A Phase III Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical Trial to Evaluate the Safety and Efficacy of MK-1439A Once-Daily Versus ATRIPLA™ Once-Daily in Treatment-Naïve HIV-1 Infected Subjects
Phase: PHASE3
Conditions: Human Immunodeficiency Virus (HIV)
Sponsor: Merck Sharp & Dohme LLC

Official Protocol Title: 
NCT number: 
NCT02403674  
Document Date: 
02-Nov-2022
A Phase III Multicenter, Double-Blind, Randomized, Active 
Comparator-Controlled Clinical Trial to Evaluate the Safety and 
Efficacy of MK-1439A Once-Daily Versus ATRIPLA™
Once-Daily in Treatment-Naïve HIV-1 Infected Subjects

Product:  MK-1439A 
1
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
THIS PROTOCOL AMENDMENT AND ALL OF THE INFORMATION RELATING 
TO IT ARE CONFIDENTIAL AND PROPRIETARY PROPERTY OF MERCK 
SHARP & DOHME LLC, RAHWAY, NJ, USA (MSD).
This protocol amendment is applicable only to Colombia, Guatemala, Honduras, 
Mexico, Peru, Australia, New Zealand, Russia, South Africa, Thailand, Portugal, Spain.
SPONSOR:
Merck Sharp & Dohme LLC
(hereafter referred to as the Sponsor or MSD)
126 East Lincoln Avenue
P.O. Box 2000
Rahway, NJ 07065 USA
Protocol-specific Sponsor Contact information can be found in the Investigator Trial File
Binder (or equivalent).
TITLE:
A Phase III Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical 
Trial to Evaluate the Safety and Efficacy of MK-1439A Once-Daily Versus ATRIPLA™ 
Once-Daily in Treatment-Naïve HIV-1 Infected Subjects
IND NUMBER: 124997
EudraCT NUMBER:  2014-003382-17
08K3V5

Product:  MK-1439A 
2
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
TABLE OF CONTENTS
DOCUMENT HISTORY ..................................................................................................... 10
SUMMARY OF CHANGES................................................................................................ 15
TRIAL SUMMARY.................................................................................................. 16
TRIAL DESIGN........................................................................................................ 17
Trial Design ........................................................................................................... 17
Trial Diagram........................................................................................................ 19
OBJECTIVE(S) & HYPOTHESIS(ES).................................................................. 21
Primary Objective(s) & Hypothesis(es).............................................................. 21
Base Study .......................................................................................................... 21
Secondary Objective(s) & Hypothesis(es)........................................................... 22
Base Study .......................................................................................................... 22
Exploratory Objectives......................................................................................... 24
Base Study .......................................................................................................... 24
Study Extension 1 ............................................................................................... 24
BACKGROUND & RATIONALE.......................................................................... 24
Background ........................................................................................................... 24
Pharmaceutical and Therapeutic Background .................................................... 24
Rationale................................................................................................................ 26
Rationale for the Trial and Selected Subject Population .................................... 26
Rationale for Dose Selection/Regimen............................................................... 26
Rationale for Endpoints ...................................................................................... 28
Efficacy Endpoints....................................................................................... 28
Safety Endpoints.......................................................................................... 29
Pharmacokinetic Endpoints ......................................................................... 30
Patient-Reported Outcome Endpoints.......................................................... 30
Planned Exploratory Biomarker .................................................................. 30
Future Biomedical Research........................................................................ 31
Rationale for Study Extensions........................................................................... 31
Benefit/Risk ........................................................................................................... 31
08K3V5

Product:  MK-1439A 
3
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
METHODOLOGY ................................................................................................... 32
Entry Criteria........................................................................................................ 32
Diagnosis/Condition for Entry into the Trial...................................................... 32
Subject Inclusion Criteria.................................................................................... 32
Subject Exclusion Criteria .................................................................................. 36
Trial Treatment(s) ................................................................................................ 37
Dose Selection .................................................................................................... 38
Dose Selection (Preparation) ....................................................................... 38
Dose Modification/Interruption (Base Study or the Study Extensions) ...... 39
Timing of Dose Administration.......................................................................... 39
Base Study ................................................................................................... 39
Study Extensions.......................................................................................... 39
Trial Blinding/Masking....................................................................................... 40
Randomization or Treatment Allocation............................................................ 40
Stratification.......................................................................................................... 40
Concomitant Medications/Vaccinations (Allowed & Prohibited).................... 41
Rescue Medications & Supportive Care............................................................. 44
Diet/Activity/Other Considerations..................................................................... 44
Subject Withdrawal/Discontinuation Criteria................................................... 44
Subject Replacement Strategy............................................................................. 46
Beginning and End of the Trial ........................................................................... 46
Clinical Criteria for Early Trial Termination ................................................... 47
TRIAL FLOW CHART ........................................................................................... 48
TRIAL PROCEDURES ........................................................................................... 55
Trial Procedures ................................................................................................... 55
Administrative Procedures.................................................................................. 55
Informed Consent......................................................................................... 55
General Informed Consent.................................................................... 55
Consent and Collection of Specimens for Future Biomedical 
Research................................................................................................ 56
Inclusion/Exclusion Criteria ........................................................................ 56
Subject Identification Card .......................................................................... 56
08K3V5

Product:  MK-1439A 
4
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Medical History ........................................................................................... 56
Prior and Concomitant Medications Review............................................... 56
Prior Medications.................................................................................. 56
Concomitant Medications..................................................................... 57
Assignment of Screening Number............................................................... 57
Assignment of Randomization Number....................................................... 57
Trial Compliance (Medication/Diet/Activity/Other)................................... 57
Patient-Reported Outcomes ......................................................................... 58
Clinical Procedures/Assessments........................................................................ 58
Physical Examination................................................................................... 58
Height Assessment....................................................................................... 59
Vital Signs and Weight................................................................................ 59
12-Lead ECG (performed locally)............................................................... 59
Adverse Events ............................................................................................ 60
Toxicity Management .................................................................................. 60
Birth Control Confirmation.......................................................................... 60
Laboratory Procedures/Assessments .................................................................. 61
Serum /Urine Pregnancy Test...................................................................... 61
Laboratory Safety Evaluations (Hematology, Chemistry and Others)........ 61
HIV/ Hepatitis Screening............................................................................. 62
Virology Test ............................................................................................... 62
Viral Resistance Testing .............................................................................. 62
CD4 Cell Counts.......................................................................................... 63
Pharmacokinetic/Pharmacodynamic Evaluations........................................ 63
Future Biomedical Research........................................................................ 64
Other Procedures................................................................................................. 64
Withdrawal/Discontinuation........................................................................ 64
Withdrawal From Future Biomedical Research ................................... 64
Blinding/Unblinding .................................................................................... 65
Calibration of Equipment............................................................................. 66
Visit Requirements.............................................................................................. 66
Screening...................................................................................................... 66
08K3V5

Product:  MK-1439A 
5
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Treatment Visits in Base Study (Visit 2 to 12)............................................ 67
Treatment Visits in Study Extension 1 (Visit 13 to Visit 19)...................... 69
Treatment Visits in Study Extension 2 (Visit 20 to Visit 25)...................... 69
Treatment Visits in Study Extension 3 (Visit 26 to Visit 31)...................... 70
Virologic Failure Confirmation Visit -
Base Study and Study 
Extension 1 .................................................................................................. 70
Early Discontinuation Visit - Base Study, Study Extension 1, Study 
Extension 2, and Study Extension 3 ............................................................ 71
Post-Trial (Base Study and Study Extensions)............................................ 72
Assessing and Recording Adverse Events .......................................................... 72
Definition of an Overdose for This Protocol and Reporting of Overdose to 
the Sponsor.......................................................................................................... 73
Reporting of Pregnancy and Lactation to the Sponsor ....................................... 73
Immediate Reporting of Adverse Events to the Sponsor.................................... 74
Serious Adverse Events ............................................................................... 74
Events of Clinical Interest............................................................................ 75
Evaluating Adverse Events................................................................................. 75
Sponsor Responsibility for Reporting Adverse Events ...................................... 78
TRIAL GOVERNANCE AND OVERSIGHT................................................... 78
Scientific Advisory Committee........................................................................... 78
Executive Oversight Committee......................................................................... 78
Data Monitoring Committee............................................................................... 78
STATISTICAL ANALYSIS PLAN ........................................................................ 79
STATISTICAL ANALYSIS PLAN SUMMARY.............................................. 79
Responsibility for Analyses/In-House Blinding ................................................. 82
Hypotheses/Estimation......................................................................................... 83
Analysis Endpoints ............................................................................................... 84
Efficacy /Pharmacokinetics Endpoints ............................................................... 84
Efficacy Endpoints....................................................................................... 84
Safety Endpoints ................................................................................................. 84
Analysis Populations............................................................................................. 86
Efficacy Analysis Populations ............................................................................ 86
Safety Analysis Populations ............................................................................... 86
08K3V5

Product:  MK-1439A 
6
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Statistical Methods................................................................................................ 86
Statistical Methods for Efficacy Analyses.......................................................... 87
Statistical Methods for Safety Analyses ............................................................. 91
Summaries of Baseline Characteristics, Demographics, and Other Analyses.... 94
Demographic and Baseline Characteristics ................................................. 94
Interim Analyses ................................................................................................... 94
Multiplicity ............................................................................................................ 94
SAMPLE SIZE AND POWER CALCULATIONS........................................... 95
Sample Size and Power for Efficacy Analyses................................................... 95
Sample Size and Power for Safety Analyses ...................................................... 96
Overall Power ..................................................................................................... 98
Subgroup Analyses and Effect of Baseline Factors (Base Study)..................... 99
Compliance (Medication Adherence).................................................................. 99
Extent of Exposure.............................................................................................. 100
LABELING, PACKAGING, STORAGE AND RETURN OF CLINICAL 
SUPPLIES ............................................................................................................... 100
Investigational Product ...................................................................................... 100
Packaging and Labeling Information ............................................................... 101
Clinical Supplies Disclosure............................................................................... 101
Storage and Handling Requirements................................................................ 102
Returns and Reconciliation................................................................................ 102
Standard Policies................................................................................................. 102
ADMINISTRATIVE AND REGULATORY DETAILS..................................... 103
Confidentiality..................................................................................................... 103
Confidentiality of Data ..................................................................................... 103
Confidentiality of Subject Records................................................................... 103
Confidentiality of Investigator Information...................................................... 103
Confidentiality of IRB/IEC Information........................................................... 104
Compliance with Financial Disclosure Requirements..................................... 104
Compliance with Law, Audit and Debarment ................................................. 104
Compliance with Trial Registration and Results Posting Requirements...... 106
Quality Management System............................................................................. 107
08K3V5

Product:  MK-1439A 
7
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Data Management............................................................................................... 107
Publications ......................................................................................................... 107
LIST OF REFERENCES....................................................................................... 108
APPENDICES......................................................................................................... 110
Code of Conduct for Clinical Trials.................................................................. 110
Collection and Management of Specimens for Future Biomedical 
Research............................................................................................................... 113
Understanding the Intent, Scope and Public Health Benefits of 
Exploratory Biomarker Research: A Guide for IRBs/IECs and 
Investigational Site Staff .................................................................................... 118
Approximate Blood Volumes Drawn/Collected by Trial Visit and by 
Sample Types....................................................................................................... 129
Base Study ........................................................................................................ 129
Week 100 Through Week 192 Including Post-Study 14-Day Follow-up 
(Study Extension 1)........................................................................................... 131
Plasma Assay—Sample Collection, Handling, Labeling, Storage, and 
Shipment.............................................................................................................. 132
List of Preferred Neuropsychiatric Adverse Events........................................ 133
List of Abbreviations and Acronyms ................................................................ 137
DIVISION OF AIDS TABLE FOR GRADING THE SEVERITY OF 
ADULT AND PEDIATRIC ADVERSE EVENTS VERSION 1.0, 
DECEMBER, 2004; CLARIFICATION AUGUST 2009 ............................... 139
SIGNATURES......................................................................................................... 146
Sponsor's Representative ................................................................................... 146
Investigator.......................................................................................................... 146
08K3V5

Product:  MK-1439A 
8
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
LIST OF TABLES
Table 1
Trial Treatment During the Base Study................................................................ 38
Table 2
Trial Treatment During the Study Extensions ...................................................... 38
Table 3
Stratification.......................................................................................................... 40
Table 4
Laboratory Tests ................................................................................................... 61
Table 5
Pharmacokinetic Sampling Timepoints................................................................ 64
Table 6
Study Drug Bottle (A and B) Components........................................................... 68
Table 7
Evaluating Adverse Events................................................................................... 76
Table 8
Definition of Study Timepoint.............................................................................. 87
Table 9
Summary of the Two Approaches to Handle Missing Values.............................. 89
Table 10
Analysis Strategy for Key Efficacy Variables...................................................... 91
Table 11
Analysis Strategy for Safety Parameters............................................................... 93
Table 12
Power (%) Under Various Assumptions (With 340 Subjects Randomized 
in Each Treatment Group) .................................................................................... 95
Table 13
Observed Percentage in MK-1439A Necessary to Demonstrate Superiority 
versus ATRIPLA™.............................................................................................. 96
Table 14
Estimate of Incidence of AEs and 95% Upper Confidence Bound Based 
on Hypothetical Numbers of Subjects with AEs Among 340 Subjects 
Randomized in Each Treatment Group................................................................. 97
Table 15
Differences in Incidences of AEs (MK-1439A q.d. minus ATRIPLA™ 
q.d.) That Can Be Ruled Out With 340 Subjects in Each Treatment Group........ 98
Table 16
Product Descriptions:  Base Study and Study Extensions.................................. 101
08K3V5

Product:  MK-1439A 
9
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
LIST OF FIGURES
Figure 1
Trial Diagram Base Study..................................................................................... 20
Figure 2
Trial Diagram Study Extensions 1, 2, and 3......................................................... 21
08K3V5

Product:  MK-1439A 
10
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
DOCUMENT HISTORY
Document
Date of Issue
Overall Rationale
Amendment 09
02-NOV-2022
This is a country-specific amendment for Colombia, Guatemala, 
Honduras, Mexico, Peru, Australia, New Zealand, Russia, South Africa, 
Thailand, Portugal, and Spain to inform regarding the Sponsor’s name and 
address change and updates that were made to the Code of Conduct in the 
previous amendment.
Note: Amendment 09 supersedes Amendment 08.
Amendment 08
23-AUG-2022
Merck Sharp & Dohme Corp. underwent an entity name and address 
change to Merck Sharp & Dohme LLC, Rahway, NJ, USA. This 
conversion resulted only in an entity name change and update to the 
address.
Note: Amendment 08 was not released to sites.
Amendment 07
(country-specific to Australia, Russia, 
South Africa, New Zealand, Israel, 
Columbia, Thailand, Peru, Honduras, 
Guatemala)
02-APR-2020

Study extension 3 was added to (1) provide continued access to MK-
1439A for participants who are deriving benefit from MK-1439A 
until the drug is available locally in countries participating in the trial 
or for an additional 2 years (whichever comes first), and (2) collect 
key safety information from participants who continue on MK-
1439A in this study extension.
08K3V5

Product:  MK-1439A 
11
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Document
Date of Issue
Overall Rationale
Amendment 06
(country-specific to United States and 
Puerto Rico)
20-NOV-2018

Added 32 weeks past the Week 192 visit so that a subject may 
continue to receive MK-1439A during this time or until commercial 
MK-1439A is locally available (whichever occurs first).

Added 2 treatment visits in the Study Extension and updated blood 
volumes.

Replaced the term HAART with cART.

Added oxcarbazepine and rifapentine as prohibited 
medications/therapy due to interaction with MK-1439.

Deleted herbal remedies from the list of prohibited medications.

Clarified that evaluation of IRIS causality applies only during the 
base study.

Clarified emergency unblinding procedures.

Changed visit windows to correctly capture data pertinent to the 
specific milestones rather than specific study days.
08K3V5

Product:  MK-1439A 
12
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Document
Date of Issue
Overall Rationale
Amendment 05
(applicable globally except for United 
States including Puerto Rico)
26-NOV-2018

Added open-label study extension 2 to provide continued access to 
MK-1439A until the drug is available locally in countries 
participating in the trial or for an additional 2 years (whichever 
comes first).

Replaced the term HAART with cART.

Added oxcarbazepine and rifapentine as prohibited 
medications/therapy due to interaction with MK-1439.

Deleted herbal remedies from the list of prohibited medications.

Clarified that evaluation of IRIS causality applies only during the 
base study.
Amendment 04
(global)
08-NOV-2016

Added open-label study extension 1 for 2 years to collect long-term 
efficacy and safety data.

Specified that concomitant medications prohibited due to interactions 
with EFV/FTC/TDF in the base study were allowed in the study 
extension.

Clarified visits during which plasma samples were tested for 
resistance.

Removed rosuvastatin as prohibited medication due to an interaction 
with DOR.
08K3V5

Product:  MK-1439A 
13
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Document
Date of Issue
Overall Rationale
Amendment 03
(global)
21-JUL-2015

Added text to explain the rationale for the selected doses of the 
lamivudine and TDF components of MK-1439A.

Added text to disallow concomitant use of interferon given that the 
occurrence of neuropsychiatric AEs associated with interferon use 
could confound the results of the trial.

Added text to ensure consistency with the EFV/FTC/TDF, 3TC, and 
TDF prescribing information.

Clarified that sites would receive the calculated creatinine clearance
in the laboratory reports from the central laboratory.
Amendment 02
(global)
21-MAY-2015

Changed the pharmacokinetics/pharmacodynamics evaluation from 
an exploratory objective to a secondary objective.

Added a baseline hemoglobin threshold (≥9.0 g/dL if female; ≥10.0 
g/dL if male) to the Inclusion Criteria (#5).

Added Exclusion Criterion #10 to exclude subjects with severe 
hepatic impairment.

Updated list of medications prohibited during the use of ATRIPLA
(EFV/FTC/TDF).

Specified additional visits for the collection of plasma for potential 
viral resistance testing.
08K3V5

Product:  MK-1439A 
14
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Document
Date of Issue
Overall Rationale
Amendment 01
(global)
18-MAR-2015

Added instructions to the Inclusion Criteria directing investigators to 
provide appropriate guidance to subjects about the use of 
contraceptives after study completion.

Modified Exclusion Criterion #4 to include the mutations D67N and 
K70R to those mutations indicative of resistance to emtricitabine, 
lamivudine, and tenofovir
Original protocol
14-JAN-2015

Not applicable.
08K3V5

Product:  MK-1439A 
15
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
SUMMARY OF CHANGES
PRIMARY REASON(S) FOR THIS AMENDMENT:
Section 
Number (s)
Section Title(s)
Description of Change (s)
Rationale
Title Page 
Colombia, Guatemala, Honduras, 
Mexico, Peru, Australia, New Zealand, 
Russia, South Africa, Thailand, 
Portugal, and Spain were added to the 
Title Page.
This is a country-specific amendment for 
Colombia, Guatemala, Honduras, Mexico, 
Peru, Australia, New Zealand, Russia, 
South Africa, Thailand, Portugal, and
Spain to inform regarding the Sponsor’s
name and address change and updates that 
were made to the Code of Conduct in the 
previous amendment. 
Note: Amendment 09 supersedes 
Amendment 08.
The following changes were made in Amendment 08; however, Amendment 08 was not released to sites. These changes are 
summarized here for clarity and implementation in the current country-specific amendment.
12.1
Throughout
Title Page
Code of Conduct for 
Clinical Trials
Sponsor entity name and address
change.
Merck Sharp & Dohme Corp. underwent 
an entity name and address change to 
Merck Sharp & Dohme LLC, Rahway, NJ, 
USA. This conversion resulted only in an 
entity name change and update to the 
address.
12.1
Code of Conduct for 
Clinical Trials 
The code of conduct was updated in 
Amendment 08.
To align with the current standard text for 
the code of conduct.
ADDITIONAL CHANGE(S) FOR THIS AMENDMENT:
No additional changes.
08K3V5

Product:  MK-1439A 
16
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
TRIAL SUMMARY
Abbreviated Title
MK-1439A versus ATRIPLA™ in treatment-naïve HIV-infected subjects.
Trial Phase
Phase 3
Clinical Indication
Treatment of HIV-1 infection   
Trial Type
Interventional
Type of control
Active control
Route of administration
Oral
Trial Blinding
Double-blind for the base study then open-label for the study extensions.
Treatment Groups
Base Study (double-blind)
Group 1: MK-1439A q.d. 
MK-1439A is a single-tablet, fixed-dose regimen (FDR) containing MK-
1439A 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 
300 mg.
Group 2: ATRIPLA™q.d. 
ATRIPLA™is a single-tablet FDR containing efavirenz 600 mg + 
emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (which is 
equivalent to 245 mg of tenofovir disoproxil).
Study Extensions (open-label)
All subjects participating in the extensions: MK-1439A q.d.
Number of trial subjects
Approximately 680 subjects will be enrolled.
Estimated duration of trial
The Sponsor estimates that the trial will require approximately 9 years from 
the time the first subject signs the informed consent until the last subject’s 
last study-related phone call or visit.
Duration of Participation
The study consists of a screening phase of up to 45 days (~6.5 weeks) 
followed by a 96-week double-blind base study, 3 open-label study 
extensions (study extensions 1, 2, and 3), and a 14-day follow-up period.  
The treatment duration of study extension 1 is 96 weeks; and the treatment
duration of study extensions 2 and 3 is up to 96 weeks for each, depending 
on when MK-1439A becomes commercially available once approved in the 
local country (whichever comes first).
The approximate cumulative durations of participation in the trial (from 
informed consent through follow-up) are 104 weeks for subjects who 
complete the base study; 200 weeks for subjects who complete the base 
study and study extension 1; up to 296 weeks for subjects who complete the 
base study and study extensions 1 and 2; and up to 392 weeks for subjects 
who complete the base study and study extensions 1, 2, and 3.
Randomization Ratio
1:1 with ~340 on MK-1439A and ~340 on ATRIPLA™
A list of abbreviations used in this document can be found in Section 12.7.
08K3V5

Product:  MK-1439A 
17
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
TRIAL DESIGN
Trial Design
This is a multicenter, double-blind (with in-house blinding), randomized, active-controlled 
trial to evaluate the safety and efficacy of MK-1439A once-daily (q.d.) compared with 
ATRIPLA™ q.d. in antiretroviral treatment-naïve subjects with human immunodeficiency 
virus type 1 (HIV-1) infection.
MK-1439A is a single tablet FDR that combines MK-1439, an NNRTI, with 3TC and TDF, 2 
approved and commercially available N(t)RTIs. As of the date of issuance of this protocol
amendment, MK-1439A has been approved in multiple markets including the US, EU, 
Canada, Switzerland and Australia for the treatment of HIV-1 infection in adult patients.
A single tablet of MK-1439A contains a full daily HIV treatment regimen of MK-1439 100 
mg + lamivudine 300 mg + TDF 300 mg.  ATRIPLA™ is a single-tablet FDR that combines 
an approved and commercially available NNRTI, efavirenz, and 2 approved and 
commercially available NRTIs, FTC and TDF.  A single tablet of ATRIPLA™contains a 
full daily HIV treatment regimen of efavirenz 600 mg + FTC 200 mg + TDF 300 mg (which 
is equivalent to 245 mg of tenofovir disoproxil).  
The study consists of a screening period of approximately 6.5 weeks, a 96-week blinded base 
study of MK-1439A compared with ATRIPLA™ followed by 3 consecutive open-label 
study extensions (study extensions 1, 2, and 3), and a 14-day post-study follow-up visit after 
the last treatment visit. The treatment duration of study extension 1 is 96 weeks; and the 
treatment duration of study extension 2 and study extension 3 is each up to 96 weeks, 
depending on when MK-1439A becomes commercially available once approved in the local 
country (whichever comes first).
The study is to be conducted in conformance with Good Clinical Practice.
Prior to enrolling in the base study and each of the study extensions, the subject must meet 
eligibility criteria (see Section 5.1.2) and provide consent. 
Further detail for the base study and the 3 study extensions is provided below.
Base Study
Approximately 680 subjects will be stratified by screening HIV-1 ribonucleic acid
(≤or >100,000 copies/mL) and Hepatitis B and/or C co-infection status (yes/no) and 
randomized within strata in a 1:1 ratio to receive either MK-1439A or ATRIPLA™.  The 
duration of treatment for a given subject is 96 weeks in the base study. The primary efficacy 
endpoint is the proportion of subjects achieving HIV-1 RNA <50 copies/mL (by the Abbott 
RealTime HIV-1 Assay) at Week 48.  The primary safety endpoint is the proportion of 
subjects with certain neuropsychiatric adverse events by Week 48.  
08K3V5

Product:  MK-1439A 
18
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
The safety of the subjects in this trial will be monitored during the base study by an eDMC 
which will provide ongoing review of the safety data with suggested periodic reviews to 
occur approximately every 6 months.  The eDMC will recommend steps to ensure the safety 
of study participants and the integrity of the trial. To guarantee the unrestricted performance 
of its task, the eDMC will receive study data from the unblinded statistician.  Details 
regarding the eDMC will be described in a charter document. 
Blood samples will be collected to support the evaluation of MK-1439 population PK from 
all subjects at Day 1 and Weeks 4, 8, 24 and 48. 
Subjects will complete a WPAI at Day 1, and Weeks 4, 8, and 48 (or the early 
discontinuation visit).  This patient-reported outcome questionnaire is designed to assess the 
quantitative impact of health conditions on loss of time and impaired productivity for 
functional activities such as work-for-pay, school work, and work around the house.
All subjects entering the study extensions will receive open-label treatment with MK-1439A
(100 mg q.d.).
Treatment group assigned during the base study will not be unblinded when a subject enters 
study extension 1; unblinding will occur after all subjects have completed the base study and 
database lock has been achieved for the base study.
Study Extension 1
At Study Week 96, eligibility for enrollment into study extension 1 will be determined, thus 
continuing study treatment for approximately 96 weeks beyond the base study for subjects 
who meet eligibility criteria. The total duration of treatment for subjects who continue into 
study extension 1 is 192 weeks (approximately 4 years). 
During study extension 1, subjects will continue to be monitored for safety and maintenance 
of virologic suppression.  Long-term safety and efficacy data will be collected during study 
extension 1 and summarized descriptively. 
Study Extension 2
At Study Week 192, eligibility for enrollment into study extension 2 will be determined. 
Subjects who meet eligibility criteria and continue into study extension 2 may continue to 
receive treatment with MK-1439A until it is commercially available once approved in the 
local country OR for an additional 96 weeks beyond study extension 1 (whichever comes 
first).  The total duration of treatment for subjects who continue into study extension 2 is up 
to 288 weeks (up to approximately 2 years beyond extension 1, depending on when MK-
1439A is commercially available once approved in the local country) (a total of 
approximately 5.5 years).  
During study extension 2, pregnancy for female subjects and SAEs for all subjects will be 
monitored and collected. Efficacy data will not be collected for study extension 2. 
08K3V5

