A Dose-Ranging Study to Compare Doravirine (MK-1439) Plus TRUVADA® Versus Efavirenz Plus TRUVADA® in Human Immunodeficiency Virus (HIV)-1 Infected Participants (MK-1439-007)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01632345
• Collaborator: (none)
• Enrollment: 342
• Arms: 5
• Actual Duration (Months): 41.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Doravirine; Drug: Efavirenz; Drug: TRUVADA®; Drug: Placebo for Doravirine; Drug: Placebo for Efavirenz	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 342 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Multicenter, Double-Blind, Randomized, 2-Part, Dose Ranging Study to Compare the Safety, and Antiretroviral Activity of MK-1439 Plus TRUVADA Versus Efavirenz Plus TRUVADA in Antiretroviral Treatment-Naive, HIV-1 Infected Patients
• Actual Study Start Date: Oct 12, 2012
• Actual Primary Completion Date: Dec 3, 2014
• Actual Study Completion Date: Mar 21, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Doravirine 25 mg Doravirine 25 mg + TRUVADA® Participants in this arm will receive doravirine 25 mg in Part I and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part II. These participants also receive placebo that matches efavirenz.	Drug: Doravirine; 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.; Other Names: MK-1439 ; Drug: TRUVADA®; 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; Drug: Placebo for Doravirine; Placebo tablets matching doravirine
Experimental: Doravirine 50 mg Doravirine 50 mg + TRUVADA® Participants in this arm will receive doravirine 50 mg in Part I and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part II. These participants also receive placebo that matches efavirenz.	Drug: Doravirine; 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.; Other Names: MK-1439 ; Drug: TRUVADA®; 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; Drug: Placebo for Doravirine; Placebo tablets matching doravirine
Experimental: Doravirine 100 mg Doravirine 100 mg + TRUVADA® Participants in this arm will receive doravirine 100 mg in Part I and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part II. These participants also receive placebo that matches efavirenz.	Drug: Doravirine; 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.; Other Names: MK-1439 ; Drug: TRUVADA®; 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; Drug: Placebo for Doravirine; Placebo tablets matching doravirine
Experimental: Doravirine 200 mg Doravirine 200 mg + TRUVADA® Participants in this arm will receive doravirine 200 mg in Part I and the selected doravirine dose (either 25 mg, 50 mg, 100 mg, or 200 mg) in Part II. These participants also receive placebo that matches efavirenz.	Drug: Doravirine; 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.; Other Names: MK-1439 ; Drug: TRUVADA®; 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; Drug: Placebo for Doravirine; Placebo tablets matching doravirine
Active Comparator: Efavirenz Efavirenz + TRUVADA® Participants in this arm will receive efavirenz in Part I and in Part II. These participants also receive placebo that matches doravirine.	Drug: Efavirenz; Efavirenz 600 mg tablet orally at bedtime taken without food on an empty stomach for 96 weeks; Drug: TRUVADA®; 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; Drug: Placebo for Efavirenz; Placebo tablets matching efavirenz

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT01632345
• Other Study ID Numbers: 1439-007; MK-1439-007; 2012-001573-93
• First Posted: Jul 2, 2012
• Last Update Posted: Jul 18, 2019
• Last Verified: Jul 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: HIV Infections; Efavirenz; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Study Results

Participant Flow

Pre-assignment Detail	210 participants were randomized to Part I and 132 participants were randomized to Part II.

Arm/Group Title	Part I: Doravirine 25 mg	Part I: Doravirine 50 mg	Part I: Doravirine 100 mg	Part I: Doravirine 200 mg	Part I: Efavirenz 600 mg	Part II: Doravirine 100 mg	Part II: Efavirenz 600 mg
Arm/Group Description	Doravirine 25 mg once daily plus TRUVADA once daily in Part I	Doravirine 50 mg once daily plus TRUVADA once daily in Part I	Doravirine 100 mg once daily plus TRUVADA once daily in Part I	Doravirine 200 mg once daily plus TRUVADA once daily in Part I	Efavirenz 600 mg once daily plus TRUVADA once daily in Part I	Doravirine 100 mg once daily plus TRUVADA once daily in Part II	Efavirenz 600 mg once daily plus TRUVADA once daily in Part II
Period Title: Randomized Participants
STARTED	41	43	42	41	43	66	66
COMPLETED	41	43	42	41	43	66	66
NOT COMPLETED	0	0	0	0	0	0	0
Period Title: Randomized Participants
STARTED	41	43	42	41	43	0	0
Treated	40	43	42	41	43	0	0
COMPLETED	29	28	32	33	30	0	0
NOT COMPLETED	12	15	10	8	13	0	0
Period Title: Randomized Participants
STARTED	0	0	0	0	0	66	66
Treated	0	0	0	0	0	66	66
COMPLETED	0	0	0	0	0	55	55
NOT COMPLETED	0	0	0	0	0	11	11

