Human Immunodeficiency Virus (HIV)
Conditions
Brief summary
The purpose of this study is to compare the antiretroviral activity of doravirine, tenofovir, lamivudine (MK-1439A), a single-tablet, once-daily (q.d.) fixed-dose combination (FDC) containing doravirine (MK-1439A) 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, with ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg, in treatment-naive participants infected with human immunodeficiency virus (HIV). The primary hypothesis is that doravirine, tenofovir, lamivudine q.d. is non-inferior to ATRIPLA™ q.d. as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) \<50 copies/mL (by the Abbott RealTime HIV-1 Assay) at Week 48. This study has a total duration of 384 weeks, including a 96-week double-blind period and an additional 288-week open-label period.
Detailed description
Participants in Australia, Colombia, Guatemala, Honduras, Israel, New Zealand, Peru, Russia, South Africa, and Thailand who are deriving benefit from doravirine, tenofovir, lamivudine are also eligible to continue receiving study drug during additional open-label extensions which will last for 2 years or until drug is available locally, whichever comes first.
Interventions
One doravirine, tenofovir, lamivudine tablet taken q.d. by mouth.
DRUGATRIPLA™
One ATRIPLA™ tablet taken q.d. by mouth
DRUGPlacebo
Placebo tablets matched to ATRIPLA® or Doravirine, Tenofovir, Lamivudine.
Sponsors
Merck Sharp & Dohme LLC
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
No
Inclusion criteria
* Is HIV-1 positive as determined by a positive result on an enzyme-immunoassay, has screening plasma HIV-1 RNA (determined by the central laboratory) ≥1000 copies/mL within 45 days prior to the treatment phase of this study, and has HIV treatment indicated based on physician assessment * Has never received antiretroviral therapy (ART) * Is highly unlikely to either become pregnant or impregnate a partner
Exclusion criteria
* Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound results of the study * Is a user of recreational or illicit drugs or has a recent history of alcohol/drug abuse * Has been treated for a viral infection other than HIV-1 (e.g., hepatitis B) with an agent that is active against HIV-1 * Has participated in a study with an investigational drug/device within 30 days prior to Screening * Has used systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this study or is anticipated to need them during the course of the study * Has a current (active) diagnosis of acute hepatitis due to any cause (note: participants with chronic hepatitis B and C may enter the study as long as they fulfill all entry criteria, have stable liver function tests, and have no significant impairment of hepatic synthetic function) * Is a female who is pregnant, breastfeeding, or expecting to conceive * Is a female and is expecting to donate eggs or is male and is expecting to donate sperm (investigators will provide appropriate guidance regarding egg and/or sperm donation after completion of the study treatment regimen) * Has evidence of decompensated liver disease manifested by the presence of or a history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver diseases, or has liver cirrhosis and a Child-Pugh Class C score or Pugh-Turcotte (CPT) score \> 9
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 | Week 48 | The percentage of participants in each arm with HIV-1 RNA levels \<50 copies/mL at Week 48 was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) snapshot approach in which all missing data are considered treatment failures, regardless of the reason. |
| Percentage of Participants With Tier-1 Neuropsychiatric Adverse Events (AEs) | Up to Week 48 | The percentage of participants in each arm experiencing ≥1 pre-specified Tier-1 neuropsychiatric AEs was determined. The list of Tier-1 neuropsychiatric AE categories included dizziness, sleep disorders and disturbances, and altered sensorium (including disturbance in attention). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96 | Week 96 | The percentage of participants in each arm with HIV-1 RNA levels \<40 copies/mL (including target detected and target not detected) at Week 96 were determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. The US Food and Drug Administration (FDA) snapshot approach (i.e., all missing data handled as treatment failures, regardless of the reason) were used for efficacy analyses. |
| Change From Baseline in CD4 Cell Counts at Week 48 | Baseline (Day 1) and Week 48 | The mean change from baseline in CD4 cell counts at Week 48 was assessed using the Observed Failure (OF) approach. With the OF approach, baseline values were carried forward for participants who discontinued prior to Week 48 due to lack of efficacy. Cell counts at Baseline and Week 48 were measured and expressed as cells/mm\^3, and percent change was then calculated as \[(Baseline counts - Week 48 counts)\*100\]. CD4 cell counts were quantified by a central laboratory using a commercially available assay. |