Product:  MK-1439A 
19
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Study Extension 3
At Study Week 288, eligibility for enrollment into study extension 3 will be determined. 
Subjects who meet eligibility criteria and continue into study extension 3 may continue to 
receive treatment with MK-1439A until it is commercially available once approved in the 
local country OR for an additional 96 weeks beyond study extension 2 (whichever comes 
first). The total duration of treatment for subjects who continue into study extension 3 is 
384 weeks (up to approximately 4 years beyond extension 1, depending on when MK-1439A 
is commercially available once approved in the local country) (a total of approximately 
7.5 years).  
During study extension 3, pregnancy for female subjects and SAEs for all subjects will be 
monitored and collected. Efficacy data will not be collected for study extension 3. 
Viral Resistance Testing 
Subjects who meet virologic failure criteria during the base study and study extension 1 (see 
Section 4.2.3.1) will return to the site for repeat viral RNA testing between one week and 4 
weeks (≥1 and ≤4 weeks) later (at a virologic failure confirmation visit). If virologic failure 
is confirmed and the viral load meets the criteria for resistance testing (>400 copies/mL), 
viral resistance testing will be performed. For subjects in the base study with confirmed 
virologic failures, the plasma sample collected for resistance testing from the virologic 
failure visit and the confirmation visit, will be sent for resistance testing provided the viral 
load meets the criteria for resistance testing. 
For subjects in study extension 1 with confirmed virologic failure, the plasma sample from 
the virologic failure confirmation visit only will be sent for resistance testing provided the 
viral load meets the criteria for resistance testing.
Plasma samples for resistance testing collected at the early discontinuation visit from subjects 
who discontinue, from either the base study or study extension 1, for reasons other than 
virologic failure will be sent for testing (if viral load >400 copies/mL). Note that if a sample 
from the early discontinuation visit is not available, a sample from the most recent previous 
visit, if available, will be sent for testing in the base study (if viral load >400 copies/mL).
In addition, phenotypic testing will be conducted on screening samples for all subjects who 
discontinue for any reason or with confirmed virologic failure. See Section 7.1.3.5.
Specific procedures to be performed during the trial, as well as their prescribed times and 
associated visit windows, are outlined in the Trial Flow Chart - Section 6.0. Details of each 
procedure are provided in Section 7.0 – Trial Procedures.
Trial Diagram
The trial design is depicted in Figure 1 (base study) and Figure 2 (study extensions 1, 2, and 
3). Note that subjects who continue into the study extension(s) will have a single 14-day 
follow-up visit at the end of their last study extension only, and not in the base study.
08K3V5

Product:  MK-1439A 
20
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Figure 1
Trial Diagram Base Study
08K3V5

Product:  MK-1439A 
21
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Figure 2
Trial Diagram Study Extensions 1, 2, and 3
OBJECTIVE(S) & HYPOTHESIS(ES)
Primary Objective(s) & Hypothesis(es)
Base Study
In HIV-1 positive, treatment-naive subjects with pre-treatment HIV RNA ≥1,000 copies/mL:
1) Objective:  To evaluate the non-inferior antiretroviral activity of MK-1439A q.d. 
compared to ATRIPLA™q.d. as measured by the proportion of subjects achieving HIV-
1 RNA <50 copies/mL (by the Abbott RealTime HIV-1 Assay) at Week 48.
Hypothesis:  MK-1439A q.d. is non-inferior to ATRIPLA™ q.d. as assessed by the 
proportion of subjects with HIV-1 RNA <50 copies/mL (by the Abbott RealTime HIV-1 
Assay) at Week 48. A margin of 10 percentage points is used to define non-inferiority. 
2) Objective: To evaluate the safety and tolerability of MK-1439A q.d. compared with 
ATRIPLA™ q.d. as measured by the proportion of subjects with neuropsychiatric 
adverse events in the following categories:

Dizziness

Sleep disorders and disturbances

Altered Sensorium
08K3V5

Product:  MK-1439A 
22
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Hypothesis:  MK-1439A q.d. is superior to ATRIPLA™ q.d. as measured by the 
proportion of subjects with neuropsychiatric adverse events in the following categories 
by Week 48 (superiority will be tested within category, sequentially, in the order
indicated below):

Dizziness

Sleep disorders and disturbances

Altered Sensorium
Secondary Objective(s) & Hypothesis(es)
Base Study
In HIV-1 positive, treatment-naive subjects with pre-treatment HIV RNA ≥1,000 copies/mL:
1) Objective:  To evaluate the safety and tolerability of MK-1439A q.d. compared to 
ATRIPLA™ q.d. as assessed by review of the accumulated safety data by Week 48 and 
Week 96.
2) Objective: To evaluate the effect of MK-1439A q.d. compared to ATRIPLA™q.d. on 
fasting LDL-C as measured by the mean change from baseline at Week 48.
Hypotheses:  MK-1439A q.d. is superior to ATRIPLA™ q.d. as assessed by the mean 
change from baseline in LDL-C at Week 48. 
3) Objective: To evaluate the effect of MK-1439A q.d. compared to ATRIPLA™q.d. on 
fasting non-HDL-C as measured by the mean change from baseline at Week 48.
Hypotheses:  MK-1439A q.d. is superior to ATRIPLA™ q.d. as assessed by the mean 
change from baseline in non-HDL-C at Week 48. 
4) Objective: To evaluate the safety and tolerability of MK-1439A q.d. compared with 
ATRIPLA™ q.d. as measured by the proportion of subjects with neuropsychiatric 
adverse events in the following categories:

Depression and suicide/self-injury

Psychosis and psychotic disorders
5) Objective:  To evaluate the safety and tolerability of MK-1439A q.d. compared with 
ATRIPLA™ q.d. as measured by the proportion of subjects with at least one
neuropsychiatric adverse event across the 5 categories of: dizziness, sleep disorders and 
disturbances, altered sensorium, depression and suicide/self-injury, and psychosis and 
psychotic disorders.
08K3V5

Product:  MK-1439A 
23
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
6) Objective: To evaluate the safety and tolerability of MK-1439A q.d. compared to 
ATRIPLA™ q.d. as measured by the time to discontinuation from study due to an 
adverse experience.
7) Objective:  To evaluate the immunologic effect of MK-1439A q.d. compared to 
ATRIPLA™ q.d., as measured by the change from baseline in CD4 cell count at 
Week 48 and Week 96.
8) Objective:  To evaluate the superior antiretroviral activity of MK-1439A q.d. compared 
to ATRIPLA™q.d. as measured by the proportion of subjects achieving HIV-1 RNA 
<50 copies/mL (by the Abbott RealTime HIV-1 Assay) at Week 48.
Hypothesis:  MK-1439A q.d. is superior to ATRIPLA™ q.d. as assessed by the 
proportion of subjects with HIV-1 RNA <50 copies/mL (by the Abbott RealTime HIV-1 
Assay) at Week 48.
9) Objective:  
To evaluate the non-inferior antiretroviral activity of MK-1439A q.d. 
compared to ATRIPLA™ q.d., as measured by the proportion of subjects achieving HIV-
1 RNA <50 copies/mL (by the Abbott RealTime HIV-1 Assay) at Week 96.
Hypothesis:  MK-1439A q.d. is non-inferior to ATRIPLA™ q.d. as assessed by the 
proportion of subjects with HIV-1 RNA <50 copies/mL (by the Abbott RealTime HIV-1 
Assay) at Week 96. A margin of 10 percentage points is used to define non-inferiority. 
10) Objective:  To evaluate the superior antiretroviral activity of MK-1439A q.d. compared 
to ATRIPLA™ q.d., as measured by the proportion of subjects achieving HIV-1 RNA
<50 copies/mL (by the Abbott RealTime HIV-1 Assay) at Week 96.
Hypothesis:  MK-1439A q.d. is superior to ATRIPLA™ q.d. as assessed by the 
proportion of subjects with HIV-1 RNA <50 copies/mL (by the Abbott RealTime HIV-1 
Assay) at Week 96. 
11) Objective:  To evaluate the antiretroviral activity of MK-1439A q.d. compared to 
ATRIPLA™q.d. as measured by the proportion of subjects achieving HIV-1 RNA below 
the limit of quantification of the Abbott RealTime HIV-1 Assay (<40 copies/mL) at 
Week 48 and Week 96.
12) Objective: To evaluate the pharmacokinetics of MK-1439, when administered as a 
component of MK-1439A, and the pharmacokinetic-pharmacodynamic association, if 
supported by the data
08K3V5

Product:  MK-1439A 
24
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Exploratory Objectives
Base Study
In HIV-1 positive, treatment-naive subjects with pre-treatment HIV RNA ≥1,000 copies/mL:
1) Objective:  To evaluate the antiretroviral activity of MK-1439A q.d. compared to 
ATRIPLA™q.d. as measured by the proportion of subjects achieving HIV-1 RNA 
<200 copies/mL at Week 48 and Week 96.
2) Objective: To evaluate the antiretroviral activity of MK-1439A q.d. compared to 
ATRIPLA™ q.d., as measured by the TLOVR.
3) Objective: To assess the development of resistance to MK-1439A in subjects who 
have virologic failure.
4) Objective: To describe the outcomes for productivity and activity impairment related 
to general health during the study in MK-1439A relative to ATRIPLA™ q.d.
5) Objective:  To explore the relationship between genetic variation and response to the 
treatment(s) administered. Variation across the human genome will be analyzed for 
association with clinical data collected in this study.
Study Extension 1
1) Objective: To assess long-term efficacy and safety of MK-1439A administered for
up to 192 weeks in subjects initially randomized to MK-1439A and enrolled in study 
extension 1.
2) Objective: To assess efficacy and safety of switching to MK-1439A for up to 96 
weeks in subjects initially randomized to ATRIPLA™q.d. and enrolled in study 
extension 1.
BACKGROUND & RATIONALE
Background
Refer to the IB for detailed background information on MK-1439A.
Pharmaceutical and Therapeutic Background
HIV infection, which causes AIDS and for many years was associated with substantial 
morbidity and mortality, has now become a chronic disease that can be controlled through 
lifelong cART or HAART. Currently, there are more than 30 individual drugs and fixed-
dose combinations available for the treatment of HIV-1 infection. These agents belong to 5
distinct mechanistic classes known as N(t)RTIs and NNRTIs, PIs, fusion inhibitors, entry 
inhibitors (CCR5 co–receptor antagonists), and InSTIs. Successful combinations of 
08K3V5

Product:  MK-1439A 
25
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
antiretroviral medications generally utilize 3 agents from at least 2 different mechanistic 
classes. The goal of cART is to suppress HIV to undetectable levels so that immune function 
is preserved or restored. Yet, while cART can delay disease progression and death, as well 
as reduce the risk of HIV transmission, it does not cure the infection. As a result, lifelong 
treatment must be maintained, which may lead to therapy fatigue and to non-compliance if 
the treatment regimen is difficult to adhere to (e.g., pill burden, frequency of treatment) and 
associated with intolerable side-effects. This can potentially lead to treatment failures with 
the possible development of resistant virus. Additionally, there is currently still significant 
concern regarding toxicities of some widely-used antiretroviral agents, including 
neuropsychiatric toxicities associated with efavirenz (EFV, an NNRTI), gastrointestinal 
toxicities such as diarrhea associated with multiple protease inhibitors (PIs), and serum lipid 
abnormalities associated with multiple mechanistic classes. Thus, potent treatment regimens 
that have an excellent safety and tolerability profile and are convenient to take are highly 
desirable. 
For initiation of combination antiretroviral therapy for HIV infection, currently available 
NNRTIs constitute an important option for use as anchor agents, along with 2 NRTIs.
Efavirenz and rilpivirine are both among the recommended therapies for treatment initiation 
according to multiple guidelines [1] [2]; however, each has limitations. For example, while 
efavirenz has shown excellent efficacy over many years of use, it is associated with 
substantial neuropsychiatric intolerance and skin rash, as well as lipid abnormalities. In 
addition it can be a perpetrator of drug-drug interactions as a mixed inducer or inhibitor of 
CYP3A and CYP2B6 enzymes. Rilpivirine has shown suboptimal efficacy in patients with 
high viral load or low baseline CD4 cells, and thus is not indicated in patients with baseline 
viral load above 100,000 copies/mL or CD4 count below 200 u/L. In addition, rilpivirine 
requires dosing with food, and while it is not a metabolic inducer or inhibitor, it is subject to 
metabolic induction/inhibition of CYP3A isoenzymes and should not be co-administered 
with proton pump inhibitors and several anticonvulsants. Importantly, high level resistance 
may occur in response to a single mutation for all currently available NNRTIs except 
etravirine, which must be dosed twice daily. Therefore, new agents of the NNRTI class that 
offer high potency, a distinct resistance profile, dosing convenience and a favorable safety 
and tolerability profile are needed.
As of the date of issuance of this protocol amendment, both MK-1439 and MK-1439A have 
been approved in multiple markets including the US, EU, Canada, Switzerland, and Australia 
for the treatment of HIV-1 infection in adult patients. MK-1439 is a potent inhibitor of HIV-1 
replication in vitro and is active against both wild type virus and the most common NNRTI 
resistant variants at concentrations achieved with once-daily dosing. MK-1439 displays 
excellent potency against wild type virus with an IC50 of 12 nM in the presence of 100% 
normal human serum. Preclinical studies also indicate a favorable in vitro resistance profile 
that is distinct from other NNRTIs, with IC50’s of 21, 31, and 55 nM against mutants 
containing the most frequently transmitted NNRTI mutations, K103N, Y181C and G190A, 
respectively, under the same conditions. The preclinical toxicity profile of MK-1439 is 
favorable in rats following dosing for up to 6 months at 3, 30, and 450 mg/kg/day, and in 
dogs following dosing for up to 9 months at 1, 10, and 1000 mg/kg/day. 
Clinical 
pharmacology studies indicate that MK-1439 can be dosed once-daily, without regard to 
08K3V5

Product:  MK-1439A 
26
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
food, and MK-1439 is not a metabolic inducer or inhibitor, reducing the likelihood of 
significant drug-drug interactions. Furthermore, the available long-term (beyond Week 48) 
data from a Phase 2 study in treatment-naive HIV-infected patients demonstrate that MK-
1439 in combination with TDF/emtricitabine has a favorable safety and tolerability profile 
and potent efficacy, with ~76% of patients receiving MK-1439 achieving undetectable viral 
load (see Section 4.2.2.). These data provide key support for the initiation of the Phase 3 
program, which includes evaluations of both MK-1439 as a single agent and MK-1439A as a 
fixed-dose regimen. 
Rationale
Rationale for the Trial and Selected Subject Population
Factors that impact HIV treatment success include efficacy, safety and tolerability, barrier to 
resistance, simplicity/convenience of administration and drug-drug interactions. There is a 
clear medical need for new regimens that are highly effective, have a high barrier to 
resistance development, are very well tolerated, and are simple to administer (and thus
facilitate increased adherence and prevent treatment fatigue). Therapies and regimens with 
these characteristics are particularly important for treatment-naïve patients for whom initial 
success is predictive of long-term outcomes and in the setting of lifelong treatment of HIV 
infection 
as 
many 
HIV 
patients
become
increasingly 
older 
with
co-morbid 
diseases/conditions.
Currently, efavirenz is the preferred NNRTI for first-line therapy of treatment-naïve HIV-
infected subjects. ATRIPLA™, an FDR consisting of efavirenz 600 mg + emtricitabine 
200 mg + TDF 300 mg, is the leading agent in HIV treatment. Efavirenz has demonstrated 
potent viral suppression but is associated with an increased risk of neuropsychiatric adverse 
experiences (AEs) (especially dizziness and sleep disorders) and lipid abnormalities relative 
to other therapies [1]. Efavirenz is also a perpetrator of numerous drug-drug interactions and,
thus, may have limitations for use in aging patients who have an increased likelihood of 
using concomitant mediations. MK-1439 has been observed to have a more favorable 
neuropsychiatric AE and lipid profile relative to efavirenz in a Phase 2b study comparing the 
2 agents, and, therefore, may result in improved patient tolerability and adherence [3] [4].
Additionally, based on in vitro data and drug-drug interactions studies conducted to date,
MK-1439 is not expected to have many of the drug-drug interaction concerns currently 
hampering the use of efavirenz. Therefore, both MK-1439 and MK-1439A will provide 
valuable new treatment options for patients. 
Rationale for Dose Selection/Regimen
The FDR of MK-1439A contains 100 mg of MK-1439, a potent NNRTI, and standard doses 
of 2 commercially available and commonly used NRTIs, TDF (300 mg) and lamivudine (300 
mg). 
A 100 mg dose of MK-1439 was selected for Phase 3 development based on Phase 1b and 2 
data and several other factors.
08K3V5

Product:  MK-1439A 
27
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
In a Phase 1b study (Protocol 005), q.d. oral administration of 25 mg and 200 mg of MK-
1439 as monotherapy for 7 days to treatment-naïve HIV-infected patients reduced plasma 
viral RNA burden as compared to placebo-treated controls. The mean change from baseline 
in log10 HIV RNA copies/mL on Day 7 (24 hours postdose) was -1.52 for the MK-1439 25 
mg group and was -1.41 for the MK-1439 200 mg group, while that for the placebo group 
was -0.15. The mean differences between MK-1439 25 mg and 200 mg versus placebo in 
change from baseline in log10 HIV RNA copies/mL were -1.37 and -1.26, respectively. 
Protocol 007 (Part 1) is a Phase 2 study designed to assess MK-1439 at doses of 25, 50, 100,
and 200 mg q.d. versus efavirenz at 600 mg q.d., both in combination with the fixed-dose 
combination of TDF/FTC (TRUVADA™) in treatment-naïve HIV-1 infected subjects. The 
MK-1439 dose range was selected based upon projections from in vitro data as well as the 
Phase 1b data in HIV-1 infected treatment-naïve individuals, which showed comparable 
virologic suppression at the 25 mg and 200 mg doses given once daily for 7 days.
In Protocol 007 (Part 1) 208 treatment-naïve HIV-1 infected subjects were treated with study 
drug (MK-1439 or efavirenz). At Week 24, all MK-1439 doses had rates of virologic 
suppression comparable to efavirenz for the key efficacy endpoints including the proportion 
of subjects with HIV-1 RNA levels <40 copies/mL (primary) or <200 copies/mL 
(secondary). All MK-1439 doses showed numerically higher response rates compared to 
efavirenz (80.0%, 76.2%, 71.4%, 78.0% versus 64.3% of patients with <40 copies/mL for the 
MK-1439 25 mg, 50 mg, 100 mg, 200 mg versus efavirenz arms, respectively) [3] [4]. The 
treatment differences (MK-1439 minus efavirenz) were not significant, and there was no 
dose response for efficacy observed. Overall 76.4% of patients receiving MK-1439 (at any 
dose) achieved <40 copies/mL compared with 64.3% for efavirenz. 
In addition, 
approximately 30% of subjects
in the study had baseline HIV RNA above 
100,000 copies/mL, and, in this subgroup, MK-1439 at all dosing levels showed virologic 
responses comparable to efavirenz. It should be acknowledged that this high viral load 
subgroup was relatively small, with approximately 12 subjects per dosing group. However, 
the totality of these efficacy data strongly support that the dose range studied (25-200 mg 
daily) was on the plateau of the dose response curve [4]. 
Similarly, the data from Protocol 007 showed an overall favorable safety and tolerability 
profile for MK-1439 compared with efavirenz, with no differentiation among MK-1439 
doses (25 mg - 200 mg daily) with regard to safety. Based upon the 24-week results of 
Protocol 007, MK-1439 at doses ranging from 25-200 mg was generally well-tolerated, with 
no apparent dose related toxicity. Fewer drug-related AEs were observed for MK-1439 than 
for efavirenz (34.9% for MK-1439 overall vs. 57.1% for EFV), and fewer neuropsychiatric
AEs were reported both at Week 8 and Week 24 (20.5% for MK-1439 overall vs. 33.3% for 
EFV at Week 8 and 23.4% for MK-1439 overall vs. 33.3% for EFV at Week 24) [3]. 
Because the safety and efficacy data from Protocol 007 did not distinguish among the doses 
tested, the selection of the MK-1439 100-mg daily dose for study in Part 2 of Protocol 007 
and in the Phase 3 studies has taken into consideration a number of additional factors. 
Firstly, MK-1439 is a substrate of CYP3A metabolism and is subject to induction and 
inhibition of CYP3A by other concomitant medications. Consequently, the 100 mg dose is 
08K3V5

Product:  MK-1439A 
28
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
more likely than the lower doses to provide adequate MK-1439 exposures even in the setting 
of moderate metabolic inducers, and it allows for a safety margin in the setting of moderate 
metabolic inhibitors (since acceptable safety and tolerability were seen at the 200 mg dose in 
the Phase 2 study as well as at multiple doses and single doses as high as 750 mg and 
1200 mg, respectively, in Phase 1 studies). 
Secondly, the 100-mg dose may provide 
forgiveness in the setting of the occasional missed dose. Thirdly, based on modeling and 
simulation, the 100-mg dose is predicted to provide adequate exposures and Ctrough
concentrations in the setting of certain common NNRTI resistance mutations against which 
MK-1439 is considered to be active in vitro, including the K103N, Y181C, and Y190A 
mutations, as well as the dual K103N/Y181C mutation. 
Patients receiving MK-1439 at 25, 50 or 200 mg in Part 1 of Protocol 007 were switched to 
100 mg after dose selection. An additional 132 patients were randomized in Part 2, 66 to 
receive MK-1439 100 mg and 66 to receive EFV 600 mg. Combining Part 1 and 2, a total of 
108 patients received MK-1439 100 mg, and 108 patients received EFV. By Week 8, at least 
one neuropsychiatric AE was reported in 22.2% of the MK-1439 group and 43.5% of the 
EFV group (p<0.001). The most commonly-reported neuropsychiatric AEs were dizziness 
(in 9.3% of patients receiving MK-1439 and 27.8% of patients receiving EFV), insomnia (in 
6.5% of patients receiving MK-1439 and 2.8% of patients receiving EFV), abnormal dreams 
(in 5.6% of patients receiving MK-1439 and 16.7% of patients receiving EFV), and 
nightmares (in 5.6% of patients receiving MK-1439 and 8.3% of patients receiving EFV). 
Standard marketed doses of lamivudine and TDF were selected for inclusion in MK-1439A 
because these dose levels have demonstrated efficacy and safety in treatment-naive subjects,
and no antagonism was observed between MK-1439 and either of these drugs in in vitro 
studies.
ATRIPLA™, the active comparator in the base study will be administered at the standard 
approved dose of one tablet once daily. Each tablet contains 600 mg of efavirenz, 300 mg of 
tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir disoproxil) and 
200 mg of emtricitabine.
Rationale for Endpoints
Efficacy Endpoints
The primary efficacy parameter in the study is viral load as measured by HIV-1 RNA, which 
is consistent with other clinical trials in HIV-infected patients and the current regulatory 
guidance. Suppressing HIV RNA to low levels preserves the immune system and prevents
the development of opportunistic infections and progression of the disease. Clinical trials of 
antiretroviral agents in multiple classes have demonstrated that suppression of HIV RNA to 
levels below 50 copies/mL is a clinically meaningful endpoint. Therefore, the primary 
efficacy endpoint of this study is the proportion of subjects achieving HIV-1 RNA 
<50 copies/mL by the Abbott RealTime HIV-1 Assay. Week 48 was chosen as the primary 
efficacy time point and Week 96 as the secondary efficacy time point, as recommended by 
regulatory agencies for HIV treatment-naïve studies.
08K3V5

Product:  MK-1439A 
29
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Secondary and exploratory measurements for efficacy include HIV RNA <40 copies/mL (the 
lower limit of quantification of the Abbott RealTime HIV-1 Assay), HIV RNA 
<200 copies/mL, change from baseline in CD4 cell counts, time to loss of virologic response 
(TLOVR), and viral resistance for subjects who meet protocol-defined virologic failure 
criteria and whose virus can be amplified. 
PDVF for this study is defined as one of the following:
1) Confirmed (2 consecutive measures at least one week apart) HIV-1 RNA ≥50 copies/mL 
after initial response of HIV-1 RNA <50 copies/mL at any time during the study
OR
2) Confirmed (2 consecutive measures at least one week apart) HIV-1 RNA 
≥200 copies/mL at Week 24 or Week 36 
OR 
3) Confirmed (2 consecutive measures at least one week apart) HIV-1 RNA ≥50 copies/mL 
at Week 48.
Subjects should be discontinued, regardless of compliance with study therapy, if they meet 
the protocol-defined virologic failure criteria. 
Safety Endpoints
The primary safety endpoint in this study is assessed in the base study. The primary safety 
endpoint is the proportion of subjects with neuropsychiatric AEs by Week 48 in three
categories; dizziness, sleep disorders, and altered sensorium (for example, depressed level of 
consciousness, lethargy, somnolence, syncope). The proportion of subjects with 
neuropsychiatric AEs by Week 48 in two additional categories, depression/suicide/self-injury 
and psychosis/psychotic disorders, will be secondary endpoints. All MedDRA preferred 
terms that fall under these categories will be grouped for the statistical tests on the difference 
in incidence rates between treatment groups within the categories. The full list of preferred 
terms defining these 5 categories is provided in Section 12.6.
Safety evaluations will include physical examinations (including vital signs) and laboratory 
tests (blood) performed at the visits indicated in the Trial Flow Chart (see Section 6.0). For
subjects who continue into study extension 1, safety evaluations
will include physical 
examinations (including vital signs) and laboratory test (blood) performed at each of the
study visits, and if applicable, at the early discontinuation visit and/or a virologic
failure confirmation visit and at a 14-day follow-up visit as shown in Trial Flow Chart B.
AEs will be evaluated at each visit and graded according to the guidelines provided in 
Section 7.2. Subjects may be asked to return for unscheduled visits in order to perform 
additional safety monitoring.
08K3V5

