HIV Infections
Conditions
Brief summary
The hypothesis tested in this study is that doravirine (MK-1439) at the final dose selected is superior to efavirenz, each given in combination with TRUVADA®, as measured by the percentage of participants with CNS events by Week 8. If superiority is established at Week 8, the same hypothesis will be tested for Week 24.
Detailed description
Part I - Dose-Ranging. Part I will evaluate the (1) safety and tolerability and (2) efficacy (antiretroviral activity) of 4 doses of doravirine compared with efavirenz, when each is given in combination with TRUVADA® for at least 24 weeks in approximately 200 participants. A single dose of doravirine will be selected for further study after all participants complete the Week 24 visit in Part I. Participants receiving any dose of doravirine in Part I will be switched to the selected doravirine dose and continue in the study for up to 96 weeks, but will not be randomized to Part II. Part II - Selected Dose. Part II will be initiated after the doravirine dose has been selected as indicated above for Part 1. Approximately 120 additional participants will be randomized in 1:1 ratio to the selected dose of doravirine or efavirenz, each in combination with TRUVADA® for 96 weeks of blinded treatment. Part II will evaluate the safety of the selected dose compared with efavirenz, particularly with regard to central nervous system (CNS) adverse events.
Interventions
DRUGDoravirine
Part I: Doravirine 25 mg, 50 mg (25 mg X 2), 100 mg, or 200 mg (100 mg X 2) depending upon randomization, taken orally every morning with or without food for at least 24 weeks. Part II: Selected dose of doravirine depending upon randomization (either 25 mg, 50 mg, 100 mg, or 200 mg) tablet orally every morning with or without food for 96 weeks.
DRUGEfavirenz
Efavirenz 600 mg tablet orally at bedtime taken without food on an empty stomach for 96 weeks
DRUGTRUVADA®
Open-label TRUVADA® (fixed combination 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate) tablet taken orally with food in the morning for 96 weeks
DRUGPlacebo for Doravirine
Placebo tablets matching doravirine
DRUGPlacebo for Efavirenz
Placebo tablets matching efavirenz
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
* HIV-1 positive * No previous use of antiretroviral therapy (ART) * No signs of active pulmonary disease within 45 days before the start of study treatment * Clinically stable with no signs or symptoms of acute infection * No change in clinical status or chronic medications for at least 2 weeks before the start of study treatment * Participants of reproductive potential agree to remain abstinent in line with their preferred and usual lifestyle or use (or have their partner use) 2 acceptable methods of birth control throughout the study and for 12 weeks post study. * Participants not of reproductive potential, not sexually active, whose current partner(s) is not of reproductive potential, or whose sexual activity is exclusively homosexual are eligible without requiring the use of contraception.
Exclusion criteria
* Males planning to impregnate or provide sperm donation for the duration of the study plus an additional 12 weeks. Females pregnant or breast-feeding or expecting to conceive or donate eggs for the duration of the study plus an additional 12 weeks. * Received any approved or experimental antiretroviral agents or is anticipated to receive such medications during the study. * Use of any immunomodulators or immunosuppressive therapy within one month before the study. Short courses of corticosteroids (e.g., for asthma exacerbation) are allowed. * Treatment for a viral infection other than HIV, such as hepatitis B, with an agent that is active against HIV * HIV resistance to emtricitabine, tenofovir disoproxil fumarate, and/or efavirenz. * History of renal or urinary obstructive disease or requires dialysis * Active Hepatitis C virus (HCV) or Hepatitis B virus (HBV) co-infection * History of alcohol or other substance abuse * Participation in a study with an investigational compound/device within one month or is anticipating to participate in such a study during this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I) | Up to Week 24 | Assessment of the percentage of participants receiving doravirine at all doses (25 mg, 50 mg, 100 mg, or 200 mg), compared with participants receiving efavirenz 600 mg, who had at least 1 AE over 24 weeks of treatment. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product.The percentage of participants in any treatment group with at least 1 AE was primarily assessed for Weeks 0-24. |
| Percentage of Participants Who Discontinued Study Therapy Due to AEs in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I) | Up to Week 24 | Assessment of the percentage of participants receiving doravirine at all doses (25 mg, 50 mg, 100 mg, or 200 mg), compared with participants receiving efavirenz 600 mg, who discontinued therapy due to an AE over 24 weeks of treatment. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product.The percentage of participants in any treatment group who discontinued therapy due to an AE was primarily assessed for Weeks 0-24. |
| Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | Up to Week 24 | Assessment of the percentage of participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg, who had at least 1 AE over 24 weeks of treatment. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product.The percentage of participants in any treatment group with at least 1 AE was assessed for Weeks 0-24. |
| Percentage of Participants With CNS Events by Week 8: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | Up to Week 8 | Assessment of the percentage of participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg, who had CNS events over 8 weeks of treatment. CNS events were pooled and evaluated as pre-specified by the protocol (depression, nightmare, confusional state, suicidal ideation, nervous system disorder, psychotic disorder, abnormal dreams, suicide attempt, acute psychosis, delirium, depressed level of consciousness, hallucination, hallucination auditory, hallucination visual, completed suicide, suicidal behavior, major depression, depressed mood, depressive symptom, insomnia, disturbance in attention, somnolence, dizziness, or concentration impaired). The percentage of participants in either treatment group with CNS events was assessed over Weeks 0-8. |
| Percentage of Participants With CNS Events by Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | Up to Week 24 | Assessment of the percentage of participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg, who had CNS events over 24 weeks of treatment. CNS events were pooled and evaluated as pre-specified by the protocol (depression, nightmare, confusional state, suicidal ideation, nervous system disorder, psychotic disorder, abnormal dreams, suicide attempt, acute psychosis, delirium, depressed level of consciousness, hallucination, hallucination auditory, hallucination visual, completed suicide, suicidal behavior, major depression, depressed mood, depressive symptom, insomnia, disturbance in attention, somnolence, dizziness, or concentration impaired). The percentage of participants in either treatment group with CNS events was assessed over Weeks 0-24. |
| Percentage of Participants With Virologic Response (HIV-1 RNA) < 40 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I) | Week 24 | Assessment of the virologic response to doravirine at all studied doses (25 mg, 50 mg, 100 mg, and 200 mg), compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with plasma HIV-1 RNA \<40 copies/mL at Week 24. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay, which has a limit of reliable quantification of 40 copies/mL. The percentage of participants in any treatment group with a virologic response was assessed at Week 24. The Non-Completer = Failure (NC=F) approach, in which participants who prematurely discontinued assigned treatment for any reason and were considered as failures thereafter, was used as the primary approach to handle missing data this analysis of efficacy.This primary outcome was analyzed for HIV-1 RNA \<40 copies/mL in Part I. |
| Percentage of Participants With Virologic Response (HIV-1 RNA <40 Copies/mL) at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | Week 24 | Assessment of the virologic response to doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with HIV-1 RNA \<40 copies/mL at Week 24. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay, which has a limit of reliable quantification of 40 copies/mL. The percentage of participants in any treatment group with a virologic response was assessed at Week 24. The NC=F approach was used as the primary approach to handle missing data this analysis of efficacy. This primary outcome was analyzed for HIV-1 RNA \<40 copies/mL in Part I & Part II combined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in CD4 Cell Count at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | Baseline, Week 24 | Assessment of the change from baseline in the CD4 cell count at Week 24 in participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg. The OF approach was used to handle missing data, and the Baseline CD4 cell count was carried forward for participants who discontinued assigned treatment due to lack of efficacy. |
| Change From Baseline in CD4 Cell Count at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | Baseline, Week 48 | Assessment of the change from baseline in the CD4 count at Week 48 in participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg. The OF approach was used to handle missing data, and the Baseline CD4 cell count was carried forward for subjects who discontinued assigned treatment due to lack of efficacy. |
| Percentage of Participants With Virologic Response (HIV-1 RNA <40 Copies/mL) at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | Week 48 | Assessment of the virologic response to doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with HIV-1 RNA \<40 copies/mL at Week 48. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay. The percentage of participants in any treatment group with a virologic response was primarily assessed for Weeks 0-24. The NC=F approach was used as the primary approach to handle missing data this analysis of efficacy. This primary outcome was analyzed for HIV-1 RNA \<40 copies/mL in Part I & Part II combined. |