| Change From Baseline in CD4 Cell Counts at Week 96 | Baseline (Day 1) and Week 96 | The mean change from baseline in CD4 cell counts at Week 96 were assessed using the OF approach. With the OF approach, baseline values were carried forward for participants who discontinued prior to Week 96 due to lack of efficacy. Cell counts at Baseline and Week 96 were measured and expressed as cells/mm\^3, and percent change was calculated as \[(Baseline counts - Week 96 counts)\*100\]. CD4 cell counts were quantified by a central laboratory using a commercially available assay. |
| Percentage of Participants Experiencing ≥1 AE | Up to Week 48 | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
| Percentage of Participants Discontinuing From Study Medication Due to an AE(s) | Up to Week 48 | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
| Percentage of Participants With Tier-2 Neuropsychiatric AEs | Up to Week 48 | The percentage of participants in each arm experiencing ≥1 pre-specified Tier-2 neuropsychiatric AEs was determined. The list of Tier-2 neuropsychiatric AE categories included depression and suicide/self-injury and psychosis and psychotic disorders. |
| Change From Baseline in Fasting LDL-C at Week 48 | Baseline (Day 1) and Week 48 | The mean percent change from baseline in fasting (fast duration of ≥8 hours) LDL-C levels at Week 48 was determined for each arm. The Last Observation Carry Forward (LOCF) approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy. |
| Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96 | Week 96 | The percentage of participants in each arm with HIV-1 RNA levels \<50 copies/mL at Week 96 were determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. The US Food and Drug Administration (FDA) snapshot approach (i.e., all missing data handled as treatment failures, regardless of the reason) were used for efficacy analyses. |
| Change From Baseline in Fasting Non-HDL-C at Week 48 | Baseline (Day 1) and Week 48 | The mean percent change from baseline in fasting (fast duration of ≥8 hours) non-HDL-C levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy. |
| Change From Baseline in Fasting Cholesterol at Week 48 | Baseline (Day 1) and Week 48 | The mean percent change from baseline in fasting (fast duration of ≥8 hours) cholesterol levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy. |
| Change From Baseline in Fasting Triglycerides at Week 48 | Baseline (Day 1) and Week 48 | The mean percent change from baseline in fasting (fast duration of ≥8 hours) triglycerides levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy. |
| Change From Baseline in Fasting HDL-C at Week 48 | Baseline (Day 1) and Week 48 | The mean percent change from baseline in fasting (fast duration of ≥8 hours) HDL-C levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy. |
| Percentage of Participants With HIV-1 RNA Below the Limit of Quantification (BLoQ) at Week 48 | Week 48 | The percentage of participants in each arm with HIV-1 RNA levels BLoQ of 40 copies/mL and target not detected at Week 48 was determined. Plasma HIV RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled as observed. |
| Percentage of Participants With HIV-1 RNA BLoQ at Week 96 | Week 96 | The percentage of participants in each arm with HIV-1 RNA levels BLoQ of 40 copies/mL and target not detected at Week 96 was determined. Plasma HIV RNA levels was quantified with the Abbott RealTime HIV-1 Assay. Data was handled as observed. |
| Plasma Concentration of Doravirine at Week 48 | 0 hours post-dose and 2 hours post-dose on Week 48 | Plasma samples were collected for analysis of doravirine concentration at Week 48. A total of 2 samples were collected: 1 prior to dosing and 1 collected between 0.5 and 2 hours post-dose. |
| Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48 | Week 48 | The percentage of participants in each arm with HIV-1 RNA levels \<40 copies/mL (including target detected and target not detected) at Week 48 was determined. Plasma HIV RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) snapshot approach in which all missing data are considered treatment failures, regardless of the reason. |
Participant flow
Recruitment details
Treatment-naïve participants with HIV-1 infection have been recruited at 141 study sites worldwide. The present results include results from the base study (first 96-weeks of the study) along with study extension 1 (week 96-192), study extension 2 (week 192-288), and study extension 3 (week 288-384).