Product:  MK-1439A 
30
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Note that after the administration of open-label study medication at Week 96, the first visit in 
study extension 1 is at Week 100, such that there is a 4-week interval following the last study 
treatment visit in the base study (Week 96). This interval was made shorter than the 12- to 
16-week intervals beginning with Week 24 in the base study (and between subsequent visits 
in study extension 1) in order to more closely monitor all subjects, including those who are
switched from ATRIPLA™to MK-1439A, since treatment in the base study remains blinded 
at the beginning of study extension 1. Treatment group assigned during the base study will 
not be unblinded when a subject enters study extension 1; unblinding will occur after all 
subjects have completed the base study and database lock has been achieved for the base 
study (96-week treatment).
During study extension 2 and study extension 3, SAEs and pregnancy test results will be 
collected at each study visit (study extension 2: Week 208, Week 224, Week 240, Week 256, 
Week 272, and Week 288; study extension 3: Week 304, Week 320, Week 336, Week 352, 
Week 368, and Week 384, as applicable, depending on when MK-1439A is commercially 
available once approved in the local country, and, if applicable, at the early discontinuation 
and 14-day follow-up visits). 
Secondary and exploratory measurements for safety include clinical and laboratory adverse 
experiences, change from baseline in fasting serum lipids, time to discontinuation due to an 
adverse experience and pre-defined limits of change in laboratory parameters. 
Pharmacokinetic Endpoints
PK samples to be assayed for MK-1439 plasma concentrations will be collected at the Day 1 
randomization visit as a predose sample. Population PK samples will also be taken at Weeks 
4, 8, 24 and 48. At Week 4, the sample is to be collected predose. At Weeks 24 and 48, the 
samples are to be collected predose and within 0.5 to 2 hours postdose; at Week 8, the 
sample may be collected irrespective of time of dose (time of last dose and time of PK 
sample collection must be documented).
Patient-Reported Outcome Endpoints
Subjects will complete a WPAI at Day 1, Week 4, Week 8, Week 16, and Week 48 (or the 
discontinuation visit). This patient-reported outcome questionnaire is designed to assess the 
quantitative impact of health conditions on loss of time and impaired productivity for 
functional activities such as work-for-pay, school work, and work around the house.
Planned Exploratory Biomarker
Understanding genetic determinants of drug response is an important endeavor during 
medical research. This research will evaluate whether genetic variation within a clinical trial 
population correlates with response to the treatment(s) under evaluation. If genetic variation 
is found to predict efficacy or adverse events, the data might inform optimal use of therapies 
in the patient population. This research contributes to understanding genetic determinants of 
efficacy and safety associated with the treatments in this study. 
08K3V5

Product:  MK-1439A 
31
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Future Biomedical Research
The Sponsor will conduct future biomedical research on specimens for which consent was 
provided during this study. This research may include genetic analyses (DNA), gene 
expression profiling (RNA), proteomics, metabolomics (serum, plasma), and/or the 
measurement of other analytes, depending on which specimens are consented for future 
biomedical research.
Such research is for biomarker testing to address emergent questions not described elsewhere 
in the protocol (as part of the main study) and will only be conducted on specimens from 
appropriately consented participants. The objective of collecting/retaining specimens for 
future biomedical research is to explore and identify biomarkers that inform the scientific 
understanding of diseases and/or their therapeutic treatments. The overarching goal is to use 
such information to develop safer, more effective drugs/vaccines, and/or to ensure that 
participants receive the correct dose of the correct drug/vaccine at the correct time. The 
details of future biomedical research are presented in Appendix 12.2. Additional 
informational material for institutional review boards/ethics committees (IRBs/ECs) and 
investigational site staff is provided in Appendix 12.3.
Rationale for Study Extensions
Because HIV infection is chronic, with treatment generally lifelong, collection of long-term 
safety and efficacy data will provide useful information on MK-1439A. Thus, after the 96-
week double-blind period to evaluate the key primary and secondary objectives and 
hypotheses, there will be an open-label study extension (“study extension 1”) for an 
additional 96-week period where all eligible subjects can continue to receive an open-label 
MK-1439A regimen. 
Study extensions 2 and 3 were added to avoid interruption of treatment with MK-1439A for 
eligible subjects who are deriving benefit from treatment until MK-1439A is commercially 
available once approved in the local countries participating in the trial. This will also reduce 
the well-recognized, but small, risk of treatment failure associated with a change from a 
successfully suppressive and tolerated cART regimen.
Benefit/Risk
Subjects in clinical trials generally cannot expect to receive direct benefit from treatment 
during participation, as clinical trials are designed to provide information about the safety 
and effectiveness of an investigational medicine.
MK-1439 is a promising new NNRTI for the treatment of HIV-1 infection. It is a potent 
inhibitor of HIV-1 replication in vitro and is active against both wild type virus and most 
common NNRTI resistant variants at concentrations achieved with once-daily dosing. In 
early studies, MK-1439 has been shown to be efficacious in combination with other ARTs in 
treatment-naïve patients. MK-1439 is not expected to have many of the safety concerns 
associated with EFV (especially neuropsychiatric AEs and dyslipidemia). In addition, MK-
08K3V5

Product:  MK-1439A 
32
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
1439 is not expected to have major drug-drug interactions that would limit its utility in 
clinical practice. Therefore, MK-1439 could represent a valuable addition to the HIV 
armamentarium for treatment-naïve patients. Additionally, the FDR, MK-1439A, which is 
used in this protocol, is a simplified regimen that could result in increased adherence, thereby 
potentially decreasing the risk of virologic failure.
Additional details regarding specific benefits and risks for subjects participating in this 
clinical trial may be found in the accompanying Investigator Brochure (IB) and Informed 
Consent documents.
METHODOLOGY
Entry Criteria
Diagnosis/Condition for Entry into the Trial
Male and female subjects 18 years of age or older who are HIV-1 positive and naïve to ART
will be enrolled in this trial.
Subject Inclusion Criteria
In order to be eligible for participation in this trial, the subject must:
1. be at least 18 years of age on the day of signing the informed consent
2. understand the study procedures and voluntarily agree to participate by giving written 
informed consent (or have a legal representative provide written informed consent, if 
considered acceptable by local regulatory agencies and/or ERCs/IRBs) for the trial.
The subject or his/her legal representative (if considered acceptable by local 
regulatory agencies and/or ERCs/IRBs) may also provide consent for Future 
Biomedical Research. However, the subject may participate in the main trial without 
participating in Future Biomedical Research. 
3. be HIV-1 positive as determined by a positive result on an enzyme immunoassay,
have screening plasma HIV-1 RNA (determined by the central laboratory) 
≥1000 copies/mL within 45 days prior to the treatment phase of this study, and have 
HIV treatment indicated based on physician assessment. Local treatment guidelines 
should be considered in the decision to initiate therapy. 
4. be naïve to ART including investigational antiretroviral agents.
Note:  Naïve is defined as having received no (0 days of) ART therapy for the 
treatment of HIV infection.
08K3V5

Product:  MK-1439A 
33
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
5. have the following laboratory values at screening within 45 days prior to the 
treatment phase of this study: 
a.
Alkaline phosphatase ≤3.0 x upper limit of normal
b. AST (SGOT) and ALT (SGPT) ≤5.0 x upper limit of normal
c.
Hemoglobin ≥9.0 g/dL (if female) or ≥10.0 g/dL (if male). 
Note: A single repeat of a laboratory screening test will be allowed for test results 
that are unexpected based on documented prior laboratory results.
6. have a calculated creatinine clearance at the time of screening ≥50 mL/min, based on 
the Cockcroft-Gault equation which is as follows:
For males:      Clcr (mL/min) = (140-age) x weight (in kg)
72 x serum creatinine (mg/dL)
For females: Clcr (mL/min) = (140-age) x weight (in kg) x 0.85
72 x serum creatinine (mg/dL)
7. in the opinion of the investigator, be considered clinically stable with no signs or 
symptoms of active infection at the time of entry into the study (i.e., clinical status 
and all chronic medications should be unchanged for at least 2 weeks prior to the start 
of treatment in this study).
8. be highly unlikely to become pregnant or to impregnate a partner since the subject 
falls into at least one of the following categories:
a.
The subject is a male who is not of reproductive potential, defined as a male who 
has azoospermia (whether due to having had a vasectomy or due to an underlying 
medical condition). 
b. The subject is a female who is not of reproductive potential, defined as a female 
who either: (1) is postmenopausal (defined as at least 12 months with no menses 
in women ≥45 years of age); (2) has had a hysterectomy and/or bilateral 
oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at 
least 6 weeks prior to screening; OR (3) has a congenital or acquired condition 
that prevents childbearing.
c.
The subject is a female or a male who is of reproductive potential and agrees to 
avoid becoming pregnant or impregnating a partner while receiving study drug 
and for 12 weeks after the last dose of study drug in the base study and 14 days 
after the last dose of study drug in the study extensions by complying with one of 
the following:  (1) practice abstinence† from heterosexual activity OR (2) use (or 
have their partner use) acceptable contraception during heterosexual activity.
Acceptable methods of contraception are‡:
08K3V5

Product:  MK-1439A 
34
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Single method (one of the following is acceptable):
•
intrauterine device (IUD)
•
vasectomy of a female subject’s male partner 
Combination method (requires use of 2 of the following):
•
diaphragm with spermicide (cannot be used in conjunction with cervical 
cap/spermicide)
•
cervical cap with spermicide (nulliparous women only)  
•
contraceptive sponge (nulliparous women only) 
•
male condom or female condom (cannot be used together)
•
hormonal contraceptive: oral contraceptive pill (estrogen/progestin pill or 
progestin-only pill), contraceptive skin patch, vaginal contraceptive ring,
contraceptive rod implanted into the skin or subcutaneous contraceptive 
injection
Use of barrier methods of contraception is strongly encouraged to reduce the risk of 
HIV-1 transmission during sexual contact.
†Abstinence (relative to heterosexual activity) can be used as the sole method of 
contraception if it is consistently employed as the subject’s preferred and usual 
lifestyle and if considered acceptable by local regulatory agencies and ERCs/IRBs.
Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation 
methods, etc.) and withdrawal are not acceptable methods of contraception. 
‡If a contraceptive method listed above is restricted by local regulations/guidelines, 
then it does not qualify as an acceptable method of contraception for subjects 
participating at sites in this country/region.
Investigators should provide appropriate guidance to the subjects regarding use of 
contraceptives after completion of the study treatment. It is recommended that all subjects 
should continue to use contraception for 12 weeks following their last dose of study 
treatment in the base study (continued contraceptive use for 12 weeks following the last dose 
of ATRIPLA™is required as per ATRIPLA™prescribing information, and patients’ study 
drug assignments will likely still be blinded following study completion). 
However, 
continued contraceptive use for 14 days following the last dose of study treatment is 
recommended in the study extensions since all subjects will be on MK-1439A.
08K3V5

Product:  MK-1439A 
35
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
In order to be eligible for participation in study extension 1 at the Week 96 visit, the subject
must:
9. have completed the Week 96 visit.
10. be considered, in the opinion of the investigator, to have derived benefit from study
participation through Week 96.
11. be considered, in the opinion of the investigator, a clinically appropriate candidate for
an additional 96 weeks of treatment with MK-1439A following the end of the base 
study.
12. understand the procedures in study extension 1 and provide written informed consent
to enter the study extension, thus continuing for approximately 2 years beyond the
base study.
In order to be eligible to continue receiving study treatment in study extension 2 at the 
Week 192 visit, the subject must: 
13. have completed the Week 192 visit.
14. be considered, in the opinion of the investigator, to have derived benefit from MK-
1439A by Week 192 of the study.
15. be considered, in the opinion of the investigator, a clinically appropriate candidate for 
an additional 2 years (additional 96 weeks) of treatment with MK-1439A.
16. understand the procedures in study extension 2 and have provided written informed 
consent to enter study extension 2, thus continuing until MK-1439A is commercially 
available once approved in the local country, or for up to approximately 2 years 
(whichever comes first) beyond study extension 1.
In order to be eligible to continue receiving study treatment in study extension 3 at the 
Week 288 visit, the subject must: 
17. have completed the Week 288 visit.
18. be considered, in the opinion of the investigator, to have derived benefit from MK-
1439A by Week 288 of the study.
19. be considered, in the opinion of the investigator, a clinically appropriate candidate for 
an additional 2 years (additional 96 weeks) of treatment with MK-1439A.
20. understand the procedures in study extension 3 and have provided written informed 
consent to enter study extension 3, thus continuing until MK-1439A is commercially 
available once approved in the local country, or for up to approximately 2 years 
(whichever comes first) beyond study extension 2.
08K3V5

Product:  MK-1439A 
36
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Subject Exclusion Criteria
The subject must be excluded from participating in the trial if the subject:
1. has a history or current evidence of any condition, therapy, laboratory abnormality or 
other circumstance that might confound the results of the study or interfere with the 
subject’s participation for the full duration of the study, such that it is not in the best 
interest of the subject to participate.
2. is, at the time of signing informed consent, a user of recreational or illicit drugs or has 
had a recent history of drug or alcohol abuse or dependence. The nature and potential 
clinical context of the subject's illicit drug use, in relation to their exclusion from this 
trial, will be at the discretion of the Investigator.
3. has been treated for a viral infection other than HIV-1, such as hepatitis B, with an 
agent that is active against HIV-1, including, but not limited to, adefovir, tenofovir, 
entecavir, emtricitabine, or lamivudine. 
Note: Subjects may be enrolled if treatment occurred prior to the diagnosis of HIV.
4. has documented or known resistance to study drugs including MK-1439, efavirenz, 
emtricitabine, lamivudine, and/or tenofovir, as defined below:  
a.
Resistance to MK-1439 or efavirenz for the purpose of this study includes the 
following NNRTI mutations: L100I, K101E, K101P, K103N, K103S, V106A, 
V106I, V106M, V108I, E138A, E138G, E138K, E138Q, E138R, V179L,
Y181C, Y181I, Y181V, Y188C, Y188H, Y188L, G190A, G190S, H221Y, 
L234I, P225H, F227C, F227L, F227V, M230L, M230I
b. Resistance to emtricitabine, lamivudine and tenofovir includes the following 
mutations: K65R, M41L, T69S (insertion complex), Q151M, M184I, M184V, 
L210W, T215F, T215Y, K219E, K219Q, D67N, K70R and K70E.
5. has participated in a study with an investigational compound/device within 30 days
prior to signing informed consent or anticipates participating in such a study 
involving an investigational compound/device during the course of this study.
6. has used systemic immunosuppressive therapy or immune modulators within 30 days 
prior to treatment in this study or is anticipated to need them during the course of the 
study. 
Note: Short courses of corticosteroids (e.g., as for asthma exacerbation) will be 
allowed.
7. requires or is anticipated to require any of the prohibited medications noted in the 
protocol (refer to Section 5.5).
08K3V5

Product:  MK-1439A 
37
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
8. has significant hypersensitivity or other contraindication to any of the components of 
the study drugs as determined by the investigator.
9. has a current (active) diagnosis of acute hepatitis due to any cause. 
Note: Subjects with chronic hepatitis B and C may enter the study as long as they 
fulfill all entry criteria, have stable liver function tests, and have no significant 
impairment of hepatic synthetic function (significant impairment of hepatic synthetic 
function is defined as a serum albumin <2.8 mg/dL or an INR >1.7 in the absence of 
another explanation for the abnormal laboratory value). 
10. has evidence of decompensated liver disease manifested by the presence of or a 
history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or 
other signs or symptoms of advanced liver diseases
or
has liver cirrhosis and a CPT score >9.
Note: To calculate the CPT score and associated Child-Pugh Class, refer to the 
following website: http://www.mdcalc.com/child-pugh-score-for-cirrhosis-mortality.
11. is pregnant, breastfeeding, or expecting to conceive.
12. is female and is expecting to donate eggs (at any time during the study) or is male and 
is expecting to donate sperm (at any time during the study).
Note: Investigators should provide appropriate guidance to the subjects regarding egg 
and sperm donation after completion of the study treatment. Consistent with the 
recommendations for contraceptive use, it is recommended that all subjects refrain 
from egg or sperm donation for 12 weeks following their last dose of study treatment
in the base study and 14 days after the last dose of study treatment in the study 
extensions.
13. is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or 
child) who is investigational site or sponsor staff directly involved with this trial.
Trial Treatment(s)
Following completion of the Day 1 procedures and confirmation of eligibility, the site will 
contact the IVRS/IWRS for assignment of the study drug to be administered (MK-1439A or 
ATRIPLA). To maintain blinding, both drugs will be administered with a placebo matched 
to the other active drug in the study. 
Sites should not call IVRS/IWRS for drug 
administration until the subject has met all criteria for the study and is ready to receive the 
first dose of study medication on Day 1. The treatment groups to be used in this trial are 
outlined below in Table 1 for the base study and Table 2 for the extensions.
08K3V5

Product:  MK-1439A 
38
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Table 1
Trial Treatment During the Base Study
Group 1
n = 340
MK-1439A one tablet PO q.d.† + placebo to match ATRIPLATM
one tablet PO q.d.#
Group 2
n = 340
ATRIPLA™ one tablet PO q.d.‡ + placebo to match MK-1439A 
one tablet PO q.d.#
† MK-1439A is a single tablet FDR containing MK-1439 100 mg, lamivudine 300 mg, and tenofovir 
disoproxil fumarate (TDF) 300 mg.
‡ ATRIPLA™ is a single tablet FDR containing efavirenz 600 mg, emtricitabine 200 mg, and TDF 300 mg 
(which is equivalent to 245 mg of tenofovir disoproxil).
# Placebos are used to maintain blinding.
Table 2
Trial Treatment During the Study Extensions
Group 1
Open-Label MK-1439A q.d.†
Group 2
† All subjects will receive MK-1439A (single-tablet, fixed-dose regimen (FDR) containing MK-1439 100 mg 
+ lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg) in the study extensions.
Subjects will receive study medication at the Day 1 visit and should take the first dose of 
medication on the same day. 
MK-1439A (during the base study and study extensions) and the placebo to match MK-
1439A are to be taken once daily without regard to food at approximately the same time each 
day. 
ATRIPLA™and the placebo to match ATRIPLA™are to be taken once daily at bedtime on 
an empty stomach.
Study medications for the base study (MK-1439A/placebo or ALTRIPA™/placebo) and for
the study extensions (MK-1439A) will be provided centrally by the Sponsor.
The investigator shall take responsibility for and shall take all steps to maintain appropriate 
records and ensure appropriate supply, storage, handling, distribution and usage of trial 
treatments in accordance with the protocol and any applicable laws and regulations.
Dose Selection
Dose Selection (Preparation)
The rationale for selection of doses to be used in this trial is provided in Section 4.0 –
Background & Rationale.  There are no specific calculations or evaluations required to be 
performed in order to administer the proper dose to each subject.
08K3V5

Product:  MK-1439A 
39
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Dose Modification/Interruption (Base Study or the Study Extensions)
Dose Modification:
No dose modification of study therapy is allowed during the study. 
Dose Interruption:
Consideration should be given to interrupting study therapy for toxicity management (see 
Section 7.1.2.6).
Interruptions from the protocol specified treatment plan that are expected to be 7 days or 
greater require consultation between the investigator and the Sponsor and written 
documentation of the collaborative decision on subject management.
Timing of Dose Administration
Base Study
Bottle A (MK-1439A or placebo):  
Subjects will be instructed to take one tablet from Bottle A once a day (q.d.) orally, with or 
without food at the approximately the same time each day. 
If a subject misses a dose of drug from Bottle A and it is less than 12 hours before the next 
dose, the missed dose should be skipped and the normal dosing schedule resumed. The 
subject should not double the next dose in order to compensate for what has been missed. If 
a subject misses a dose and it is greater than 12 hours before the next dose, the missed dose 
should be taken and the normal dosing schedule resumed.
Bottle B (ATRIPLA™ or placebo):  
Subjects will be instructed to take one tablet from Bottle B once a day orally, on an empty 
stomach at bedtime. 
If a subject misses a dose of drug from Bottle B and it is less than 12 hours before the next 
dose, the missed dose should be skipped and the normal dosing schedule resumed. The 
subject should not double the next dose in order to compensate for what has been missed. If 
a subject misses a dose and it is greater than 12 hours before the next dose, the missed dose 
should be taken and the normal dosing schedule resumed.
Study Extensions
Bottle C (MK-1439A), open-label:  
Subjects will be instructed to take one tablet from Bottle C once a day (q.d.) orally, with or 
without food at the approximately the same time each day. 
08K3V5

Product:  MK-1439A 
40
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
If a subject misses a dose of drug from Bottle C and it is less than 12 hours before the next 
dose, the missed dose should be skipped and the normal dosing schedule resumed. The 
subject should not double the next dose in order to compensate for what has been missed. If 
a subject misses a dose and it is greater than 12 hours before the next dose, the missed dose 
should be taken and the normal dosing schedule resumed.
Trial Blinding/Masking
A double-blind/masking technique will be used. 
MK-1439A, ATRIPLA™, and their 
respective placebos will be packaged so that blind/masking is maintained in the base trial.
The subject, the investigator and Sponsor personnel or delegate(s) who are involved in the 
treatment or clinical evaluation of the subjects are unaware of the group assignments. During 
the trial extensions, MK-1439A will be provided open-label.
See Section 7.1.4.2, Blinding/Unblinding, for a description of the method of unblinding a 
subject during the trial, should such action be warranted.
Randomization or Treatment Allocation
Randomization will occur centrally using an interactive voice response system / integrated 
web response system (IVRS/IWRS). There are 2 treatment arms.  Subjects will be assigned 
randomly in a 1:1 ratio to MK-1439A q.d. or ATRIPLA™q.d. in the base study. 
Stratification
Randomization in the base study will be stratified according to the following factors:
1. Screening HIV-1 RNA (≤100,000 or >100,000 copies/mL), based on central laboratory 
result
2. Chronic Hepatitis B and/or C infection status (yes or no). Hepatitis status is defined by
serologic evidence of chronic hepatitis B surface antigen and/or evidence of HCV RNA
by a PCR quantitative test for hepatitis C virus. 
Thus, IVRS/IWRS will randomize subjects within 4 strata as outlined in Table 3.
Table 3
Stratification
Stratum
Screen HIV-1 RNA levels
(copies/mL)
Chronic Hepatitis B and/or 
Chronic Hepatitis C
I
≤100,000
No
II
≤100,000
Yes
III
>100,000
No
IV
>100,000
Yes
08K3V5

Product:  MK-1439A 
41
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Concomitant Medications/Vaccinations (Allowed & Prohibited)
Medications or vaccinations specifically prohibited in the exclusion criteria are not allowed 
during the ongoing trial.  If there is a clinical indication for any medication or vaccination
specifically prohibited during the trial, discontinuation from trial therapy or vaccination may 
be required.  The investigator should discuss any questions regarding this with the Sponsor
Clinical Director.  The final decision on any supportive therapy or vaccination rests with the 
investigator and/or the subject's primary physician.  However, the decision to continue the 
subject on trial therapy or vaccination schedule requires the mutual agreement of the 
investigator, the Sponsor and the subject.
No medications are to be taken within 30 days of the start of the study without the knowledge 
of the investigator. 
Listed below are specific restrictions for concomitant therapy or vaccination during the 
course of the trial:
Permitted Concomitant Medications/Therapies
The concomitant use of other medications/therapies is allowed unless specifically prohibited 
in the Prohibited Concomitant Medications/Therapies section below. 
Before placing a 
subject on a specific medication/therapy, it is the responsibility of the investigator to check 
on potential drug-drug interactions between that medication/therapy and ATRIPLA™.
1. Use of oral or other hormonal contraception is permitted. 
2. Newly approved regimens for the treatment of HCV infection are permitted, as long 
as there are no known potential drug-drug interactions between those treatments and 
any of the study medications. The MSD Clinical Director or designee should be 
contacted if there are any questions about whether there is a potential drug-drug 
interaction with a specific treatment that the Investigator is planning to give the 
subject.
Prohibited Concomitant Medications/Therapies
In general, concomitant use of immune therapy agents or other immunosuppressive therapy,
including interferon-based treatment for hepatitis, is not allowed during the course of the 
study. Important exceptions to this rule include:

Short courses of corticosteroids (e.g., as for asthma exacerbation) are allowed.

Intralesional or localized electron beam therapy for cutaneous Kaposi’s sarcoma is 
permitted. 

