BMD at Week 48 in the Blinded Phase | 0.512 Percent Change | Standard Deviation 2.9854 |
| Truvada (TVD) | Percent Change From Baseline in Spine BMD at Week 48 in the Blinded Phase | -1.061 Percent Change | Standard Deviation 2.9382 |
Comparison: Spine BMD results were compared between the 2 treatment groups using ANOVA, which included baseline TVD for PrEP and treatment as fixed effects.p-value: <0.000195% CI: [0.913, 2.22]ANOVA
Secondary
Percent Change From Baseline in Spine BMD at Week 96 in the Blinded Phase
Percent Change = Change from baseline at Week 96 visit/value at baseline \* 100%.
Time frame: Baseline, Week 96
Population: Participants in Spine DXA Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Descovy (DVY) | Percent Change From Baseline in Spine BMD at Week 96 in the Blinded Phase | 0.831 Percent Change | Standard Deviation 3.4608 |
| Truvada (TVD) | Percent Change From Baseline in Spine BMD at Week 96 in the Blinded Phase | -1.426 Percent Change | Standard Deviation 3.5508 |
Comparison: Spine BMD results were compared between the 2 treatment groups using ANOVA, which included baseline TVD for PrEP and treatment as fixed effects.p-value: <0.000195% CI: [1.437, 3.069]ANOVA
Secondary
Percent Change From Baseline in Urine Beta-2-Microglobulin to Creatinine Ratio at Week 48 in the Blinded Phase
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Descovy (DVY) | Percent Change From Baseline in Urine Beta-2-Microglobulin to Creatinine Ratio at Week 48 in the Blinded Phase | -10.6 Percent Change |
| Truvada (TVD) | Percent Change From Baseline in Urine Beta-2-Microglobulin to Creatinine Ratio at Week 48 in the Blinded Phase | 15.4 Percent Change |
p-value: <0.0001Van Elteren test
Secondary
Percent Change From Baseline in Urine Beta-2-Microglobulin to Creatinine Ratio at Week 96 in the Blinded Phase
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
Population: Participants in Safety Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Descovy (DVY) | Percent Change From Baseline in Urine Beta-2-Microglobulin to Creatinine Ratio at Week 96 in the Blinded Phase | -14.5 Percent Change |
| Truvada (TVD) | Percent Change From Baseline in Urine Beta-2-Microglobulin to Creatinine Ratio at Week 96 in the Blinded Phase | 14.1 Percent Change |
p-value: <0.0001Van Elteren test
Secondary
Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96 in the Blinded Phase
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
Population: Participants in Safety Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Descovy (DVY) | Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96 in the Blinded Phase | 0.3 Percent Change |
| Truvada (TVD) | Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96 in the Blinded Phase | 21.4 Percent Change |
p-value: <0.0001Van Elteren test
Secondary
Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48 in the Blinded Phase
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
Population: Participants in Safety Analysis Set with available data were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Descovy (DVY) | Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48 in the Blinded Phase | 0.1 Percent Change |
| Truvada (TVD) | Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48 in the Blinded Phase | 20.0 Percent Change |
p-value: <0.0001Van Elteren test