Participants by arm
| Arm | Count |
|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) Treatment-naive participants with HIV-1 infection took MK-1439A, a single-tablet fixed dose combination (FDC) containing doravirine (DOR) 100 mg + lamivudine (3TC) 300 mg + tenofovir disoproxil fumarate (TDF) 300 mg, once daily (q.d.) by mouth for 96 weeks. Participants also took 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384). | 364 |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) Treatment-naive participants with HIV-1 infection took ATRIPLA™, a single-tablet FDC containing efavirenz (EFV) 600 mg + emtricitabine (FTC) 200 mg + tenofovir disoproxil fumarate (TDF) 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 96 weeks. Participants also took 1 placebo tablet matched to MK-1439A q.d. by mouth for 96 weeks in order to maintain blinding. Eligible participants from the Base Study (Day 1 to Week 96) may have entered open-label optional study extensions to receive MK-1439A (FDC containing DOR 100 mg + 3TC 300 mg + TDF 300 mg), taken q.d. during Study Extension 1 (Weeks 96 to 192), Extension 2 (Weeks 192 to 288), and Extension 3 (Weeks 288 to 384). | 364 |
| Total | 728 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Base Study | Adverse Event | 11 | 26 |
| Base Study | Death | 1 | 4 |
| Base Study | Lack of Efficacy | 31 | 23 |
| Base Study | Lost to Follow-up | 6 | 8 |
| Base Study | Non-Compliance with study drug | 1 | 4 |
| Base Study | Physician Decision | 2 | 2 |
| Base Study | Pregnancy | 2 | 2 |
| Base Study | Protocol Violation | 8 | 4 |
| Base Study | Withdrawal by Subject | 10 | 17 |
| Study Extension 1 (Open-Label) | Adverse Event | 1 | 4 |
| Study Extension 1 (Open-Label) | Availability of study drug locally | 22 | 19 |
| Study Extension 1 (Open-Label) | Death | 1 | 0 |
| Study Extension 1 (Open-Label) | Lack of Efficacy | 10 | 13 |
| Study Extension 1 (Open-Label) | Lost to Follow-up | 8 | 5 |
| Study Extension 1 (Open-Label) | Non-Compliance | 2 | 3 |
| Study Extension 1 (Open-Label) | Physician Decision | 2 | 5 |
| Study Extension 1 (Open-Label) | Pregnancy | 4 | 2 |
| Study Extension 1 (Open-Label) | Withdrawal by Subject | 11 | 13 |
| Study Extension 2 (Open-Label) | Availability of study drug locally | 27 | 23 |
| Study Extension 2 (Open-Label) | Death | 2 | 2 |
| Study Extension 2 (Open-Label) | Lack of Efficacy | 1 | 1 |
| Study Extension 2 (Open-Label) | Lost to Follow-up | 1 | 7 |
| Study Extension 2 (Open-Label) | Non-Compliance with study drug | 2 | 0 |
| Study Extension 2 (Open-Label) | Physician Decision | 1 | 1 |
| Study Extension 2 (Open-Label) | Pregnancy | 0 | 1 |
| Study Extension 2 (Open-Label) | Withdrawal by Subject | 8 | 6 |
| Study Extension 3 (Open-Label) | Availability of study drug locally | 14 | 13 |
| Study Extension 3 (Open-Label) | Lost to Follow-up | 5 | 4 |
| Study Extension 3 (Open-Label) | Physician Decision | 1 | 5 |
| Study Extension 3 (Open-Label) | Pregnancy | 0 | 1 |
| Study Extension 3 (Open-Label) | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Total | ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | MK-1439A (DOR/3TC/TDF From Day 1) |
|---|---|---|---|