If a subject develops a malignancy (for example lymphoma) after randomization, the 
subject may receive chemotherapy (including cancer immunotherapy) and remain in 
the study if, in the opinion of the investigator, the benefits outweigh the risks.
08K3V5

Product:  MK-1439A 
42
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Depending on the type of chemotherapy, study medication may need to be interrupted 
until completion of the chemotherapy.
Antiretroviral therapies other than those used in the study (MK-1439A, and ATRIPLA™) are 
also not permitted during the course of the study. 
Investigational agents must be discontinued 30 days prior to treatment in this study and are 
not permitted during the course of the study.
Prohibited Concomitant Therapy Due to Potential Interactions with MK-1439A
MK-1439 is expected to be eliminated mainly via CYP-mediated oxidation. 
The medications and/or substances below are prohibited in this study because they are 
moderate or potent inducers of CYP3A4 and their co-administration with MK-1439A could 
possibly result in reduced drug levels of MK-1439 or has the potential for additional drug-
drug interactions. 
Since this list is not comprehensive, the investigator should use his/her medical judgment 
when a subject presents with a medication not on the list or call the Sponsor Clinical Director 
or Designee for clarification.
Prohibited Medication/Therapy 
Due to MK-1439 Interactions
During the Base Study and Study Extensions
Carbamazepine
Enzalutamide 
Mitotane 
Oxcarbazepine
Rifapentine
Phenobarbital
Phenytoin
Rifabutin
Rifampin
St. John’s Wort
Modafinil
Bosentan
Nafcillin
Prohibited Concomitant Therapy Due to Potential Interactions with ATRIPLA™
Specific medications are prohibited during the base study due to potential interactions with 
ATRIPLA™. Efavirenz induces CYP3A4 metabolism and may significantly reduce the 
exposure of CYP3A4 substrates. 
In addition, there are some medications that may
significantly alter the metabolism of efavirenz. In some cases, co-administration of certain 
08K3V5

Product:  MK-1439A 
43
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
drugs with ATRIPLA™may lead to significant safety risks. The following medications are 
prohibited in this study because they: (1) are contraindicated for concomitant use with 
ATRIPLA™(according to one or more available ATRIPLA™package circulars), (2) may 
alter the plasma concentration of one or more of the ATRIPLA™components and/or (3) may 
have significant changes in their plasma concentrations when co-dosed with ATRIPLA™
that would require additional monitoring or dose adjustment, which is not feasible in the 
setting of a double-blind trial. 
Prohibited Medication/Therapy 
Due to ATRIPLA™ Interactions
During the Base Study
Artermether
Astemiazole
Bepridil
Boceprevir
Carbamazepine†
Cisapride
Clarithromycin
Cyclosporine
Dihydroatenisinin
Ergot derivatives
Itraconazole
Ketoconazole
Lumefantrine
Midazolam
Phenobarbital†
Phenytoin†
Pimozide
Rifabutin†
Rifampin†
Simeprevir
Sirolimus
St. John’s Wort†
Tacrolimus
Telaprevir
Terfenadine
Triazolam
Voriconazole
† Several of these medications are also 
prohibited during the study extensions
because of interaction with MK-1439A:
specifically, carbamazepine, phenobarbital, 
phenytoin, rifabutin, rifampin and St. John’s 
Wort are prohibited throughout the base 
study and the study extensions.
08K3V5

Product:  MK-1439A 
44
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
The investigator should discuss any questions regarding this with the Sponsor Clinical 
Director. 
Concomitant Therapy to be Used With Caution
For complete information, please refer to the ATRIPLA™ package circular available locally
for drugs that are permitted in the protocol but that should be used with caution, since they 
have established drug interactions with ATRIPLA™.
Rescue Medications & Supportive Care
No rescue or supportive medications are specified to be used in this trial.
Diet/Activity/Other Considerations
Diet
MK-1439A (or placebo) can be taken without regard to food and should generally be taken at 
approximately the same time each day.
ATRIPLA™(or placebo) should be taken at bedtime on an empty stomach. 
Alcohol/Substance Abuse
Subjects should be questioned about their estimated daily intake of alcohol and about 
substance abuse during the screening evaluation of eligibility. Any subject who in the 
opinion of the investigator has an excessive intake of any of these substances must be 
excluded from the study. 
Subject Withdrawal/Discontinuation Criteria
Subjects may withdraw consent at any time for any reason or be dropped from the trial at the 
discretion of the investigator should any untoward effect occur.  In addition, a subject may be 
withdrawn by the investigator or the Sponsor if enrollment into the trial is inappropriate, the 
trial plan is violated, or for administrative and/or other safety reasons.  Specific details 
regarding discontinuation or withdrawal procedures; including specific details regarding 
withdrawal from Future Biomedical Research, are provided in Section 7.1.4 – Other 
Procedures.
Discontinuation from treatment is “permanent”.  Once a subject is discontinued, he/she shall 
not be allowed to restart treatment.
A subject must be discontinued from the trial for any of the following reasons:
●
The subject or legal representative (such as a parent or legal guardian) withdraws 
consent.
08K3V5

Product:  MK-1439A 
45
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Note:  Please provide additional detail for the reason the subject withdrew consent on 
the Subject Disposition eCRF.

The subject has a medical condition or personal circumstance which, in the opinion of 
the investigator and/or Sponsor, places the subject at unnecessary risk through 
continued participation in the trial or does not allow the subject to adhere to the 
requirements of the protocol; these may include, but are not limited to:
o
clinical or laboratory findings suggestive of lactic acidosis or pronounced 
hepatotoxicity (which may include symptomatic hyperlactatemia, metabolic/lactic 
acidosis, progressive hepatomegaly, rapidly elevating aminotransferase levels, 
and hepatomegaly and steatosis even in the absence of marked transaminase 
elevations).
o
severe rash associated with blistering, desquamation, mucosal involvement or 
fever (base study)
o
severe depression, psychosis or suicidal ideation (base study).

The subject has a confirmed positive serum/urine pregnancy test.
Note: Subjects who become pregnant during the study will be asked to join a 
pregnancy registry which collects information about the outcome of the pregnancy.

The subject fails to comply with the dosing, evaluations, or other requirements of the 
trial.

A physician investigator feels it is in the best interest of the subject to discontinue.

The subject has an adverse experience or tolerability issue related to study medication 
which requires discontinuation of the medication. 

Subject has a creatinine clearance of <50 mL/min (confirmed by repeat measurement)
based on the Cockcroft-Gault equation:
Male: 
Clcr (mL/min) = (140-age) x weight (in kg)
72 x serum creatinine (mg/dL)
Female:
Clcr (mL/min) = (140-age) x weight (in kg) X 0.85
72 x serum creatinine (mg/dL) 
or subject has serum phosphorous <0.32 mmol/l. 
Note:  Subjects with serum phosphorous <0.48 mmol/l should be closely monitored.
08K3V5

Product:  MK-1439A 
46
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential

Subject requires interferon-based treatment for hepatitis. 

Subjects should be discontinued, regardless of compliance with study therapy, if they 
meet the protocol-defined virologic failure criteria in Section 4.2.3.1.

Subjects who participate in study extension 2 or study extension 3 should be 
discontinued at the next scheduled visit after MK-1439A is commercially available
once approved in the local country.
Subjects who require discontinuation of study therapy must be discontinued from the trial. 
Subjects who discontinue study therapy prior to the last scheduled treatment visit should 
have an Early Discontinuation visit and a 14-day follow-up visit conducted.
Due to the potential for severe acute exacerbations of hepatitis B following discontinuation 
of ATRIPLA™, lamivudine and tenofovir, subjects who are co-infected with hepatitis B who 
stop their assigned study therapy at or prior to the end of the study must be closely monitored 
for such exacerbations for at least 6 months. This requirement applies to subjects in both 
treatment arms. 
If approved by the Sponsor, a subject can remain on study if they cannot make it to regularly 
scheduled study visits due to unforeseen circumstances but are able to remain on study 
therapy and the Investigator believes it is in the best interest of the subject to do so.
Once discontinued from the base study, a subject is not eligible to enter study extension 1. A 
subject who completes the base study and does not elect to participate in study extension 1 is 
considered to have completed the study. Once discontinued from study extension 1, a subject 
is not eligible to enter study extension 2. Once discontinued from study extension 2, a subject 
is not eligible to enter study extension 3. 
Subject Replacement Strategy
A subject who discontinues from the trial will not be replaced.
Beginning and End of the Trial
The overall trial begins when the first subject signs the informed consent form.  The overall 
trial ends when the last subject completes the last study-related phone call or visit, 
discontinues from the trial or is lost to follow-up (i.e. the subject is unable to be contacted by 
the investigator).
08K3V5

Product:  MK-1439A 
47
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Clinical Criteria for Early Trial Termination
Early trial termination will be the result of the criteria specified below:
1. The eDMC recommends the trial be terminated and the EOC agrees.
Further recruitment in the trial or at a particular trial site(s) may be stopped due to 
insufficient compliance with the protocol, GCP, and/or other applicable regulatory 
requirements, procedure-related problems, or the number of discontinuations for 
administrative reasons is too high.
08K3V5

Product:  MK-1439A 
48
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
TRIAL FLOW CHART
Flow Chart A applies to all subjects in the base study from screening through follow-up after the Week 96 visit. Flow Chart B applies 
to those subjects continuing into study extension 1 from Week 96 through follow-up after the Week 192 visit. Flow Chart C applies to 
those subjects continuing into study extension 2 from Week 208 through follow-up after the Week 288 visit. Flow Chart D applies to 
those subjects continuing into study extension 3 from Week 304 through follow-up after the Week 384 visit. 
Flow Chart A (Base Study): Screening Through Week 96 Plus 14 Days Follow-upb
Visit Number/Title:
1
2
Random-
ization
3
4
5
6
7
8
9
10
11
12
U (Virologic 
Failure 
Confirmation)
U (Early 
Discon-
tinuation)
99
Trial Period
Screen-
ing
Treatmenta
Post-
treatmentb
Trial Procedures
Screen
Fastingc
Day 1d
WK
4
WK
8
WK
16
Fast-
ingc
WK 
24
WK 
36
Fast-
ingc
WK 
48
WK
60
WK 
72
WK 
84
Fast-
ingc
WK 
96
≥1 to ≤4 wks
after initial 
virologic 
failure
At time of 
Discon
Post-study 
14-day 
follow-upb
Administrative Procedures
Informed Consent
X
Xe
Informed Consent for Future 
Biomedical Researchf
X
Inclusion/Exclusion Criteria
X
X
Xe
Provide Subject Identification Card
X
Medical Historyg
X
Concomitant Medication Review
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Treatment Allocation/Randomization
X
Register Study Visit via Interactive 
Voice (Web) Response System 
(IVRS/IWRS)
X
X
X
X
X
X
X
X
X
X
X
X
X
Dispense Study Therapy via 
IVRS/IWRS
X
X
X
X
X
X
X
X
X
X
Xh
Provide/Review Study Medication 
Diary
X
X
X
X
X
X
X
X
X
X
X
X
Patient-Reported Outcomesi
X
X
X
X
X
Xj
Assess Subject Eligibility for Study 
Extension 1e
X
08K3V5

Product:  MK-1439A 
49
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Visit Number/Title:
1
2
Random-
ization
3
4
5
6
7
8
9
10
11
12
U (Virologic 
Failure 
Confirmation)
U (Early 
Discon-
tinuation)
99
Trial Period
Screen-
ing
Treatmenta
Post-
treatmentb
Trial Procedures
Screen
Fastingc
Day 1d
WK
4
WK
8
WK
16
Fast-
ingc
WK 
24
WK 
36
Fast-
ingc
WK 
48
WK
60
WK 
72
WK 
84
Fast-
ingc
WK 
96
≥1 to ≤4 wks
after initial 
virologic 
failure
At time of 
Discon
Post-study 
14-day 
follow-upb
Clinical Procedures/Assessments
Full Physical Examination
X
Directed Physical Examination
X
X
X
X
X
X
X
X
X
X
X
X
X
Height
X
Vital Signs (including pulse rate, 
blood pressure, respiratory rate, and 
body temperature) and Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-Lead Electrocardiogram (ECG) 
(Local)k
Xk,l
Adverse Events Monitoring
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Birth Control Confirmation
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Laboratory Procedures/Assessments
Serum Pregnancy Testm
X
Urine Pregnancy Testm
Xl
X
X
X
X
X
X
X
X
X
X
X
X
Collect Blood for Safety Laboratory 
Tests (Hematology/Chemistry)n
Xl
X
X
X
X
X
X
X
X
X
X
X
Xo
X
X
Hemostatic Function Testp
Xl
HIV/Hepatitis Screenq
Xl
Virology Test Plasma HIV viral RNA 
quantification test (Abbott Real Time 
HIV-1)
Xl
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Collect Blood for CD4 Cell Count
X
X
X
X
X
X
X
Collect Blood for MK-1439 PKr
X
X
X
X
X
Collect Plasma for Viral Resistance 
Test
X
X
X
X
X
X
X
X
X
X
X
X
Xs
Collect Blood (DNA) for Genetic 
Analysisf
X
Collect Plasma for Future Biomedical 
Researchf
X
X
X
08K3V5

Product:  MK-1439A 
50
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Visit Number/Title:
1
2
Random-
ization
3
4
5
6
7
8
9
10
11
12
U (Virologic 
Failure 
Confirmation)
U (Early 
Discon-
tinuation)
99
Trial Period
Screen-
ing
Treatmenta
Post-
treatmentb
Trial Procedures
Screen
Fastingc
Day 1d
WK
4
WK
8
WK
16
Fast-
ingc
WK 
24
WK 
36
Fast-
ingc
WK 
48
WK
60
WK 
72
WK 
84
Fast-
ingc
WK 
96
≥1 to ≤4 wks
after initial 
virologic 
failure
At time of 
Discon
Post-study 
14-day 
follow-upb
a.
Visit window periods are approximately ±3 days for the Week 4 to Week 24 visits and approximately ±7 days for the Week 36 to Week 96 visits. The timing of each visit is 
relative to the randomization (Day 1) visit. Every attempt must be made to keep subjects on schedule. 
b. The follow-up visit 14 days after the Week 96 visit in the base study applies only to subjects who do not enter study extension 1. The visit window period for the Post-study 
14-day follow-up visit is approximately -2 to 0 days. 
c.
Fasting for at least 8 hours. Fasting is required at these visits for lipids measurement. 
d. Within 45 days of screening visit and prior to the first dose on Day 1.
e.
If the subject is eligible and elects to enter study extension 1, he/she will be considered to have completed the base study and will, after providing informed consent for study 
extension 1, immediately enter study extension 1.
f.
This sample should be drawn for planned genetic analysis of DNA and drug response unless there is either a documented law or regulation prohibiting collection, or unless
the IRB/IEC does not approve of the collection of the sample for these purposes. If the sample is collected, any leftover extracted DNA will be stored for future biomedical 
research if the subject signs the Future Biomedical Research consent. Plasma samples for Future Biomedical Research should be collected at Day 1, and Weeks 48 and 96. 
g. Includes smoking history. 
h. For Week 96, drug will be dispensed only to subjects who enter study extension 1, after providing informed consent.
i.
Includes 1 questionnaire: Work Productivity and Activity Impairment Questionnaire (WPAI). 
j.
Not applicable for subjects who discontinue after Week 48.
k. A local ECG should be performed prior to the subject’s first dose of study medication (within 7 days prior to the Study Day 1 visit). 
l.
Results of test must be available prior to randomization.
m. For women of childbearing potential.
n. Refer to Table 4 for listing of specific blood safety tests.
o. For creatinine clearance only.
p. Hemostatic Function Test includes: Prothrombin time (PT), Activated Partial Thromboplastin Time (APTT), and International Normalized Ratio (INR).
q. HIV/Hepatitis Screen tests includes:  Enzyme immunoassay HIV antibody screen, Serum Hepatitis B surface antigen, Serum Hepatitis B surface antibody, Serum Hepatitis B 
e-antigen and Serum Hepatitis C antibody. A plasma hepatitis C virus PCR quantitative test will be performed if the Hepatitis C antibody test is positive.
r.
One sample for assay of MK-1439 plasma concentrations will be collected at Day 1 (Pre-dose), Week 4 (pre-dose), and Week 8 (random). At Weeks 24 and 48, 2 samples 
will be collected, pre-dose and 30 mins to 2 hours postdose (the subject should be fasting for both samples). 
s.
If virologic failure is confirmed (with a confirmatory HIV-1 RNA at least one week later), and the decision is made to discontinue the subject, plasma for resistance need not 
be collected again at the early discontinuation visit. All other early discontinuation tests should be performed at the early discontinuation visit.
08K3V5

Product:  MK-1439A 
51
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Flow Chart B (Study Extension 1): Week 100 Through Week 192 Plus 14 Days Follow-up
Visit Number/Title:
13a
14
15
16
17
18
19
U (Virologic Failure 
Confirmation)
U (Early 
Discontinuation)
99
Trial Period
Treatmentb
TRIAL PROCEDURES
WK 
100
WK 
116
WK 
132
Fasting 
WK 
148
WK
164
WK
180
Fasting 
WK
192
>1 to <4 wks 
after the time virologic 
failure is first identified
At time of 
Discontinuation
Post-study
14-day 
follow-up
Administrative Procedures
Concomitant Medication Review
X
X
X
X
X
X
X
X
X
Register Study Visit via Interactive Voice Response 
System (IVRS/IWRS)c
X
X
X
X
X
X
X
X
Dispense Study Therapy (Open-Label MK-1439A)
X
X
X
X
X
X
Xd
Provide/Review Study Medication Diary
X
X
X
X
X
X
X
X
Assess Subject Eligibility for Study Extension 2e
X
Informed Consent for Study Extension 2e
X
Clinical Procedures/Assessments
Directed Physical Examination
X
X
X
X
X
X
X
X
X
Vital Signs (including pulse rate, blood pressure, 
respiratory rate, & body temperature) and Weight
X
X
X
X
X
X
X
X
X
Adverse Events Monitoring
X
X
X
X
X
X
X
X
X
Laboratory Procedures/Assessments 
Urine Pregnancy testf
X
X
X
X
X
X
X
X
X
Collect Blood for Safety Laboratory Tests 
Hematology/Chemistryg
X
X
X
Xh
X
X
Xh
Xi
X
X
Virology Test Plasma HIV viral RNA quantification 
test (Abbott RealTime HIV-1)
X
X
X
X
X
X
X
X
X
X
Collect Blood for CD4 Cell Count
X
X
X
Collect Plasma for Viral Resistance Test
X
Xj
08K3V5

Product:  MK-1439A 
52
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Visit Number/Title:
13a
14
15
16
17
18
19
U (Virologic Failure 
Confirmation)
U (Early 
Discontinuation)
99
Trial Period
Treatmentb
TRIAL PROCEDURES
WK 
100
WK 
116
WK 
132
Fasting 
WK 
148
WK
164
WK
180
Fasting 
WK
192
>1 to <4 wks 
after the time virologic 
failure is first identified
At time of 
Discontinuation
Post-study
14-day 
follow-up
a. Subjects who enter study extension 1 are considered enrolled in study extension 1 upon providing written informed consent for study extension 1 at the Week 96 study visit
of the base study.
b. The visit window for Week 100 is approximately ±7 days, for all visits from Week 116 through Week 192 the windows are approximately ±14 days and, for the post-study 
14-day follow-up visit, the window is approximately –2 to 0 days. The timing of each visit is relative to the randomization (Day 1) visit. Every attempt must be made to 
keep subjects on schedule.
c. IVRS/IWRS will be used to allocate drug and to manage distribution of clinical supplies.
d. Study drug for extension 2 will be dispensed at Week 192, if subject is continuing into extension 2.
e. If the subject is eligible and elects to enter study extension 2, he/she will be considered to have completed study extension 1 and will, after providing informed consent, 
immediately enter study extension 2 and be dispensed MK-1439A.
f.
For women of childbearing potential.
g. Refer to Table 4 for listing of specific blood safety and chemistry tests.
h. Fasting at least 8 hours prior to study visit is required for lipids measurement at Week 148 and Week 192. 
i.
For creatinine clearance only.
j.
If virologic failure is confirmed (with a confirmatory HIV-1 RNA at least one week later), and the decision is made to discontinue the subject, plasma for resistance need not 
be collected again at the early discontinuation visit. All other early discontinuation tests should be performed at the early discontinuation visit.
08K3V5

Product:  MK-1439A 
53
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Flow Chart C (Study Extension 2): Week 208 Through Up to Week 288 Plus 14 Days Follow-up
Visit Number/Title
20a
21
22
23
24
25
U (Early 
Discontinuation)
99
Trial Period
Treatmentb,c
TRIAL PROCEDURES
WK 
208
WK 
224
WK 
240
WK 
256
WK
272
WK
288
At time of 
Discontinuation
Post-study 
14-day follow-upd
Administrative Procedures
Register Study Visit via Interactive Voice Response System (IVRS/IWRS)
X
X
X
X
X
X
X
Dispense Study Therapy (Open-Label MK-1439A) e
X
X
X
X
X
Xf
Assess Subject Eligibility for Study Extension 3
X g
Informed Consent for Study Extension 3
X g
Clinical Procedures/Assessments
Serious Adverse Events Monitoring
X
X
X
X
X
X
X
X
Birth Control Confirmation
X
X
X
X
X
X
X
X
Laboratory Procedures/Assessments 
Urine Pregnancy testh
X
X
X
X
X
X
X
X
a.
Subjects who enter study extension 2 are considered enrolled in study extension 2 upon providing written informed consent for study extension 2 at the Week 192 study visit 
of study extension 1. 
b. The total duration is dependent on when MK-1439A becomes locally available, with a maximum total duration of treatment of 288 weeks.  Subjects should discontinue at 
the next scheduled visit after MK-1439A becomes locally available in the market.
c.
The visit windows are approximately ±14 days for all visits from Week 208 through Week 288.  The timing of each visit is relative to the randomization (Day 1) visit.  
Every attempt must be made to keep subjects on schedule. 
d. The visit window for the post-study 14-day follow-up visit is approximately –2 to 0 days. 
e.
IVRS/IWRS will be used to allocate drug and to manage distribution of clinical supplies.
f.
Study drug for extension 3 will be dispensed at Week 288, if subject is continuing into extension 3.
g. If the subject is eligible and elects to enter study extension 3, he/she will be considered to have completed study extension 2 and will, after providing informed consent, 
immediately enter study extension 3 and be dispensed MK-1439A.
h. For women of childbearing potential.
08K3V5

Product:  MK-1439A 
54
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Flow Chart D (Study Extension 3):  Week 304 Through Up to Week 384 Plus 14 Days Follow-up
Visit Number/Title
26a
27
28
29
30
31
U (Early 
Discontinuation)
99
Trial Period
Treatmentb,c
TRIAL PROCEDURES
WK 
304
WK 
320
WK 
336
WK 
352
WK
368
WK
384b
At time of 
Discontinuation
Post-study 
14-day follow-upd
Administrative Procedures
Register Study Visit via Interactive Voice Response System (IVRS/IWRS)
X
X
X
X
X
X
X
Dispense Study Therapy (Open-Label MK-1439A) e
X
X
X
X
X
Clinical Procedures/Assessments
Serious Adverse Events Monitoring
X
X
X
X
X
X
X
X
Birth Control Confirmation
X
X
X
X
X
X
X
X
Laboratory Procedures/Assessments 
Urine Pregnancy testf
X
X
X
X
X
X
X
X
a.
Subjects who enter study extension 3 are considered enrolled in study extension 3 upon providing written informed consent for study extension 3 at the Week 288 study visit 
of study extension 2.
b.
The total duration is dependent on when MK-1439A becomes locally available, with a maximum total duration of treatment of 384 weeks.  Subjects should discontinue at the 
next scheduled visit after MK-1439A becomes locally available in the market.
c.
The visit windows are approximately ±14 days for all visits from Week 304 through Week 384.  The timing of each visit is relative to the randomization (Day 1) visit.  
Every attempt must be made to keep subjects on schedule. 
d.
The visit window for the post-study 14-day follow-up visit is approximately –2 to 0 days.
e.
IVRS/IWRS will be used to allocate drug and to manage distribution of clinical supplies.
f.
For women of childbearing potential. 
08K3V5

Product:  MK-1439A 
55
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
TRIAL PROCEDURES
Trial Procedures
The Trial Flow Chart - Section 6.0 summarizes the trial procedures to be performed at each 
visit.  Individual trial procedures are described in detail below.  It may be necessary to 
perform these procedures at unscheduled time points if deemed clinically necessary by the 
investigator.
Furthermore, additional evaluations/testing may be deemed necessary by the investigator and 
or the Sponsor for reasons related to subject safety. In some cases, such evaluation/testing 
may be potentially sensitive in nature (e.g., HIV, Hepatitis C, etc.), and thus local regulations 
may require that additional informed consent be obtained from the subject.  In these cases, 
such evaluations/testing will be performed in accordance with those regulations.
Administrative Procedures
Informed Consent
The investigator or qualified designee must obtain documented consent from each potential 
subject or each subject’s legally acceptable representative prior to participating in a clinical 
trial or Future Biomedical Research.
General Informed Consent
Consent must be documented by the subject’s dated signature or by the subject’s legally 
acceptable representative’s dated signature on a consent form along with the dated signature 
of the person conducting the consent discussion. 
A copy of the signed and dated consent form should be given to the subject before 
participation in the trial.
The initial informed consent form, any subsequent revised written informed consent form 
and any written information provided to the subject must receive the IRB/ERC’s 
approval/favorable opinion in advance of use.  The subject or his/her legally acceptable 
representative should be informed in a timely manner if new information becomes available 
that may be relevant to the subject’s willingness to continue participation in the trial.  The 
communication of this information will be provided and documented via a revised consent 
form or addendum to the original consent form that captures the subject’s dated signature or 
by the subject’s legally acceptable representative’s dated signature.
Specifics about a trial and the trial population will be added to the consent form template at 
the protocol level.  
The informed consent will adhere to IRB/ERC requirements, applicable laws and regulations 
and Sponsor requirements.
08K3V5