| Percentage of Participants With At Least 1 AE in Weeks 0-48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | Up to Week 48 | A secondary outcome in Part I/II combined was the percentage of participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg, who had at least 1 AE over 48 weeks of treatment. The percentage of participants in any treatment group with at least 1 AE was primarily assessed for Weeks 0-48. |
| Percentage of Participants With At Least 1 AE in Weeks 0-96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | Up to Week 96 | A secondary outcome in Part I/II combined was the percentage of participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg, who had at least 1 AE over 96 weeks of treatment. The percentage of participants in any treatment group with at least 1 AE was primarily assessed for Weeks 0-96. |
| Change From Baseline in CD4 Cell Count at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | Baseline, Week 96 | A secondary endpoint in Part I/II combined was the change from baseline in the CD4 count at Week 96 in participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg. The OF approach was used to handle missing data, and the Baseline CD4 cell count was carried forward for subjects who discontinued assigned treatment due to lack of efficacy. |
| Percentage of Participants With Virologic Response (HIV-1 RNA <40 Copies/mL) at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | Week 96 | Assessment of the virologic response to doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with HIV-1 RNA \<40 copies/mL at Week 96. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay. The percentage of participants in any treatment group with a virologic response was primarily assessed for Weeks 0-24. The NC=F approach was used as the primary approach to handle missing data this analysis of efficacy. This primary outcome was analyzed for HIV-1 RNA \<40 copies/mL in Part I & Part II combined. |
| Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I) | Week 24 | Assessment of the virologic response to doravirine at all studied doses (25 mg, 50 mg, 100 mg, and 200 mg), compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with plasma HIV-1 RNA \<200 copies/mL at Week 24. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay.The percentage of participants in any treatment group with a virologic response was assessed at Week 24. The NC=F approach was used as the primary approach to handle missing data for this analysis of efficacy. This primary outcome was analyzed for HIV-1 RNA \<200 copies/mL in Part I. |
| Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | Week 24 | Assessment of the virologic response to doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with plasma HIV-1 RNA \<200 copies/mL at Week 24. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay. The percentage of participants in any treatment group with a virologic response was primarily assessed for Weeks 0-24. The NC=F approach was used as the primary approach to handle missing data for this analysis of efficacy. This secondary outcome was analyzed for HIV-1 RNA \<200 copies/mL in Part I & Part II combined. |
| Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | Week 48 | Evaluation of the antiretroviral activity of doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA for 24 weeks, as measured by the percentage of participants with HIV-1 RNA \<200 copies/mL at Week 48. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay. This primary outcome was analyzed for RNA \<200 copies/mL in Part I & Part II combined. |
| Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | Week 96 | Assessment of the virologic response to doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with plasma HIV-1 RNA \<200 copies/mL at Week 96. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay. The percentage of participants in any treatment group with a virologic response was primarily assessed for Weeks 0-96. The Non-Completer = Failure (NC=F) approach, in which participants who prematurely discontinued assigned treatment for any reason and were considered as failures thereafter, was used as the primary approach to handle missing data this analysis of efficacy. This primary outcome was analyzed for HIV-1 RNA \<200 copies/mL in Part I & Part II combined. |
| Change From Baseline in CD4 T Lymphocyte Cell Count at Week 24: Doravirine (All Doses) vs Efavirenz (Part I) | Baseline, Week 24 | Evaluation of the change from baseline in the CD4 cell count at Week 24 in participants receiving doravirine at all doses (25 mg, 50 mg, 100 mg, and 200 mg), compared with participants receiving efavirenz 600 mg. The Observed Failure (OF) approach was used to handle missing data, and the Baseline CD4 cell count was carried forward for participants who discontinued assigned treatment due to lack of efficacy. |
Participant flow
Pre-assignment details
210 participants were randomized to Part I and 132 participants were randomized to Part II.