| Age, Continuous | 33.1 Years STANDARD_DEVIATION 10.2 | 32.7 Years STANDARD_DEVIATION 9.9 | 33.6 Years STANDARD_DEVIATION 10.5 |
| Baseline cluster of differentiation 4 (CD4) cell counts | 425.2 cells/mm^3 STANDARD_DEVIATION 214.3 | 415.5 cells/mm^3 STANDARD_DEVIATION 210.6 | 434.9 cells/mm^3 STANDARD_DEVIATION 217.9 |
| Baseline fasting cholesterol | 156.68 mg/dL STANDARD_DEVIATION 36.45 | 156.07 mg/dL STANDARD_DEVIATION 36.51 | 157.29 mg/dL STANDARD_DEVIATION 36.43 |
| Baseline fasting high-density lipoprotein cholesterol (HDL-C) | 41.67 mg/dL STANDARD_DEVIATION 12.38 | 41.44 mg/dL STANDARD_DEVIATION 13.08 | 41.90 mg/dL STANDARD_DEVIATION 11.67 |
| Baseline fasting low-density lipoprotein cholesterol (LDL-C) | 91.27 mg/dL STANDARD_DEVIATION 31.48 | 90.47 mg/dL STANDARD_DEVIATION 30.64 | 92.08 mg/dL STANDARD_DEVIATION 32.32 |
| Baseline fasting non-high-density lipoprotein cholesterol (non-HDL-C) | 115.01 mg/dL STANDARD_DEVIATION 34.09 | 114.63 mg/dL STANDARD_DEVIATION 33.55 | 115.39 mg/dL STANDARD_DEVIATION 34.67 |
| Baseline fasting triglycerides | 122.04 mg/dL STANDARD_DEVIATION 82.84 | 123.23 mg/dL STANDARD_DEVIATION 82.73 | 120.85 mg/dL STANDARD_DEVIATION 83.06 |
| Race (NIH/OMB) American Indian or Alaska Native | 16 Participants | 6 Participants | 10 Participants |
| Race (NIH/OMB) Asian | 124 Participants | 65 Participants | 59 Participants |
| Race (NIH/OMB) Black or African American | 135 Participants | 68 Participants | 67 Participants |
| Race (NIH/OMB) More than one race | 106 Participants | 55 Participants | 51 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 347 Participants | 170 Participants | 177 Participants |
| Sex: Female, Male Female | 112 Participants | 53 Participants | 59 Participants |
| Sex: Female, Male Male | 616 Participants | 311 Participants | 305 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 368 | 4 / 366 | 2 / 291 | 0 / 269 | 2 / 192 | 2 / 173 | 0 / 121 | 0 / 111 |
| other Total, other adverse events | 231 / 364 | 281 / 364 | 111 / 291 | 110 / 269 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 22 / 364 | 30 / 364 | 19 / 291 | 12 / 269 | 8 / 192 | 9 / 173 | 2 / 121 | 7 / 111 |
Outcome results
Primary
Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48
The percentage of participants in each arm with HIV-1 RNA levels \<50 copies/mL at Week 48 was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) snapshot approach in which all missing data are considered treatment failures, regardless of the reason.
Time frame: Week 48
Population: The analysis population consists of all randomized participants who received ≥1 dose of study medication and had baseline HIV-1 RNA data available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 | 84.3 Percentage of Participants |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48 | 80.8 Percentage of Participants |
95% CI: [-1.951, 9.026]
Primary
Percentage of Participants With Tier-1 Neuropsychiatric Adverse Events (AEs)
The percentage of participants in each arm experiencing ≥1 pre-specified Tier-1 neuropsychiatric AEs was determined. The list of Tier-1 neuropsychiatric AE categories included dizziness, sleep disorders and disturbances, and altered sensorium (including disturbance in attention).