Product:  MK-1439A 
56
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Consent and Collection of Specimens for Future Biomedical Research
The investigator or qualified designee will explain the Future Biomedical Research consent 
to the subject, answer all of his/her questions, and obtain written informed consent before 
performing any procedure related to Future Biomedical Research.  A copy of the informed 
consent will be given to the subject.
Inclusion/Exclusion Criteria
All inclusion and exclusion criteria will be reviewed by the investigator or qualified designee 
to ensure that the subject qualifies for the trial. A review of these criteria should occur at the 
Screening visit and on the Day 1 visit (prior to randomization). For subjects who wish to
continue into study extension 1, the additional inclusion criteria (9 to 12, Section 5.1.2) are 
to be reviewed at the Week 96 study visit. For subjects who wish to continue into study
extension 2, the additional inclusion criteria (13 to 16, Section 5.1.2) are to be reviewed at 
the Week 192 study visit. For subjects who wish to continue into study extension 3, the 
additional inclusion criteria (17 to 20, Section 5.1.2) are to be reviewed at the Week 288
study visit.  
Subject Identification Card
All subjects will be given a Subject Identification Card identifying them as participants in a 
research trial.  The card will contain trial site contact information (including direct telephone 
numbers) to be utilized in the event of an emergency.  The investigator or qualified designee 
will provide the subject with a Subject Identification Card immediately after the subject 
provides written informed consent.
The subject identification card also contains contact information for the emergency 
unblinding call center so that a health care provider can obtain information about trial 
medication/vaccination in emergency situations where the investigator is not available.
Medical History
A medical history will be obtained by the investigator or qualified designee at the Screening 
visit. The medical history should include information pertaining to the diagnosis of HIV 
infection and the year diagnosed. If a subject has previously been diagnosed with any AIDS 
defining condition, or CD4 <200, the condition as well as a corresponding medical history of 
Acquired Immune Deficiency Syndrome must be reported. In addition, the subject’s history 
of smoking should be obtained and recorded on the appropriate eCRF.
Prior and Concomitant Medications Review
Prior Medications
The investigator or qualified designee will review prior medication use and record all 
medication taken by the subject within 30 days before starting the study.
08K3V5

Product:  MK-1439A 
57
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Investigational agents must be discontinued 30 days prior to receiving study therapy.
Concomitant Medications
The investigator or qualified designee will record medication, if any, taken by the subject 
during the trial.
Assignment of Screening Number
All consented subjects will be given a unique screening number that will be used to identify 
the subject for all procedures that occur prior to randomization or allocation.  Each subject 
will be assigned only one screening number.  Screening numbers must not be re-used for 
different subjects.  
The site must access the IVRS/IWRS system to register each screening subject. 
Specific details on the screening visit requirements are provided in Section 7.1.5.1.
Assignment of Randomization Number
All eligible subjects will be randomly allocated and will receive a randomization number.  
The randomization number identifies the subject for all procedures occurring after 
randomization.  Once a randomization number is assigned to a subject, it can never be re-
assigned to another subject.
A single subject cannot be assigned more than 1 randomization number.
Trial Compliance (Medication/Diet/Activity/Other)
Subject Diary Cards will be used to ensure and document drug compliance for the base study
and study extension 1. 
On Day 1, the investigator/study coordinator will give the subject a diary card to be 
completed during the study period. The study coordinator will be responsible for entering 
the subject’s identification (randomization number) before giving the diary card to the 
subject. The subject should follow the instructions on the diary card for recording all study 
drugs. Aside from the initial information entered by the study coordinator, only the subject
should enter information on the diary card. The subject is to return the completed diary card 
at each scheduled visit. The study coordinator will be responsible for reviewing the diary 
card for completeness and accuracy with the subject. Only the subject shall make any 
changes to the entries on the card. The subject will initial the card to confirm that the 
information is accurate. The study coordinator will be responsible for transferring the 
appropriate information from the diary card onto the appropriate case report form. 
Rigorous monitoring is especially important during the early part of the study, specifically 
between the Day 1 and Week 4 visits to ascertain if there are problems with non-compliance 
08K3V5

Product:  MK-1439A 
58
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
as early as possible, to access whether the subject is taking study medication as directed and 
to ensure that subjects experiencing difficulties are re-educated, as appropriate. 
Subject Medication Diary will not be used during study extension 2 or study extension 3. 
Sites are responsible for source documentation of drug accountability. 
Interruptions from the protocol specified treatment plan that are expected to be 7 days or 
greater due to non-compliance require consultation between the investigator and the Sponsor 
and written documentation of the collaborative decision on subject management.
Patient-Reported Outcomes
Subjects will complete the WPAI at Day 1, Weeks 4, 8, 16, and 48 or at the Early 
Discontinuation visit if the subject discontinues from the study early.
Work Productivity and Activity Impairment Questionnaire
This WPAI is a validated 6-item questionnaire that was created as a patient-reported 
quantitative assessment of the amount of absenteeism, presenteeism and daily activity 
impairment attributable to general health or a specific health problem. The questionnaire 
utilizes a one-week recall period. The measure assesses the quantitative impact of health 
conditions on loss of time and impaired productivity for functional activities such as work-
for-pay, school work, and work around the house. The WPAI has been used in studies of 
HIV-infected patients.
Administration
Subjects are to complete the questionnaire on their own at the site using an electronic data 
capture tool at the beginning of the appropriate study visit (see trial flow chart). Every 
attempt should be made for the subjects to complete the questionnaire prior to receiving 
study treatment, discussing any medical conditions with the study personnel, or receiving any 
medical results. Subjects will be eligible to complete the questionnaire only if language 
translations are available in the subject’s native language. 
Clinical Procedures/Assessments
Physical Examination
All physical examinations should be performed as indicated in the Trial Flow Charts
(Section 6.0). All physical examinations must be performed by the principal investigator or 
subinvestigator (physician, physician assistant or nurse practitioner). 
A complete (full) physical examination (including vital signs [weight, pulse, respiratory rate, 
blood pressure, and body temperature]) must be obtained at the Screening visit. A complete 
physical examination generally includes the following assessments: general appearance, 
head, eyes, ears/nose/ throat, neck, lymph nodes, skin, lungs, heart, abdomen, 
08K3V5

Product:  MK-1439A 
59
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
musculoskeletal, and neurologic evaluations. Breast, rectal, and genitourinary/pelvic exams 
should be performed when clinically indicated. 
Physical examinations after the Screening visit will be directed exams and will include vital 
signs. Any significant changes between the Screening and Day 1 visits should be noted in 
the Medical History eCRF at Day 1. Any significant changes in the physical examination 
after receiving study therapy at Day 1 must be reported as adverse events and entered on the 
adverse event eCRF. If the subject is discontinued for any reason during the treatment phase, 
every attempt should be made to perform a final physical examination.
Height Assessment
The subject's height should be assessed as indicated in the Trial Flow Chart (Section 6.0). If 
height is measured after the Screening visit, the site should indicate whether or not the result 
is clinically significant and the result should be documented in the subject’s chart. If the 
result is clinically significant, it should be captured as an adverse event on the eCRF. 
Vital Signs and Weight
Vital signs, including pulse rate, respiratory rate, blood pressure and body temperature, and 
weight should be assessed as indicated in the Trial Flow Charts (Section 6.0). Subjects 
should be resting in a semi-recumbent position for at least 10 minutes prior to having vital 
sign measurements obtained. 
Note:  Oral temperatures should be taken. If an oral temperature measurement is not 
possible, a tympanic, rectal, or axillary temperature measurement may be taken and should 
be recorded appropriately. 
After the Screening visit, the site should indicate whether or not the result is clinically 
significant and document in the subject's chart. If any result is clinically significant, it should 
be captured as an adverse event on the eCRF. 
12-Lead ECG (performed locally)
A local 12-Lead ECG should also be performed prior to the subject’s first dose of study 
medication (within 7 days prior to the Study Day 1 visit), as indicated in the Trial Flow Chart
A (Section 6.0), and any abnormalities documented. Results must be available prior to 
subject randomization. Subjects should be resting in a semi-recumbent position for at least 
10 minutes prior to having ECG readings obtained. Clinically significant findings from the 
pre-Day 1/Day 1 ECG must be documented in the subject's chart and captured in the medical 
history eCRF. 
If an ECG is performed for any medical reason while patient is on the study treatment, or 
during the follow-up period, any clinically significant changes compared with the Day 1 
ECG must be captured as AEs on the eCRF and documented in the subject’s chart.
08K3V5

Product:  MK-1439A 
60
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Adverse Events
When evaluating an adverse event, the investigator should document in the eCRF if there is a 
likely causality relationship to IRIS during the base study.
If a subject has been diagnosed with an AIDS defining condition following randomization, 
the condition must be reported as an AE. 
Due to the use of lamivudine and ATRIPLA™in this trial, subjects should be monitored for 
symptoms of hyperlactatemia in the base study and in the study extensions. 
Details on assessing and recording adverse events can be found in Section 7.2.
Toxicity Management
Guidelines for grading the severity of laboratory adverse events are based on criteria for 
grading severity of adverse events (Section 12.8). Decisions to temporarily withhold study 
therapy because of an adverse experience will be reviewed on a case-by-case basis by the 
investigator. 
The investigator should consider temporarily withholding study therapy if the severity 
of the adverse experience is Grade 3 or above and/or if clinically indicated. The 
decision to interrupt study therapy should take into account the subject’s baseline 
laboratory values and any concomitant medication that could be contributory. At the 
discretion of the investigator, therapy may generally be reinitiated when laboratory 
abnormalities or clinical adverse events return to near normal or baseline values.
If the adverse experience is considered serious and may have been caused by study 
medication (as defined in Section 7.2.4) or if re-exposure to the test drug poses additional 
potential significant risk to the subject, then the rechallenge must be approved in advance by 
the MSD Clinical Director or Designee and, if required, by the Independent Ethics 
Committee/Institutional Review Board and a rechallenge consent is needed prior to re-
initiation of study therapy. If advance approval of rechallenge is not required by local 
regulations, the IEC/IRB will receive notification for information only. 
If, after re-initiation of study therapy, there is a recurrence of the laboratory abnormality or 
clinical adverse event, consideration should be given to permanently discontinuing all study 
therapy. Whenever study drugs are interrupted, the MSD Clinical Director or Designee 
should be notified. 
Birth Control Confirmation
Care must be taken to avoid pregnancy in female subjects of childbearing potential and in the 
female partners of childbearing potential of male subjects. 
Site personnel must confirm that subjects and their partner(s) are using acceptable methods 
of contraception. This confirmation must be documented in the subject's chart.
08K3V5

Product:  MK-1439A 
61
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Laboratory Procedures/Assessments
Details regarding specific laboratory procedures/assessments to be performed in this trial are 
provided below. The total amount of blood/tissue to be drawn/collected over the course of 
the trial (from pre-trial to post-trial visits), including approximate blood/tissue volumes 
drawn/collected by visit and by sample type per subject can be found in Section 12.4. 
Serum /Urine Pregnancy Test 
For women of childbearing potential, serum pregnancy is to be done at the Screening visit, 
and urine pregnancy is to be done at the Day 1 visit prior to randomization. Urine pregnancy 
tests must also be subsequently done at each study visit (except at Virologic Failure 
Confirmation) including the Early Discontinuation Visit (if applicable) and 14-day Follow-up 
visits in both the base study and the study extensions. Results must be documented in the 
subject’s chart. A subject found to be pregnant must be discontinued from the study.
Laboratory Safety Evaluations (Hematology, Chemistry and Others)
Laboratory tests (hematology, chemistry and other) which are to be performed during the 
base study and study extension 1 are specified in Table 4. 
Table 4
Laboratory Tests
Hematology
Chemistry9
Other
Hematocrit
Aspartate aminotransferase (AST, 
SGOT)
Prothrombin time (PT)3
Hemoglobin
Alanine aminotransferase (ALT, 
SGPT)
Activated partial thromboplastin 
time (APTT)3
Platelet count
Alkaline phosphatase
International Normalized Ratio 
(INR)3
Red Blood Cell Count
Creatine Kinase
Hepatitis B Virus surface antigen3
Erythrocyte Mean corpuscular 
volume
Total Bilirubin  
Hepatitis B Virus surface antibody3
White Blood Cell Count (Total 
and Differential)
Direct Bilirubin
Hepatitis B e-Antigen3
CD4% and Absolute CD4/ 
Lymphocytes
Indirect Bilirubin
Hepatitis C Antibody3
CD8% and Absolute 
CD8/Lymphocytes
Amylase
Plasma hepatitis C virus PCR 
quantitative4
CD4/CD8 ratio
Lipase
Enzyme immunoassay HIV antibody 
(with confirmation WB)3
Glucose, fasting1
HIV viral RNA Quantification
Glucose, non-fasting2
Serum -human chorionic 
gonadotropin (hCG) test5
Blood Urea Nitrogen
Urine -human chorionic 
gonadotropin (hCG) test6
Creatinine8
HIV Viral resistance7
Calcium
08K3V5

Product:  MK-1439A 
62
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Hematology
Chemistry9
Other
Phosphorus
Magnesium
Protein
Albumin
Sodium
Potassium
Chloride
Bicarbonate
High density lipoprotein cholesterol 
(HDL-C) (Fasting1)
Low-density lipoprotein cholesterol 
(LDL-C) (fasting1)
Triglycerides (fasting1)
Total Cholesterol (fasting1)
1. Perform at Randomization (Day 1), and the Weeks 24, 48, and 96 visits in base study; and at the Week 148 and 192 visits in study 
extension 1. Subjects should be fasting for 8 hours. 
2. Perform at the Screening and Randomization visits, the Week 4, 8, 16, 36, 60, 72 and 84 visits in base study; in study extension 1 at the 
Week 100, 116, 132, 164 and 180 visits; and the 14-day follow-up visit.
3. Perform at the screening visit only.
4. If the result of the Hepatitis C Antibody testing is positive, then a plasma hepatitis C virus PCR quantitative test will also be performed.
5. Serum hCG test at the Screening visit to be performed by central laboratory.
6. Urine hCG test to be performed at the investigator site at Day 1 and every study visit thereafter.
7. Collect plasma samples at the Screening visit, all scheduled study visits in the base study (except the Day 1 and Post-Study 14-day 
follow-up visit), the Virologic Failure confirmation visit, and the Early Discontinuation visit (if not collected at Virologic Failure 
confirmation visit). In study extension 1, sample will be collected at the Virologic Failure Confirmation visit and at the Early 
Discontinuation Visit (if not already obtained at Virologic Failure Confirmation visit). The samples will be tested as specified in 
Section 7.1.3.5 Viral Resistance Testing. 
8. Creatinine clearance will be computed at every visit by the central laboratory and provided to the site in the report that the site receives 
from the central laboratory
9. Sample taken at virologic failure confirmation visits for creatinine clearance only.
HIV/ Hepatitis Screening 
At the Screening visit, serum HIV/Hepatitis screening tests will be performed including:  
Enzyme immunoassay HIV antibody (with confirmation WB), serum Hepatitis B surface 
antigen, serum Hepatitis B surface antibody, serum Hepatitis B e-antigen and serum Hepatitis 
C antibody. A plasma hepatitis C virus PCR quantitative test will be performed if the 
Hepatitis C antibody test is positive.
Virology Test
Plasma HIV-1 RNA quantification will be performed at all visits in the base study and study 
extension 1. The testing will be performed at the central laboratory using the Abbott 
RealTime HIV-1 assay.
Viral Resistance Testing
Blood samples will be collected for genotypic HIV viral resistance testing at the Screening
visit to determine MK-1439, efavirenz, emtricitabine, tenofovir, and lamivudine resistance.
Additional resistance testing on screening samples may be performed. In the base study, 
blood samples will also be collected for potential HIV viral resistance testing at all scheduled
08K3V5

Product:  MK-1439A 
63
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
study visits (except the Day 1 and Post-Study 14-day follow-up visit), the Virologic Failure 
Confirmation visit and at the Early Discontinuation Visit (if not already obtained at Virologic 
Failure Confirmation visit). In study extension 1, resistance sample will be collected at the 
Virologic Failure Confirmation Visit and at the Early Discontinuation Visit (if not already 
obtained at Virologic Failure Confirmation Visit). All resistance testing in the base study 
and in study extension 1 will be performed by the central laboratory.
CD4 Cell Counts
CD4 cell count (absolute and percentage) will be determined at Screening, Day 1, and at the 
Week 8, 24, 48, 72, and 96 visits in the base study; for subjects who continue into study 
extension 1, CD4 cell count will also be determined at the Week 100, 148, and 192 visits.
The testing (in the base study and study extension 1) will be performed at the central 
laboratory using a commercially available assay. 
Pharmacokinetic/Pharmacodynamic Evaluations
MK-1439 population PK samples will be collected from all subjects as outlined in Table 5.
The exact time the dose of study medication (Bottle A) was taken prior to the sample 
collection will be recorded on the appropriate eCRF. The type of meal (full, medium, light 
or no meal) consumed with the last dose of study medication (Bottle A) prior to the 
collection of the PK sample will also be recorded on the appropriate eCRF. The type of meal 
is defined as the following:  

No Meal - the subject did not have a meal

Light Meal - the subject consumed a snack (less than 250 calories)

Medium Meal - the subject consumed a small meal (from 250 to 750 calories)

Full Meal - the subject consumed a large meal (greater than 750 calories)
Note:  At Week 24 (Visit 6) and Week 48 (Visit 8), 2 PK samples will be collected, one pre-
dose and one 0.5-2.0 hours post-dose. Subjects should be fasting for the collection of both 
samples. Subjects will be given their dose of Bottle A in the office following the collection 
of the pre-dose sample and may stay in the office or return to the office for the collection of 
the post-dose sample. 
08K3V5

Product:  MK-1439A 
64
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Table 5
Pharmacokinetic Sampling Timepoints
Visit 
Number
Study 
Day/Week
Time Relative to Bottle A Dose 
(MK-1439 or placebo)
2
Day 1
Sample to be collected predose 
3
Week 4
Sample to be collected predose
4
Week 8
Sample to be collected pre or postdose
6
Week 24
Sample to be collected predose and within 0.5 to 2 hours 
postdose (Subject should remain fasting until the postdose PK 
sample is collected).
8
Week 48
Sample to be collected predose and within 0.5 to 2 hours 
postdose (Subject should remain fasting until the postdose PK 
sample is collected).
Sample collection, storage and shipment instructions for the PK samples will be provided in 
the operations/laboratory manual. 
Future Biomedical Research
The following specimens are to be obtained as part of Future Biomedical Research:

Leftover DNA for future use

Plasma for future biomedical research
Other Procedures
Withdrawal/Discontinuation
When a subject discontinues/withdraws from participation in the trial, all applicable activities 
scheduled for the Early Discontinuation Visit should be performed at the time of 
discontinuation. 
 
Any 
adverse 
events 
which 
are 
present 
at 
the 
time 
of 
discontinuation/withdrawal should be followed in accordance with the safety requirements 
outlined in Section 7.2 - Assessing and Recording Adverse Events. 
In addition, all 
investigative products must be retrieved from the subject.
Withdrawal From Future Biomedical Research
Subjects may withdraw their consent for Future Biomedical Research and have their 
specimens and all derivatives destroyed.   Subjects may withdraw consent at any time by 
08K3V5

Product:  MK-1439A 
65
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
contacting the principal investigator for the main trial.  If medical records for the main trial 
are still available, the investigator will contact the Sponsor using the designated mailbox 
(clinical.specimen.management@MSD.com), and a form will be provided by the Sponsor to 
obtain appropriate information to complete specimen withdrawal.  Subsequently, the 
subject's specimens will be removed from the biorepository and be destroyed.  A letter will 
be sent from the Sponsor to the investigator confirming the destruction. It is the 
responsibility of the investigator to inform the subject of completion of destruction.  Any 
analyses in progress at the time of request for destruction or already performed prior to the 
request being received by the Sponsor will continue to be used as part of the overall research 
trial data and results.   No new analyses would be generated after the request is received.
In the event that the medical records for the main trial are no longer available (e.g., if the 
investigator is no longer required by regulatory authorities to retain the main trial records) or 
the specimens have been completely anonymized, there will no longer be a link between the 
subject’s personal information and their specimens. 
In this situation, the request for 
specimen destruction cannot be processed.
Blinding/Unblinding
Procedures for blinding and unblinding apply only to the base study; treatment during the 
study extensions is open-label.
STUDY TREATMENT IDENTIFICATION INFORMATION IS TO BE UNMASKED 
ONLY IF NECESSARY FOR THE WELFARE OF THE SUBJECT. EVERY EFFORT 
SHOULD BE MADE NOT TO UNBLIND THE SUBJECT UNLESS NECESSARY.
For emergency situations where the investigator or subinvestigator needs to identify the drug 
used by a subject and/or the dosage administered in case of emergency, he/she will contact 
the emergency unblinding call center by telephone and make a request for emergency 
unblinding.  As requested by the investigator or subinvestigator the emergency unblinding 
call center will provide the information to him/her promptly and report unblinding to the 
sponsor.  The emergency unblinding call center will make a record promptly however, the 
investigator or subinvestigator must enter the intensity of the adverse experiences observed, 
their relation to study drug, the reason thereof, etc., in the medical chart etc., before 
unblinding is performed.
Additionally, the investigator must go into the IVRS system and perform the unblind in the 
IVRS system to update drug disposition.  In the event that the emergency unblinding call 
center is not available for a given site in this trial, IVRS/IWRS should be used for emergency 
unblinding in the event that this is required for subject safety.
Study treatment identification information is to be unmasked ONLY if necessary for the 
welfare of the subject. Every effort should be made not to unblind the subject unless 
necessary. 
08K3V5

Product:  MK-1439A 
66
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
In the event that unblinding has occurred, the circumstances around the unblinding (eg, date, 
reason and person performing the unblinding) must be documented promptly, and the 
Sponsor Clinical Director notified as soon as possible. Once an emergency unblinding has 
taken place, the principal investigator, site personnel, and Sponsor personnel may be
unblinded so that the appropriate follow-up medical care can be provided to the subject.
Calibration of Equipment
The investigator or qualified designee has the responsibility to ensure that any device or 
instrument used for a clinical evaluation/test during a clinical study that provides information 
about inclusion/exclusion criteria and/or safety or efficacy parameters shall be suitably 
calibrated and/or maintained to ensure that the data obtained is reliable and/or reproducible. 
Documentation of equipment calibration must be retained as source documentation at the 
study site.
Please refer to the central laboratory manuals for equipment requirements and necessary 
maintenance or calibration.
Visit Requirements
Visit requirements are outlined in Section 6.0 - Trial Flow Chart.   Specific procedure-related 
details are provided above in Section 7.1 - Trial Procedures.
Screening
Written informed consent/assent must be obtained from the subject prior to performing any 
study-specific procedures. Potential subjects will be evaluated to determine if they fulfill the 
Inclusion/Exclusion entry requirements as set forth in Section 5.1. The investigator will 
discuss with each potential subject the study, its requirements, and its restrictions. The study 
screening period is 45 days.

All procedures listed for the Screening visit (Visit 1) in the Trial Flow Chart (Section 6.0) 
must be completed and the subjects eligibility confirmed by the investigator prior to the 
subject’s randomization and drug administration on Day 1.

Blood will be collected for safety laboratory evaluations, hemostatic function tests, 
HIV/Hepatitis Screen, HIV-1 RNA quantification, CD4 cell counts, and viral resistance 
testing. These samples will be sent to the appropriate central laboratory(ies) following 
the procedure(s) set forth in the manual(s).

Female subjects of childbearing potential will have a serum pregnancy test (hCG) 
collected at the screening visit. Women who are found to be pregnant will be excluded 
from the study.

Subjects will be instructed about the restrictions for concomitant medications, as noted in 
Section 5.5.
08K3V5

Product:  MK-1439A 
67
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential

Subjects will be given a study participation identification card. The card will contain 
contact information (including direct telephone numbers) to be utilized in the event of an 
emergency.
Treatment Visits in Base Study (Visit 2 to 12)
Randomization Day 1 (Visit 2)

Procedures listed for Day 1 (Visit 2) on the Trial Flow Chart A (Section 6.0) should be 
performed prior to the subject’s randomization and drug administration on Day 1, unless 
otherwise specified.

For a female subject who is of childbearing potential, a urine pregnancy test will be 
performed at the site prior to study drug initiation. If the urine pregnancy test result is 
negative and the subject meets the other criteria, the subject will be eligible for 
randomization and the remainder of the pre-treatment (Day 1) testing/procedures will be 
performed. 
If the urine pregnancy test result is positive, the subject must not be 
randomized. 

Fasting blood will be collected for safety laboratory evaluations, HIV-1 RNA 
quantification, CD4 cell counts, and PK measurements. These samples will be sent to the 
appropriate central laboratory(ies) following the procedure(s) set forth in the manual(s). 

Following completion of the Day 1 pre-treatment procedures and confirmation of 
eligibility, the site pharmacist or study coordinator will contact the IVRS/IWRS for 
assignment of the drug to be administered. Sites should not call IVRS/IWRS for drug 
administration until the subject has met all criteria for the study and are ready to receive 
the first dose of study medication on Day 1. 

Randomized subjects will receive a 4-week supply of study medication (1 bottle each
labeled A and B) on Day 1 (Visit 2). Subjects will be instructed to take their first dose of 
all study medication on the same day as the Day 1 study visit. 

The investigator/study coordinator will give the subject a study medication diary to be 
completed starting on Day 1 and continuing through the treatment period. The site must 
ensure that the subject is properly trained and comfortable with completing the 
medication diary prior to leaving the clinic.
Drug Administration
Subjects will be dispensed study drug as outlined in Table 6 for the base study. 
08K3V5

Product:  MK-1439A 
68
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Table 6
Study Drug Bottle (A and B) Components  
Bottle Label
Component
Bottle A
MK-1439A or placebo
Bottle B
ATRIPLA™ or placebo
Subjects will be instructed to take the study medication as follows:
All Subjects will take one tablet once-daily from each of the bottles as follows:
Bottle A (MK-1439A or placebo):  
Subjects will be instructed to take one tablet from Bottle A once a day (q.d.) orally, with or 
without food at approximately the same time each day. Tablets from Bottle A must be kept 
in the bottle prior to taking study medication since the formulation being used in this study is 
moisture sensitive.
Bottle B (ATRIPLA™or placebo):  
Subjects will be instructed to take one tablet from Bottle B once a day (q.d.) orally, at 
bedtime, on an empty stomach. 
Note: Study medication should be taken directly from the study bottle. 
Week 4 (Visit 3) to Week 96 (Visit 12)

All procedures for treatment Week 4 (Visit 3) to Week 96 (Visit 12) listed on the Trial 
Flow Chart A (Section 6.0) should be performed. 