Participants by arm
| Arm | Count |
|---|---|
| Doravirine 25 mg: Part I/II Combined Doravirine 25 mg once daily plus TRUVADA once daily | 40 |
| Doravirine 50 mg Part I/II Combined Doravirine 50 mg once daily plus TRUVADA once daily | 43 |
| Doravirine 100 mg: Part I/II Combined Doravirine 100 mg once daily plus TRUVADA once daily | 108 |
| Doravirine 200 mg: Part I/II Combined Doravirine 200 mg once daily plus TRUVADA once daily | 41 |
| Efavirenz 600 mg: Part I/II Combined Efavirenz 600 mg once daily plus TRUVADA once daily | 108 |
| Total | 340 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Treatment: Part I | Adverse Event | 1 | 4 | 2 | 1 | 3 | 0 | 0 |
| Treatment: Part I | Lack of Efficacy | 0 | 1 | 0 | 1 | 1 | 0 | 0 |
| Treatment: Part I | Lost to Follow-up | 3 | 2 | 1 | 3 | 4 | 0 | 0 |
| Treatment: Part I | Non-Compliance with Study Drug | 3 | 2 | 2 | 1 | 0 | 0 | 0 |
| Treatment: Part I | Physician Decision | 2 | 1 | 0 | 0 | 1 | 0 | 0 |
| Treatment: Part I | Pregnancy | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Treatment: Part I | Protocol Deviation | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
| Treatment: Part I | Withdrawal by Subject | 3 | 4 | 4 | 1 | 4 | 0 | 0 |
| Treatment: Part II | Adverse Event | 0 | 0 | 0 | 0 | 0 | 3 | 8 |
| Treatment: Part II | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 3 | 1 |
| Treatment: Part II | Non-Compliance with Study Drug | 0 | 0 | 0 | 0 | 0 | 3 | 0 |
| Treatment: Part II | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 2 | 2 |
Baseline characteristics
| Characteristic | Doravirine 25 mg: Part I/II Combined | Doravirine 50 mg Part I/II Combined | Doravirine 100 mg: Part I/II Combined | Doravirine 200 mg: Part I/II Combined | Efavirenz 600 mg: Part I/II Combined | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 38.9 years STANDARD_DEVIATION 13.42 | 38.3 years STANDARD_DEVIATION 10.71 | 36.8 years STANDARD_DEVIATION 11.31 | 34.4 years STANDARD_DEVIATION 8.85 | 35.2 years STANDARD_DEVIATION 9.08 | 36.4 years STANDARD_DEVIATION 10.62 |
| Sex: Female, Male Female | 2 Participants | 6 Participants | 9 Participants | 1 Participants | 7 Participants | 25 Participants |
| Sex: Female, Male Male | 38 Participants | 37 Participants | 99 Participants | 40 Participants | 101 Participants | 315 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 31 / 40 | 35 / 43 | 78 / 108 | 36 / 41 | 82 / 108 |
| serious Total, serious adverse events | 4 / 40 | 1 / 43 | 11 / 108 | 3 / 41 | 13 / 108 |
Outcome results
Primary
Percentage of Participants Who Discontinued Study Therapy Due to AEs in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I)
Assessment of the percentage of participants receiving doravirine at all doses (25 mg, 50 mg, 100 mg, or 200 mg), compared with participants receiving efavirenz 600 mg, who discontinued therapy due to an AE over 24 weeks of treatment. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product.The percentage of participants in any treatment group who discontinued therapy due to an AE was primarily assessed for Weeks 0-24.
Time frame: Up to Week 24
Population: The analyzed population consisted of all randomized participants who received at least 1 dose of study treatment in Part I.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 25 mg: Part I | Percentage of Participants Who Discontinued Study Therapy Due to AEs in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I) | 2.5 Percentage of participants |
| Doravirine 50 mg: Part I | Percentage of Participants Who Discontinued Study Therapy Due to AEs in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I) | 7.0 Percentage of participants |
| Doravirine 100 mg : Part I | Percentage of Participants Who Discontinued Study Therapy Due to AEs in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I) | 2.4 Percentage of participants |
| Doravirine 200 mg: Part I | Percentage of Participants Who Discontinued Study Therapy Due to AEs in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I) | 0.0 Percentage of participants |
| Efavirenz 600 mg: Part I | Percentage of Participants Who Discontinued Study Therapy Due to AEs in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I) | 4.8 Percentage of participants |
95% CI: [-13.7, 8.8]
95% CI: [-9.9, 14.7]
95% CI: [-13.8, 8.2]
95% CI: [-15.9, 4.1]
Primary
Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the percentage of participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg, who had at least 1 AE over 24 weeks of treatment. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product.The percentage of participants in any treatment group with at least 1 AE was assessed for Weeks 0-24.
Time frame: Up to Week 24
Population: The analyzed population consisted of all randomized participants who received at least 1 dose of study treatment in either Part I or Part II.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 25 mg: Part I | Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 75.0 Percentage of participants |
| Doravirine 50 mg: Part I | Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 85.2 Percentage of participants |
95% CI: [-20.9, 0.5]
Primary
Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I)
Assessment of the percentage of participants receiving doravirine at all doses (25 mg, 50 mg, 100 mg, or 200 mg), compared with participants receiving efavirenz 600 mg, who had at least 1 AE over 24 weeks of treatment. An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product.The percentage of participants in any treatment group with at least 1 AE was primarily assessed for Weeks 0-24.