Baseline Characteristics

Arm/Group Title	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
Arm/Group Description	Doravirine 25 mg once daily plus TRUVADA once daily	Doravirine 50 mg once daily plus TRUVADA once daily	Doravirine 100 mg once daily plus TRUVADA once daily	Doravirine 200 mg once daily plus TRUVADA once daily	Efavirenz 600 mg once daily plus TRUVADA once daily	Total of all reporting groups
Overall Participants	40	43	108	41	108	340
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.9 (13.42)	38.3 (10.71)	36.8 (11.31)	34.4 (8.85)	35.2 (9.08)	36.4 (10.62)
Sex: Female, Male (Count of Participants)
Female	2 5%	6 14%	9 8.3%	1 2.4%	7 6.5%	25 7.4%
Male	38 95%	37 86%	99 91.7%	40 97.6%	101 93.5%	315 92.6%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I)
Description	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

Outcome Measure Data

Analysis Population Description

The analyzed population consisted of all randomized participants who received at least 1 dose of study treatment in Part I.

Arm/Group Title	Doravirine 25 mg: Part I	Doravirine 50 mg: Part I	Doravirine 100 mg : Part I	Doravirine 200 mg: Part I	Efavirenz 600 mg: Part I
Arm/Group Description	Doravirine 25 mg once daily plus TRUVADA once daily received in Part I	Doravirine 50 mg once daily plus TRUVADA once daily received in Part I	Doravirine 100 mg once daily plus TRUVADA once daily received in Part I	Doravirine 200 mg once daily plus TRUVADA once daily received in Part I	Efavirenz 600 mg once daily plus TRUVADA once daily received in Part I
Measure Participants	40	43	42	41	42
Number (95% Confidence Interval) [Percentage of participants]	90.0 225%	93.0 216.3%	71.4 66.1%	85.4 208.3%	83.3 77.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (Doravirine - Efavirenz)
	Estimated Value	6.7
	Confidence Interval	(2-Sided) 95%; -9.0 to 22.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	A negative value would be considered as favoring doravirine over efavirenz.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Doravirine 50 mg: Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (Doravirine - Efavirenz)
	Estimated Value	9.7
	Confidence Interval	(2-Sided) 95%; -4.6 to 24.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	A negative value would be considered as favoring doravirine over efavirenz.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Doravirine 100 mg : Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (Doravirine - Efavirenz)
	Estimated Value	-11.9
	Confidence Interval	(2-Sided) 95%; -27.9 to 6.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	A negative value would be considered as favoring doravirine over efavirenz.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Doravirine 200 mg: Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (Doravirine - Efavirenz)
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95%; -14.5 to 18.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	A negative value would be considered as favoring doravirine over efavirenz.

2. Primary Outcome

Title	Percentage of Participants Who Discontinued Study Therapy Due to AEs in Weeks 0-24: Doravirine (All Doses) vs Efavirenz (Part I)
Description	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

Outcome Measure Data

Analysis Population Description

The analyzed population consisted of all randomized participants who received at least 1 dose of study treatment in Part I.

Arm/Group Title	Doravirine 25 mg: Part I	Doravirine 50 mg: Part I	Doravirine 100 mg: Part I	Doravirine 200 mg: Part I	Efavirenz 600 mg: Part I
Arm/Group Description	Doravirine 25 mg once daily plus TRUVADA once daily received in Part I	Doravirine 50 mg once daily plus TRUVADA once daily received in Part I	Doravirine 100 mg once daily plus TRUVADA once daily received in Part I	Doravirine 200 mg once daily plus TRUVADA once daily received in Part I	Efavirenz 600 mg once daily plus TRUVADA once daily received in Part I
Measure Participants	40	43	42	41	42
Number (95% Confidence Interval) [Percentage of participants]	2.5 6.3%	7.0 16.3%	2.4 2.2%	0.0 0%	4.8 4.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (Doravirine - Efavirenz)
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -13.7 to 8.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	A negative value would be considered as favoring doravirine over efavirenz.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Doravirine 50 mg: Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (Doravirine - Efavirenz)
	Estimated Value	2.2
	Confidence Interval	(2-Sided) 95%; -9.9 to 14.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	A negative value would be considered as favoring doravirine over efavirenz.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Doravirine 100 mg : Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (Doravirine - Efavirenz)
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -13.8 to 8.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	A negative value would be considered as favoring doravirine over efavirenz.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Doravirine 200 mg: Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference (Doravirine - Efavirenz)
	Estimated Value	-4.8
	Confidence Interval	(2-Sided) 95%; -15.9 to 4.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	A negative value would be considered as favoring doravirine over efavirenz.

