Trial Outcomes & Findings for Safety and Efficacy of Doravirine (MK-1439) in Participants With Human Immunodeficiency Virus 1 (HIV-1) (MK-1439-018) (NCT NCT02275780)

Last Updated: 2024-10-01

Results Overview

The percentage of participants in each arm achieving HIV-1 RNA levels \<50 copies/mL at Week 48 was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) "snapshot" approach and all missing data were considered treatment failures, regardless of the reason.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

769 participants

Primary outcome timeframe

Week 48

Results posted on

2024-10-01

Participant Flow

A total of 1027 participants were screened and 769 were randomized.

Participant milestones

Participant milestones
Measure	Doravirine 100 mg Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study. Eligible participants continued in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for an additional 96 weeks. Eligible participants continued to receive the Doravirine regimen in Study Extension 2 for an additional 96 weeks, and in Study Extension 3 for an additional 96 weeks.	Daurunavir 800 mg + Ritonavir 100 mg → Doravirine 100 mg Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study. Eligible participants continued in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for an additional 96 weeks. Eligible participants continued to receive the Doravirine regimen in Study Extension 2 for an additional 96 weeks, and in Study Extension 3 for an additional 96 weeks.
Base Study: 96 Weeks STARTED	385	384
Base Study: 96 Weeks Treated	383	383
Base Study: 96 Weeks COMPLETED	292	273
Base Study: 96 Weeks NOT COMPLETED	93	111
Study Extension 1: Week 96 to Week 192 STARTED	259	233
Study Extension 1: Week 96 to Week 192 COMPLETED	210	190
Study Extension 1: Week 96 to Week 192 NOT COMPLETED	49	43
Study Extension 2: Week 192 to Week 288 STARTED	148	129
Study Extension 2: Week 192 to Week 288 COMPLETED	101	91
Study Extension 2: Week 192 to Week 288 NOT COMPLETED	47	38
Study Extension 3: Week 288 to Week 384 STARTED	50	36
Study Extension 3: Week 288 to Week 384 COMPLETED	36	23
Study Extension 3: Week 288 to Week 384 NOT COMPLETED	14	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Doravirine 100 mg Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study. Eligible participants continued in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for an additional 96 weeks. Eligible participants continued to receive the Doravirine regimen in Study Extension 2 for an additional 96 weeks, and in Study Extension 3 for an additional 96 weeks.	Daurunavir 800 mg + Ritonavir 100 mg → Doravirine 100 mg Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study. Eligible participants continued in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for an additional 96 weeks. Eligible participants continued to receive the Doravirine regimen in Study Extension 2 for an additional 96 weeks, and in Study Extension 3 for an additional 96 weeks.
Base Study: 96 Weeks Physician Decision	2	4
Base Study: 96 Weeks Pregnancy	2	1
Base Study: 96 Weeks Randomized not treated	2	1
Study Extension 1: Week 96 to Week 192 Adverse Event	6	1
Study Extension 1: Week 96 to Week 192 Availability of study medication locally	2	0
Study Extension 1: Week 96 to Week 192 Lack of Efficacy	8	11
Study Extension 1: Week 96 to Week 192 Lost to Follow-up	8	7
Study Extension 1: Week 96 to Week 192 Non-compliance with study drug	1	2
Study Extension 1: Week 96 to Week 192 Physician Decision	3	7
Study Extension 1: Week 96 to Week 192 Pregnancy	2	1
Study Extension 1: Week 96 to Week 192 Withdrawal by Subject	19	14
Study Extension 2: Week 192 to Week 288 Adverse Event	0	1
Study Extension 2: Week 192 to Week 288 Availability of study medication locally	38	29
Study Extension 2: Week 192 to Week 288 Lack of Efficacy	2	3
Study Extension 2: Week 192 to Week 288 Lost to Follow-up	0	1
Study Extension 2: Week 192 to Week 288 Non-compliance with study drug	2	0
Study Extension 2: Week 192 to Week 288 Physician Decision	1	1
Study Extension 2: Week 192 to Week 288 Withdrawal by Subject	4	3
Study Extension 3: Week 288 to Week 384 Availability of study medication locally	6	6
Study Extension 3: Week 288 to Week 384 Death	0	1
Study Extension 3: Week 288 to Week 384 Lost to Follow-up	1	3
Study Extension 3: Week 288 to Week 384 Non-compliance with study drug	1	1
Study Extension 3: Week 288 to Week 384 Physician Decision	1	0
Study Extension 3: Week 288 to Week 384 Withdrawal by Subject	5	2
Base Study: 96 Weeks Adverse Event	6	14
Base Study: 96 Weeks Death	3	1
Base Study: 96 Weeks Lack of Efficacy	21	32
Base Study: 96 Weeks Lost to Follow-up	28	24
Base Study: 96 Weeks Protocol Violation	1	6
Base Study: 96 Weeks Withdrawal by Subject	19	22
Base Study: 96 Weeks Noncompliance with drug	9	6

