Trial Outcomes & Findings for A Study to Evaluate the Safety and Efficacy of an Investigational Drug in HIV Infected Patients (0518-004)(COMPLETED) (NCT NCT00100048)

NCT ID: NCT00100048

Last Updated: 2015-09-09

Results Overview

Mean change from baseline on Day 10 in plasma Human Immunodeficiency Virus (HIV) Ribonucleic acid (RNA) (copies/mL)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

206 participants

Primary outcome timeframe

Baseline and Day 10

Results posted on

2015-09-09

Participant Flow

Primary therapy period: For Part I (10 day monotherapy): 24-Jan-2005 to 04-May-2005 Part II (Dose Ranging): 14-Jun-2005 to 04-Oct-2006 (48 weeks); 14-Jun-2005 to 12-Jul-2010 (240 weeks) Multicenter (29) in the United States (14) and Ex-US (15)

Patients with Human Immunodeficiency Virus (HIV) Ribonucleic acid (RNA) of at least 5000 copies/mL and cluster of differentiation 4 (CD4) cell counts of at least 100 cells/mm3. All patients must have met laboratory criteria. 206 enrolled; 5 from Cohort I did not continue to the combination phase. Therefore 201 entered the combination phase.

Participant milestones

Participant milestones
Measure	MK0518 100 mg b.i.d. Cohort I-Monotherapy Phase MK0518 100 mg twice daily (b.i.d.) Cohort II Combined-Combination Therapy Phase MK0518 100 mg + tenofovir + lamivudine	MK0518 200 mg b.i.d Cohort I-Monotherapy Phase MK0518 200 mg b.i.d Cohort II Combined-Combination Therapy Phase MK0518 200 mg + tenofovir + lamivudine	MK0518 400 mg b.i.d. Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine	Placebo Cohort I-Monotherapy Phase Placebo to MK0518 b.i.d.	Efavirenz 600 mg q.h.s. Cohort II Combined-Combination Therapy Phase efavirenz 600 mg every night at bedtime (q.h.s.)
Cohort I-Monotherapy Phase 10 Days STARTED	7	7	6	8	7	0
Cohort I-Monotherapy Phase 10 Days Treated	7	7	6	8	7	0
Cohort I-Monotherapy Phase 10 Days COMPLETED	7	7	6	8	7	0
Cohort I-Monotherapy Phase 10 Days NOT COMPLETED	0	0	0	0	0	0
Cohort I & II-Combination Therapy Phase STARTED	41	40	41	40	0	39
Cohort I & II-Combination Therapy Phase Treated	39	40	41	40	0	38
Cohort I & II-Combination Therapy Phase Never Treated	2	0	0	0	0	1
Cohort I & II-Combination Therapy Phase COMPLETED	27	31	28	30	0	26
Cohort I & II-Combination Therapy Phase NOT COMPLETED	14	9	13	10	0	13

Reasons for withdrawal

Reasons for withdrawal
Measure	MK0518 100 mg b.i.d. Cohort I-Monotherapy Phase MK0518 100 mg twice daily (b.i.d.) Cohort II Combined-Combination Therapy Phase MK0518 100 mg + tenofovir + lamivudine	MK0518 200 mg b.i.d Cohort I-Monotherapy Phase MK0518 200 mg b.i.d Cohort II Combined-Combination Therapy Phase MK0518 200 mg + tenofovir + lamivudine	MK0518 400 mg b.i.d. Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine	Efavirenz 600 mg q.h.s. Cohort II Combined-Combination Therapy Phase efavirenz 600 mg every night at bedtime (q.h.s.)
Cohort I & II-Combination Therapy Phase Never Treated	2	0	0	0	1
Cohort I & II-Combination Therapy Phase Adverse Event	0	1	2	0	1
Cohort I & II-Combination Therapy Phase Lack of Efficacy	1	3	0	0	2
Cohort I & II-Combination Therapy Phase Lost to Follow-up	2	1	3	2	3
Cohort I & II-Combination Therapy Phase Withdrawal by Subject	1	2	2	5	4
Cohort I & II-Combination Therapy Phase Other Reason	7	1	4	2	0
Cohort I & II-Combination Therapy Phase Completed Base Study, Did Not Continue	1	1	2	0	2
Cohort I & II-Combination Therapy Phase Laboratory Adverse Experience	0	0	0	1	0