3. Primary Outcome

Title	Percentage of Participants With At Least 1 AE in Weeks 0-24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Doravirine 100 mg: Part I/II (Combined)	Efavirenz 600 mg: Part I/II (Combined)
Arm/Group Description	Doravirine 100 mg once daily plus TRUVADA once daily received in either Part I or Part II	Efavirenz 600 mg once daily plus TRUVADA once daily received in either Part I or Part II
Measure Participants	108	108
Number (95% Confidence Interval) [Percentage of participants]	75.0 187.5%	85.2 198.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Doravirine 50 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-10.2
	Confidence Interval	(2-Sided) 95%; -20.9 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	A negative value would be considered as favoring doravirine over efavirenz.

4. Primary Outcome

Title	Percentage of Participants With CNS Events by Week 8: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Doravirine 100 mg: Part I/II (Combined)	Efavirenz 600 mg: Part I/II (Combined)
Arm/Group Description	Doravirine 100 mg once daily plus TRUVADA once daily received in either Part I or Part II	Efavirenz 600 mg once daily plus TRUVADA once daily received in either Part I or Part II
Measure Participants	108	108
Number (95% Confidence Interval) [Percentage of participants]	24.1 60.3%	44.4 103.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Doravirine 50 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	Superiority analysis
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference (Doravirine - Efavirenz)
	Estimated Value	-20.4
	Confidence Interval	(2-Sided) 95%; -32.4 to -7.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	A negative value would be considered as favoring doravirine over efavirenz.

5. Primary Outcome

Title	Percentage of Participants With CNS Events by Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Doravirine 100 mg: Part I/II (Combined)	Efavirenz 600 mg: Part I/II (Combined)
Arm/Group Description	Doravirine 100 mg once daily plus TRUVADA once daily received in either Part I or Part II	Efavirenz 600 mg once daily plus TRUVADA once daily received in either Part I or Part II
Measure Participants	108	108
Number (95% Confidence Interval) [Percentage of participants]	26.9 67.3%	47.2 109.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Doravirine 50 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	Superiority analysis
	Method	Miettinen and Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference (Doravirine - Efavirenz)
	Estimated Value	-20.4
	Confidence Interval	(2-Sided) 95%; -32.6 to -7.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	A negative value would be considered as favoring doravirine over efavirenz.

6. Primary Outcome

Title	Percentage of Participants With Virologic Response (HIV-1 RNA) < 40 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Doravirine 25 mg: Part I	Doravirine 50 mg: Part I	Doravirine 100 mg: Part I	Doravirine 200 mg: Part I	Efavirenz 600 mg: Part I
Arm/Group Description	Doravirine 25 mg once daily plus TRUVADA once daily received in Part I	Doravirine 50 mg once daily plus TRUVADA once daily received in Part I	Doravirine 100 mg once daily plus TRUVADA once daily received in Part I	Doravirine 200 mg once daily plus TRUVADA once daily received in Part I	Efavirenz 600 mg once daily plus TRUVADA once daily received in Part I
Measure Participants	40	43	42	41	42
Number (95% Confidence Interval) [Percentage of participants]	80.0 200%	74.4 173%	71.4 66.1%	80.5 196.3%	64.3 59.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % response
	Estimated Value	15.7
	Confidence Interval	(2-Sided) 95%; -4.1 to 34.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Doravirine 50 mg: Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % response
	Estimated Value	10.0
	Confidence Interval	(2-Sided) 95%; -9.6 to 29.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Doravirine 100 mg : Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % response
	Estimated Value	6.6
	Confidence Interval	(2-Sided) 95%; -13.2 to 26.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Doravirine 200 mg: Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % response
	Estimated Value	15.9
	Confidence Interval	(2-Sided) 95%; -3.4 to 34.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

7. Primary Outcome

Title	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)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Doravirine 100 mg: Part I/II (Combined)	Efavirenz 600 mg: Part I/II (Combined)
Arm/Group Description	Doravirine 100 mg once daily plus TRUVADA once daily received in either Part I or Part II	Efavirenz 600 mg once daily plus TRUVADA once daily received in either Part I or Part II
Measure Participants	107	108
Number (95% Confidence Interval) [Percentage of participants]	72.9 182.3%	73.1 170%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Doravirine 50 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % response
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -13.2 to 11.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

8. Secondary Outcome

Title	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)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Doravirine 100 mg: Part I/II (Combined)	Efavirenz 600 mg: Part I/II (Combined)
Arm/Group Description	Doravirine 100 mg once daily plus TRUVADA once daily received in either Part I or Part II	Efavirenz 600 mg once daily plus TRUVADA once daily received in either Part I or Part II
Measure Participants	108	107
Number (95% Confidence Interval) [Percentage of participants]	77.8 194.5%	79.4 184.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Doravirine 50 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % response
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) 95%; -12.9 to 9.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

9. Secondary Outcome

Title	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)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Doravirine 100 mg: Part I/II (Combined)	Efavirenz 600 mg: Part I/II (Combined)
Arm/Group Description	Doravirine 100 mg once daily plus TRUVADA once daily received in either Part I or Part II	Efavirenz 600 mg once daily plus TRUVADA once daily received in either Part I or Part II
Measure Participants	108	108
Number (95% Confidence Interval) [Percentage of participants]	75.0 187.5%	75.9 176.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Doravirine 50 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % response
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -12.4 to 10.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