Baseline Characteristics

Participants with baseline data

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Doravirine 100 mg n=385 Participants Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.	Daurunavir 800 mg + Ritonavir 100 mg n=384 Participants Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.	Total n=769 Participants Total of all reporting groups
Age, Continuous	34.9 Years STANDARD_DEVIATION 10.7 • n=385 Participants	35.7 Years STANDARD_DEVIATION 10.7 • n=384 Participants	35.3 Years STANDARD_DEVIATION 10.7 • n=769 Participants
Sex: Female, Male Female	65 Participants n=385 Participants	58 Participants n=384 Participants	123 Participants n=769 Participants
Sex: Female, Male Male	320 Participants n=385 Participants	326 Participants n=384 Participants	646 Participants n=769 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	93 Participants n=385 Participants	86 Participants n=384 Participants	179 Participants n=769 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	286 Participants n=385 Participants	291 Participants n=384 Participants	577 Participants n=769 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=385 Participants	7 Participants n=384 Participants	13 Participants n=769 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=385 Participants	3 Participants n=384 Participants	6 Participants n=769 Participants
Race (NIH/OMB) Asian	7 Participants n=385 Participants	7 Participants n=384 Participants	14 Participants n=769 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=385 Participants	2 Participants n=384 Participants	3 Participants n=769 Participants
Race (NIH/OMB) Black or African American	87 Participants n=385 Participants	89 Participants n=384 Participants	176 Participants n=769 Participants
Race (NIH/OMB) White	281 Participants n=385 Participants	280 Participants n=384 Participants	561 Participants n=769 Participants
Race (NIH/OMB) More than one race	6 Participants n=385 Participants	2 Participants n=384 Participants	8 Participants n=769 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=385 Participants	1 Participants n=384 Participants	1 Participants n=769 Participants
Mean Cluster of Differentiation 4 (CD4+) T-cell Count	432.6 Cells/mm^3 STANDARD_DEVIATION 208.4 • n=383 Participants • Participants with baseline data	411.9 Cells/mm^3 STANDARD_DEVIATION 229.6 • n=383 Participants • Participants with baseline data	422.2 Cells/mm^3 STANDARD_DEVIATION 219.4 • n=766 Participants • Participants with baseline data
Plasma HIV-1 RNA	27073.0 Copies/mL n=383 Participants • Participants with baseline data	27357.0 Copies/mL n=382 Participants • Participants with baseline data	27073.0 Copies/mL n=765 Participants • Participants with baseline data

PRIMARY outcome

Timeframe: Week 48

Population: All randomized participants who received at least 1 dose of study drug

Outcome measures

Outcome measures
Measure	Doravirine 100 mg n=383 Participants Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.	Daurunavir 800 mg + Ritonavir 100 mg n=383 Participants Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.
Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 48	83.8 Percentage of participants	79.9 Percentage of participants

SECONDARY outcome

Timeframe: Week 96

Population: All randomized participants who received at least 1 dose of study drug and had data for the outcome measure. Participants with missing HIV-1 RNA due to an Abbott RealTime manufacturing agent recall were excluded from the analysis.

The percentage of participants in each arm achieving HIV-1 RNA levels \<50 copies/mL at Week 96 was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) "snapshot" approach and all missing data were considered treatment failures, regardless of the reason.