Baseline Characteristics

A Study to Evaluate the Safety and Efficacy of an Investigational Drug in HIV Infected Patients (0518-004)(COMPLETED)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK0518 100 mg b.i.d. n=41 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100 mg twice daily (b.i.d.) Cohort II Combined-Combination Therapy Phase (48 Weeks) MK0518 100 mg b.i.d	MK0518 200 mg b.i.d n=40 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 200 mg b.i.d Cohort II Combined-Combination Therapy Phase (48 Weeks) MK0518 200 mg + tenofovir + lamivudine	MK0518 400 mg b.i.d. n=41 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase (48 Weeks) MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. n=42 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase (48 Weeks) MK0518 600 mg + tenofovir + lamivudine	Placebo / Efavirenz 600 mg Once Daily (q.d.) n=42 Participants Cohort I-Monotherapy Phase (10 Days) Placebo to MK0518 b.i.d. Cohort II Combined-Combination Therapy Phase (48 Weeks) Efavirenz + Tenofovir + Lamivudine	Total n=206 Participants Total of all reporting groups
Age, Continuous Cohort I	46 Years n=93 Participants	37 Years n=4 Participants	41 Years n=27 Participants	39 Years n=483 Participants	36 Years n=36 Participants	40 Years n=10 Participants
Age, Continuous Cohort II	34 Years n=93 Participants	31 Years n=4 Participants	34 Years n=27 Participants	36 Years n=483 Participants	36 Years n=36 Participants	35 Years n=10 Participants
Age, Continuous Cohort I & II Combined	37 Years n=93 Participants	34 Years n=4 Participants	36 Years n=27 Participants	37 Years n=483 Participants	36 Years n=36 Participants	36 Years n=10 Participants
Sex/Gender, Customized Female (Cohort I)	0 participants n=93 Participants	1 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	1 participants n=36 Participants	2 participants n=10 Participants
Sex/Gender, Customized Male (Cohort I)	7 participants n=93 Participants	6 participants n=4 Participants	6 participants n=27 Participants	8 participants n=483 Participants	6 participants n=36 Participants	33 participants n=10 Participants
Sex/Gender, Customized Female (Cohort II)	6 participants n=93 Participants	10 participants n=4 Participants	4 participants n=27 Participants	11 participants n=483 Participants	8 participants n=36 Participants	39 participants n=10 Participants
Sex/Gender, Customized Male (Cohort II)	27 participants n=93 Participants	23 participants n=4 Participants	31 participants n=27 Participants	23 participants n=483 Participants	26 participants n=36 Participants	130 participants n=10 Participants
Sex/Gender, Customized Never Treated Cohort II	1 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	1 participants n=36 Participants	2 participants n=10 Participants
Race/Ethnicity, Customized White (Cohort I)	4 participants n=93 Participants	4 participants n=4 Participants	3 participants n=27 Participants	8 participants n=483 Participants	3 participants n=36 Participants	22 participants n=10 Participants
Race/Ethnicity, Customized Black (Cohort I)	1 participants n=93 Participants	1 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	0 participants n=36 Participants	2 participants n=10 Participants
Race/Ethnicity, Customized Asian (Cohort I)	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	1 participants n=36 Participants	1 participants n=10 Participants
Race/Ethnicity, Customized Hispanic (Cohort I)	2 participants n=93 Participants	2 participants n=4 Participants	3 participants n=27 Participants	0 participants n=483 Participants	3 participants n=36 Participants	10 participants n=10 Participants
Race/Ethnicity, Customized White (Cohort II)	4 participants n=93 Participants	10 participants n=4 Participants	11 participants n=27 Participants	8 participants n=483 Participants	10 participants n=36 Participants	43 participants n=10 Participants
Race/Ethnicity, Customized Black (Cohort II)	1 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants	0 participants n=483 Participants	0 participants n=36 Participants	3 participants n=10 Participants
Race/Ethnicity, Customized Asian (Cohort II)	3 participants n=93 Participants	6 participants n=4 Participants	8 participants n=27 Participants	7 participants n=483 Participants	8 participants n=36 Participants	32 participants n=10 Participants
Race/Ethnicity, Customized Hispanic (Cohort II)	12 participants n=93 Participants	9 participants n=4 Participants	10 participants n=27 Participants	9 participants n=483 Participants	10 participants n=36 Participants	50 participants n=10 Participants
Race/Ethnicity, Customized Other (Cohort II)	13 participants n=93 Participants	7 participants n=4 Participants	5 participants n=27 Participants	10 participants n=483 Participants	6 participants n=36 Participants	41 participants n=10 Participants
Race/Ethnicity, Customized Never Treated (Cohort II)	1 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	1 participants n=36 Participants	2 participants n=10 Participants
Cluster of differentiation 4 (CD4) Cell Count Cohort I	415 cells/mm^3 n=93 Participants	343 cells/mm^3 n=4 Participants	256 cells/mm^3 n=27 Participants	569 cells/mm^3 n=483 Participants	343 cells/mm^3 n=36 Participants	394 cells/mm^3 n=10 Participants
Cluster of differentiation 4 (CD4) Cell Count Cohort II	293 cells/mm^3 n=93 Participants	292 cells/mm^3 n=4 Participants	348 cells/mm^3 n=27 Participants	245 cells/mm^3 n=483 Participants	276 cells/mm^3 n=36 Participants	291 cells/mm^3 n=10 Participants
Cluster of differentiation 4 (CD4) Cell Count Cohort I and II Combined	272 cells/mm^3 n=93 Participants	277 cells/mm^3 n=4 Participants	293 cells/mm^3 n=27 Participants	244 cells/mm^3 n=483 Participants	225 cells/mm^3 n=36 Participants	266 cells/mm^3 n=10 Participants
Plasma Human Immunodeficiency Virus (HIV) Ribonucleic acid (RNA) Cohort I	44989 copies/mL n=93 Participants	34143 copies/mL n=4 Participants	37728 copies/mL n=27 Participants	93911 copies/mL n=483 Participants	58412 copies/mL n=36 Participants	51496 copies/mL n=10 Participants
Plasma Human Immunodeficiency Virus (HIV) Ribonucleic acid (RNA) Cohort II	65982 copies/mL n=93 Participants	73646 copies/mL n=4 Participants	47019 copies/mL n=27 Participants	61929 copies/mL n=483 Participants	76752 copies/mL n=36 Participants	63965 copies/mL n=10 Participants
Plasma Human Immunodeficiency Virus (HIV) Ribonucleic acid (RNA) Cohort I and II Combined	58206 copies/mL n=93 Participants	64715 copies/mL n=4 Participants	43083 copies/mL n=27 Participants	57919 copies/mL n=483 Participants	67554 copies/mL n=36 Participants	57437 copies/mL n=10 Participants