Time frame: Up to Week 48
Population: The analysis population consists of all randomized participants who received ≥1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) | Percentage of Participants With Tier-1 Neuropsychiatric Adverse Events (AEs) | Dizziness | 8.8 Percentage of Participants |
| MK-1439A (DOR/3TC/TDF From Day 1) | Percentage of Participants With Tier-1 Neuropsychiatric Adverse Events (AEs) | Sleep disorders and disturbances | 12.1 Percentage of Participants |
| MK-1439A (DOR/3TC/TDF From Day 1) | Percentage of Participants With Tier-1 Neuropsychiatric Adverse Events (AEs) | Altered sensorium | 4.4 Percentage of Participants |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Percentage of Participants With Tier-1 Neuropsychiatric Adverse Events (AEs) | Dizziness | 37.1 Percentage of Participants |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Percentage of Participants With Tier-1 Neuropsychiatric Adverse Events (AEs) | Sleep disorders and disturbances | 25.5 Percentage of Participants |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Percentage of Participants With Tier-1 Neuropsychiatric Adverse Events (AEs) | Altered sensorium | 8.2 Percentage of Participants |
Comparison: Dizziness differencep-value: <0.00195% CI: [-34, -22.5]t-test, 2 sided
Comparison: Sleep disorders and disturbances differencep-value: <0.00195% CI: [-19.1, -7.9]t-test, 2 sided
Comparison: Altered sensorium differencep-value: 0.03395% CI: [-7.6, -0.3]t-test, 2 sided
Secondary
Change From Baseline in CD4 Cell Counts at Week 48
The mean change from baseline in CD4 cell counts at Week 48 was assessed using the Observed Failure (OF) approach. With the OF approach, baseline values were carried forward for participants who discontinued prior to Week 48 due to lack of efficacy. Cell counts at Baseline and Week 48 were measured and expressed as cells/mm\^3, and percent change was then calculated as \[(Baseline counts - Week 48 counts)\*100\]. CD4 cell counts were quantified by a central laboratory using a commercially available assay.
Time frame: Baseline (Day 1) and Week 48
Population: The analysis population consisted of all randomized participants who received ≥1 dose of study medication and had baseline and Week 48 CD4 data available.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) | Change From Baseline in CD4 Cell Counts at Week 48 | 198.4 Percent Change from Baseline |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Change From Baseline in CD4 Cell Counts at Week 48 | 188.4 Percent Change from Baseline |
95% CI: [-16.1, 36.3]
Secondary
Change From Baseline in CD4 Cell Counts at Week 96
The mean change from baseline in CD4 cell counts at Week 96 were assessed using the OF approach. With the OF approach, baseline values were carried forward for participants who discontinued prior to Week 96 due to lack of efficacy. Cell counts at Baseline and Week 96 were measured and expressed as cells/mm\^3, and percent change was calculated as \[(Baseline counts - Week 96 counts)\*100\]. CD4 cell counts were quantified by a central laboratory using a commercially available assay.
Time frame: Baseline (Day 1) and Week 96
Population: The analysis population consisted of all randomized participants who received ≥1 dose of study medication and had baseline and week 96 CD4 data available.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) | Change From Baseline in CD4 Cell Counts at Week 96 | 237.7 Percentage Change from Baseline |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Change From Baseline in CD4 Cell Counts at Week 96 | 223.0 Percentage Change from Baseline |
95% CI: [-18.7, 48.2]
Secondary
Change From Baseline in Fasting Cholesterol at Week 48
The mean percent change from baseline in fasting (fast duration of ≥8 hours) cholesterol levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.
Time frame: Baseline (Day 1) and Week 48
Population: The analysis population consists of all randomized participants who had baseline cholesterol data available as well as ≥1 cholesterol measurement after initiating study treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) | Change From Baseline in Fasting Cholesterol at Week 48 | -1.97 Percent Change from Baseline |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Change From Baseline in Fasting Cholesterol at Week 48 | 21.77 Percent Change from Baseline |
95% CI: [-27.57, -19.32]
Secondary
Change From Baseline in Fasting HDL-C at Week 48
The mean percent change from baseline in fasting (fast duration of ≥8 hours) HDL-C levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.
Time frame: Baseline (Day 1) and Week 48
Population: The analysis population consists of all randomized participants who had baseline HDL-C data available as well as ≥1 HDL-C measurement after initiating study treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) | Change From Baseline in Fasting HDL-C at Week 48 | 1.86 Percent Change from Baseline |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Change From Baseline in Fasting HDL-C at Week 48 | 8.51 Percent Change from Baseline |
95% CI: [-7.97, -4.96]
Secondary
Change From Baseline in Fasting LDL-C at Week 48
The mean percent change from baseline in fasting (fast duration of ≥8 hours) LDL-C levels at Week 48 was determined for each arm. The Last Observation Carry Forward (LOCF) approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.