Outcome measures

Outcome measures
Measure	Doravirine 100 mg n=379 Participants Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.	Daurunavir 800 mg + Ritonavir 100 mg n=376 Participants Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.
Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 96	73.1 Percentage of participants	66.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: All randomized participants who received at least 1 dose of study drug and had data for the outcome measure. Baseline values were carried forward for participants who discontinued therapy due to lack of efficacy.

CD4+ T-cell counts were quantified by a central laboratory using a commercially available assay.

Outcome measures

Outcome measures
Measure	Doravirine 100 mg n=363 Participants Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.	Daurunavir 800 mg + Ritonavir 100 mg n=353 Participants Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.
Change From Baseline in Mean CD4+ T-cell Count at Week 48	192.7 Cells/mm^3 Interval 171.5 to 213.9	185.6 Cells/mm^3 Interval 167.5 to 203.6

SECONDARY outcome

Timeframe: Baseline and Week 96

CD4+ T-cell counts were quantified by a central laboratory using a commercially available assay.

Outcome measures

Outcome measures
Measure	Doravirine 100 mg n=342 Participants Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.	Daurunavir 800 mg + Ritonavir 100 mg n=327 Participants Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.
Change From Baseline in Mean CD4+ T-cell Count at Week 96	224.1 Cells/mm^3 Interval 200.8 to 247.4	206.7 Cells/mm^3 Interval 184.9 to 228.5

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: All randomized participants who received at least 1 dose of study drug and had a measurement at Baseline and at the time point assessed.

Serum LDL-C was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The Last Observation Carry Forward (LOCF) approach was applied for missing data or data collected after modifying lipid-lowering therapy.

Outcome measures

Outcome measures
Measure	Doravirine 100 mg n=326 Participants Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.	Daurunavir 800 mg + Ritonavir 100 mg n=318 Participants Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.
Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 Baseline	91.10 mg/dL Standard Deviation 28.61	91.76 mg/dL Standard Deviation 30.36
Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 Change from Baseline	-4.51 mg/dL Standard Deviation 20.64	9.92 mg/dL Standard Deviation 27.31

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: All randomized participants who received at least 1 dose of study drug and had a measurement at Baseline and at the time point assessed.

Serum non-HDL-C was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy.

Outcome measures

Outcome measures
Measure	Doravirine 100 mg n=329 Participants Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.	Daurunavir 800 mg + Ritonavir 100 mg n=325 Participants Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.
Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 Baseline	113.34 mg/dL Standard Deviation 34.25	114.44 mg/dL Standard Deviation 35.01
Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 Change from Baseline	-5.30 mg/dL Standard Deviation 23.28	13.75 mg/dL Standard Deviation 31.08

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: All randomized participants who received at least 1 dose of study drug and had a measurement at Baseline and at the time point assessed.

Serum HDL-C was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy.

Outcome measures

Outcome measures
Measure	Doravirine 100 mg n=329 Participants Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.	Daurunavir 800 mg + Ritonavir 100 mg n=325 Participants Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.
Mean Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 48 Baseline	43.58 mg/dL Standard Deviation 12.99	43.27 mg/dL Standard Deviation 13.96
Mean Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 48 Change from Baseline	3.94 mg/dL Standard Deviation 10.66	4.15 mg/dL Standard Deviation 11.01

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: All randomized participants who received at least 1 dose of study drug and had a measurement at Baseline and at the time point assessed.

Serum total cholesterol was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy.

Outcome measures

Outcome measures
Measure	Doravirine 100 mg n=329 Participants Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.	Daurunavir 800 mg + Ritonavir 100 mg n=325 Participants Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.
Mean Change From Baseline in Fasting Total Cholesterol at Week 48 Baseline	156.92 mg/dL Standard Deviation 35.82	157.71 mg/dL Standard Deviation 37.34
Mean Change From Baseline in Fasting Total Cholesterol at Week 48 Change from Baseline	-1.37 mg/dL Standard Deviation 25.47	17.90 mg/dL Standard Deviation 33.95

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: All randomized participants who received at least 1 dose of study drug and had a measurement at Baseline and at the time point assessed.