PRIMARY outcome

Timeframe: Baseline and Day 10

Population: The analysis population is based upon the modified intent to treat (MITT) approach, where patients are included in the treatment group to which they were randomized. Patients who were randomized but never dosed are not included in the analysis.

Mean change from baseline on Day 10 in plasma Human Immunodeficiency Virus (HIV) Ribonucleic acid (RNA) (copies/mL)

Outcome measures

Outcome measures
Measure	EFV Combo Therapy n=7 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=7 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=7 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. n=6 Participants Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. n=8 Participants Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Change From Baseline in Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) on Day 10 (Cohort I)	-0.17 copies/mL Interval -0.42 to 0.07	-1.93 copies/mL Interval -2.44 to -1.42	-1.98 copies/mL Interval -2.49 to -1.47	-1.66 copies/mL Interval -1.99 to -1.34	-2.16 copies/mL Interval -2.55 to -1.77

PRIMARY outcome

Timeframe: 10 days

Population: The analysis population is based upon the All Patients As Treated (APaT) approach.

An adverse experience (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. Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose.

Outcome measures

Outcome measures
Measure	EFV Combo Therapy n=7 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=7 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=7 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. n=6 Participants Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. n=8 Participants Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Patients With Clinical Adverse Experiences (CAEs) and Number of Patients With Serious CAEs at Day 10 (Cohort I) With Serious CAEs	0 participants	0 participants	0 participants	0 participants	0 participants
Number of Patients With Clinical Adverse Experiences (CAEs) and Number of Patients With Serious CAEs at Day 10 (Cohort I) Without Serious CAEs	7 participants	7 participants	7 participants	6 participants	8 participants
Number of Patients With Clinical Adverse Experiences (CAEs) and Number of Patients With Serious CAEs at Day 10 (Cohort I) With CAEs	5 participants	4 participants	2 participants	3 participants	5 participants
Number of Patients With Clinical Adverse Experiences (CAEs) and Number of Patients With Serious CAEs at Day 10 (Cohort I) Without CAEs	2 participants	3 participants	5 participants	3 participants	3 participants

PRIMARY outcome

Timeframe: Week 24

Outcome measures

Outcome measures
Measure	EFV Combo Therapy n=34 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=33 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=33 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. n=35 Participants Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. n=34 Participants Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 24 (Cohort II)	32 participants	31 participants	27 participants	35 participants	32 participants

PRIMARY outcome

Timeframe: 48 weeks

Population: The analysis population is based upon the All Patients As Treated (APaT) approach.

Outcome measures

Outcome measures
Measure	EFV Combo Therapy n=38 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=39 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=40 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. n=41 Participants Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. n=40 Participants Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Patients With Clinical Adverse Experiences (CAEs) With CAEs	34 participants	31 participants	35 participants	36 participants	35 participants
Number of Patients With Clinical Adverse Experiences (CAEs) Without CAEs	4 participants	8 participants	5 participants	5 participants	5 participants

PRIMARY outcome

Timeframe: 48 weeks

Population: The analysis population is based upon the All Patients As Treated (APaT) approach.

Serious CAEs are any AEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose

Outcome measures

Outcome measures
Measure	EFV Combo Therapy n=38 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=39 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=40 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. n=41 Participants Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. n=40 Participants Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Patients With Serious CAEs (Cohort I and II Combined) With Serious CAEs	2 participants	2 participants	5 participants	0 participants	2 participants
Number of Patients With Serious CAEs (Cohort I and II Combined) Without Serious CAEs	36 participants	37 participants	35 participants	41 participants	38 participants

PRIMARY outcome

Timeframe: 144 Weeks

Population: The analysis population is based upon the All Patients As Treated (APaT) approach.