10. Secondary Outcome

Title	Percentage of Participants With Virologic Response (HIV-1 RNA <200 Copies/mL) at Week 24: Doravirine (All Doses) vs Efavirenz (Part I)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Doravirine 25 mg: Part I	Doravirine 50 mg: Part I	Doravirine 100 mg: Part I	Doravirine 200 mg: Part I	Efavirenz 600 mg: Part I
Arm/Group Description	Doravirine 25 mg once daily plus TRUVADA once daily received in Part I	Doravirine 50 mg once daily plus TRUVADA once daily received in Part I	Doravirine 100 mg once daily plus TRUVADA once daily received in Part I	Doravirine 200 mg once daily plus TRUVADA once daily received in Part I	Efavirenz 600 mg once daily plus TRUVADA once daily received in Part I
Measure Participants	40	43	42	41	42
Number (95% Confidence Interval) [Percentage of participants]	85.0 212.5%	83.7 194.7%	92.9 86%	90.2 220%	81.0 75%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % response
	Estimated Value	4.5
	Confidence Interval	(2-Sided) 95%; -12.5 to 21.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Doravirine 50 mg: Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % response
	Estimated Value	2.8
	Confidence Interval	(2-Sided) 95%; -13.9 to 19.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Doravirine 100 mg : Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % response
	Estimated Value	12.2
	Confidence Interval	(2-Sided) 95%; -2.5 to 28.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Doravirine 200 mg: Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % response
	Estimated Value	9.5
	Confidence Interval	(2-Sided) 95%; -6.2 to 25.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

11. Secondary Outcome

Title	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)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Doravirine 100 mg: Part I/II (Combined)	Efavirenz 600 mg: Part I/II (Combined)
Arm/Group Description	Doravirine 100 mg once daily plus TRUVADA once daily received in either Part I or Part II	Efavirenz 600 mg once daily plus TRUVADA once daily received in either Part I or Part II
Measure Participants	107	108
Number (95% Confidence Interval) [Percentage of participants]	89.7 224.3%	87.0 202.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Doravirine 50 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % response
	Estimated Value	2.7
	Confidence Interval	() 95%; -6.1 to 11.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

12. Secondary Outcome

Title	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)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Doravirine 100 mg: Part I/II (Combined)	Efavirenz 600 mg: Part I/II (Combined)
Arm/Group Description	Doravirine 100 mg once daily plus TRUVADA once daily received in either Part I or Part II	Efavirenz 600 mg once daily plus TRUVADA once daily received in either Part I or Part II
Measure Participants	108	107
Number (95% Confidence Interval) [Percentage of participants]	85.2 213%	85.0 197.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Doravirine 50 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % response
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -9.7 to 9.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

13. Secondary Outcome

Title	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)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Doravirine 100 mg: Part I/II (Combined)	Efavirenz 600 mg: Part I/II (Combined)
Arm/Group Description	Doravirine 100 mg once daily plus TRUVADA once daily received in either Part I or Part II	Efavirenz 600 mg once daily plus TRUVADA once daily received in either Part I or Part II
Measure Participants	108	108
Number (95% Confidence Interval) [Percentage of participants]	79.6 199%	75.9 176.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Doravirine 50 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in % response
	Estimated Value	3.9
	Confidence Interval	(2-Sided) 95%; -7.3 to 15.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

14. Secondary Outcome

Title	Change From Baseline in CD4 T Lymphocyte Cell Count at Week 24: Doravirine (All Doses) vs Efavirenz (Part I)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Doravirine 25 mg: Part I	Doravirine 50 mg: Part I	Doravirine 100 mg: Part I	Doravirine 200 mg: Part I	Efavirenz 600 mg: Part I
Arm/Group Description	Doravirine 25 mg once daily plus TRUVADA once daily received in Part I	Doravirine 50 mg once daily plus TRUVADA once daily received in Part I	Doravirine 100 mg once daily plus TRUVADA once daily received in Part I	Doravirine 200 mg once daily plus TRUVADA once daily received in Part I	Efavirenz 600 mg once daily plus TRUVADA once daily received in Part I
Measure Participants	38	41	41	40	40
Mean (95% Confidence Interval) [cells/mm^3]	154.1	112.9	133.6	140.7	121.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CD4 change
	Estimated Value	33.0
	Confidence Interval	(2-Sided) 95%; -28.1 to 94.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Doravirine 50 mg: Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CD4 change
	Estimated Value	-8.3
	Confidence Interval	(2-Sided) 95%; -68.5 to 51.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Doravirine 100 mg : Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CD4 change
	Estimated Value	12.5
	Confidence Interval	(2-Sided) 95%; -44.6 to 69.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Doravirine 200 mg: Part I, Efavirenz 600 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CD4 change
	Estimated Value	19.6
	Confidence Interval	(2-Sided) 95%; -45.1 to 84.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