Time frame: Baseline (Day 1) and Week 48
Population: The analysis population consists of all randomized participants who had baseline LDL-C data available as well as ≥1 LDL-C measurement after initiating study treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) | Change From Baseline in Fasting LDL-C at Week 48 | -1.58 Percent Change from Baseline |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Change From Baseline in Fasting LDL-C at Week 48 | 8.74 Percent Change from Baseline |
p-value: <0.000195% CI: [-13.53, -6.49]ANCOVA
Secondary
Change From Baseline in Fasting Non-HDL-C at Week 48
The mean percent change from baseline in fasting (fast duration of ≥8 hours) non-HDL-C levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.
Time frame: Baseline (Day 1) and Week 48
Population: The analysis population consists of all randomized participants who had baseline non-HDL-C data available as well as ≥1 non-HDL-C measurement after initiating study treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) | Change From Baseline in Fasting Non-HDL-C at Week 48 | -3.83 Percent Change from Baseline |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Change From Baseline in Fasting Non-HDL-C at Week 48 | 13.26 Percent Change from Baseline |
p-value: <0.000195% CI: [-20.89, -13.16]ANCOVA
Secondary
Change From Baseline in Fasting Triglycerides at Week 48
The mean percent change from baseline in fasting (fast duration of ≥8 hours) triglycerides levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.
Time frame: Baseline (Day 1) and Week 48
Population: The analysis population consists of all randomized participants who had baseline triglyceride data available as well as ≥1 triglyceride measurement after initiating study treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) | Change From Baseline in Fasting Triglycerides at Week 48 | -12.40 Percent Change from Baseline |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Change From Baseline in Fasting Triglycerides at Week 48 | 22.01 Percent Change from Baseline |
95% CI: [-47.1, -24.82]
Secondary
Percentage of Participants Discontinuing From Study Medication Due to an AE(s)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to Week 48
Population: The analysis population consisted of all randomized participants who received ≥1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) | Percentage of Participants Discontinuing From Study Medication Due to an AE(s) | 3.0 Percentage of participants |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Percentage of Participants Discontinuing From Study Medication Due to an AE(s) | 6.6 Percentage of participants |
95% CI: [-6.9, -0.5]
Secondary
Percentage of Participants Experiencing ≥1 AE
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to Week 48
Population: The analysis population consisted of all randomized participants who received ≥1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) | Percentage of Participants Experiencing ≥1 AE | 82.7 Percentage of participants |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Percentage of Participants Experiencing ≥1 AE | 90.7 Percentage of participants |
95% CI: [-13, -3.1]
Secondary
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48
The percentage of participants in each arm with HIV-1 RNA levels \<40 copies/mL (including target detected and target not detected) at Week 48 was determined. Plasma HIV RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) snapshot approach in which all missing data are considered treatment failures, regardless of the reason.
Time frame: Week 48
Population: The analysis population consists of all randomized participants who received ≥1 dose of study medication and had baseline HIV-1 RNA data available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) | Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48 | 83.8 Percentage of Participants |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48 | 79.7 Percentage of Participants |
95% CI: [-1.5, 9.7]
Secondary
Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96
The percentage of participants in each arm with HIV-1 RNA levels \<40 copies/mL (including target detected and target not detected) at Week 96 were determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. The US Food and Drug Administration (FDA) snapshot approach (i.e., all missing data handled as treatment failures, regardless of the reason) were used for efficacy analyses.
Time frame: Week 96
Population: The analysis population consisted of all randomized participants who received ≥1 dose of study medication and had baseline HIV-1 RNA data available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) | Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96 | 76.1 Percentage of participants |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96 | 72.8 Percentage of participants |
95% CI: [-3.057, 9.593]
Secondary
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96
The percentage of participants in each arm with HIV-1 RNA levels \<50 copies/mL at Week 96 were determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. The US Food and Drug Administration (FDA) snapshot approach (i.e., all missing data handled as treatment failures, regardless of the reason) were used for efficacy analyses.
Time frame: Week 96
Population: The analysis population will consist of all randomized participants who received ≥1 dose of study medication and had baseline HIV-1 RNA data available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) | Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96 | 77.5 Percentage of participants |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96 | 73.6 Percentage of participants |
95% CI: [-2.412, 10.042]
Secondary
Percentage of Participants With HIV-1 RNA Below the Limit of Quantification (BLoQ) at Week 48
The percentage of participants in each arm with HIV-1 RNA levels BLoQ of 40 copies/mL and target not detected at Week 48 was determined. Plasma HIV RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled as observed.
Time frame: Week 48
Population: The analysis population consists of all randomized participants who received ≥1 dose of study medication and had baseline HIV-1 RNA data available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) | Percentage of Participants With HIV-1 RNA Below the Limit of Quantification (BLoQ) at Week 48 | 59.6 Percentage of Participants |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Percentage of Participants With HIV-1 RNA Below the Limit of Quantification (BLoQ) at Week 48 | 55.5 Percentage of Participants |
Secondary
Percentage of Participants With HIV-1 RNA BLoQ at Week 96
The percentage of participants in each arm with HIV-1 RNA levels BLoQ of 40 copies/mL and target not detected at Week 96 was determined. Plasma HIV RNA levels was quantified with the Abbott RealTime HIV-1 Assay. Data was handled as observed.
Time frame: Week 96
Population: The analysis population consisted of all randomized participants who received ≥1 dose of study medication and had baseline HIV-1 RNA data available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) | Percentage of Participants With HIV-1 RNA BLoQ at Week 96 | 59.3 Percentage of Participants |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Percentage of Participants With HIV-1 RNA BLoQ at Week 96 | 59.1 Percentage of Participants |
Secondary
Percentage of Participants With Tier-2 Neuropsychiatric AEs
The percentage of participants in each arm experiencing ≥1 pre-specified Tier-2 neuropsychiatric AEs was determined. The list of Tier-2 neuropsychiatric AE categories included depression and suicide/self-injury and psychosis and psychotic disorders.
Time frame: Up to Week 48
Population: The analysis population consists of all randomized participants who received ≥1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) | Percentage of Participants With Tier-2 Neuropsychiatric AEs | Depression and suicide/self-injury | 4.1 Percentage of Participants |
| MK-1439A (DOR/3TC/TDF From Day 1) | Percentage of Participants With Tier-2 Neuropsychiatric AEs | Psychosis and psychotic disorders | 0.3 Percentage of Participants |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Percentage of Participants With Tier-2 Neuropsychiatric AEs | Depression and suicide/self-injury | 6.6 Percentage of Participants |
| ATRIPLA™ (Switch From EFV/FTC/TDF at Week 96) | Percentage of Participants With Tier-2 Neuropsychiatric AEs | Psychosis and psychotic disorders | 1.1 Percentage of Participants |
Comparison: Depression and suicide/self-injury differencep-value: <0.00195% CI: [-5.9, 0.8]t-test, 2 sided
Comparison: Psychosis and psychotic disorders differencep-value: <0.00195% CI: [-2.5, 0.5]t-test, 2 sided
Secondary
Plasma Concentration of Doravirine at Week 48
Plasma samples were collected for analysis of doravirine concentration at Week 48. A total of 2 samples were collected: 1 prior to dosing and 1 collected between 0.5 and 2 hours post-dose.
Time frame: 0 hours post-dose and 2 hours post-dose on Week 48
Population: The analysis population consists of all randomized participants in the MK-1439A arm who received ≥1 dose of study drug and had doravirine concentration data available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MK-1439A (DOR/3TC/TDF From Day 1) | Plasma Concentration of Doravirine at Week 48 | Pre-dose | 1290 nM | Standard Deviation 799 |
| MK-1439A (DOR/3TC/TDF From Day 1) | Plasma Concentration of Doravirine at Week 48 | 0.5 to 2 hours post-dose | 2330 nM | Standard Deviation 1230 |