An adverse experience (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 An adverse experience (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

Outcome measures

Outcome measures
Measure	EFV Combo Therapy EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=160 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=38 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Patients With Serious CAEs and Non-serious CAEs at Week 144 With CAEs	—	153 participants	35 participants	—	—
Number of Patients With Serious CAEs and Non-serious CAEs at Week 144 Without CAEs	—	7 participants	3 participants	—	—
Number of Patients With Serious CAEs and Non-serious CAEs at Week 144 With serious CAEs	—	18 participants	4 participants	—	—
Number of Patients With Serious CAEs and Non-serious CAEs at Week 144 Without serious CAEs	—	142 participants	34 participants	—	—

PRIMARY outcome

Timeframe: Week 240

Population: The analysis population was based upon the All Patients As Treated (APaT) approach.

An AE was defined as any unfavorable \& unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to its use. Any worsening of a preexisting condition which was temporally associated with the use of the study drug, was also an AE. A SAE was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was cancer, or was an overdose.

Outcome measures

Outcome measures
Measure	EFV Combo Therapy EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=160 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=38 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Participants With Clinical Adverse Experiences (AEs)and Serious Adverse Experiences (SAEs) Adverse experiences	—	154 Participants	35 Participants	—	—
Number of Participants With Clinical Adverse Experiences (AEs)and Serious Adverse Experiences (SAEs) Serious adverse experiences	—	25 Participants	4 Participants	—	—

PRIMARY outcome

Timeframe: Week 240

Population: Modified-Intention-to-Treat (MITT): participants were included in the treatment group to which they were randomized, regardless of adherence to the entry criteria, treatment actually received, and deviation from the protocol. Participants who were randomized but never dosed were not included in the analyses.

HIV RNA levels were determined by AMPLICOR HIV-1 Monitor™ UltraSensitive Assay.

Outcome measures

Outcome measures
Measure	EFV Combo Therapy EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=160 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=38 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Participants With HIV RNA (Human Immunodeficiency Virus Ribonucleic Acid) Levels Below 50 Copies/mL at Week 240	—	110 Participants	24 Participants	—	—

SECONDARY outcome

Timeframe: Week 24

Outcome measures

Outcome measures
Measure	EFV Combo Therapy n=34 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=33 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=33 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. n=35 Participants Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. n=34 Participants Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Participants With HIV RNA Levels Below 50 Copies/mL at Week 24 (Cohort II)	31 participants	28 participants	27 participants	33 participants	32 participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Mean change from baseline at Week 24 in plasma HIV RNA (copies/mL)

Outcome measures

Outcome measures
Measure	EFV Combo Therapy n=34 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=33 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=31 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. n=35 Participants Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. n=32 Participants Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Change From Baseline in Plasma HIV RNA at Week 24 (Cohort II)	-2.44 copies/mL Interval -2.69 to -2.19	-2.39 copies/mL Interval -2.58 to -2.21	-2.20 copies/mL Interval -2.55 to -1.86	-2.33 copies/mL Interval -2.51 to -2.14	-2.49 copies/mL Interval -2.72 to -2.26

SECONDARY outcome

Timeframe: Baseline and Week 24

Mean change from baseline at Week 24 in CD4 Cell Count (cells/mm3)

Outcome measures

Outcome measures
Measure	EFV Combo Therapy n=32 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=33 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=31 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. n=34 Participants Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. n=31 Participants Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24 (Cohort II)	101 cells/mm3 Interval 59.6 to 142.8	184 cells/mm3 Interval 144.4 to 223.6	122 cells/mm3 Interval 73.7 to 169.2	147 cells/mm3 Interval 112.3 to 182.6	134 cells/mm3 Interval 100.8 to 166.3

SECONDARY outcome

Timeframe: 96 Weeks

Outcome measures

Outcome measures
Measure	EFV Combo Therapy EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=160 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=38 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Patients With HIV RNA Level Below 50 Copies/mL and HIV RNA Level Below 400 Copies/mL at Week 96 HIV RNA <50 copies/mL	—	133 participants	32 participants	—	—
Number of Patients With HIV RNA Level Below 50 Copies/mL and HIV RNA Level Below 400 Copies/mL at Week 96 HIV RNA <400 copies/mL	—	135 participants	32 participants	—	—

SECONDARY outcome

Timeframe: Baseline and Week 96

Outcome measures

Outcome measures
Measure	EFV Combo Therapy EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=144 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=35 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Change From Baseline in Plasma HIV RNA at Week 96	—	-2.30 copies/mL Interval -2.42 to -2.19	-2.28 copies/mL Interval -2.57 to -2.0	—	—

SECONDARY outcome

Timeframe: Baseline and Week 96

Outcome measures

Outcome measures
Measure	EFV Combo Therapy EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=143 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=35 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Change From Baseline in CD4 Cell Count at Week 96	—	221.2 cells/mm3 Interval 196.8 to 245.7	232.4 cells/mm3 Interval 179.6 to 285.2	—	—

SECONDARY outcome

Timeframe: Week 240

HIV RNA levels were determined by AMPLICOR HIV-1 Monitor™ Standard Assay.