15. Secondary Outcome

Title	Change From Baseline in CD4 Cell Count at Week 24: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Doravirine 100 mg: Part I/II (Combined)	Efavirenz 600 mg: Part I/II (Combined)
Arm/Group Description	Doravirine 100 mg once daily plus TRUVADA once daily received in either Part I or Part II	Efavirenz 600 mg once daily plus TRUVADA once daily received in either Part I or Part II
Measure Participants	106	101
Mean (95% Confidence Interval) [cells/mm^3]	152.3	146.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Doravirine 50 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CD4 change
	Estimated Value	6.3
	Confidence Interval	(2-Sided) 95%; -38.2 to 50.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

16. Secondary Outcome

Title	Change From Baseline in CD4 Cell Count at Week 48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Doravirine 100 mg: Part I/II (Combined)	Efavirenz 600 mg: Part I/II (Combined)
Arm/Group Description	Doravirine 100 mg once daily plus TRUVADA once daily received in either Part I or Part II	Efavirenz 600 mg once daily plus TRUVADA once daily received in either Part I or Part II
Measure Participants	102	100
Mean (95% Confidence Interval) [cells/mm^3]	191.9	194.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Doravirine 50 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CD4 change
	Estimated Value	-2.6
	Confidence Interval	(2-Sided) 95%; -46.5 to 41.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

17. Secondary Outcome

Title	Change From Baseline in CD4 Cell Count at Week 96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Doravirine 100 mg: Part I/II (Combined)	Efavirenz 600 mg: Part I/II (Combined)
Arm/Group Description	Doravirine 100 mg once daily plus TRUVADA once daily received in either Part I or Part II	Efavirenz 600 mg once daily plus TRUVADA once daily received in either Part I or Part II
Measure Participants	95	93
Mean (95% Confidence Interval) [cells/mm^3]	259.2	263.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Doravirine 50 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in CD4 change
	Estimated Value	-4.4
	Confidence Interval	(2-Sided) 95%; -64.0 to 55.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	A positive value would be considered as favoring doravirine over efavirenz.

18. Secondary Outcome

Title	Percentage of Participants With At Least 1 AE in Weeks 0-48: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Doravirine 100 mg: Part I/II (Combined)	Efavirenz 600 mg: Part I/II (Combined)
Arm/Group Description	Doravirine 100 mg once daily plus TRUVADA once daily received in either Part I or Part II	Efavirenz 600 mg once daily plus TRUVADA once daily received in either Part I or Part II
Measure Participants	108	108
Number (95% Confidence Interval) [Percentage of participants]	87.0 217.5%	89.8 208.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Doravirine 50 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-2.8
	Confidence Interval	(2-Sided) 95%; -11.7 to 6.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	A negative value would be considered as favoring doravirine over efavirenz.

19. Secondary Outcome

Title	Percentage of Participants With At Least 1 AE in Weeks 0-96: Doravirine 100 mg vs Efavirenz (Part I & Part II Combined)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Doravirine 100 mg: Part I/II (Combined)	Efavirenz 600 mg: Part I/II (Combined)
Arm/Group Description	Doravirine 100 mg once daily plus TRUVADA once daily received in either Part I or Part II	Efavirenz 600 mg once daily plus TRUVADA once daily received in either Part I or Part II
Measure Participants	108	108
Number (95% Confidence Interval) [Percentage of participants]	89.8 224.5%	96.3 224%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Doravirine 25 mg: Part I, Doravirine 50 mg: Part I
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-6.5
	Confidence Interval	(2-Sided) 95%; -14.1 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	A negative value would be considered as favoring doravirine over efavirenz.