Time frame: Up to Week 24
Population: The analyzed population consisted of all randomized participants who received at least 1 dose of study treatment in Part I.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 25 mg: Part I | Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I) | 90.0 Percentage of participants |
| Doravirine 50 mg: Part I | Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I) | 93.0 Percentage of participants |
| Doravirine 100 mg : Part I | Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I) | 71.4 Percentage of participants |
| Doravirine 200 mg: Part I | Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I) | 85.4 Percentage of participants |
| Efavirenz 600 mg: Part I | Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I) | 83.3 Percentage of participants |
95% CI: [-9, 22.4]
95% CI: [-4.6, 24.9]
95% CI: [-27.9, 6.3]
95% CI: [-14.5, 18.4]
Primary
Percentage of Participants With CNS Events by Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the percentage of participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg, who had CNS events over 24 weeks of treatment. CNS events were pooled and evaluated as pre-specified by the protocol (depression, nightmare, confusional state, suicidal ideation, nervous system disorder, psychotic disorder, abnormal dreams, suicide attempt, acute psychosis, delirium, depressed level of consciousness, hallucination, hallucination auditory, hallucination visual, completed suicide, suicidal behavior, major depression, depressed mood, depressive symptom, insomnia, disturbance in attention, somnolence, dizziness, or concentration impaired). The percentage of participants in either treatment group with CNS events was assessed over Weeks 0-24.
Time frame: Up to Week 24
Population: The analyzed population consisted of all randomized participants who received at least 1 dose of study treatment in either Part I or Part II.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 25 mg: Part I | Percentage of Participants With CNS Events by Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 26.9 Percentage of participants |
| Doravirine 50 mg: Part I | Percentage of Participants With CNS Events by Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 47.2 Percentage of participants |
p-value: 0.00295% CI: [-32.6, -7.5]Miettinen and Nurminen method
Primary
Percentage of Participants With CNS Events by Week 8: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the percentage of participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg, who had CNS events over 8 weeks of treatment. CNS events were pooled and evaluated as pre-specified by the protocol (depression, nightmare, confusional state, suicidal ideation, nervous system disorder, psychotic disorder, abnormal dreams, suicide attempt, acute psychosis, delirium, depressed level of consciousness, hallucination, hallucination auditory, hallucination visual, completed suicide, suicidal behavior, major depression, depressed mood, depressive symptom, insomnia, disturbance in attention, somnolence, dizziness, or concentration impaired). The percentage of participants in either treatment group with CNS events was assessed over Weeks 0-8.
Time frame: Up to Week 8
Population: The analyzed population consisted of all randomized participants who received at least 1 dose of study treatment in either Part I or Part II.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 25 mg: Part I | Percentage of Participants With CNS Events by Week 8: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 24.1 Percentage of participants |
| Doravirine 50 mg: Part I | Percentage of Participants With CNS Events by Week 8: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 44.4 Percentage of participants |
p-value: 0.00295% CI: [-32.4, -7.8]Miettinen and Nurminen method
Primary
Percentage of Participants With Virologic Response (HIV-1 RNA <40 Copies/mL) at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the virologic response to doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with HIV-1 RNA \<40 copies/mL at Week 24. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay, which has a limit of reliable quantification of 40 copies/mL. The percentage of participants in any treatment group with a virologic response was assessed at Week 24. The NC=F approach was used as the primary approach to handle missing data this analysis of efficacy. This primary outcome was analyzed for HIV-1 RNA \<40 copies/mL in Part I & Part II combined.
Time frame: Week 24
Population: The analyzed population consisted of all randomized participants who received at least one dose of blinded study treatment in either Part I or Part II, and had at least one post-randomization observation for the analysis of HIV-1 RNA (\<40 copies/mL) at 24 weeks of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 25 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA <40 Copies/mL) at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 72.9 Percentage of participants |
| Doravirine 50 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA <40 Copies/mL) at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 73.1 Percentage of participants |
95% CI: [-13.2, 11.2]
Primary
Percentage of Participants With Virologic Response (HIV-1 RNA) < 40 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I)
Assessment of the virologic response to doravirine at all studied doses (25 mg, 50 mg, 100 mg, and 200 mg), compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with plasma HIV-1 RNA \<40 copies/mL at Week 24. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay, which has a limit of reliable quantification of 40 copies/mL. The percentage of participants in any treatment group with a virologic response was assessed at Week 24. The Non-Completer = Failure (NC=F) approach, in which participants who prematurely discontinued assigned treatment for any reason and were considered as failures thereafter, was used as the primary approach to handle missing data this analysis of efficacy.This primary outcome was analyzed for HIV-1 RNA \<40 copies/mL in Part I.