Outcome measures

Outcome measures
Measure	EFV Combo Therapy EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=160 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=38 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 240	—	115 Participants	25 Participants	—	—

SECONDARY outcome

Timeframe: Baseline and Week 240

HIV RNA levels were determined by AMPLICOR HIV-1 Monitor™ Standard Assay.

Outcome measures

Outcome measures
Measure	EFV Combo Therapy EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=123 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=31 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Change From Baseline in Plasma HIV RNA at Week 240	—	-2.29 Log10Copies/mL Interval -2.43 to -2.15	-2.07 Log10Copies/mL Interval -2.45 to -1.69	—	—

SECONDARY outcome

Timeframe: Baseline and Week 240

Change in number of CD4 cells/mm\^3 from baseline to Week 240.

Outcome measures

Outcome measures
Measure	EFV Combo Therapy EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=123 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=31 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Change From Baseline in CD4 (T-helper) Cell Count at Week 240	—	301.7 cells/mm^3 Interval 268.0 to 335.5	275.6 cells/mm^3 Interval 209.9 to 341.3	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 48 weeks

Outcome measures

Outcome measures
Measure	EFV Combo Therapy n=38 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=39 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=40 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. n=41 Participants Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. n=40 Participants Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 48	33 participants	38 participants	34 participants	40 participants	36 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 48 weeks

Population: The analysis population is based upon the All Patients As Treated (APaT) approach.

Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) CAEs

Outcome measures

Outcome measures
Measure	EFV Combo Therapy n=38 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=39 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=40 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. n=41 Participants Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. n=40 Participants Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Patients With Drug-related CAEs Without drug-related CAEs	11 participants	21 participants	20 participants	22 participants	21 participants
Number of Patients With Drug-related CAEs With drug-related CAEs	27 participants	18 participants	20 participants	19 participants	19 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 48 Weeks

Population: The analysis population is based upon the All Patients As Treated (APaT) approach

Outcome measures

Outcome measures
Measure	EFV Combo Therapy n=38 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=39 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=40 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. n=41 Participants Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. n=40 Participants Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Patients With Serious Drug-related CAEs With Serious drug-related CAEs	0 participants	0 participants	0 participants	0 participants	0 participants
Number of Patients With Serious Drug-related CAEs Without Serious drug-related CAEs	38 participants	39 participants	40 participants	41 participants	40 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 48 Weeks

Population: The analysis population is based upon the All Patients As Treated (APaT) approach.

Outcome measures

Outcome measures
Measure	EFV Combo Therapy n=38 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=39 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=40 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. n=41 Participants Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. n=40 Participants Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Patients That Discontinued With CAEs Did Not Discontinue with CAEs	38 participants	39 participants	40 participants	41 participants	40 participants
Number of Patients That Discontinued With CAEs Discontinued with CAEs	0 participants	0 participants	0 participants	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 48 Weeks

Population: The analysis population is based upon the All Patients As Treated (APaT) approach.

A laboratory adverse experience (LAE) is defined as any unfavorable and unintended change in the 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

Outcome measures

Outcome measures
Measure	EFV Combo Therapy n=38 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=39 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=40 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. n=41 Participants Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. n=40 Participants Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Patients With Laboratory Adverse Experiences (LAEs) With LAEs	8 participants	8 participants	7 participants	11 participants	5 participants
Number of Patients With Laboratory Adverse Experiences (LAEs) Without LAEs	30 participants	31 participants	33 participants	30 participants	35 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 48 Weeks

Population: The analysis population is based upon the All Patients As Treated (APaT) approach.

Serious LAEs are any LAEs occurring at any dose that; Results in death; or Is life threatening; or Results in a persistent or significant disability/incapacity; or Results in or prolongs an existing inpatient hospitalization; or Is a congenital anomaly/birth defect; or Is a cancer; or Is an overdose

Outcome measures

Outcome measures
Measure	EFV Combo Therapy n=38 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=39 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=40 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. n=41 Participants Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. n=40 Participants Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Patients With Serious LAEs With serious LAEs	0 participants	0 participants	0 participants	0 participants	0 participants
Number of Patients With Serious LAEs Without serious LAEs	38 participants	39 participants	40 participants	41 participants	40 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 48 Weeks

Population: The analysis population is based upon the All Patients As Treated (APaT) approach.