Blood will be collected for safety laboratory evaluations, HIV-1 RNA quantification, 
CD4 cell counts, HIV viral resistance and PK measurements at the time points specified 
on the Trial Flow Chart. 
These samples will be sent to the appropriate central 
laboratory(ies) following the procedure(s) set forth in the manual(s).

For a female subject who is of childbearing potential, a urine pregnancy test will be 
performed at all study visits. If the urine pregnancy test result is positive, the subject 
must be discontinued. 

Subjects will be required to fast for at least 8 hours prior to study visits at Weeks 24, 48,
and 96. 

All bottles of study drug will be returned to the study coordinator at each visit, at which 
time the drug supplies for the following time period will be dispensed. The number of 
08K3V5

Product:  MK-1439A 
69
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
tablets remaining in the bottle will be counted and recorded in the source documentation.
The primary source of adherence data, however, will be the subjects study medication 
diary.

Subjects will receive a 4-week supply of study drug (1 bottle each labeled A and B) at 
Week 4 (Visit 3); an 8-week supply (2 bottles each labeled A and B) at Week 8 (Visit 4) 
and Week 16 (Visit 5); and a 12-week supply (3 bottles each labeled A and B) at each 
visit from Week 24 (Visit 6) through Week 84 (Visit 11). 

At Week 96 (Visit 12), subjects who continue into study extension 1 will receive a 
4-week supply of unblinded study drug: this will consist, for all subjects, of MK-1439A, 
packaged in a single bottle labeled ‘Bottle C’. 

At each treatment visit, the study coordinator and subject will review the study 
medication diary information.
Treatment Visits in Study Extension 1 (Visit 13 to Visit 19)

All procedures listed in the Trial Flow Chart B (Section 6.0) should be performed, as 
applicable to each study visit, including collection of blood and urine (urine only for 
female subjects of childbearing potential) for laboratory evaluations. 

Subjects will be required to fast for at least 8 hours prior to the Week 148 (Visit 16) and 
Week 192 (Visit 19) visits.

In study extension 1, subjects will receive a 16-week supply of MK-1439A at each study
visit through Week 164 (Visit 17) and a 12-week supply of MK-1439A at Week 180
(Visit 18). Subjects continuing into study extension 2, if applicable, will receive a 16-
week supply of study drug for study extension 2 at Week 192 (Visit 19).

All bottles of study drug will be returned to the study coordinator at each visit, at which 
time the drug supplies for the following time period will be dispensed (except for Week 
192 for subjects not continuing into extension 2). The number of tablets remaining in the 
bottle will be counted and recorded in the source documentation. The primary source of 
adherence data, however, will be the subject’s study medication diary.

At each visit, the study coordinator and subject will review the study medication diary 
information.
Treatment Visits in Study Extension 2 (Visit 20 to Visit 25)

All procedures for Study Week 208 (Visit 20), Week 224 (Visit 21), Week 240 (Visit 22), 
Week 256 (Visit 23), Week 272 (Visit 24), and Week 288 (Visit 25) listed on Study Flow 
Chart C (Section 6.0) should be performed. 
08K3V5

Product:  MK-1439A 
70
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential

For a female subject who is of childbearing potential, a urine pregnancy test will be 
performed at all study visits. If the urine pregnancy test result is positive, the subject 
must be discontinued. 

All bottles of study drug will be returned to the study coordinator at each visit, at which 
time the drug supplies for the following time period will be dispensed. The number of 
tablets remaining in the bottle will be counted and recorded in the source documentation. 
Only first dose, last dose, overdose (if applicable) and study drug interruption (if 
applicable) due to any toxicity, ECI or (S)AE will be collected in the database.

Site staff will access the IVRS/IWRS for registration of visits. 

In study extension 2, starting at Week 192 (Visit 19), subjects will receive a 16-week 
supply of MK-1439A at each study visit through Week 272 (Visit 24), as applicable.
Subjects continuing into study extension 3, if applicable, will receive a 16-week supply
of study drug for study extension 3 at Week 288 (Visit 25).
Treatment Visits in Study Extension 3 (Visit 26 to Visit 31)

All procedures for Study Week 304 (Visit 26), Week 320 (Visit 27), Week 336 (Visit 28), 
Week 352 (Visit 29), Week 368 (Visit 30), and Week 384 (Visit 31) listed on Study Flow 
Chart D (Section 6.0) should be performed. 

For a female subject who is of childbearing potential, a urine pregnancy test will be 
performed at all study visits.  If the urine pregnancy test result is positive, the subject 
must be discontinued. 

All bottles of study drug will be returned to the study coordinator at each visit, at which 
time the drug supplies for the following time period will be dispensed.  The number of 
tablets remaining in the bottle will be counted and recorded in the source documentation.  
Only first dose, last dose, overdose (if applicable) and study drug interruption (if 
applicable) due to any toxicity, ECI or (S)AE will be collected in the database.

Site staff will access the IVRS/IWRS for registration of visits. 

In study extension 3, starting at Week 288 (Visit 25), subjects will receive a 16-week 
supply of MK-1439A at each study visit through Week 368 (Visit 30), as applicable.
Virologic Failure Confirmation Visit - Base Study and Study Extension 1

When a subject has a virologic failure confirmation visit performed, all procedures for the 
virologic failure confirmation visit listed on the Trial Flow Charts should be performed.
08K3V5

Product:  MK-1439A 
71
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
PDVF for this study is defined as one of the following:
1) Confirmed (2 consecutive measures at least one week apart) HIV-1 RNA ≥50 copies/mL 
after initial response of HIV-1 RNA <50 copies/mL at any time during the study
OR
2) Confirmed (2
consecutive measures at least one week apart) HIV-1 RNA 
≥200 copies/mL at Week 24 or Week 36 
OR 
3) Confirmed (2 consecutive measures at least one week apart) HIV-1 RNA ≥50 copies/mL 
at Week 48.
The virologic failure confirmation visit should be done between 1 and 4 weeks after the first 
measurement of HIV-1 RNA ≥50 copies/ml.
Subjects should be discontinued, regardless of compliance with study therapy, if they meet 
the protocol-defined virologic failure criteria.
Early Discontinuation Visit - Base Study, Study Extension 1, Study Extension 
2, and Study Extension 3

When a subject discontinues/withdraws from participation in the trial, all procedures for 
the Early Discontinuation visit listed on the Trial Flow Charts should be performed.
At a minimum, the following information should be collected when a subject 
discontinues:  
o
The reason the subject discontinued
o
The date of the last dose of study medications from the trial
o
The date of the last assessment and/or contact
o
All adverse events (including serious adverse events) in the base study and 
study extension 1

Only serious adverse events in study extension 2 and study extension 3. Any adverse 
events which are present at the time of discontinuation/withdrawal should be followed in 
accordance with the safety requirements outlined in Section 7.2 - Assessing and 
Recording Adverse Events.

Subjects who discontinue early from the study are expected to return for a 14-day post 
therapy follow-up visit. 
08K3V5

Product:  MK-1439A 
72
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Post-Trial (Base Study and Study Extensions)

Following the completion of study therapy in the base study (at 96 weeks) or in the study 
extensions (at 192, 288, or 384 weeks) or in the event of early discontinuation, subjects 
will be required to return to the clinic approximately 14 days after the last dose of study 
drug for the post-study visit as outlined in the Trial Flow Charts (Section 6.0). 

If the post-study visit occurs less than 14 days after the last dose of study drug, a 
subsequent follow-up phone call should be made at 14 days post the last dose of study 
drug to determine if any adverse events have occurred since the post-study clinic visit.
Assessing and Recording Adverse Events
An adverse event is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not necessarily 
have to have a causal relationship with this treatment. An adverse event can therefore be any 
unfavourable and unintended sign (including an abnormal laboratory finding, for example), 
symptom, or disease temporally associated with the use of a medicinal product or protocol-
specified procedure, whether or not considered related to the medicinal product or protocol-
specified procedure.  Any worsening (i.e., any clinically significant adverse change in 
frequency and/or intensity) of a preexisting condition that is temporally associated with the 
use of the Sponsor’s product, is also an adverse event.
Changes resulting from normal growth and development that do not vary significantly in 
frequency or severity from expected levels are not to be considered adverse events.  
Examples of this may include, but are not limited to, teething, typical crying in infants and 
children and onset of menses or menopause occurring at a physiologically appropriate time.
Sponsor's product includes any pharmaceutical product, biological product, device, 
diagnostic agent or protocol-specified procedure, whether investigational (including placebo 
or active comparator medication) or marketed, manufactured by, licensed by, provided by or 
distributed by the Sponsor for human use.
Adverse events may occur during clinical trials, or as prescribed in clinical practice, from 
overdose (whether accidental or intentional), from abuse and from withdrawal.
All adverse events that occur after the consent form is signed but before treatment 
allocation/randomization must be reported by the investigator if they cause the subject to be 
excluded from the trial, or are the result of a protocol-specified intervention, including but 
not limited to washout or discontinuation of usual therapy, diet, placebo treatment or a 
procedure. From the time of treatment allocation/randomization through 14 days following 
cessation of treatment, all adverse events must be reported by the investigator during the base 
study and study extension 1 as specified in Section 2. During study extension 2 and study 
extension 3, serious adverse events must be reported by the investigator as specified in 
Section 2; and if an investigator chooses to report a non-serious adverse event (NSAE), it 
should be submitted using the same process used to submit NSAEs in the base study and 
08K3V5

Product:  MK-1439A 
73
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
study extension 1. Such events will be recorded at each examination on the Adverse Event 
case report forms/worksheets.  The reporting timeframe for adverse events meeting any 
serious criteria is described in section 7.2.3.1. The investigator will make every attempt to 
follow all subjects with non-serious adverse events for outcome.
Electronic reporting procedures can be found in the EDC data entry guidelines. Paper
reporting procedures can be found in the Investigator Trial File Binder (or equivalent).
Definition of an Overdose for This Protocol and Reporting of Overdose to the 
Sponsor
In this trial, an overdose is any dose higher than twice the recommended daily dose in a 
calendar day.
If an adverse event(s) is associated with (“results from”) the overdose of Sponsor's product or 
vaccine, the adverse event(s) is reported as a serious adverse event, even if no other 
seriousness criteria are met.
If a dose of Sponsor's product or vaccine meeting the protocol definition of overdose is taken 
without any associated clinical symptoms or abnormal laboratory results, the overdose is 
reported as a non-serious Event of Clinical Interest (ECI), using the terminology “accidental 
or intentional overdose without adverse effect.”
All reports of overdose with and without an adverse event must be reported within 24 hours 
to the Sponsor either by electronic media or paper.  Sponsor Contact information can be 
found in the Investigator Trial File Binder (or equivalent).
Reporting of Pregnancy and Lactation to the Sponsor
Although pregnancy and lactation are not considered adverse events, it is the responsibility of 
investigators or their designees to report any pregnancy or lactation in a subject 
(spontaneously reported to them) that occurs during the trial.
Pregnancies and lactations that occur after the consent form is signed but before treatment 
allocation/randomization must be reported by the investigator if they cause the subject to be 
excluded from the trial, or are the result of a protocol-specified intervention, including but 
not limited to washout or discontinuation of usual therapy, diet, placebo treatment or a 
procedure.  Pregnancies and lactations that
occur from the time of treatment 
allocation/randomization through 14 days following cessation of Sponsor’s product must be 
reported by the investigator.  All reported pregnancies must be followed to the 
completion/termination of the pregnancy. Pregnancy outcomes of spontaneous abortion, 
missed abortion, benign hydatidiform mole, blighted ovum, fetal death, intrauterine death, 
miscarriage and stillbirth must be reported as serious events (Important Medical Events). If 
the pregnancy continues to term, the outcome (health of infant) must also be reported.
08K3V5

Product:  MK-1439A 
74
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Such events must be reported within 24 hours to the Sponsor either by electronic media or
paper. Electronic reporting procedures can be found in the EDC data entry guidelines. Paper 
reporting procedures can be found in the Investigator Trial File Binder (or equivalent).
Immediate Reporting of Adverse Events to the Sponsor
Serious Adverse Events
A serious adverse event is any adverse event occurring at any dose or during any use of 
Sponsor's product that:
●
Results in death;
●
Is life threatening;
●
Results in persistent or significant disability/incapacity;
●
Results in or prolongs an existing inpatient hospitalization;
●
Is a congenital anomaly/birth defect;
●
Is an other important medical event 
Note: In addition to the above criteria, adverse events meeting either of the below criteria, 
although not serious per ICH definition, are reportable to the Sponsor in the same timeframe 
as SAEs to meet certain local requirements. Therefore, these events are considered serious by 
the Sponsor for collection purposes.
●
Is a cancer;
●
Is associated with an overdose.
Refer to Table 7 for additional details regarding each of the above criteria.
For the time period beginning when the consent form is signed until treatment 
allocation/randomization, any serious adverse event, or follow up to a serious adverse event, 
including death due to any cause, that occurs to any subject must be reported within 24 hours 
to the Sponsor if it causes the subject to be excluded from the trial, or is the result of a 
protocol-specified intervention, including but not limited to washout or discontinuation of 
usual therapy, diet, placebo treatment or a procedure.
For the time period beginning at treatment allocation/randomization through 14 days 
following cessation of treatment, any serious adverse event, or follow up to a serious adverse 
event, including death due to any cause, whether or not related to the Sponsor's product, must 
be reported within 24 hours to the Sponsor either by electronic media or paper. Electronic 
reporting procedures can be found in the EDC data entry guidelines. Paper reporting 
procedures can be found in the Investigator Trial File Binder (or equivalent).
Additionally, any serious adverse event, considered by an investigator who is a qualified 
physician to be related to the Sponsor's product that is brought to the attention of the 
investigator at any time outside of the time period specified in the previous paragraph also 
must be reported immediately to the Sponsor.
08K3V5

Product:  MK-1439A 
75
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
All subjects with serious adverse events must be followed up for outcome.
Events of Clinical Interest
Selected non-serious and serious adverse events are also known as Events of Clinical Interest 
(ECI) and must be reported to the Sponsor.
For the time period beginning when the consent form is signed until treatment 
allocation/randomization, any ECI, or follow up to an ECI, that occurs to any subject must be 
reported within 24 hours to the Sponsor if it causes the subject to be excluded from the trial, 
or is the result of a protocol-specified intervention, including but not limited to washout or 
discontinuation of usual therapy, diet, placebo treatment or a procedure.
For the time period beginning at treatment allocation/randomization through 14 days 
following cessation of treatment, any ECI, or follow up to an ECI, whether or not related to 
the Sponsor’s product, must be reported within 24 hours to the Sponsor, either by electronic 
media or paper.  Electronic reporting procedures can be found in the EDC data entry 
guidelines.  Paper reporting procedures can be found in the Investigator Trial File Binder (or 
equivalent).
Events of clinical interest for this trial include:
1. an overdose of Sponsor's product, as defined in Section 7.2.1 - Definition of an 
Overdose for This Protocol and Reporting of Overdose to the Sponsor, that is not 
associated with clinical symptoms or abnormal laboratory results. 
2. an elevated AST or ALT lab value that is greater than or equal to 3X the upper limit 
of normal and an elevated total bilirubin lab value that is greater than or equal to 2X 
the upper limit of normal and, at the same time, an alkaline phosphatase lab value that 
is less than 2X the upper limit of normal, as determined by way of protocol-specified 
laboratory testing or unscheduled laboratory testing.*
*Note:  These criteria are based upon available regulatory guidance documents. The 
purpose of the criteria is to specify a threshold of abnormal hepatic tests that may require 
an additional evaluation for an underlying etiology.  The trial site guidance for 
assessment and follow up of these criteria can be found in the Investigator Trial File 
Binder (or equivalent).
Evaluating Adverse Events
An investigator who is a qualified physician will evaluate all adverse events with respect to 
the elements outlined in Table 7. The investigator’s assessment of causality is required for 
each adverse event.  Refer to Table 7 and Appendix 12.8 for additional instructions for
evaluating adverse events.
08K3V5

Product:  MK-1439A 
76
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Table 7
Evaluating Adverse Events
Maximum
Mild
awareness of sign or symptom, but easily tolerated  (for pediatric trials, awareness of symptom, but easily tolerated)
Intensity
Moderate
discomfort enough to cause interference with usual activity (for pediatric trials, definitely acting like something is wrong)
Severe
incapacitating with inability to work or do usual activity (for pediatric trials, extremely distressed or unable to do usual activities)
Seriousness
A serious adverse event (AE) is any adverse event occurring at any dose or during any use of Sponsor's product that:
†Results in death; or
†Is life threatening; or places the subject, in the view of the investigator, at immediate risk of death from the event as it occurred [Note: This does not include an 
adverse event  that, had it occurred in a more severe form, might have caused death.]; or
†Results in a persistent or significant disability/incapacity (substantial disruption of one’s ability to conduct normal life functions); or
†Results in or prolongs an existing inpatient hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay, even if the 
hospitalization is a precautionary measure for continued observation.   (Note: Hospitalization for an elective procedure to treat a pre-existing condition that has not 
worsened is not a serious adverse event.  A pre-existing condition is a clinical condition that is diagnosed prior to the use of an MSD product and is documented in the 
patient’s medical history.); or
†Is a congenital anomaly/birth defect  (in offspring of subject taking the product regardless of time to diagnosis); or
Is a cancer (although not serious per ICH definition, is reportable to the Sponsor within 24 hours to meet certain local requirements); or
Is associated with an overdose (whether accidental or intentional).  Any adverse event associated with an overdose is considered a serious adverse event for collection 
purposes. An overdose that is not associated with an adverse event is considered a non-serious event of clinical interest and must be reported within 24 hours.
Other important medical events that may not result in death, not be life threatening, or not require hospitalization may be considered a serious adverse event when, 
based upon appropriate medical judgment, the event may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed 
previously (designated above by a †).
Duration
Record the start and stop dates of the adverse event.  If less than 1 day, indicate the appropriate length of time and units
Action taken 
Did the adverse event cause the Sponsor's product to be discontinued?
Relationship to 
Sponsor's 
Product
Did the Sponsor's product cause the adverse event?   The determination of the likelihood that the Sponsor's product caused the adverse event will be provided by an 
investigator who is a qualified physician.  The investigator’s signed/dated initials on the source document or worksheet that supports the causality noted on the AE form, 
ensures that a medically qualified assessment of causality was done.  This initialed document must be retained for the required regulatory time frame.  The criteria below 
are intended as reference guidelines to assist the investigator in assessing the likelihood of a relationship between the test drug and the adverse event based upon the 
available information
The following components are to be used to assess the relationship between the Sponsor's product and the AE; the greater the correlation with the components and 
their respective elements (in number and/or intensity), the more likely the Sponsor's product caused the adverse event:
Exposure
Is there evidence that the subject was actually exposed to the Sponsor's product such as:  reliable history, acceptable compliance assessment (pill 
count, diary, etc.), expected pharmacologic effect, or measurement of drug/metabolite in bodily specimen?
Time Course
Did the AE follow in a reasonable temporal sequence from administration of the Sponsor's product? 
Is the time of onset of the AE compatible with a drug-induced effect (applies to trials with investigational medicinal product)?
Likely Cause
Is the AE not reasonably explained by another etiology such as underlying disease, other drug(s)/vaccine(s), or other host or environmental factors
08K3V5

Product:  MK-1439A 
77
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Relationship
The following components are to be used to assess the relationship between the Sponsor's product and the AE:  (continued)
to Sponsor's 
Product
(continued) 
Dechallenge
Was the Sponsor's product discontinued or dose/exposure/frequency reduced?
      If yes, did the AE resolve or improve?
           If yes, this is a positive dechallenge.    If no, this is a negative dechallenge.
(Note:  This criterion is not applicable if:  (1) the AE resulted in death or permanent disability; (2) the AE resolved/improved despite continuation 
of the Sponsor's product; (3) the trial is a single-dose drug trial); or (4) Sponsor's product(s) is/are only used one time.)
Rechallenge
Was the subject re-exposed to the Sponsor's product in this trial?
      If yes, did the AE recur or worsen?
          If yes, this is a positive rechallenge.    If no, this is a negative rechallenge.
(Note:  This criterion is not applicable if:  (1) the initial AE resulted in death or permanent disability, or (2) the trial is a single-dose drug trial); or 
(3) Sponsor's product(s) is/are used only one time.)
NOTE:  IF A RECHALLENGE IS PLANNED FOR AN ADVERSE EVENT WHICH WAS SERIOUS AND WHICH MAY HAVE BEEN 
CAUSED BY THE SPONSOR'S PRODUCT, OR IF RE-EXPOSURE TO THE SPONSOR'S PRODUCT POSES ADDITIONAL POTENTIAL 
SIGNIFICANT RISK TO THE SUBJECT THEN THE RECHALLENGE MUST BE APPROVED IN ADVANCE BY THE SPONSOR
CLINICAL DIRECTOR AND IF REQUIRED, BY THE INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE.  IF 
ADVANCED APPROVAL OF RECHALLENGE IS NOT REQUIRED BY LOCAL REGULATIONS, THE IRB/IEC WILL RECEIVE 
NOTIFICATION OF INFORMATION ONLY.
Consistency with 
Trial Treatment 
Profile
Is the clinical/pathological presentation of the AE consistent with previous knowledge regarding the Sponsor's product or drug class pharmacology 
or toxicology?
The assessment of relationship will be reported on the case report forms /worksheets by an investigator who is a qualified physician according to his/her best clinical judgment, including 
consideration of the above elements.
Record one of the following:
Use the following scale of criteria as guidance (not all criteria must be present to be indicative of a Sponsor's product relationship).
Yes, there is a reasonable possibility 
of Sponsor's product relationship.
There is evidence of exposure to the Sponsor's product.  The temporal sequence of the AE onset relative to the administration of the Sponsor's 
product is reasonable.  The AE is more likely explained by the Sponsor's product than by another cause. 
No, there is not a reasonable 
possibility of Sponsor's product 
relationship
Subject did not receive the Sponsor's product OR temporal sequence of the AE onset relative to administration of the Sponsor's product is not 
reasonable OR the AE is more likely explained by another cause than the Sponsor’s product.  (Also entered for a subject with overdose without an 
associated AE.)
08K3V5

Product:  MK-1439A 
78
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Sponsor Responsibility for Reporting Adverse Events
All Adverse Events will be reported to regulatory authorities, IRB/IECs and investigators in 
accordance with all applicable global laws and regulations, i.e., per ICH Topic E6 (R1) 
Guidelines for Good Clinical Practice.
TRIAL GOVERNANCE AND OVERSIGHT
Scientific Advisory Committee
This trial was developed in collaboration with a Scientific Advisory Committee (SAC).  The 
SAC comprises both Sponsor and non-Sponsor scientific experts who provide input with 
respect to trial design, interpretation of trial results and subsequent peer-reviewed scientific 
publications.
Executive Oversight Committee
The Executive Oversight Committee (EOC) comprises members of Sponsor Senior 
Management.  The EOC will receive and decide upon any recommendations made by the
eDMC regarding the trial.
Data Monitoring Committee
To supplement the routine trial monitoring outlined in this protocol, an external Data 
Monitoring Committee (DMC) will monitor the interim data from this trial.  The voting 
members of the committee are external to the Sponsor.  The members of the DMC must not 
be involved with the trial in any other way (e.g., they cannot be trial investigators) and must 
have no competing interests that could affect their roles with respect to the trial. The DMC 
will include at least 3 clinicians experienced in Infectious Disease and 1 external statistician; 
this is in addition to the unblinded trial statistician who will be a non-voting member of the 
committee. The eDMC will monitor the trial at an appropriate frequency, with suggested 
periodic reviews to occur approximately every 6 months during the base trial; there will be 
no involvement of the eDMC in the trial extensions. Details regarding the eDMC will be 
described in a charter document.
The DMC will make recommendations to the EOC regarding steps to ensure both subject 
safety and the continued ethical integrity of the trial.  Also, the DMC will review interim trial 
results, consider the overall risk and benefit to trial participants (see Section 8.7 - Interim 
Analyses) and recommend to the EOC if the trial should continue in accordance with the 
protocol.
Specific details regarding composition, responsibilities, and governance, including the roles 
and responsibilities of the various members and the Sponsor protocol team; meeting 
facilitation; the trial governance structure; and requirements for and proper documentation of 
DMC reports, minutes, and recommendations will be described in a separate charter that is 
reviewed and approved by the DMC.  The DMC will monitor the trial at an appropriate 
08K3V5

Product:  MK-1439A 
79
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
frequency, as described in the detailed DMC charter.  The DMC will also make 
recommendations to the Sponsor protocol team regarding steps to ensure both subject safety 
and the continued ethical integrity of the trial.
STATISTICAL ANALYSIS PLAN
This section outlines the statistical analysis strategy and procedures for the study. If, after 
the study has begun, but prior to any unblinding, changes are made to primary and/or key 
secondary hypotheses, or the statistical methods related to those hypotheses, then the 
protocol will be amended (consistent with ICH Guideline E-9). Changes to exploratory or 
other non-confirmatory analyses made after the protocol has been finalized, but prior to 
unblinding, will be documented in a supplemental statistical analysis plan (sSAP) and 
referenced in the CSR for the study. Separate analysis plans (i.e., separate documents from 
the sSAP) will be developed to detail other planned analyses (analysis of PK data, patient-
reported outcomes, and future biomedical research). Post hoc exploratory analyses will be 
clearly identified in the CSR. 
The key objectives and hypotheses are to be addressed by the base study (double-blind with 
active comparator for 96 weeks). Thus, between treatment comparisons that address key 
efficacy and safety objectives will be limited to data from the base study.
Demography, 
efficacy and safety data from study extension 1 for those subjects who continue into the 
extension 1 will be summarized separately using descriptive statistics only. Serious adverse 
event data from study extension 2 and study extension 3 will be summarized separately from 
data for the base and study extension 1 portions of the study.
STATISTICAL ANALYSIS PLAN SUMMARY
Key elements of the SAP are summarized below; the comprehensive plan is provided in 
Sections 8.2 through 8.12. 
Study Design Overview
A Phase III Multicenter, Double-Blind, Randomized, Active Comparator-
Controlled Clinical Trial to Evaluate the Safety and Efficacy of MK-1439A 
Once-Daily Versus ATRIPLA™ Once-Daily in Treatment-Naïve HIV-1 
Infected Subjects
Treatment Assignment
Approximately 680 subjects will be randomized in a 1:1 ratio with ~340 on 
MK-1439A and ~340 on ATRIPLA™ in a double-blind fashion with 
stratification for screening viral load (HIV RNA ≤100,000 vs. >100,000 
copies /mL) and chronic hepatitis B and/or C status (yes, no).
Analysis Populations
Efficacy: Treatment Full Analysis Set (FAS)
Safety: All Subjects as Treated (ASaT)
Primary Endpoints
1.
Proportion of subjects with HIV-1 RNA <50 copies/mL (by the Abbott 
RealTime HIV-1 Assay) at Week 48
2.
Proportion of subjects with neuropsychiatric AEs in the following 
categories by Week 48:
o
Dizziness
o
Sleep disorders and disturbances
o
Altered Sensorium
08K3V5