Adverse Events

Time Frame	96 weeks
Adverse Event Reporting Description	All Treated participants randomized to doravirine or efavirenz using an IVRS
Arm/Group Title	Doravirine 25 mg (n=40)		Doravirine 50 mg (n=43)		Doravirine 100 mg (n=108)		Doravirine 200 mg (n=41)		Efavirenz 600 mg: Part I (n=108)
Arm/Group Description	Doravirine 25 mg once daily plus TRUVADA once daily received in Part I		Doravirine 50 mg once daily plus TRUVADA once daily received in Part I		Doravirine 100 mg once daily plus TRUVADA once daily received in Part I & Part II (Combined)		Doravirine 200 mg once daily plus TRUVADA once daily received in Part I		Efavirenz 600 mg once daily plus TRUVADA once daily received in Part I & Part II (Combined)
All Cause Mortality
	Doravirine 25 mg (n=40)		Doravirine 50 mg (n=43)		Doravirine 100 mg (n=108)		Doravirine 200 mg (n=41)		Efavirenz 600 mg: Part I (n=108)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Doravirine 25 mg (n=40)		Doravirine 50 mg (n=43)		Doravirine 100 mg (n=108)		Doravirine 200 mg (n=41)		Efavirenz 600 mg: Part I (n=108)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/40 (10%)		1/43 (2.3%)		11/108 (10.2%)		3/41 (7.3%)		13/108 (12%)
Cardiac disorders
Cardiomyopathy	0/40 (0%)	0	0/43 (0%)	0	0/108 (0%)	0	1/41 (2.4%)	1	0/108 (0%)	0
Pericardial effusion	0/40 (0%)	0	0/43 (0%)	0	0/108 (0%)	0	1/41 (2.4%)	1	0/108 (0%)	0
Ear and labyrinth disorders
Deafness	0/40 (0%)	0	0/43 (0%)	0	1/108 (0.9%)	1	0/41 (0%)	0	0/108 (0%)	0
Hepatobiliary disorders
Biliary dyskinesia	0/40 (0%)	0	0/43 (0%)	0	0/108 (0%)	0	1/41 (2.4%)	1	0/108 (0%)	0
Cholecystitis	0/40 (0%)	0	0/43 (0%)	0	1/108 (0.9%)	1	0/41 (0%)	0	0/108 (0%)	0
Cholecystitis acute	1/40 (2.5%)	1	0/43 (0%)	0	0/108 (0%)	0	0/41 (0%)	0	0/108 (0%)	0
Hepatitis toxic	0/40 (0%)	0	0/43 (0%)	0	0/108 (0%)	0	0/41 (0%)	0	1/108 (0.9%)	1
Infections and infestations
Abdominal abscess	0/40 (0%)	0	0/43 (0%)	0	0/108 (0%)	0	0/41 (0%)	0	1/108 (0.9%)	1
Acute hepatitis C	1/40 (2.5%)	1	0/43 (0%)	0	0/108 (0%)	0	0/41 (0%)	0	0/108 (0%)	0
Cellulitis	1/40 (2.5%)	1	0/43 (0%)	0	0/108 (0%)	0	0/41 (0%)	0	0/108 (0%)	0
Cryptosporidiosis infection	0/40 (0%)	0	0/43 (0%)	0	0/108 (0%)	0	1/41 (2.4%)	1	0/108 (0%)	0
Diverticulitis	0/40 (0%)	0	0/43 (0%)	0	0/108 (0%)	0	0/41 (0%)	0	1/108 (0.9%)	1
Gastroenteritis shigella	0/40 (0%)	0	0/43 (0%)	0	1/108 (0.9%)	1	0/41 (0%)	0	0/108 (0%)	0
Hepatitis C	0/40 (0%)	0	0/43 (0%)	0	0/108 (0%)	0	0/41 (0%)	0	1/108 (0.9%)	1
Pharyngotonsillitis	0/40 (0%)	0	1/43 (2.3%)	1	0/108 (0%)	0	0/41 (0%)	0	1/108 (0.9%)	1
Pneumonia	1/40 (2.5%)	1	0/43 (0%)	0	0/108 (0%)	0	1/41 (2.4%)	1	0/108 (0%)	0
Sinusitis	0/40 (0%)	0	0/43 (0%)	0	0/108 (0%)	0	0/41 (0%)	0	1/108 (0.9%)	1
Injury, poisoning and procedural complications
Foreign body	0/40 (0%)	0	0/43 (0%)	0	0/108 (0%)	0	0/41 (0%)	0	1/108 (0.9%)	1
Jaw fracture	0/40 (0%)	0	0/43 (0%)	0	1/108 (0.9%)	1	0/41 (0%)	0	0/108 (0%)	0
Tendon rupture	0/40 (0%)	0	0/43 (0%)	0	0/108 (0%)	0	0/41 (0%)	0	1/108 (0.9%)	1