Patients with drug-related (as assessed by an investigator who is a qualified physician according to his/her best clinical judgment) LAEs

Outcome measures

Outcome measures
Measure	EFV Combo Therapy n=38 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=39 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=40 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. n=41 Participants Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. n=40 Participants Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Patients With Drug-related LAEs With drug-related LAEs	3 participants	3 participants	6 participants	4 participants	2 participants
Number of Patients With Drug-related LAEs Without drug-related LAEs	35 participants	36 participants	34 participants	37 participants	38 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 48 Weeks

Population: The analysis population is based upon the All Patients As Treated (APaT) approach.

Outcome measures

Outcome measures
Measure	EFV Combo Therapy n=38 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=39 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=40 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. n=41 Participants Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. n=40 Participants Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Patients With Serious Drug-related LAEs With serious LAEs	0 participants	0 participants	0 participants	0 participants	0 participants
Number of Patients With Serious Drug-related LAEs Without serious LAEs	38 participants	39 participants	40 participants	41 participants	40 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 48 Weeks

Population: The analysis population is based upon the All Patients As Treated (APaT) approach.

Outcome measures

Outcome measures
Measure	EFV Combo Therapy n=38 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 b.i.d. n=39 Participants Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	EFV Combo Therapy n=40 Participants EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.	MK0518 400 mg b.i.d. n=41 Participants Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine	MK0518 600 mg b.i.d. n=40 Participants Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
Number of Patients That Discontinued With LAEs Discontinued With LAEs	0 participants	0 participants	0 participants	0 participants	1 participants
Number of Patients That Discontinued With LAEs Did Not Discontinue With LAEs	38 participants	39 participants	40 participants	41 participants	39 participants

Adverse Events

MK-0518 b.i.d.

Serious events: 25 serious events

Other events: 147 other events

Deaths: 0 deaths

Efavirenz

Serious events: 4 serious events

Other events: 35 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MK-0518 b.i.d. n=160 participants at risk Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	Efavirenz n=38 participants at risk EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.
Eye disorders Retinal vein occlusion	0.62% 1/160 • Number of events 1	0.00% 0/38
Gastrointestinal disorders Abdominal pain	0.00% 0/160	2.6% 1/38 • Number of events 1
Gastrointestinal disorders Peptic ulcer	0.62% 1/160 • Number of events 1	0.00% 0/38
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.62% 1/160 • Number of events 1	0.00% 0/38
General disorders Chest pain	0.62% 1/160 • Number of events 1	0.00% 0/38
Infections and infestations Amoebic dysentery	0.62% 1/160 • Number of events 1	0.00% 0/38
Infections and infestations Bronchitis	0.62% 1/160 • Number of events 1	0.00% 0/38
Infections and infestations Cellulitis	0.62% 1/160 • Number of events 1	0.00% 0/38
Infections and infestations Dengue fever	0.62% 1/160 • Number of events 1	0.00% 0/38
Infections and infestations Gastroenteritis bacterial	0.62% 1/160 • Number of events 1	0.00% 0/38
Infections and infestations Pharyngitis	0.00% 0/160	2.6% 1/38 • Number of events 1
Infections and infestations Pneumonia	0.62% 1/160 • Number of events 1	0.00% 0/38
Infections and infestations Pyelonephritis	0.62% 1/160 • Number of events 1	0.00% 0/38
Injury, poisoning and procedural complications Ankle fracture	0.62% 1/160 • Number of events 1	0.00% 0/38
Injury, poisoning and procedural complications Burns second degree	0.62% 1/160 • Number of events 1	0.00% 0/38
Injury, poisoning and procedural complications Burns third degree	0.62% 1/160 • Number of events 1	0.00% 0/38
Injury, poisoning and procedural complications Intentional overdose	1.9% 3/160 • Number of events 3	0.00% 0/38
Injury, poisoning and procedural complications Overdose	0.62% 1/160 • Number of events 1	0.00% 0/38
Injury, poisoning and procedural complications Post procedural complication	0.62% 1/160 • Number of events 1	0.00% 0/38
Injury, poisoning and procedural complications Tibia fracture	0.62% 1/160 • Number of events 1	0.00% 0/38
Injury, poisoning and procedural complications Ulna fracture	0.62% 1/160 • Number of events 1	0.00% 0/38
Musculoskeletal and connective tissue disorders Back pain	0.62% 1/160 • Number of events 1	0.00% 0/38
Musculoskeletal and connective tissue disorders Muscular weakness	0.62% 1/160 • Number of events 1	0.00% 0/38
Musculoskeletal and connective tissue disorders Osteonecrosis	0.62% 1/160 • Number of events 2	0.00% 0/38
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.62% 1/160 • Number of events 1	0.00% 0/38
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.62% 1/160 • Number of events 1	0.00% 0/38
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal carcinoma	0.00% 0/160	2.6% 1/38 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Kaposi's sarcoma AIDS related	1.2% 2/160 • Number of events 2	0.00% 0/38
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer metastatic	0.62% 1/160 • Number of events 1	0.00% 0/38
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.62% 1/160 • Number of events 1	2.6% 1/38 • Number of events 1
Nervous system disorders Cervicobrachial syndrome	0.00% 0/160	2.6% 1/38 • Number of events 2
Nervous system disorders Dizziness	0.00% 0/160	2.6% 1/38 • Number of events 1
Psychiatric disorders Alcohol abuse	0.62% 1/160 • Number of events 1	0.00% 0/38
Psychiatric disorders Depression	0.62% 1/160 • Number of events 1	0.00% 0/38
Psychiatric disorders Psychotic disorder	0.62% 1/160 • Number of events 1	0.00% 0/38
Psychiatric disorders Suicidal ideation	1.2% 2/160 • Number of events 2	0.00% 0/38
Psychiatric disorders Suicide attempt	1.2% 2/160 • Number of events 2	0.00% 0/38
Renal and urinary disorders Calculus urinary	0.62% 1/160 • Number of events 2	0.00% 0/38
Reproductive system and breast disorders Uterine haemorrhage	0.00% 0/160	2.6% 1/38 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.62% 1/160 • Number of events 1	0.00% 0/38
Skin and subcutaneous tissue disorders Hypoaesthesia facial	0.62% 1/160 • Number of events 1	0.00% 0/38
Vascular disorders Deep vein thrombosis	0.00% 0/160	2.6% 1/38 • Number of events 1