Product:  MK-1439A 
80
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Key Secondary 
Endpoints
1.
Safety and tolerability by Week 48 and Week 96
2.
Fasting LDL-C as measured by the mean change from baseline at Week 48
3.
Fasting non-HDL-C as measured by the mean change from baseline at 
Week 48
4.
Proportion of subjects with neuropsychiatric AEs in the following 
categories by Week 48:
o
Depression and suicide/self-injury
o
Psychosis and psychotic disorders
5.
Proportion of subjects with at least one neuropsychiatric AE in any of the 
5 categories of: dizziness, sleep disorders and disturbances, altered 
sensorium, depression and suicide/self-injury, and psychosis and psychotic 
disorders. 
6.
Time to discontinuation from study due to an adverse experience 
7.
Change from baseline in CD4 cell count at Week 48 and Week 96
8.
The proportion of subjects achieving HIV-1 RNA <50 copies/mL (by the 
Abbott RealTime HIV-1 Assay) at Week 96 
9.
The proportion of subjects achieving HIV-1 RNA <40 copies/mL (BLoQ) 
(by the Abbott RealTime HIV-1 Assay) at Week 48 and Week 96
10. PK of MK-1439 and the PK/PD association
Statistical Methods for 
Key Efficacy Analyses
The primary hypothesis will be assessed based upon the proportion of subjects 
maintaining HIV-1 RNA <50 copies/mL (by the Abbott RealTime HIV-1 
Assay) at Week 48 post-randomization. 
The Non-Completer=Failure 
approach (NC=F) as defined by the FDA “snapshot” approach will be used as 
the primary approach for handling missing data. All missing data will be 
treated as failures regardless of the reason. 
The difference in proportions of subjects with HIV-1 RNA <50 copies/mL 
between treatment groups and the associated 95% confidence interval will be 
calculated using the stratum-adjusted Mantel-Haenszel method with the 
difference weighted by the harmonic mean of the sample size per arm for each 
stratum (screening HIV RNA ≤100,000 or >100,000 copies/mL).
Chronic 
hepatitis B or C co-infection is not considered to be associated with virologic 
response; therefore, stratification by hepatitis B or C status will not be 
included in the analyses of virologic response.
For the primary hypothesis, MK-1439A will be considered non-inferior to 
ATRIPLA™ if the lower bound of the two-sided 95% confidence interval (CI) 
for the between treatment difference in proportion of subjects with HIV-1 
RNA <50 copies/mL at Week 48 (MK-1439A minus ATRIPLA™ ) is greater 
than -10 percentage points (non-inferiority margin). 
It can be further 
concluded that MK-1439A is superior to ATRIPLA™ if the lower bound of 
the two-sided 95% CI for the difference in the response rates (MK-1439A 
minus ATRIPLA™) is greater than zero contingent upon satisfying the 
multiplicity criteria. A similar approach will be used for the supportive 
secondary efficacy hypotheses for non-inferiority and superiority at Week 96.
08K3V5

Product:  MK-1439A 
81
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Statistical Methods for 
Key Safety Analyses
Neither stratification factor is considered to be associated with the Tier I 
safety endpoints; therefore, stratification will not be included in the analyses 
of Tier I events.
Tier I
Neuropsychiatric AEs (primary safety hypothesis):
The treatment differences and the associated 95% confidence intervals will be 
calculated using the Miettinen and Nurminen method [5]. The treatment 
differences (95% confidence intervals) will be provided for the proportion of 
subjects with at least one neuropsychiatric AE in any category as well as at 
least one AE in each category, and p-values will be provided for dizziness, 
sleep disorders and disturbances, and altered sensorium. MK-1439A will be 
considered superior to ATRIPLA™ if the upper bound of the two-sided 95% 
CI for the difference in proportion of subjects with neuropsychiatric AEs 
(each category separately) by Week 48 (MK-1439A minus ATRIPLA™) is 
less than zero. 
Lipids (secondary safety hypothesis):
The change from baseline in fasting lipids (total cholesterol, LDL-C, non-
HDL-C, and triglycerides) will be analyzed using Analysis of Covariance 
models adjusted by baseline lipid level and treatment group. The treatment 
differences (95% confidence intervals) will be provided for all lipid 
parameters, and p-values for between treatment comparisons will be provided 
for LDL-C and non-HDL-C.
Tier II
The treatment differences and the associated 95% confidence intervals will be 
provided for the percentage of subjects with the following events based on 
specific AE categories (i.e., Tier-2 events): (1) at least one adverse 
experience; (2) at least one drug-related adverse experience; (3) at least one 
serious adverse experience; (4) at least one serious and drug-related adverse 
experience; (5) discontinued study therapy due to an adverse experience. 
Other Tier-2 events require a minimum of 4 subjects in at least one treatment 
group. These analyses will be performed using the Miettinen and Nurminen
[5] method, an unconditional, asymptotic method.
Interim Analyses
No interim analyses for efficacy are planned.
However, an external data 
monitoring committee will convene to review safety data approximately every 
6 months during the study.
08K3V5

Product:  MK-1439A 
82
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Multiplicity
The following hypotheses will be tested sequentially at the one-sided Type 1 
error rate of 2.5% (unadjusted for the efficacy hypotheses [#1,7] and after 
adjusting for interim DMC safety reviews for the safety hypotheses [#2-6]) in 
the following order:
1)
Primary efficacy hypothesis testing non-inferiority at Week 48
2)
Primary safety hypothesis for dizziness
3)
Primary safety hypothesis for sleep disorders and disturbances
4)
Primary safety hypothesis for altered sensorium
5)
Secondary safety hypothesis for LDL-C
6)
Secondary safety hypothesis for non-HDL-C
7)
Secondary efficacy hypothesis testing superiority at Week 48 
Testing will stop with the first of these tests failing to reach statistical 
significance and all subsequent tests would not be considered for statistical 
significance. In this way, the overall one-sided Type 1 error rate in testing 
these hypotheses is strongly controlled at a 2.5% level.
Note the secondary efficacy hypotheses testing non-inferiority and superiority 
at Week 96 are supportive only to the primary and secondary efficacy 
hypotheses at Week 48 and are not considered in the strong control for the 
Type 1 error for this study. 
There are no other hypotheses that will be tested and analyses associated with
objectives without hypotheses
will be considered supportive and/or 
explanatory. 
Sample Size and Power 
The planned sample size is 340 subjects in each treatment group (680 total) to 
achieve 90% power to demonstrate the primary hypothesis that MK-1439A is 
non-inferior to ATRIPLA™at an overall one-sided 2.5% alpha level, as 
measured by the proportion of subjects achieving HIV-1 RNA <50 copies/mL 
at Week 48 (by the Abbott RealTime HIV-1 Assay). The power calculation 
assumes a true response rate of 80% at Week 48 for both MK-1439A and 
ATRIPLA™ using the NC=F approach as defined by the FDA “snapshot” 
approach. 
Responsibility for Analyses/In-House Blinding
The statistical analysis of the data obtained from this study will be the responsibility of the 
Clinical Biostatistics department of the Sponsor.
The base study will be conducted as a double-blind study under in-house blinding 
procedures; the study extensions, for eligible subjects who elect to continue into the 
extensions, will be conducted as an open-label study. At Week 48 of the base study, when 
the primary efficacy hypothesis will be evaluated, a copy of the database will be frozen after 
medical/scientific review has been completed and data have been declared final and 
complete. This version of the database will be used for initial regulatory submissions. The 
study (after Week 48, when longer-term safety and efficacy data will be evaluated) will be 
unblinded to the Sponsor with the exception of a limited group of Sponsor personnel who 
will remain blinded at the subject level and continue to be responsible for the integrity of the 
database for ongoing study management. All Sponsor personnel who are unblinded at the 
subject level for the base period will be excluded from any future data review at the 
08K3V5

Product:  MK-1439A 
83
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
individual subject level. The Week 96 analysis for the base study will follow the same 
approach as the Week 48 analysis. For the purpose of the final analysis (after all subjects 
complete their final visit in the base study), the official clinical database will not be 
unblinded until medical/scientific review has been completed, and data have been declared 
final and complete. Results from the Week 96 (base study) and from the study extensions
will be presented in separate CSRs (separate from the CSR for the Week 48 analysis of the 
base study).
The designee/Clinical Biostatistics department will generate the randomized allocation 
schedule(s) for study treatment assignment. Randomization will be implemented in an 
IVRS/IWRS.
Treatment-level results of the periodic safety reviews will be provided by the unblinded 
statistician (external to the Sponsor) to the DMC. Limited additional Sponsor personnel may 
be unblinded to the treatment-level results of the safety analyses, if required, in order to act 
on the recommendations of the DMC. The extent to which individuals are unblinded with 
respect to results of safety reviews will be documented by the unblinded statistician.
The DMC will serve as the primary reviewer of the safety results from this study with respect 
to the periodic safety reviews and will make recommendations for discontinuation of or 
modifications to the study to an executive committee of the Sponsor. 
If the DMC 
recommends modifications to the design of the protocol or discontinuation of the study, this 
executive oversight committee (internal to the Sponsor) may be unblinded to results at the 
treatment level in order to act on these recommendations. Additional logistical details will 
be provided in the DMC Charter. Key aspects of the periodic safety reviews are described in 
Section 8.7.
Prior to final study unblinding, the unblinded statistician will not be involved in any 
discussions regarding modifications to the protocol, statistical methods, identification of 
protocol violators, or data validation efforts after the initial safety review.
PK data may be unblinded early for the purpose of preparing a population PK model. A 
separate Modeling and Simulation Plan authored by the department of Quantitative 
Pharmacology and Pharmacometrics will describe the modeling work to be performed. If 
early unblinding occurs, a Clinical Research Organization, external to the Sponsor, will 
perform the modeling. Efficacy and safety data will not be unblinded. Interim data or results 
will be not shared with the study team prior to study unblinding. No alpha adjustment will be 
made for this early unblinding for modeling and simulation analysis. 
Hypotheses/Estimation
Objectives and hypotheses of the study are stated in Section 2.1.
08K3V5

Product:  MK-1439A 
84
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Analysis Endpoints
Efficacy and safety endpoints for the base study and study extension 1 that will be evaluated 
for within- and/or between treatment differences are listed below, followed by the 
descriptions of the derivations of selected endpoints.
Efficacy /Pharmacokinetics Endpoints
Efficacy Endpoints
An initial description of efficacy measures is provided in Section 4.2.3.
Proportions of Subjects Achieving HIV-1 RNA <50 copies/mL, <40 copies/mL and 
<200 copies/mL (by the Abbott RealTime HIV-1 Assay)
The proportions of subjects achieving HIV-1 RNA <50 copies/mL (and <40 and 
<200 copies/mL) will be estimated at each time point. The Abbott RealTime HIV-1 Assay, 
which has a lower limit of reliable quantification of 40 copies/mL, will be used to measure 
the HIV-1 RNA level in blood samples obtained at each visit. 
The primary hypothesis will be assessed based upon the proportion of subjects achieving 
HIV-1 RNA <50 copies/mL at Week 48. 
Change from Baseline in CD4 Cell Count
Change from baseline in CD4 cell count will be estimated at each time point at which CD4 
cell count is collected with a key interest at Week 48. 
For the calculations of change from baseline, baseline measurements are defined as the Day 1 
(Randomization) value for each subject.
In the rare event when data for this visit are 
missing, the value obtained at the most recent screening visit will be used as baseline. This 
rule will also be applied to define the baseline measurements for other laboratory tests.
Protocol-Defined Virologic Failure
Subjects with PDVF as defined in Section 4.2.3.1 will be identified and summarized for each 
treatment group.
Safety Endpoints
An initial description of safety measures is provided in Section 4.2.3.
08K3V5

Product:  MK-1439A 
85
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Neuropsychiatric Adverse Events
The following categories of specific neuropsychiatric adverse events will be used to address 
the primary and secondary safety objectives:

Dizziness

Sleep disorders and disturbances

Altered Sensorium

Depression and suicide/self-injury

Psychosis and psychotic disorders 
A complete list of the preferred terms (based on MedDRA version 17.0) that will be used to 
define the neuropsychiatric categories can be found in Section 12.6.
Change From Baseline in Fasting Lipids
The change from baseline in fasting lipids (LDL-C, non-HDL-C, total cholesterol, HDL-C, 
and triglycerides) will be analyzed with primary interest in LDL-C and non-HDL-C.
Adverse Experiences
The following clinical and laboratory adverse experiences will be summarized: 1) subjects 
with at least one adverse experience; 2) subjects with at least one drug-related adverse 
experience; 3) subjects with at least one serious adverse experience; 4) subjects with at least 
one serious and drug-related adverse experience; and 5) subjects who discontinued study 
therapy due to an adverse experience.
Time to Discontinuation From Study Due to Adverse Experience
In addition to the counts of subjects who discontinued study therapy due to an adverse 
experience, the time to discontinuation from study due to an adverse experience will also be 
estimated.
Predefined Limits of Change in Laboratory Parameters
For the summaries of laboratory tests, subjects must have both a baseline and post-
randomization on-treatment measurement to be included. Subjects’ laboratory values (based 
on their most abnormal laboratory test values, in the direction of interest, while on study 
therapy) will be classified as to whether or not they fall outside of the PDLC and are worse in 
grade (i.e., more abnormal in the direction of interest) than at baseline. The criteria are 
adapted from DIVISION OF AIDS TABLE FOR GRADING THE SEVERITY OF ADULT 
AND PEDIATRIC ADVERSE EVENTS, PUBLISH DATE: AUGUST 2009 Version 1 
(Section 12.8). A listing of the subjects who meet the criteria will be provided.  
08K3V5

Product:  MK-1439A 
86
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Analysis Populations
Efficacy Analysis Populations
The Full Analysis Set (FAS) population will serve as the primary population for the analysis 
of efficacy data in this study. The FAS population consists of all randomized subjects who:  

receive at least one dose of study treatment,

have baseline data for those analyses that require baseline data
Subjects will be included in the treatment group to which they are randomized for the 
analysis of efficacy data using the FAS population. Details on the approach to handling 
missing data are provided in Section 8.6 Statistical Methods.  
Safety Analysis Populations
The ASaT population will be used for the analysis of safety data in this study. The ASaT 
population consists of all randomized subjects who received at least one dose of study 
treatment. Subjects will be included in the treatment group corresponding to the study 
treatment they actually received for the analysis of safety data using the ASaT population. 
For most subjects this will be the treatment group to which they are randomized. Subjects 
who take incorrect study treatment for the entire treatment period will be included in the 
treatment group corresponding to the study treatment actually received. Otherwise, subjects 
will be included in their randomized treatment group.
At least one laboratory or vital sign measurement obtained subsequent to at least one dose of 
study treatment is required for inclusion in the analysis of each specific parameter. To assess 
change from baseline, a baseline measurement is also required.
Details on the approach to handling missing data for safety analyses are provided in Section 
8.6 Statistical Methods.
Statistical Methods
Statistical testing and inference for safety analyses are described in Section 8.6.2. Efficacy 
results that will be deemed to be statistically significant after consideration of the Type I 
error control strategy are described in Section 8.8, Multiplicity. Nominal p-values may be
computed for other efficacy analyses, but should be interpreted with caution due to potential 
issues of multiplicity, sample size, etc. Unless otherwise stated, all statistical tests will be 
conducted at the α=0.025 (1-sided) level.
The key objectives and hypotheses are to be addressed by the base study (double-blind with 
active comparator for 96 weeks). Thus, between treatment comparisons that address key 
efficacy and safety objectives will be limited to data from the base study. Demography, 
efficacy and safety data from study extension 1, for those subjects who continue into the 
study extension 1, will be summarized separately using descriptive statistics only. Serious 
08K3V5

Product:  MK-1439A 
87
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
adverse event data will be collected and summarized for study extension 2 and study 
extension 3 separately.
Statistical Methods for Efficacy Analyses
Time Window
Table 8 lists the definition of time windows and the target relative day for the scheduled 
visits in the study which will be used for all analyses by timepoint. The measurement closest 
to the target date within a window will be used for analyses at a specific timepoint.
Table 8
Definition of Study Timepoint
Treatment Phase
Treatment 
Period
Protocol
Time
Day-Range Rules
Target 
Day
CSR Time
Pre-treatment
Baseline
Day 1 
(Baseline)
1
1
Day 1
Treatment
Double-Blind
(Base Study)
Week 4
>1 and 42
29
Week 4
Week 8
43 and 84
57
Week 8
Week 16
85 and 140
113
Week 16
Week 24
141and 210
169
Week 24
Week 36
211 and 294
253
Week 36
Week 48
295 and 378
337
Week 48
Week 60
379 and 462
421
Week 60
Week 72
463 and 546
505
Week 72
Week 84
547 and 630
589
Week 84
Week 96
631 and the last day 
of double-blind 
treatment period
673
Week 96
Treatment
Open-label 
(Study 
Extension 1)
Week 100
the first day of open-
label extension 
treatment period and 
756
701
Week 100
Week 116
757 and 868
813
Week 116
Week 132
869 and 980
925
Week 132
Week 148
981 and 1092
1037
Week 148
Week 164
1093 and 1204
1149
Week 164
Week 180
1205 and 1302
1261
Week 180
Week 192
1303 and ≤the last day 
of open-label 
extension 1 treatment 
period
1345
Week 192
Relative days and target day are counted from the first day of study medication. 
The clinical study report (CSR) time is the time label to be used in the analysis tables.
08K3V5

Product:  MK-1439A 
88
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Missing Values
There are 3 types of missing values:
intermittent missing values due to a missed or skipped visit or due to an inadequate 
sample;
non-intermittent missing values due to premature discontinuations because of treatment-
related reasons such as, “clinical adverse experience” (regardless of relationship to study 
drug), “laboratory adverse experience” (regardless of relationship to study drug), and 
“withdrew based on HIV-1 RNA results”;
non-intermittent missing values due to premature discontinuations because of other 
reasons which are not related to treatment such as loss to follow-up, protocol violation, 
subject withdrew consent, etc.
Two approaches will be used to handle missing values (Table 9). The primary approach for 
the analysis of the proportion of subjects achieving HIV-1 RNA <50 copies/mL is the NC=F 
approach as defined by the FDA “snapshot” approach. Under this approach, only subjects 
meeting the following can be classified as virologic success at a given time point: 1) subject 
is on study-assigned double-blind-treatment, 2) subject has HIV-1 RNA measurement(s) 
within the time window specified in Table 8, and 3) subject has the measurement closest to 
the target date of the time point <50 copies/mL. The other subjects, either with an HIV-1 
RNA measurement of ≥50 copies/mL or no virologic data within the time window due to 
intermittent missing or premature discontinuation regardless of reasons, will be considered as 
failures in the analyses of the proportion of subjects achieving HIV-1 RNA <50 copies/mL at 
that timepoint.
A second approach, the OF approach will be performed as a sensitivity analysis for the 
proportion of subjects achieving HIV-1 RNA<50 copies/mL at Week 48.
Under this 
approach, non-intermittent missing data for subjects who prematurely discontinued assigned 
treatment due to lack of efficacy are considered as failures at timepoints thereafter. Subjects 
with other reasons for missing data will be excluded from the analyses. 
The same approaches as described above will be used for the analysis of the proportion of 
subjects achieving HIV-1 RNA <40 and <200 copies/mL.  
08K3V5

Product:  MK-1439A 
89
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Table 9
Summary of the Two Approaches to Handle Missing Values
Approaches§
Intermittent 
Missing
Non-intermittent Missing 
Not Related to Treatment
Non-intermittent Missing 
Related to Treatment
Success at Study 
Therapy 
Discontinuation
Failure at Study 
Therapy 
Discontinuation
Study Therapy 
Discontinuation 
Due to 
Clinical/Lab 
Adverse 
Experience
Study Therapy 
Discontinuation 
Due to Lack of 
Efficacy
OF
Excluded
Excluded
Failures
Excluded
Failures
NC=F
Failure
Failures
Failures
Failures
Failures
§ OF (Observed Failure); NC=F (Non-Completer=Failure) is the primary approach.
Proportion of Subjects Achieving HIV-1 RNA <50 copies/mL
The proportion of subjects achieving HIV-1 RNA <50 copies/mL will be summarized by 
treatment group at each time point, with primary interest at Week 48. For each time point of 
interest, the difference in proportions between treatment groups and the associated 95% 
confidence interval will be calculated using the stratum-adjusted Mantel-Haenszel method 
with the difference weighted by the harmonic mean of the sample size per arm for each 
stratum (screening HIV-1 RNA ≤100,000 copies/mL or HIV-1 RNA >100,000 copies/mL).
The study has 2 stratification factors: screening HIV-1 RNA level and chronic hepatitis B or 
C status. Chronic hepatitis B or C co-infection may be associated with serious liver function 
abnormalities but is not considered to be associated with virologic response; therefore, 
stratification by hepatitis B or C status will not be included in the analyses of virologic 
response.
The NC=F approach as defined by FDA “snapshot” approach will be used as the primary 
approach to analysis with respect to the proportion of subjects with virologic response (HIV-
1 RNA <50 copies/mL). All missing data will be treated as failures regardless of the reason.
To provide a full picture of virologic outcome at a timepoint, subjects who are not classified 
as virologic success will be further categorized as virologic failure (HIV-1 RNA 
≥50 copies/mL) or as having no virologic data at the time window with reasons of 1) 
discontinued study due to an AE, 2) discontinued study for other reasons (includes withdraw 
consent, loss to follow-up, moved, etc.), or 3) on study but missing data in window. The full 
categorization of virologic outcome at Week 48 and Week 96 will be summarized by 
treatment group.
A sensitivity analysis will be performed using the OF approach under which non-intermittent 
missing data for subjects who prematurely discontinued assigned treatment due to lack of 
efficacy are considered as failures at timepoints thereafter. This sensitivity analysis will be 
limited to the primary efficacy analysis only (i.e., the proportion of subjects achieving HIV-1 
RNA <50 copies/mL at Week 48).
08K3V5

Product:  MK-1439A 
90
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
A margin of 10 percentage points is used to define the non-inferiority of MK-1439A q.d. to 
ATRIPLA™ q.d.; this is consistent with regulatory recommendations. MK-1439A q.d. will 
be concluded non-inferior to ATRIPLA™ q.d. if the lower bound of the two-sided 95% CI 
for the difference in the proportion of subjects with HIV-1 RNA <50 copies/mL at Week 48
(MK-1439A minus ATRIPLA™ q.d) is greater than -10 percentage points. It can be further 
concluded that MK-1439A q.d. is superior to ATRIPLA™ q.d. if the lower bound of the two-
sided 95% CI for the difference in response rates (MK-1439A minus ATRIPLA™ q.d) is 
greater than zero contingent upon satisfying the multiplicity criteria.
For the summary of virologic response over time, the difference in proportions between 
treatment groups at each time point will also be estimated and the associated two-sided 95% 
CI will be derived in a similar fashion to that described for the primary efficacy analysis.
Change from Baseline in CD4 cell counts
Change from baseline in CD4 cell counts will be summarized by treatment group at each 
time point at which CD4 cell count is collected, with a key interest at Week 48.
The 
treatment difference in changes from baseline in CD4 cell count at each time point will be 
estimated between the 2 treatment groups. However, these estimates will not be subject to an 
absolute criterion for similarity. The clinical interpretation of the treatment difference is 
dependent upon the absolute value at baseline, and the magnitude and direction of the CD4 
changes seen in each treatment arm. 
The OF approach will be used for the calculations of change from baseline in CD4 cell count.
Under this approach, baseline values will be carried forward for subjects who discontinue 
due to lack of efficacy.
Protocol-Defined Virologic Failure
The number of subjects with protocol-defined virologic failure will be summarized for each 
treatment group.
Table 10 summarizes the key efficacy analyses.
08K3V5