Serum triglyceride was determined after an overnight fast. Change from Baseline was analyzed using ANCOVA models with terms for Baseline lipid level and treatment group. The LOCF approach was applied for missing data or data collected after modifying lipid-lowering therapy.

Outcome measures

Outcome measures
Measure	Doravirine 100 mg n=329 Participants Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.	Daurunavir 800 mg + Ritonavir 100 mg n=325 Participants Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.
Mean Change From Baseline in Fasting Triglyceride at Week 48 Baseline	111.16 mg/dL Standard Deviation 75.31	117.02 mg/dL Standard Deviation 97.30
Mean Change From Baseline in Fasting Triglyceride at Week 48 Change from Baseline	-3.14 mg/dL Standard Deviation 68.81	21.97 mg/dL Standard Deviation 92.59

SECONDARY outcome

Timeframe: Up to 98 weeks

Population: All randomized participants who received at least 1 dose of study drug

An adverse event (AE) is defined as any untoward medical occurrence in a study participant and which does not necessarily have to have a causal relationship to treatment. An adverse event can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the study treatment or protocol-specified procedure, whether or not considered related to study treatment or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the study treatment is also an AE. The percentage of participants with any AE was assessed.

Outcome measures

Outcome measures
Measure	Doravirine 100 mg n=383 Participants Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.	Daurunavir 800 mg + Ritonavir 100 mg n=383 Participants Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.
Percentage of Participants With Any Adverse Event	84.6 Percentage of participants	82.8 Percentage of participants

SECONDARY outcome

Timeframe: Up to 98 weeks

Population: All randomized participants who received at least 1 dose of study drug

A serious adverse event is an AE that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs a hospitalization, is a congenital anomaly or birth defect, is a cancer, is associated with an overdose, or is another important medical event. The percentage of participants with any SAE was assessed.

Outcome measures

Outcome measures
Measure	Doravirine 100 mg n=383 Participants Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.	Daurunavir 800 mg + Ritonavir 100 mg n=383 Participants Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.
Percentage of Participants With Any Serious Adverse Event	7.0 Percentage of participants	8.6 Percentage of participants

SECONDARY outcome

Timeframe: Up to 98 weeks

Population: All randomized participants who received at least 1 dose of study drug

The investigator was to determine if an AE had a reasonable possibility of a relationship to the study drug. The percentage of participants with any drug-related AE was assessed.

Outcome measures

Outcome measures
Measure	Doravirine 100 mg n=383 Participants Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.	Daurunavir 800 mg + Ritonavir 100 mg n=383 Participants Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.
Percentage of Participants With Any Drug-related Adverse Event	32.1 Percentage of participants	32.1 Percentage of participants

SECONDARY outcome

Timeframe: Up to 98 weeks

Population: All randomized participants who received at least 1 dose of study drug

The percentage of participants with any drug-related SAE was assessed.

Outcome measures

Outcome measures
Measure	Doravirine 100 mg n=383 Participants Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.	Daurunavir 800 mg + Ritonavir 100 mg n=383 Participants Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.
Percentage of Participants With Any Drug-related Serious Adverse Event	0.3 Percentage of participants	0.3 Percentage of participants

SECONDARY outcome

Timeframe: Up to 96 weeks

Population: All randomized participants who received at least 1 dose of study drug

The percentage of participants who discontinued study treatment due to an AE was assessed.

Outcome measures

Outcome measures
Measure	Doravirine 100 mg n=383 Participants Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.	Daurunavir 800 mg + Ritonavir 100 mg n=383 Participants Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.
Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event	1.6 Percentage of participants	3.4 Percentage of participants

SECONDARY outcome

Timeframe: Week 48

Population: All randomized participants who received at least 1 dose of study drug

The percentage of participants in each arm achieving HIV-1 RNA levels \<40 copies/mL at Week 48 was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) "snapshot" approach and all missing data were considered treatment failures, regardless of the reason.

Outcome measures

Outcome measures
Measure	Doravirine 100 mg n=383 Participants Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.	Daurunavir 800 mg + Ritonavir 100 mg n=383 Participants Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.
Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 48	83.3 Percentage of participants	79.1 Percentage of participants

SECONDARY outcome

Timeframe: Week 96

The percentage of participants in each arm achieving HIV-1 RNA levels \<40 copies/mL at Week 96 was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) "snapshot" approach and all missing data were considered treatment failures, regardless of the reason.

Outcome measures

Outcome measures
Measure	Doravirine 100 mg n=379 Participants Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.	Daurunavir 800 mg + Ritonavir 100 mg n=376 Participants Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study.
Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 96	72.0 Percentage of participants	64.4 Percentage of participants

Adverse Events

Doravirine 100 mg

Serious events: 45 serious events

Other events: 264 other events

Deaths: 3 deaths

Daurunavir 800 mg + Ritonavir 100 mg → Doravirine 100 mg

Serious events: 49 serious events

Other events: 247 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Publication restrictions are in place

Restriction type: OTHER

Measure	Doravirine 100 mg n=383 participants at risk Double-blind Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study. Eligible participants continued in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for an additional 96 weeks. Eligible participants continued to receive the Doravirine regimen in Study Extension 2 for an additional 96 weeks, and in Study Extension 3 for an additional 96 weeks.	Daurunavir 800 mg + Ritonavir 100 mg → Doravirine 100 mg n=383 participants at risk Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study. Eligible participants continued in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator-selected TRUVADA™ or EPZICOM™/ KIVEXA™ administered p.o. q.d. for an additional 96 weeks. Eligible participants continued to receive the Doravirine regimen in Study Extension 2 for an additional 96 weeks, and in Study Extension 3 for an additional 96 weeks.
Gastrointestinal disorders Abdominal pain	5.2% 20/383 • Number of events 22 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	5.2% 20/383 • Number of events 25 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain upper	7.0% 27/383 • Number of events 30 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	3.9% 15/383 • Number of events 18 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	18.8% 72/383 • Number of events 87 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	26.1% 100/383 • Number of events 136 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	13.6% 52/383 • Number of events 65 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	14.1% 54/383 • Number of events 64 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Vomiting	5.2% 20/383 • Number of events 32 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	3.1% 12/383 • Number of events 14 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.
General disorders Fatigue	9.9% 38/383 • Number of events 40 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	7.3% 28/383 • Number of events 30 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.
General disorders Pyrexia	5.5% 21/383 • Number of events 21 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	2.6% 10/383 • Number of events 10 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.
Infections and infestations Bronchitis	8.1% 31/383 • Number of events 43 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	9.7% 37/383 • Number of events 42 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.
Infections and infestations Gastroenteritis	5.7% 22/383 • Number of events 25 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	6.0% 23/383 • Number of events 28 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.
Infections and infestations Influenza	6.3% 24/383 • Number of events 29 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	4.2% 16/383 • Number of events 20 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	15.9% 61/383 • Number of events 110 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	15.9% 61/383 • Number of events 102 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.
Infections and infestations Syphilis	7.6% 29/383 • Number of events 39 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	10.2% 39/383 • Number of events 47 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.
Infections and infestations Upper respiratory tract infection	16.7% 64/383 • Number of events 115 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	10.4% 40/383 • Number of events 59 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	6.8% 26/383 • Number of events 29 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	5.7% 22/383 • Number of events 27 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	9.7% 37/383 • Number of events 45 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	3.4% 13/383 • Number of events 16 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.
Nervous system disorders Dizziness	6.5% 25/383 • Number of events 28 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	6.3% 24/383 • Number of events 28 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.
Nervous system disorders Headache	16.4% 63/383 • Number of events 106 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	15.4% 59/383 • Number of events 92 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.
Psychiatric disorders Insomnia	7.0% 27/383 • Number of events 27 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	6.0% 23/383 • Number of events 27 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	9.9% 38/383 • Number of events 48 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.	3.7% 14/383 • Number of events 15 • Up to Week 386 The analysis population for All-Cause Mortality included all randomized participants. The analysis population for Serious and Other Adverse Events included all participants who received at least 1 dose of study drug.