Other adverse events

Other adverse events
Measure	MK-0518 b.i.d. n=160 participants at risk Cohort I-Monotherapy Phase (10 Days) MK0518 100, 200, 400, or 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 100, 200, 400, or 600 mg + tenofovir + lamivudine	Efavirenz n=38 participants at risk EFV Combo Therapy Phase - Cohort II efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine This arm included participants from Cohort I who were randomized to placebo.
Blood and lymphatic system disorders Anaemia	0.62% 1/160 • Number of events 1	5.3% 2/38 • Number of events 2
Blood and lymphatic system disorders Lymphadenopathy	1.2% 2/160 • Number of events 3	5.3% 2/38 • Number of events 2
Eye disorders Conjunctivitis	4.4% 7/160 • Number of events 8	7.9% 3/38 • Number of events 3
Gastrointestinal disorders Abdominal pain	6.2% 10/160 • Number of events 11	5.3% 2/38 • Number of events 2
Gastrointestinal disorders Anorectal discomfort	0.00% 0/160	5.3% 2/38 • Number of events 2
Gastrointestinal disorders Constipation	2.5% 4/160 • Number of events 5	5.3% 2/38 • Number of events 2
Gastrointestinal disorders Diarrhoea	26.2% 42/160 • Number of events 67	26.3% 10/38 • Number of events 19
Gastrointestinal disorders Flatulence	6.9% 11/160 • Number of events 12	2.6% 1/38 • Number of events 1
Gastrointestinal disorders Gastritis	4.4% 7/160 • Number of events 8	10.5% 4/38 • Number of events 4
Gastrointestinal disorders Nausea	21.9% 35/160 • Number of events 40	18.4% 7/38 • Number of events 8
Gastrointestinal disorders Toothache	5.6% 9/160 • Number of events 10	2.6% 1/38 • Number of events 1
Gastrointestinal disorders Vomiting	8.1% 13/160 • Number of events 20	18.4% 7/38 • Number of events 9
General disorders Fatigue	8.1% 13/160 • Number of events 17	7.9% 3/38 • Number of events 4
General disorders Influenza like illness	6.9% 11/160 • Number of events 14	7.9% 3/38 • Number of events 3
General disorders Malaise	3.1% 5/160 • Number of events 10	7.9% 3/38 • Number of events 6
General disorders Oedema peripheral	1.9% 3/160 • Number of events 3	5.3% 2/38 • Number of events 2
General disorders Pyrexia	7.5% 12/160 • Number of events 16	5.3% 2/38 • Number of events 2
Infections and infestations Anogenital warts	2.5% 4/160 • Number of events 4	7.9% 3/38 • Number of events 4
Infections and infestations Body tinea	3.8% 6/160 • Number of events 7	7.9% 3/38 • Number of events 5
Infections and infestations Bronchitis	14.4% 23/160 • Number of events 31	5.3% 2/38 • Number of events 3
Infections and infestations Gastroenteritis	4.4% 7/160 • Number of events 10	5.3% 2/38 • Number of events 7
Infections and infestations Herpes simplex	6.2% 10/160 • Number of events 12	0.00% 0/38
Infections and infestations Herpes zoster	5.6% 9/160 • Number of events 9	15.8% 6/38 • Number of events 6
Infections and infestations Influenza	1.9% 3/160 • Number of events 3	10.5% 4/38 • Number of events 6
Infections and infestations Localised infection	0.62% 1/160 • Number of events 1	5.3% 2/38 • Number of events 2
Infections and infestations Nasopharyngitis	18.8% 30/160 • Number of events 57	21.1% 8/38 • Number of events 13
Infections and infestations Onychomycosis	3.1% 5/160 • Number of events 7	10.5% 4/38 • Number of events 5
Infections and infestations Pharyngitis	11.9% 19/160 • Number of events 21	5.3% 2/38 • Number of events 3
Infections and infestations Sinusitis	10.0% 16/160 • Number of events 19	5.3% 2/38 • Number of events 5
Infections and infestations Syphilis	5.6% 9/160 • Number of events 10	7.9% 3/38 • Number of events 3
Infections and infestations Upper respiratory tract infection	24.4% 39/160 • Number of events 74	26.3% 10/38 • Number of events 13