Time frame: Week 24
Population: The analyzed population consisted of all randomized participants who received at least one dose of blinded study treatment in Part I, and had at least one post-randomization observation for the analysis of HIV-1 RNA (\<40 copies/mL) at 24 weeks of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 25 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA) < 40 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I) | 80.0 Percentage of participants |
| Doravirine 50 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA) < 40 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I) | 74.4 Percentage of participants |
| Doravirine 100 mg : Part I | Percentage of Participants With Virologic Response (HIV-1 RNA) < 40 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I) | 71.4 Percentage of participants |
| Doravirine 200 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA) < 40 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I) | 80.5 Percentage of participants |
| Efavirenz 600 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA) < 40 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I) | 64.3 Percentage of participants |
95% CI: [-4.1, 34.4]
95% CI: [-9.6, 29.1]
95% CI: [-13.2, 26]
95% CI: [-3.4, 34.4]
Secondary
Change From Baseline in CD4 Cell Count at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the change from baseline in the CD4 cell count at Week 24 in participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg. The OF approach was used to handle missing data, and the Baseline CD4 cell count was carried forward for participants who discontinued assigned treatment due to lack of efficacy.
Time frame: Baseline, Week 24
Population: The analyzed population consisted of all randomized participants who received at least one dose of blinded study treatment in either Part I or Part II, and had at least one post-randomization observation for the analysis of CD4 cell count at 24 weeks of study treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Doravirine 25 mg: Part I | Change From Baseline in CD4 Cell Count at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 152.3 cells/mm^3 |
| Doravirine 50 mg: Part I | Change From Baseline in CD4 Cell Count at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 146.0 cells/mm^3 |
95% CI: [-38.2, 50.8]
Secondary
Change From Baseline in CD4 Cell Count at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the change from baseline in the CD4 count at Week 48 in participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg. The OF approach was used to handle missing data, and the Baseline CD4 cell count was carried forward for subjects who discontinued assigned treatment due to lack of efficacy.
Time frame: Baseline, Week 48
Population: The analyzed population consisted of all randomized subjects who had baseline data, received at least 1 dose of blinded study medication in either Part I or Part II, and had at least 1 post-randomization observation for the analysis of CD4 cell count at 48 weeks of study treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Doravirine 25 mg: Part I | Change From Baseline in CD4 Cell Count at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 191.9 cells/mm^3 |
| Doravirine 50 mg: Part I | Change From Baseline in CD4 Cell Count at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 194.5 cells/mm^3 |
95% CI: [-46.5, 41.3]
Secondary
Change From Baseline in CD4 Cell Count at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
A secondary endpoint in Part I/II combined was the change from baseline in the CD4 count at Week 96 in participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg. The OF approach was used to handle missing data, and the Baseline CD4 cell count was carried forward for subjects who discontinued assigned treatment due to lack of efficacy.
Time frame: Baseline, Week 96
Population: The analyzed population consisted of all randomized subjects who had baseline data, received at least 1 dose of blinded study medication in either Part I or Part II, and had at least 1 post-randomization observation for the analysis of CD4 cell count at 96 weeks of study treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Doravirine 25 mg: Part I | Change From Baseline in CD4 Cell Count at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 259.2 cells/mm^3 |
| Doravirine 50 mg: Part I | Change From Baseline in CD4 Cell Count at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 263.6 cells/mm^3 |
95% CI: [-64, 55.1]
Secondary
Change From Baseline in CD4 T Lymphocyte Cell Count at Week 24: Doravirine (All Doses) vs Efavirenz (Part I)
Evaluation of the change from baseline in the CD4 cell count at Week 24 in participants receiving doravirine at all doses (25 mg, 50 mg, 100 mg, and 200 mg), compared with participants receiving efavirenz 600 mg. The Observed Failure (OF) approach was used to handle missing data, and the Baseline CD4 cell count was carried forward for participants who discontinued assigned treatment due to lack of efficacy.
Time frame: Baseline, Week 24
Population: The analyzed population consisted of all randomized participants who received at least one dose of blinded study treatment in Part I, and had at least one post-randomization observation for the analysis of CD4 cell count at 24 weeks of study treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Doravirine 25 mg: Part I | Change From Baseline in CD4 T Lymphocyte Cell Count at Week 24: Doravirine (All Doses) vs Efavirenz (Part I) | 154.1 cells/mm^3 |
| Doravirine 50 mg: Part I | Change From Baseline in CD4 T Lymphocyte Cell Count at Week 24: Doravirine (All Doses) vs Efavirenz (Part I) | 112.9 cells/mm^3 |
| Doravirine 100 mg : Part I | Change From Baseline in CD4 T Lymphocyte Cell Count at Week 24: Doravirine (All Doses) vs Efavirenz (Part I) | 133.6 cells/mm^3 |
| Doravirine 200 mg: Part I | Change From Baseline in CD4 T Lymphocyte Cell Count at Week 24: Doravirine (All Doses) vs Efavirenz (Part I) | 140.7 cells/mm^3 |
| Efavirenz 600 mg: Part I | Change From Baseline in CD4 T Lymphocyte Cell Count at Week 24: Doravirine (All Doses) vs Efavirenz (Part I) | 121.1 cells/mm^3 |
95% CI: [-28.1, 94]
95% CI: [-68.5, 51.9]
95% CI: [-44.6, 69.5]
95% CI: [-45.1, 84.2]
Secondary
Percentage of Participants With At Least 1 AE in Weeks 0-48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
A secondary outcome in Part I/II combined was the percentage of participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg, who had at least 1 AE over 48 weeks of treatment. The percentage of participants in any treatment group with at least 1 AE was primarily assessed for Weeks 0-48.
Time frame: Up to Week 48
Population: The analyzed population consisted of all randomized participants who received at least 1 dose of study treatment in either Part I or Part II.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 25 mg: Part I | Percentage of Participants With At Least 1 AE in Weeks 0-48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 87.0 Percentage of participants |
| Doravirine 50 mg: Part I | Percentage of Participants With At Least 1 AE in Weeks 0-48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 89.8 Percentage of participants |
95% CI: [-11.7, 6]
Secondary
Percentage of Participants With At Least 1 AE in Weeks 0-96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
A secondary outcome in Part I/II combined was the percentage of participants receiving doravirine at 100 mg, compared with participants receiving efavirenz 600 mg, who had at least 1 AE over 96 weeks of treatment. The percentage of participants in any treatment group with at least 1 AE was primarily assessed for Weeks 0-96.
Time frame: Up to Week 96
Population: The analyzed population consisted of all randomized participants who received at least 1 dose of study treatment in either Part I or Part II.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 25 mg: Part I | Percentage of Participants With At Least 1 AE in Weeks 0-96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 89.8 Percentage of participants |
| Doravirine 50 mg: Part I | Percentage of Participants With At Least 1 AE in Weeks 0-96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 96.3 Percentage of participants |
95% CI: [-14.1, 0.3]
Secondary
Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the virologic response to doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with plasma HIV-1 RNA \<200 copies/mL at Week 24. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay. The percentage of participants in any treatment group with a virologic response was primarily assessed for Weeks 0-24. The NC=F approach was used as the primary approach to handle missing data for this analysis of efficacy. This secondary outcome was analyzed for HIV-1 RNA \<200 copies/mL in Part I & Part II combined.
Time frame: Week 24
Population: The analyzed population consisted of all randomized participants who received at least one dose of blinded study treatment in either Part I or Part II, and had at least one post-randomization observation for the analysis of HIV-1 RNA (\<200 copies/mL) at 24 weeks of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 25 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 89.7 Percentage of participants |
| Doravirine 50 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 87.0 Percentage of participants |
95% CI: [-6.1, 11.7]
Secondary
Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I)
Assessment of the virologic response to doravirine at all studied doses (25 mg, 50 mg, 100 mg, and 200 mg), compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with plasma HIV-1 RNA \<200 copies/mL at Week 24. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay.The percentage of participants in any treatment group with a virologic response was assessed at Week 24. The NC=F approach was used as the primary approach to handle missing data for this analysis of efficacy. This primary outcome was analyzed for HIV-1 RNA \<200 copies/mL in Part I.
Time frame: Week 24
Population: The analyzed population consisted of all randomized participants who received at least one dose of blinded study treatment in Part I, and had at least one post-randomization observation for the analysis of HIV-1 RNA (\<200 copies/mL) at 24 weeks of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 25 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I) | 85.0 Percentage of participants |
| Doravirine 50 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I) | 83.7 Percentage of participants |
| Doravirine 100 mg : Part I | Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I) | 92.9 Percentage of participants |
| Doravirine 200 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I) | 90.2 Percentage of participants |
| Efavirenz 600 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I) | 81.0 Percentage of participants |
95% CI: [-12.5, 21.5]
95% CI: [-13.9, 19.8]
95% CI: [-2.5, 28]
95% CI: [-6.2, 25.7]
Secondary
Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Evaluation of the antiretroviral activity of doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA for 24 weeks, as measured by the percentage of participants with HIV-1 RNA \<200 copies/mL at Week 48. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay. This primary outcome was analyzed for RNA \<200 copies/mL in Part I & Part II combined.
Time frame: Week 48
Population: The analyzed population consisted of all randomized participants who received at least one dose of blinded study treatment in either Part I or Part II, and had at least one post-randomization observation for the analysis of HIV RNA (\<200 copies/mL) at 48 weeks of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 25 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 85.2 Percentage of participants |
| Doravirine 50 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 85.0 Percentage of participants |
95% CI: [-9.7, 9.9]
Secondary
Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the virologic response to doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with plasma HIV-1 RNA \<200 copies/mL at Week 96. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay. The percentage of participants in any treatment group with a virologic response was primarily assessed for Weeks 0-96. The Non-Completer = Failure (NC=F) approach, in which participants who prematurely discontinued assigned treatment for any reason and were considered as failures thereafter, was used as the primary approach to handle missing data this analysis of efficacy. This primary outcome was analyzed for HIV-1 RNA \<200 copies/mL in Part I & Part II combined.
Time frame: Week 96
Population: The analyzed population consisted of all randomized participants who received at least one dose of blinded study treatment in either Part I or Part II, and had at least one post-randomization observation for the analysis of HIV-1 RNA (\<200 copies/mL) at 96 weeks of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 25 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 79.6 Percentage of participants |
| Doravirine 50 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 75.9 Percentage of participants |
95% CI: [-7.3, 15]
Secondary
Percentage of Participants With Virologic Response (HIV-1 RNA <40 Copies/mL) at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the virologic response to doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with HIV-1 RNA \<40 copies/mL at Week 48. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay. The percentage of participants in any treatment group with a virologic response was primarily assessed for Weeks 0-24. The NC=F approach was used as the primary approach to handle missing data this analysis of efficacy. This primary outcome was analyzed for HIV-1 RNA \<40 copies/mL in Part I & Part II combined.
Time frame: Week 48
Population: The analyzed population consisted of all randomized participants who received at least one dose of blinded study treatment in either Part I or Part II, and had at least one post-randomization observation for the analysis of HIV-1 RNA (\<40 copies/mL) at 48 weeks of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 25 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA <40 Copies/mL) at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 77.8 Percentage of participants |
| Doravirine 50 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA <40 Copies/mL) at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 79.4 Percentage of participants |
95% CI: [-12.9, 9.2]
Secondary
Percentage of Participants With Virologic Response (HIV-1 RNA <40 Copies/mL) at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Assessment of the virologic response to doravirine at 100 mg, compared to efavirenz, each in combination with TRUVADA, as measured by the percentage of participants with HIV-1 RNA \<40 copies/mL at Week 96. HIV RNA levels were determined using the Abbott RealTime HIV-1 Assay. The percentage of participants in any treatment group with a virologic response was primarily assessed for Weeks 0-24. The NC=F approach was used as the primary approach to handle missing data this analysis of efficacy. This primary outcome was analyzed for HIV-1 RNA \<40 copies/mL in Part I & Part II combined.
Time frame: Week 96
Population: The analyzed population consisted of all randomized participants who received at least one dose of blinded study treatment in either Part I or Part II, and had at least one post-randomization observation for the analysis of HIV-1 RNA (\<40 copies/mL) at 96 weeks of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doravirine 25 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA <40 Copies/mL) at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 75.0 Percentage of participants |
| Doravirine 50 mg: Part I | Percentage of Participants With Virologic Response (HIV-1 RNA <40 Copies/mL) at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined) | 75.9 Percentage of participants |
95% CI: [-12.4, 10.7]