Musculoskeletal and connective tissue disorders
Costochondritis	0/40 (0%)	0	0/43 (0%)	0	0/108 (0%)	0	0/41 (0%)	0	1/108 (0.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell unclassifiable lymphoma high grade	0/40 (0%)	0	0/43 (0%)	0	1/108 (0.9%)	1	0/41 (0%)	0	0/108 (0%)	0
Basal cell carcinoma	0/40 (0%)	0	0/43 (0%)	0	1/108 (0.9%)	1	0/41 (0%)	0	0/108 (0%)	0
Hodgkin's disease	0/40 (0%)	0	0/43 (0%)	0	1/108 (0.9%)	1	0/41 (0%)	0	0/108 (0%)	0
Kaposi's sarcoma	0/40 (0%)	0	0/43 (0%)	0	1/108 (0.9%)	1	0/41 (0%)	0	0/108 (0%)	0
Nervous system disorders
Dizziness	0/40 (0%)	0	0/43 (0%)	0	0/108 (0%)	0	0/41 (0%)	0	1/108 (0.9%)	1
Headache	0/40 (0%)	0	0/43 (0%)	0	1/108 (0.9%)	1	0/41 (0%)	0	0/108 (0%)	0
Hemiparesis	0/40 (0%)	0	0/43 (0%)	0	0/108 (0%)	0	0/41 (0%)	0	1/108 (0.9%)	1
Peroneal nerve palsy	0/40 (0%)	0	0/43 (0%)	0	0/108 (0%)	0	0/41 (0%)	0	1/108 (0.9%)	1
Psychiatric disorders
Bipolar I disorder	0/40 (0%)	0	0/43 (0%)	0	1/108 (0.9%)	1	0/41 (0%)	0	0/108 (0%)	0
Depression	0/40 (0%)	0	0/43 (0%)	0	0/108 (0%)	0	0/41 (0%)	0	1/108 (0.9%)	1
Drug abuse	0/40 (0%)	0	0/43 (0%)	0	1/108 (0.9%)	1	0/41 (0%)	0	0/108 (0%)	0
Suicidal ideation	0/40 (0%)	0	0/43 (0%)	0	1/108 (0.9%)	1	0/41 (0%)	0	2/108 (1.9%)	2
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/40 (0%)	0	0/43 (0%)	0	0/108 (0%)	0	1/41 (2.4%)	1	0/108 (0%)	0
Vascular disorders
Deep vein thrombosis	0/40 (0%)	0	0/43 (0%)	0	0/108 (0%)	0	0/41 (0%)	0	1/108 (0.9%)	1
Other (Not Including Serious) Adverse Events
	Doravirine 25 mg (n=40)		Doravirine 50 mg (n=43)		Doravirine 100 mg (n=108)		Doravirine 200 mg (n=41)		Efavirenz 600 mg: Part I (n=108)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/40 (77.5%)		35/43 (81.4%)		78/108 (72.2%)		36/41 (87.8%)		82/108 (75.9%)
Ear and labyrinth disorders
Ear pain	3/40 (7.5%)	3	0/43 (0%)	0	0/108 (0%)	0	0/41 (0%)	0	0/108 (0%)	0
Gastrointestinal disorders
Abdominal pain	3/40 (7.5%)	3	3/43 (7%)	3	5/108 (4.6%)	5	0/41 (0%)	0	4/108 (3.7%)	4
Abdominal pain upper	1/40 (2.5%)	2	3/43 (7%)	3	4/108 (3.7%)	5	2/41 (4.9%)	2	5/108 (4.6%)	9
Constipation	2/40 (5%)	2	4/43 (9.3%)	4	2/108 (1.9%)	2	0/41 (0%)	0	4/108 (3.7%)	4
Diarrhea	10/40 (25%)	10	4/43 (9.3%)	4	16/108 (14.8%)	18	5/41 (12.2%)	5	18/108 (16.7%)	20
Hemorrhoids	1/40 (2.5%)	1	1/43 (2.3%)	1	4/108 (3.7%)	4	0/41 (0%)	0	6/108 (5.6%)	6
Nausea	3/40 (7.5%)	3	7/43 (16.3%)	8	13/108 (12%)	16	9/41 (22%)	9	11/108 (10.2%)	12
Vomiting	4/40 (10%)	4	1/43 (2.3%)	1	6/108 (5.6%)	7	1/41 (2.4%)	1	7/108 (6.5%)	8
General disorders
Fatigue	7/40 (17.5%)	7	5/43 (11.6%)	7	6/108 (5.6%)	9	5/41 (12.2%)	7	7/108 (6.5%)	7
Pyrexia	1/40 (2.5%)	1	1/43 (2.3%)	1	6/108 (5.6%)	7	0/41 (0%)	0	3/108 (2.8%)	4
Infections and infestations
Acute sinusitis	1/40 (2.5%)	1	3/43 (7%)	3	2/108 (1.9%)	2	2/41 (4.9%)	2	1/108 (0.9%)	2
Bronchitis	5/40 (12.5%)	7	3/43 (7%)	5	5/108 (4.6%)	5	5/41 (12.2%)	7	12/108 (11.1%)	13
Conjunctivitis	1/40 (2.5%)	1	2/43 (4.7%)	2	6/108 (5.6%)	7	0/41 (0%)	0	3/108 (2.8%)	3