Injury, poisoning and procedural complications Joint sprain	1.9% 3/160 • Number of events 3	5.3% 2/38 • Number of events 2
Investigations Alanine aminotransferase increased	8.1% 13/160 • Number of events 29	10.5% 4/38 • Number of events 10
Investigations Aspartate aminotransferase increased	8.8% 14/160 • Number of events 19	15.8% 6/38 • Number of events 7
Investigations Blood creatine phosphokinase increased	5.0% 8/160 • Number of events 12	10.5% 4/38 • Number of events 5
Investigations Blood triglycerides increased	2.5% 4/160 • Number of events 8	5.3% 2/38 • Number of events 5
Investigations Weight decreased	1.9% 3/160 • Number of events 3	5.3% 2/38 • Number of events 2
Metabolism and nutrition disorders Overweight	5.6% 9/160 • Number of events 10	2.6% 1/38 • Number of events 1
Musculoskeletal and connective tissue disorders Arthralgia	8.8% 14/160 • Number of events 17	2.6% 1/38 • Number of events 1
Musculoskeletal and connective tissue disorders Back pain	13.8% 22/160 • Number of events 23	5.3% 2/38 • Number of events 2
Musculoskeletal and connective tissue disorders Myalgia	4.4% 7/160 • Number of events 7	7.9% 3/38 • Number of events 3
Musculoskeletal and connective tissue disorders Pain in extremity	5.0% 8/160 • Number of events 10	7.9% 3/38 • Number of events 4
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	5.0% 8/160 • Number of events 9	5.3% 2/38 • Number of events 3
Nervous system disorders Disturbance in attention	2.5% 4/160 • Number of events 4	5.3% 2/38 • Number of events 2
Nervous system disorders Dizziness	18.1% 29/160 • Number of events 33	34.2% 13/38 • Number of events 15
Nervous system disorders Headache	20.6% 33/160 • Number of events 56	42.1% 16/38 • Number of events 31
Nervous system disorders Lethargy	1.9% 3/160 • Number of events 3	5.3% 2/38 • Number of events 2
Psychiatric disorders Abnormal dreams	8.1% 13/160 • Number of events 13	21.1% 8/38 • Number of events 9
Psychiatric disorders Anxiety	6.2% 10/160 • Number of events 11	10.5% 4/38 • Number of events 4
Psychiatric disorders Depression	12.5% 20/160 • Number of events 23	13.2% 5/38 • Number of events 6
Psychiatric disorders Insomnia	15.6% 25/160 • Number of events 29	13.2% 5/38 • Number of events 5
Psychiatric disorders Nightmare	0.62% 1/160 • Number of events 1	10.5% 4/38 • Number of events 4
Respiratory, thoracic and mediastinal disorders Asthma	1.9% 3/160 • Number of events 6	5.3% 2/38 • Number of events 2
Respiratory, thoracic and mediastinal disorders Cough	5.0% 8/160 • Number of events 10	5.3% 2/38 • Number of events 2
Respiratory, thoracic and mediastinal disorders Nasal congestion	1.9% 3/160 • Number of events 3	5.3% 2/38 • Number of events 2
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.4% 7/160 • Number of events 7	7.9% 3/38 • Number of events 3
Skin and subcutaneous tissue disorders Dermatitis	5.6% 9/160 • Number of events 9	5.3% 2/38 • Number of events 3
Skin and subcutaneous tissue disorders Pruritus	7.5% 12/160 • Number of events 14	5.3% 2/38 • Number of events 3
Skin and subcutaneous tissue disorders Rash	6.9% 11/160 • Number of events 14	5.3% 2/38 • Number of events 2
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/160	7.9% 3/38 • Number of events 3
Skin and subcutaneous tissue disorders Seborrhoeic dermatitis	1.9% 3/160 • Number of events 6	5.3% 2/38 • Number of events 2
Skin and subcutaneous tissue disorders Skin lesion	5.0% 8/160 • Number of events 11	7.9% 3/38 • Number of events 3
Skin and subcutaneous tissue disorders Urticaria	1.2% 2/160 • Number of events 2	5.3% 2/38 • Number of events 2

Additional Information

Vice President, Late Stage Development Group Leader

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER