HIV-1
Conditions
Brief summary
To establish a new treatment option for treatment-naïve participants with HIV-1, the efficacy and safety of doravirine will be determined relative to a protease inhibitor (PI). Participants will receive double-blind treatment during the 96-week Base Study. Eligible participants in either of the Base Study groups will continue to receive the doravirine-containing regimen open label for an additional 96 weeks in the Study Extension 1. Eligible participants who are deriving benefit will continue in Study Extension 2 to receive the doravirine-containing regimen open label until doravirine becomes locally available or for an additional 96 weeks, whichever comes first. The primary hypothesis is that doravirine 100 mg once a day (q.d.) is non-inferior to darunavir/ritonavir (800 mg/100 mg) q.d., each in combination with TRUVADA™ or EPZICOM™/KIVEXA™, as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) \<50 copies/mL at Week 48. If non-inferiority is established, then the superiority of doravirine 100 mg q.d. compared to darunavir/ ritonavir (800 mg/100 mg) q.d. will be assessed.
Detailed description
Participants in Australia, Russia, and South Africa who are deriving benefit from MK-1439A are also eligible to continue receiving study drug during Study Extension 3, which will last for 2 years or until drug is available locally, whichever comes first.
Interventions
DRUGDoravirine
Doravirine 100 mg tablet administered p.o. q.d.
DRUGDarunavir
Darunavir 800 mg tablet administered p.o. q.d.
DRUGRitonavir
Ritonavir 100 mg tablet administered p.o. q.d.
DRUGTRUVADA™ or EPZICOM™/KIVEXA™
The investigator selects either TRUVADA™, a tablet containing 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate p.o. q.d. or EPZICOM™/KIVEXA™, a tablet containing 600 mg abacavir sulfate and 300 mg lamivudine, p.o. q.d.
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 and has HIV treatment indicated based on physician assessment. * Has received no (0 days of) antiretroviral therapy (ART), including investigational antiretroviral agents. * Is considered clinically stable with no signs or symptoms of active infection for at least 2 weeks prior to the start of treatment. * Female is highly unlikely to become pregnant, or male is highly unlikely to impregnate a partner because they are not of reproductive potential, or agree to practice abstinence or use acceptable contraception for up to 14 days after the last dose of study drug. * Eligibility for the Study Extension 1 at the Week 96 visit: 1) completed the Week 96 visit, 2) derived benefit from participation through Week 96 in the opinion of the investigator, 3) is a clinically-appropriate candidate for an additional 96 weeks of treatment with the Study Extension regimen. * Eligibility for the Study Extension 2 at the Week 192 visit: 1) completed the Week 192 visit, 2) derived benefit from participation through Week 192 in the opinion of the investigator, 3) is a clinically-appropriate candidate for 96 weeks of treatment with the Study Extension regimen.
Exclusion criteria
* Uses or has had a recent history of using recreational or illicit drugs. * Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1. * Has documented or known resistance to study drugs including doravirine, darunavir, ritonavir, emtricitabine, tenofovir, abacavir and/or lamivudine. * Has participated in a study with an investigational compound/device within the prior month, or anticipates doing so during this study. * Has used systemic immunosuppressive therapy or immune modulators within the prior 30 days, or anticipates doing so during this study. * Has significant hypersensitivity or other contraindication to any of the components of the study drugs. * Has a current (active) diagnosis of acute hepatitis due to any cause. * Is pregnant, breastfeeding or expecting to conceive at any time during the study. * Female who expects to donate eggs, or male who expects to donate sperm at any time during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 48 | Week 48 | The percentage of participants in each arm achieving 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 and all missing data were considered treatment failures, regardless of the reason. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean CD4+ T-cell Count at Week 48 | Baseline and Week 48 | CD4+ T-cell counts were quantified by a central laboratory using a commercially available assay. |
| Change From Baseline in Mean CD4+ T-cell Count at Week 96 | Baseline and Week 96 | CD4+ T-cell counts were quantified by a central laboratory using a commercially available assay. |
| Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 | Baseline and Week 48 | Serum LDL-C was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The Last Observation Carry Forward (LOCF) approach was applied for missing data or data collected after modifying lipid-lowering therapy. |
| Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 | Baseline and Week 48 | Serum non-HDL-C was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy. |
| Mean Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 48 | Baseline and Week 48 | Serum HDL-C was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy. |
| Mean Change From Baseline in Fasting Total Cholesterol at Week 48 | Baseline and Week 48 | Serum total cholesterol was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy. |
| Mean Change From Baseline in Fasting Triglyceride at Week 48 | Baseline and Week 48 | Serum triglyceride was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy. |
| Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 96 | Week 96 | The percentage of participants in each arm achieving HIV-1 RNA levels \<50 copies/mL at Week 96 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 and all missing data were considered treatment failures, regardless of the reason. |
| Percentage of Participants With Any Serious Adverse Event | Up to 98 weeks | A serious adverse event is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs a hospitalization, is a congenital anomaly or birth defect, is a cancer, is associated with an overdose, or is another important medical event. The percentage of participants with any SAE was assessed. |
| Percentage of Participants With Any Drug-related Adverse Event | Up to 98 weeks | The investigator was to determine if an AE had a reasonable possibility of a relationship to the study drug. The percentage of participants with any drug-related AE was assessed. |
| Percentage of Participants With Any Drug-related Serious Adverse Event | Up to 98 weeks | The percentage of participants with any drug-related SAE was assessed. |
| Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event | Up to 96 weeks | The percentage of participants who discontinued study treatment due to an AE was assessed. |
| Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 48 | Week 48 | The percentage of participants in each arm achieving HIV-1 RNA levels \<40 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 and all missing data were considered treatment failures, regardless of the reason. |
| Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 96 | Week 96 | The percentage of participants in each arm achieving HIV-1 RNA levels \<40 copies/mL at Week 96 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 and all missing data were considered treatment failures, regardless of the reason. |
| Percentage of Participants With Any Adverse Event | Up to 98 weeks | An adverse event (AE) is defined as any untoward medical occurrence in a study participant and which does not necessarily have to have a causal relationship to treatment. An adverse event can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the study treatment or protocol-specified procedure, whether or not considered related to study treatment or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study treatment is also an AE. The percentage of participants with any AE was assessed. |
Participant flow
Pre-assignment details
A total of 1027 participants were screened and 769 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Doravirine 100 mg Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study. | 385 |
| Daurunavir 800 mg + Ritonavir 100 mg Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study. | 384 |
| Total | 769 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Base Study: 96 Weeks | Adverse Event | 6 | 14 |
| Base Study: 96 Weeks | Death | 3 | 1 |
| Base Study: 96 Weeks | Lack of Efficacy | 21 | 32 |
| Base Study: 96 Weeks | Lost to Follow-up | 28 | 24 |
| Base Study: 96 Weeks | Noncompliance with drug | 9 | 6 |
| Base Study: 96 Weeks | Physician Decision | 2 | 4 |
| Base Study: 96 Weeks | Pregnancy | 2 | 1 |
| Base Study: 96 Weeks | Protocol Violation | 1 | 6 |
| Base Study: 96 Weeks | Randomized not treated | 2 | 1 |
| Base Study: 96 Weeks | Withdrawal by Subject | 19 | 22 |
| Study Extension 1: Week 96 to Week 192 | Adverse Event | 6 | 1 |
| Study Extension 1: Week 96 to Week 192 | Availability of study medication locally | 2 | 0 |
| Study Extension 1: Week 96 to Week 192 | Lack of Efficacy | 8 | 11 |
| Study Extension 1: Week 96 to Week 192 | Lost to Follow-up | 8 | 7 |
| Study Extension 1: Week 96 to Week 192 | Non-compliance with study drug | 1 | 2 |
| Study Extension 1: Week 96 to Week 192 | Physician Decision | 3 | 7 |
| Study Extension 1: Week 96 to Week 192 | Pregnancy | 2 | 1 |
| Study Extension 1: Week 96 to Week 192 | Withdrawal by Subject | 19 | 14 |
| Study Extension 2: Week 192 to Week 288 | Adverse Event | 0 | 1 |
| Study Extension 2: Week 192 to Week 288 | Availability of study medication locally | 38 | 29 |
| Study Extension 2: Week 192 to Week 288 | Lack of Efficacy | 2 | 3 |
| Study Extension 2: Week 192 to Week 288 | Lost to Follow-up | 0 | 1 |
| Study Extension 2: Week 192 to Week 288 | Non-compliance with study drug | 2 | 0 |
| Study Extension 2: Week 192 to Week 288 | Physician Decision | 1 | 1 |
| Study Extension 2: Week 192 to Week 288 | Withdrawal by Subject | 4 | 3 |
| Study Extension 3: Week 288 to Week 384 | Availability of study medication locally | 6 | 6 |
| Study Extension 3: Week 288 to Week 384 | Death | 0 | 1 |
| Study Extension 3: Week 288 to Week 384 | Lost to Follow-up | 1 | 3 |
| Study Extension 3: Week 288 to Week 384 | Non-compliance with study drug | 1 | 1 |
| Study Extension 3: Week 288 to Week 384 | Physician Decision | 1 | 0 |
| Study Extension 3: Week 288 to Week 384 | Withdrawal by Subject | 5 | 2 |
Baseline characteristics
| Characteristic | Doravirine 100 mg | Total | Daurunavir 800 mg + Ritonavir 100 mg |
|---|---|---|---|
| Age, Continuous | 34.9 Years STANDARD_DEVIATION 10.7 | 35.3 Years STANDARD_DEVIATION 10.7 | 35.7 Years STANDARD_DEVIATION 10.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 93 Participants | 179 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 286 Participants | 577 Participants | 291 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 13 Participants | 7 Participants |
| Mean Cluster of Differentiation 4 (CD4+) T-cell Count | 432.6 Cells/mm^3 STANDARD_DEVIATION 208.4 | 422.2 Cells/mm^3 STANDARD_DEVIATION 219.4 | 411.9 Cells/mm^3 STANDARD_DEVIATION 229.6 |
| Plasma HIV-1 RNA | 27073.0 Copies/mL | 27073.0 Copies/mL | 27357.0 Copies/mL |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 14 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 87 Participants | 176 Participants | 89 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 8 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 281 Participants | 561 Participants | 280 Participants |
| Sex: Female, Male Female | 65 Participants | 123 Participants | 58 Participants |
| Sex: Female, Male Male | 320 Participants | 646 Participants | 326 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 385 | 3 / 384 |
| other Total, other adverse events | 264 / 383 | 247 / 383 |
| serious Total, serious adverse events | 45 / 383 | 49 / 383 |
Outcome results
Primary
Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 48
The percentage of participants in each arm achieving 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 and all missing data were considered treatment failures, regardless of the reason.
Time frame: Week 48
Population: All randomized participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 100 mg | Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 48 | 83.8 Percentage of participants |
| Daurunavir 800 mg + Ritonavir 100 mg | Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 48 | 79.9 Percentage of participants |
95% CI: [-1.59, 9.415]
Secondary
Change From Baseline in Mean CD4+ T-cell Count at Week 48
CD4+ T-cell counts were quantified by a central laboratory using a commercially available assay.
Time frame: Baseline and Week 48
Population: All randomized participants who received at least 1 dose of study drug and had data for the outcome measure. Baseline values were carried forward for participants who discontinued therapy due to lack of efficacy.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Doravirine 100 mg | Change From Baseline in Mean CD4+ T-cell Count at Week 48 | 192.7 Cells/mm^3 |
| Daurunavir 800 mg + Ritonavir 100 mg | Change From Baseline in Mean CD4+ T-cell Count at Week 48 | 185.6 Cells/mm^3 |
95% CI: [-20.8, 35]
Secondary
Change From Baseline in Mean CD4+ T-cell Count at Week 96
CD4+ T-cell counts were quantified by a central laboratory using a commercially available assay.
Time frame: Baseline and Week 96
Population: All randomized participants who received at least 1 dose of study drug and had data for the outcome measure. Baseline values were carried forward for participants who discontinued therapy due to lack of efficacy.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Doravirine 100 mg | Change From Baseline in Mean CD4+ T-cell Count at Week 96 | 224.1 Cells/mm^3 |
| Daurunavir 800 mg + Ritonavir 100 mg | Change From Baseline in Mean CD4+ T-cell Count at Week 96 | 206.7 Cells/mm^3 |
95% CI: [-14.5, 49.3]
Secondary
Mean Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 48
Serum HDL-C was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy.
Time frame: Baseline and Week 48
Population: All randomized participants who received at least 1 dose of study drug and had a measurement at Baseline and at the time point assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Doravirine 100 mg | Mean Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 48 | Baseline | 43.58 mg/dL | Standard Deviation 12.99 |
| Doravirine 100 mg | Mean Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 48 | Change from Baseline | 3.94 mg/dL | Standard Deviation 10.66 |
| Daurunavir 800 mg + Ritonavir 100 mg | Mean Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 48 | Baseline | 43.27 mg/dL | Standard Deviation 13.96 |
| Daurunavir 800 mg + Ritonavir 100 mg | Mean Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 48 | Change from Baseline | 4.15 mg/dL | Standard Deviation 11.01 |
Secondary
Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48
Serum LDL-C was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The Last Observation Carry Forward (LOCF) approach was applied for missing data or data collected after modifying lipid-lowering therapy.
Time frame: Baseline and Week 48
Population: All randomized participants who received at least 1 dose of study drug and had a measurement at Baseline and at the time point assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Doravirine 100 mg | Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 | Baseline | 91.10 mg/dL | Standard Deviation 28.61 |
| Doravirine 100 mg | Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 | Change from Baseline | -4.51 mg/dL | Standard Deviation 20.64 |
| Daurunavir 800 mg + Ritonavir 100 mg | Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 | Baseline | 91.76 mg/dL | Standard Deviation 30.36 |
| Daurunavir 800 mg + Ritonavir 100 mg | Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 | Change from Baseline | 9.92 mg/dL | Standard Deviation 27.31 |
p-value: <0.000195% CI: [-18.15, -11.06]ANCOVA
Secondary
Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48
Serum non-HDL-C was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy.
Time frame: Baseline and Week 48
Population: All randomized participants who received at least 1 dose of study drug and had a measurement at Baseline and at the time point assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Doravirine 100 mg | Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 | Baseline | 113.34 mg/dL | Standard Deviation 34.25 |
| Doravirine 100 mg | Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 | Change from Baseline | -5.30 mg/dL | Standard Deviation 23.28 |
| Daurunavir 800 mg + Ritonavir 100 mg | Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 | Baseline | 114.44 mg/dL | Standard Deviation 35.01 |
| Daurunavir 800 mg + Ritonavir 100 mg | Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 | Change from Baseline | 13.75 mg/dL | Standard Deviation 31.08 |
p-value: <0.000195% CI: [-23.33, -15.35]ANCOVA
Secondary
Mean Change From Baseline in Fasting Total Cholesterol at Week 48
Serum total cholesterol was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy.
Time frame: Baseline and Week 48
Population: All randomized participants who received at least 1 dose of study drug and had a measurement at Baseline and at the time point assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Doravirine 100 mg | Mean Change From Baseline in Fasting Total Cholesterol at Week 48 | Baseline | 156.92 mg/dL | Standard Deviation 35.82 |
| Doravirine 100 mg | Mean Change From Baseline in Fasting Total Cholesterol at Week 48 | Change from Baseline | -1.37 mg/dL | Standard Deviation 25.47 |
| Daurunavir 800 mg + Ritonavir 100 mg | Mean Change From Baseline in Fasting Total Cholesterol at Week 48 | Baseline | 157.71 mg/dL | Standard Deviation 37.34 |
| Daurunavir 800 mg + Ritonavir 100 mg | Mean Change From Baseline in Fasting Total Cholesterol at Week 48 | Change from Baseline | 17.90 mg/dL | Standard Deviation 33.95 |
Secondary
Mean Change From Baseline in Fasting Triglyceride at Week 48
Serum triglyceride was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy.
Time frame: Baseline and Week 48
Population: All randomized participants who received at least 1 dose of study drug and had a measurement at Baseline and at the time point assessed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Doravirine 100 mg | Mean Change From Baseline in Fasting Triglyceride at Week 48 | Baseline | 111.16 mg/dL | Standard Deviation 75.31 |
| Doravirine 100 mg | Mean Change From Baseline in Fasting Triglyceride at Week 48 | Change from Baseline | -3.14 mg/dL | Standard Deviation 68.81 |
| Daurunavir 800 mg + Ritonavir 100 mg | Mean Change From Baseline in Fasting Triglyceride at Week 48 | Baseline | 117.02 mg/dL | Standard Deviation 97.3 |
| Daurunavir 800 mg + Ritonavir 100 mg | Mean Change From Baseline in Fasting Triglyceride at Week 48 | Change from Baseline | 21.97 mg/dL | Standard Deviation 92.59 |
Secondary
Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 48
The percentage of participants in each arm achieving HIV-1 RNA levels \<40 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 and all missing data were considered treatment failures, regardless of the reason.
Time frame: Week 48
Population: All randomized participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 100 mg | Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 48 | 83.3 Percentage of participants |
| Daurunavir 800 mg + Ritonavir 100 mg | Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 48 | 79.1 Percentage of participants |
95% CI: [-1.404, 9.743]
Secondary
Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 96
The percentage of participants in each arm achieving HIV-1 RNA levels \<40 copies/mL at Week 96 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 and all missing data were considered treatment failures, regardless of the reason.
Time frame: Week 96
Population: All randomized participants who received at least 1 dose of study drug and had data for the outcome measure. Participants with missing HIV-1 RNA due to an Abbott RealTime manufacturing agent recall were excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 100 mg | Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 96 | 72.0 Percentage of participants |
| Daurunavir 800 mg + Ritonavir 100 mg | Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 96 | 64.4 Percentage of participants |
95% CI: [0.98, 14.232]
Secondary
Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 96
The percentage of participants in each arm achieving HIV-1 RNA levels \<50 copies/mL at Week 96 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 and all missing data were considered treatment failures, regardless of the reason.
Time frame: Week 96
Population: All randomized participants who received at least 1 dose of study drug and had data for the outcome measure. Participants with missing HIV-1 RNA due to an Abbott RealTime manufacturing agent recall were excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 100 mg | Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 96 | 73.1 Percentage of participants |
| Daurunavir 800 mg + Ritonavir 100 mg | Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 96 | 66.0 Percentage of participants |
95% CI: [0.508, 13.656]
Secondary
Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event
The percentage of participants who discontinued study treatment due to an AE was assessed.
Time frame: Up to 96 weeks
Population: All randomized participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 100 mg | Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event | 1.6 Percentage of participants |
| Daurunavir 800 mg + Ritonavir 100 mg | Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event | 3.4 Percentage of participants |
Secondary
Percentage of Participants With Any Adverse Event
An adverse event (AE) is defined as any untoward medical occurrence in a study participant and which does not necessarily have to have a causal relationship to treatment. An adverse event can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the study treatment or protocol-specified procedure, whether or not considered related to study treatment or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study treatment is also an AE. The percentage of participants with any AE was assessed.
Time frame: Up to 98 weeks
Population: All randomized participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 100 mg | Percentage of Participants With Any Adverse Event | 84.6 Percentage of participants |
| Daurunavir 800 mg + Ritonavir 100 mg | Percentage of Participants With Any Adverse Event | 82.8 Percentage of participants |
Secondary
Percentage of Participants With Any Drug-related Adverse Event
The investigator was to determine if an AE had a reasonable possibility of a relationship to the study drug. The percentage of participants with any drug-related AE was assessed.
Time frame: Up to 98 weeks
Population: All randomized participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 100 mg | Percentage of Participants With Any Drug-related Adverse Event | 32.1 Percentage of participants |
| Daurunavir 800 mg + Ritonavir 100 mg | Percentage of Participants With Any Drug-related Adverse Event | 32.1 Percentage of participants |
Secondary
Percentage of Participants With Any Drug-related Serious Adverse Event
The percentage of participants with any drug-related SAE was assessed.
Time frame: Up to 98 weeks
Population: All randomized participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 100 mg | Percentage of Participants With Any Drug-related Serious Adverse Event | 0.3 Percentage of participants |
| Daurunavir 800 mg + Ritonavir 100 mg | Percentage of Participants With Any Drug-related Serious Adverse Event | 0.3 Percentage of participants |
Secondary
Percentage of Participants With Any Serious Adverse Event
A serious adverse event is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs a hospitalization, is a congenital anomaly or birth defect, is a cancer, is associated with an overdose, or is another important medical event. The percentage of participants with any SAE was assessed.
Time frame: Up to 98 weeks
Population: All randomized participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 100 mg | Percentage of Participants With Any Serious Adverse Event | 7.0 Percentage of participants |
| Daurunavir 800 mg + Ritonavir 100 mg | Percentage of Participants With Any Serious Adverse Event | 8.6 Percentage of participants |