Gastroenteritis	1/40 (2.5%)	2	2/43 (4.7%)	3	9/108 (8.3%)	10	2/41 (4.9%)	2	1/108 (0.9%)	1
Influenza	6/40 (15%)	9	2/43 (4.7%)	2	3/108 (2.8%)	3	5/41 (12.2%)	5	2/108 (1.9%)	2
Nasopharyngitis	3/40 (7.5%)	4	5/43 (11.6%)	12	19/108 (17.6%)	31	12/41 (29.3%)	17	13/108 (12%)	16
Oral herpes	0/40 (0%)	0	1/43 (2.3%)	1	2/108 (1.9%)	3	3/41 (7.3%)	3	3/108 (2.8%)	3
Pharyngitis	0/40 (0%)	0	5/43 (11.6%)	5	5/108 (4.6%)	7	2/41 (4.9%)	2	3/108 (2.8%)	4
Sinusitis	2/40 (5%)	2	2/43 (4.7%)	2	5/108 (4.6%)	7	3/41 (7.3%)	4	5/108 (4.6%)	7
Syphilis	4/40 (10%)	6	1/43 (2.3%)	2	6/108 (5.6%)	7	6/41 (14.6%)	7	8/108 (7.4%)	9
Tinea pedis	3/40 (7.5%)	3	0/43 (0%)	0	1/108 (0.9%)	1	0/41 (0%)	0	0/108 (0%)	0
Tonsillitis	2/40 (5%)	2	1/43 (2.3%)	1	1/108 (0.9%)	1	3/41 (7.3%)	3	4/108 (3.7%)	4
Upper respiratory tract infection	4/40 (10%)	5	2/43 (4.7%)	6	10/108 (9.3%)	14	3/41 (7.3%)	3	13/108 (12%)	19
Injury, poisoning and procedural complications
Accidental overdose	4/40 (10%)	4	1/43 (2.3%)	3	4/108 (3.7%)	5	3/41 (7.3%)	10	5/108 (4.6%)	6
Musculoskeletal and connective tissue disorders
Arthralgia	2/40 (5%)	2	2/43 (4.7%)	2	6/108 (5.6%)	6	3/41 (7.3%)	3	3/108 (2.8%)	3
Back pain	2/40 (5%)	2	5/43 (11.6%)	7	6/108 (5.6%)	7	2/41 (4.9%)	2	10/108 (9.3%)	14
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts	0/40 (0%)	0	1/43 (2.3%)	1	4/108 (3.7%)	5	2/41 (4.9%)	2	6/108 (5.6%)	6
Nervous system disorders
Dizziness	5/40 (12.5%)	5	5/43 (11.6%)	6	16/108 (14.8%)	17	3/41 (7.3%)	3	32/108 (29.6%)	38
Headache	5/40 (12.5%)	6	6/43 (14%)	8	14/108 (13%)	27	7/41 (17.1%)	7	15/108 (13.9%)	26
Somnolence	3/40 (7.5%)	3	0/43 (0%)	0	1/108 (0.9%)	1	0/41 (0%)	0	1/108 (0.9%)	1
Psychiatric disorders
Abnormal dreams	5/40 (12.5%)	6	9/43 (20.9%)	9	7/108 (6.5%)	9	4/41 (9.8%)	4	19/108 (17.6%)	21
Anxiety	1/40 (2.5%)	1	2/43 (4.7%)	2	3/108 (2.8%)	4	0/41 (0%)	0	6/108 (5.6%)	9
Depression	1/40 (2.5%)	1	3/43 (7%)	4	4/108 (3.7%)	4	0/41 (0%)	0	11/108 (10.2%)	12
Insomnia	1/40 (2.5%)	1	6/43 (14%)	6	10/108 (9.3%)	10	3/41 (7.3%)	4	6/108 (5.6%)	7
Nightmare	1/40 (2.5%)	1	1/43 (2.3%)	1	9/108 (8.3%)	10	0/41 (0%)	0	10/108 (9.3%)	12
Sleep disorder	1/40 (2.5%)	1	2/43 (4.7%)	2	6/108 (5.6%)	6	0/41 (0%)	0	8/108 (7.4%)	11
Respiratory, thoracic and mediastinal disorders
Asthma	2/40 (5%)	5	0/43 (0%)	0	0/108 (0%)	0	3/41 (7.3%)	3	2/108 (1.9%)	2
Cough	3/40 (7.5%)	7	1/43 (2.3%)	1	3/108 (2.8%)	4	3/41 (7.3%)	3	6/108 (5.6%)	10
Dyspnea	3/40 (7.5%)	3	0/43 (0%)	0	0/108 (0%)	0	0/41 (0%)	0	0/108 (0%)	0
Nasal congestion	1/40 (2.5%)	1	3/43 (7%)	3	3/108 (2.8%)	3	0/41 (0%)	0	3/108 (2.8%)	3
Skin and subcutaneous tissue disorders
Acne	2/40 (5%)	2	3/43 (7%)	3	2/108 (1.9%)	2	0/41 (0%)	0	0/108 (0%)	0
Night sweats	1/40 (2.5%)	1	0/43 (0%)	0	1/108 (0.9%)	2	0/41 (0%)	0	6/108 (5.6%)	6
Pruritus	0/40 (0%)	0	3/43 (7%)	3	4/108 (3.7%)	4	0/41 (0%)	0	3/108 (2.8%)	3
Rash	1/40 (2.5%)	1	3/43 (7%)	6	6/108 (5.6%)	6	2/41 (4.9%)	2	9/108 (8.3%)	10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.