Product:  MK-1439A 
91
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Table 10
Analysis Strategy for Key Efficacy Variables
Endpoint/Variable
(Description, Time Point)
Primary vs. 
Supportive 
Approach†
Statistical Method
Analysis 
Population
Missing Data 
Approach
Primary Hypothesis
Proportion of subjects 
achieving HIV-1 RNA 
<50 copies/mL at Week 48
P
Stratum-adjusted 
Mantel-Haenszel‡
FAS
NC=F approach
Proportion of subjects 
achieving HIV-1 RNA 
<50 copies/mL at Week 48
S
Stratum-adjusted 
Mantel-Haenszel‡
FAS
OF approach
Secondary Objectives
Proportion of subjects 
achieving HIV-1 RNA 
<50 copies/mL at Week 96
P
Stratum-adjusted 
Mantel-Haenszel‡
FAS
NC=F approach
Change from baseline in CD4 
cell counts at Week 48 and 
Week 96
P
Two sample t-test
FAS
OF approach 
assuming 
baseline-carried-
forward
†
P=Primary approach; S=Secondary approach.
‡
Stratum-adjusted (screening HIV RNA-1 ≤100,000 vs. >100,000 copies /mL) Mantel-Haenszel method with the difference weighted by 
the harmonic mean of the sample size per arm for each stratum.
The strategy to address multiplicity issues with regard to multiple treatment comparisons, 
multiple endpoints, multiple timepoints, and/or interim analyses is described in Section 8.7, 
Interim Analyses and in Section 8.8, Multiplicity.
Statistical Methods for Safety Analyses
Safety and tolerability will be assessed by clinical review of all relevant parameters including 
AEs, laboratory tests and vital signs.  
The analysis of safety results will follow a tiered approach Table 11. The tiers differ with 
respect to the analyses that will be performed. Safety parameters or adverse experiences of 
special interest that are identified a priori constitute “Tier 1” safety endpoints that will be 
subject to inferential testing for statistical significance with p-values and 95% confidence 
intervals provided for between-group comparisons. 
Other safety parameters will be 
considered Tier 2 or Tier 3. Tier 2 parameters will be assessed via point estimates with 95% 
confidence intervals provided for between-group comparisons; only point estimates by 
treatment group are provided for Tier 3 safety parameters.  
AEs (specific terms as well as system organ class terms) and predefined limits of change in 
laboratory parameters that are not pre-specified as Tier-1 endpoints will be classified as 
belonging to "Tier 2" or "Tier 3", based on the number of events observed. Membership in 
Tier 2 requires that at least 4 subjects in any treatment group exhibit the event; all other 
adverse experiences and predefined limits of change will belong to Tier 3.
08K3V5

Product:  MK-1439A 
92
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
The threshold of at least 4 events was chosen because the 95% confidence interval for the 
between-group difference in percent incidence will always include zero when treatment 
groups of equal size each have less than 4 events and thus would add little to the 
interpretation of potentially meaningful differences. Because many 95% confidence intervals 
may be provided without adjustment for multiplicity, the confidence intervals should be 
regarded as a helpful descriptive measure to be used in review, not a formal method for 
assessing the statistical significance of the between-group differences in adverse experiences 
and predefined limits of change.
Continuous measures such as changes from baseline in laboratory and vital signs parameters 
that are not pre-specified as Tier-1 endpoints will be considered Tier 3 safety parameters.
Summary statistics for baseline, on-treatment, and change from baseline values will be 
provided by treatment group in table format. 
For this protocol, the proportion of subjects with neuropsychiatric AEs by Week 48 in 3 pre-
specified categories (dizziness, sleep disorders and disturbances, and altered sensorium with 
each tested separately) and the change from baseline in fasting LDL-C and non-HDL-C at 
Week 48 are considered Tier 1 events.
The proportion of subjects with neuropsychiatric AEs by Week 48 in the depression and 
suicide/self-injury and psychosis and psychotic disorders categories as well as the proportion 
of subjects experiencing one or more AE in any of the 5 pre-specified categories of 
neuropsychiatric adverse events will be considered Tier 2 events. For these as well as Tier 1 
neuropsychiatric AEs, the treatment difference and the associated 95% confidence interval 
will be calculated using the Miettinen and Nurminen’s method (1985) [5], an unconditional, 
asymptotic method, and p-values based on this method will be provided for the Tier 1 
categories of dizziness, sleep disorders and disturbances, and altered sensorium. 
Note that there is no adjustment for safety stratification (Hepatitis B/C status) in the 
calculation of the confidence intervals or p-values, since the purpose of this stratification 
factor is to help balance the treatment groups for better interpretation of any potential 
imbalance in serious liver function abnormalities. This stratification factor has no expected 
impact on the primary safety endpoint of neuropsychiatric AEs.
The change from baseline in fasting lipids will be analyzed using ANCOVA models adjusted 
by baseline lipid level and treatment group. The treatment differences and 95% confidence 
intervals will be provided for all lipid parameters, and the p-value for the between treatment 
comparison will be provided for LDL-C and non-HDL-C. The missing lipid data will be 
handled by the following principle: For subjects who have missing lipid data, the last lipid 
observation after randomization will be carried forward.
For subjects who modify (start, 
stop, increase or decrease dosage) lipid-lowering therapy use during the study, the last lipid 
observation before modifying the lipid-lowering therapy use will be carried forward for later 
time points.
The percentages of subjects who modify lipid-lowering therapy during the study will be 
summarized by treatment group. The difference in percentages between treatment groups 
08K3V5

Product:  MK-1439A 
93
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
and the associated 95% confidence interval will be calculated using Miettinen and 
Nurminen’s method.
In addition, the broad clinical and laboratory AE categories consisting of the percentage of 
subjects with any AE, with a drug-related AE, with a serious AE, with an AE which is both 
drug-related and serious, and who discontinued due to an AE will be considered Tier 2 
endpoints. The 95% confidence intervals will be provided for between treatment differences 
in the percentage of subjects with events; these analyses will be performed using the 
Miettinen and Nurminen method.
Table 11
Analysis Strategy for Safety Parameters
Safety Tier
Safety Endpoint†
p-Value
95% CI for 
Treatment 
Comparison
Descriptive 
Statistics
Tier 1
Proportion of subjects with neuropsychiatric AEs 
in the following categories:
Dizziness
Sleep disorders and disturbances
Altered Sensorium
Change from baseline in fasting LDL-C and non-
HDL-C
X
X
X
Tier 2
Proportion of subjects with neuropsychiatric AEs 
in the following categories:
Depression and suicide/self-injury
Psychosis and psychotic disorders 
Proportion of subjects with one or more
neuropsychiatric AEs 
Change from baseline in fasting lipids
not 
classified as Tier 1
X
X
X
X
Starting lipid-lowering therapy
X
X
Any AE
X
X
Any Serious AE
X
X
Any Drug-Related AE
X
X
Any Serious and Drug-Related AE
X
X
Discontinuation due to AE
X
X
Specific AEs, SOCs, or PDLCs‡ (incidence ≥4 of 
subjects in one of the treatment groups)
X
X
Tier 3
Specific AEs, SOCs or PDLCs‡ (incidence <4 of 
subjects in all of the treatment groups)
X
Change from Baseline Results (Labs, Vital Signs)
X
†
Adverse Experience references refer to both Clinical and Laboratory AEs.
‡
Includes only those endpoints not pre-specified as Tier 1 and not already pre-specified as Tier-2 endpoints.
Note: SOC = System Organ Class; PDLC = Pre-Defined Limit of Change; X  = results will be provided.
08K3V5

Product:  MK-1439A 
94
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Summaries of Baseline Characteristics, Demographics, and Other Analyses
Demographic and Baseline Characteristics
The comparability of the treatment groups for each relevant characteristic will be assessed by 
the use of tables and/or graphs. No statistical hypothesis tests will be performed on these 
characteristics. The number and percentage of subjects screened, randomized, the primary 
reasons for screening failure, and the primary reason for discontinuation will be displayed. 
Demographic variables (e.g., age, gender, race, region, etc.), baseline characteristics, primary 
and secondary diagnoses, and prior and concomitant therapies will be summarized by 
treatment either by descriptive statistics or categorical tables.
Interim Analyses
No interim analyses for efficacy are planned for this study.
However, an external data 
monitoring committee will convene to review safety data approximately every 6 months 
during the study.
Multiplicity
There are no interim analyses for efficacy and no plans to stop for favorable safety in this 
study as part of the periodic (~every 6 months) DMC safety reviews. However, as it is 
customary to spend a small amount of alpha for interim analyses for safety performed by the 
DMC when there is a primary safety hypothesis, an alpha level of 0.00001 will be allocated 
for each DMC safety review through Week 48 before testing the primary safety hypothesis
and subsequent safety hypotheses.
The primary efficacy hypothesis for non-inferiority will be tested at an unadjusted one-sided 
alpha level of 0.025 because no interim efficacy analysis will be performed. Furthermore, 
provided all safety hypotheses are satisfied after establishing the primary efficacy hypothesis, 
the superiority hypothesis for efficacy will be tested at the unadjusted alpha level of 0.025 as 
well.
The following hypotheses will be tested sequentially at the one-sided Type 1 error rate of 
2.5% (unadjusted for the efficacy hypotheses [#1,7] and after adjusting for interim DMC 
safety reviews for the safety hypotheses [#2-6]) in the following order:
1) Primary efficacy hypothesis testing non-inferiority at Week 48
2) Primary safety hypothesis for dizziness
3) Primary safety hypothesis for sleep disorders and disturbances
4) Primary safety hypothesis for altered sensorium
5) Secondary safety hypothesis for LDL-C
08K3V5

Product:  MK-1439A 
95
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
6) Secondary safety hypothesis for non-HDL-C
7) Secondary efficacy hypothesis testing superiority at Week 48 
Testing will stop with the first of these tests failing to reach statistical significance and all 
subsequent tests would not be considered for statistical significance. In this way, the overall 
one-sided Type 1 error rate in testing these hypotheses is strongly controlled at a 2.5% level.
Note the secondary efficacy hypotheses testing non-inferiority and superiority at Week 96 are 
only supportive to the primary and secondary efficacy hypotheses at Week 48 and are not 
considered in the strong control strategy for the Type 1 error for this study. 
There are no other hypotheses that will be tested and analyses associated with objectives 
without hypotheses will be considered supportive and/or explanatory. 
SAMPLE SIZE AND POWER CALCULATIONS 
Sample Size and Power for Efficacy Analyses
The study will randomize 340 subjects into each treatment arm to achieve 90% power to 
demonstrate the primary hypothesis that MK-1439A q.d. is non-inferior to ATRIPLA™ q.d., 
at an overall one-sided 2.5% alpha level, as measured by the proportion of subjects achieving 
HIV-1 RNA <50 copies/mL (by the Abbott RealTime HIV-1 Assay) at Week 48. The power 
calculation assumes a true response rate of 80% at Week 48 for both the MK-1439A q.d. arm 
and the ATRIPLA™ q.d arm using the NC=F approach as defined by the FDA “snapshot” 
approach. A margin of 10 percentage points is used to define the non-inferiority of MK-
1439A q.d. versus ATRIPLA™ q.d.; this is consistent with regulatory recommendations.
Given the non-inferiority margin of 10%, the assumed response rates and the chosen sample 
size, non-inferiority may be established when the observed difference in response rates (MK-
1439A q.d. minus ATRIPLA™ q.d.) is approximately -3.7% or larger; superiority may be 
concluded when the observed difference in response rates is approximately 5.7% or larger
under the multiplicity testing strategy in Section 8.8. The power calculation is based on an 
asymptotic method proposed by Farrington and Manning (1990) [6] and is carried out using 
SAS v9.3.
Table 12 summarizes the power for the primary comparison under various 
assumptions for the control response rate and underlying difference in response rates. 
Table 12
Power (%) Under Various Assumptions (With 340 Subjects Randomized in Each 
Treatment Group)
Response Rate (%) in 
ATRIPLA™ q.d.
Underlying Difference in Response Rates (%)
(MK-1439A q.d. – ATRIPLA™ q.d.)
-3
-2
-1
0
1
2
3
74
54
65
76
84
91
95
98
77
56
68
79
87
93
96
98
80
60
72
83
90
95
98
99
83
65
77
87
93
97
99
>99
86
70
82
91
96
98
>99
>99
Note:  The power is calculated based on 340 subjects expected to be included in the analysis for each treatment group
08K3V5

Product:  MK-1439A 
96
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Sample Size and Power for Safety Analyses
Neuropsychiatric Adverse Experiences
MK-1439 Protocol 007 studied 4 doses of MK-1439 versus efavirenz, each in combination 
therapy with TRUVADATM, in HIV-1 infected treatment-naïve subjects. Based on data 
from Protocol 007, the expected proportions of subjects with events in each of the 
categories of pre-specified neuropsychiatric adverse events through Week 48 are as 
follows: dizziness (5% vs 24%), sleep disorders and disturbances (16% vs 29%), altered 
sensorium (3% vs 10%), depression and suicide/self-injury (4% vs 10%), and psychosis and 
psychotic disorders (2%  vs 2%) in t h e  MK-1439A group and the ATRIPLA™group, 
respectively. Due to multiplicity and power considerations, only the first 3 neuropsychiatric 
adverse event categories (dizziness, sleep disorders and disturbances, and altered sensorium) 
were selected for statistical testing. If the proportions of subjects with neuropsychiatric AEs
in this study are similar to those observed in Protocol 007, the power to detect a difference
between MK-1439A and ATRIPLA™in the respective Tier 1 categories (dizziness, sleep 
disorders and disturbances, and altered sensorium) with 340 subjects in each treatment arm is 
>99%, 97%, and 95%, respectively. Table 13 displays the observed percentage of subjects in 
each category by treatment group that would be necessary to demonstrate superiority of MK-
1439A versus ATRIPLA™assuming the efavirenz event percentages from Protocol 007 for 
ATRIPLA™:
Table 13
Observed Percentage in MK-1439A Necessary to Demonstrate Superiority versus 
ATRIPLA™
MK-1439A q.d.
Superiority will be achieved 
provided the observed % is less 
than or equal to
ATRIPLA™q.d.
(same as efavirenz in P007)
Dizziness
17%
24%
Sleep disorders and disturbances
22%
29%
Altered Sensorium
5%
10%
Lipids
The change from baseline in fasting LDL-C and non-HDL-C at Week 48 will be analyzed 
using ANCOVA models adjusted by baseline lipids level and treatment group. MK-1439A
q.d. will be concluded to be superior to ATRIPLA™ q.d. if the mean change from baseline in 
LDL-C for the MK-1439A group is significantly lower than that for the ATRIPLA™ group.
If superiority for LDL-C is established, sequential testing for non-HDL-C will be conducted.
If we assume that ATRIPLA™ q.d. has an effect on lipids at least as large as efavirenz, the 
treatment difference in mean change from baseline in lipids observed in Protocol 007 can be 
used as an estimate for the power calculation for this study.
08K3V5

Product:  MK-1439A 
97
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
The estimated between treatment differences in mean changes in fasting LDL-C and non-
HDL-C, based on the interim data from MK-1439 Protocol 007, were 7.7 mg/dL (standard 
deviation of 20 mg/dL) and 20 mg/dL (standard deviation of 25 mg/dL), respectively. With 
340 subjects in each treatment group, the study has >99% power to detect a between 
treatment difference of 7.7 mg/dL for mean change from baseline in LDL-C. The study also 
has >99% power to detect a between treatment difference of 20 mg/dL for mean change from 
baseline in non-HDL-C.  
Adverse Experiences
The probability of observing at least one of a particular type of adverse experience in this 
study depends on the number of subjects treated and the underlying percentage of subjects 
with that adverse experience in the study population. If the underlying incidence of a 
particular adverse experience is 1% (1 of every 100 subjects receiving the drug), there is a 
96.7% chance of observing at least one adverse experience among 340 subjects in any 
treatment group. If no adverse experience of that type is observed among the 340 subjects in 
any treatment group, this study will provide 95% confidence that the underlying percentage 
of subjects with that particular adverse experience is <1.1% for the treatment group.
The estimate of, and the upper bound of the 95% confidence interval for, the underlying 
percentage of subjects with an AE given various hypothetical observed number of subjects 
with the AE within each treatment group are provided in Table 14. These calculations are 
based on the exact binomial method proposed by Clopper and Pearson (1934) [7].
Table 14
Estimate of Incidence of AEs and 95% Upper Confidence Bound Based on 
Hypothetical Numbers of Subjects with AEs Among 340 Subjects Randomized in Each 
Treatment Group
Hypothetical Number of Subjects
With An Adverse Event
Estimate of 
Incidence
95% Upper Confidence Bound†
0
0%
1.1
5
1.5%
3.4
10
2.9%
5.3
15
4.4%
7.2
20
5.9%
8.9
25
7.4%
10.7
30
8.8%
12.4
† Based on the two-tailed exact confidence interval for a binomial proportion (Clopper and Pearson, 1934 [7]).
Table 15 gives the difference in the incidence of adverse experiences (MK-1439A q.d. –
ATRIPLA™q.d.) that can be ruled out with different power levels and 95% confidence 
when there are 340 subjects in each treatment group. The underlying incidence of adverse 
experiences is assumed to be the same for the 2 treatment groups. For a reasonably common 
adverse experience which occurs in 20% of subjects either in the MK-1439A q.d. arm or 
08K3V5

Product:  MK-1439A 
98
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
ATRIPLA™q.d. arm, the study has 90% power to declare with 95% confidence that the true 
difference between the treatment groups is no more than 9.9 percentage points.
The 
calculations are based on an asymptotic method proposed by Farrington and Manning (1990) 
[6].
Table 15
Differences in Incidences of AEs (MK-1439A q.d. minus ATRIPLA™q.d.) That 
Can Be Ruled Out With 340 Subjects in Each Treatment Group
Difference† in Percentage Points That Can Be Ruled Out with Target Power 
Assuming the Underlying Incidence of the AE is
Target Power
10%
20%
30%
40%
50%
80
6.4
8.6
9.8
10.5
10.7
85
6.9
9.2
10.5
11.3
11.5
90
7.5
9.9
11.4
12.2
12.4
95
8.3
11.1
12.7
13.5
13.8
†The upper bound of the two-sided 95% confidence interval (Farrington and Manning (1990) for the difference in AE 
incidences (MK-1439 100 mg q.d. minus darunavir/ritonavir [800 mg/100mg] q.d.) assuming the incidences are the same.
Overall Power
The following hypotheses will be tested sequentially at the one-sided Type 1 error rate of 
2.5% (unadjusted for the efficacy hypotheses [#1,7] and after adjusting for interim DMC 
safety reviews for the safety hypotheses [#2-6]) in the following order:
1) Primary efficacy hypothesis testing non-inferiority at Week 48
2) Primary safety hypothesis for dizziness
3) Primary safety hypothesis for sleep disorders and disturbances
4) Primary safety hypothesis for altered sensorium
5) Secondary safety hypothesis for LDL-C
6) Secondary safety hypothesis for non-HDL-C
7) Secondary efficacy hypothesis testing superiority at Week 48 
Testing will stop with the first of these tests failing to reach statistical significance and all 
subsequent tests would not be considered for statistical significance. In this way, the overall
one-sided Type 1 error rate in testing these hypotheses is strongly controlled at a 2.5% level.
The probability to reach steps 2 through 7 for statistical testing (could also be considered the 
power to establish the hypotheses in steps 1 through 6) is approximately 90%, 89%, 86%, 
82%, 81%, and 80%, respectively.
08K3V5

Product:  MK-1439A 
99
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Subgroup Analyses and Effect of Baseline Factors (Base Study)
To determine whether the treatment effect is consistent across various subgroups, the 
estimate of the between-group treatment effect (with a nominal 95% CI unadjusted for 
stratification factors) for the primary endpoint will be calculated and plotted within each 
category of the following classification variables:

Age category (≤median vs. >median)

Gender (female, male)

Region (North America, South America, Europe, Asia, Africa, etc.) 

Race (White, Black, Asian, Other)

Ethnicity (Hispanic/Latino, not Hispanic/Latino)

Screening HIV-1 RNA categories (HIV-1 RNA ≤100,000 copies/mL, HIV-1 RNA 
>100,000 copies/mL)

Baseline HIV-1 RNA categories (HIV-1 RNA ≤100,000 copies/mL, HIV-1 RNA 
>100,000 copies/mL)

Chronic Hepatitis B or C status (HBV/HCV-infected or HBV/HCV-uninfected)

Baseline CD4 categories (<50, 50-200, and >200 cells/mm3)
The Observed Failure approach will be used to handle missing values in these subgroup 
analyses.
Compliance (Medication Adherence)
Study Medication Diary Cards will be used to ensure and document the drug compliance in 
the base study and study extension 1.
Subjects are to take one pill once daily from each of the 2 bottles (A & B) of study 
medication during the base study. For the main analysis of compliance in the base study, a 
day within the study will be considered an “On-Therapy” day if the subject takes at least one 
tablet from any bottle provided for this study. 
For a subject who is followed for the entire study period, the “Number of Days Should be on 
Therapy” is the total number of days from Day 1 to the last scheduled day for treatment
administration for that subject. For a subject who discontinued from the study permanently, 
the “Number of Days Should be on Therapy” is the total number of days from Day 1 to the 
date of the last dose of study medication.
For each subject, percent compliance will then be calculated using the following formula:
Percent Compliance=
Number of Days on Therapy
x 100
Number of Days Should be on Therapy
08K3V5

Product:  MK-1439A 
100
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Summary statistics will be provided on percent compliance by treatment group for the FAS 
population.
A second analysis in the base study using a different definition of compliance will also be 
conducted. In this analysis, a day within the study will be considered an “On-Therapy” day 
only if the subject takes the required number of tablets from all bottles provided for this study 
(as noted in Section 7.1.5.2) will also be summarized.
During the study extensions, MK-1439A will be provided as study medication by the 
sponsor. 
Compliance with MK-1439A administration will be summarized for study 
extension 1. A day within the study will be considered an “On-Therapy” day if the subject 
takes 1 tablet of MK-1439A.
Data from the study medication diary, rather than the returned pill count will serve as the 
primary data for compliance.
Compliance data will not be collected and analyzed for study extension 2 or for study 
extension 3.
Extent of Exposure
The extent of exposure to study therapy for all randomized and treated subjects will be 
summarized. The number of subjects exposed to various doses (actual total daily dose) for 
defined periods of time will be listed, along with a summary of the mean (range) duration 
subjects were exposed to various doses.
LABELING, PACKAGING, STORAGE AND RETURN OF CLINICAL 
SUPPLIES
Investigational Product
The investigator shall take responsibility for and shall take all steps to maintain appropriate 
records and ensure appropriate supply, storage, handling, distribution and usage of 
investigational product in accordance with the protocol and any applicable laws and 
regulations.
Clinical Supplies will be provided by the Sponsor as summarized in Table 16.
08K3V5

Product:  MK-1439A 
101
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Table 16
Product Descriptions: Base Study and Study Extensions
Product Name & Potency
Dosage Form
Base Study
MK-1439A 100 mg/ 300 mg/ 300 mg or Placebo to match MK-1439A 100 
mg/ 300 mg/ 300 mg
Tablet
Efavirenz 600 mg / emtricitabine 200mg / tenofovir disoproxil fumarate 
300 mg (which is equivalent to 245 mg of tenofovir disoproxil). 
(ATRIPLA™) or Placebo to match Efavirenz 600 mg / emtricitabine 200
mg / tenofovir disoproxil fumarate 300 mg (which is equivalent to 245 mg 
of tenofovir disoproxil). (ATRIPLA™)
Tablet
Study Extensions
MK-1439A 100 mg/ 300 mg/ 300 mg
Tablet
All placebos were created by the Sponsor to match the active product.
Packaging and Labeling Information
Clinical supplies will be affixed with a clinical label in accordance with regulatory 
requirements.
During the base study, subjects will receive blinded monthly bottles. No kitting is required.
During the study extensions, subjects will receive open-label MK-1439A.
Clinical Supplies Disclosure
The emergency unblinding call center will use the randomization schedule for the trial to 
unblind subjects and to unmask treatment. The emergency unblinding call center should only 
be used in cases of emergency (see Section 7.1.4.2). In the event that the emergency 
unblinding call center is not available for a given site in this trial, the central electronic 
randomization system (IVRS/IWRS) should be used in order to unblind subjects and to 
unmask treatment/vaccine identity.
The Sponsor will provide random code/disclosure 
envelopes or lists to the emergency unblinding call center.
Treatment identification information is to be unmasked ONLY if necessary for the welfare of 
the subject.  Every effort should be made not to unblind the subject unless necessary. 
In the event that unblinding has occurred, the circumstances around the unblinding (eg, date, 
reason and person performing the unblinding) must be documented promptly, and the 
Sponsor Clinical Director notified as soon as possible. Once an emergency unblinding has 
08K3V5

Product:  MK-1439A 
102
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
taken place, the principal investigator, site personnel, and Sponsor personnel may be
unblinded so that the appropriate follow-up medical care can be provided to the subject.
Storage and Handling Requirements
Clinical supplies must be stored in a secure, limited-access location under the storage 
conditions specified on the label.  
Receipt and dispensing of trial medication must be recorded by an authorized person at the 
trial site.
Clinical supplies may not be used for any purpose other than that stated in the protocol.
Returns and Reconciliation
The investigator is responsible for keeping accurate records of the clinical supplies received 
from the Sponsor or designee, the amount dispensed to and returned, and the amount 
remaining at the conclusion of the trial. For all trial sites, the local country Sponsor personnel 
or designee will provide appropriate documentation that must be completed for drug 
accountability and return, or local discard and destruction if appropriate. Where local discard 
and destruction is appropriate, the investigator is responsible for ensuring that a local 
discard/destruction procedure is documented.
Standard Policies
Trial site personnel will have access to a central electronic randomization system 
(IVRS/IWRS system) to allocate subjects, to assign treatment to subjects and to manage the 
distribution of clinical supplies. Each person accessing the IVRS system must be assigned an 
individual unique PIN.  They must use only their assigned PIN to access the system, and they 
must not share their assigned PIN with anyone.
At the close of the trial after unblinding, a letter is to be sent by the investigator to those 
subjects who received placebos in the image of the competitor’s product to provide the 
following advice: 
“You have participated in a trial conducted by the Sponsor. This is to advise you that you 
were among those who received a look-alike tablet created by the Sponsor to resemble the 
drug ATRIPLA™(efavirenz 600 mg / emtricitabine 200 mg / tenofovir disoproxil fumarate 
300 mg) as much as possible. You did not receive the active  drug ATRIPLA™ (efavirenz 
600 mg / emtricitabine 200 mg / tenofovir disoproxil fumarate 300 mg [which is equivalent 
to 245 mg of tenofovir disoproxil]) as manufactured by Gilead Sciences.”
08K3V5

Product:  MK-1439A 
103
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
ADMINISTRATIVE AND REGULATORY DETAILS
Confidentiality
Confidentiality of Data 
By signing this protocol, the investigator affirms to the Sponsor that information furnished to 
the investigator by the Sponsor will be maintained in confidence, and such information will 
be divulged to the institutional review board, ethics review committee (IRB/ERC) or similar 
or expert committee; affiliated institution and employees, only under an appropriate 
understanding of confidentiality with such board or committee, affiliated institution and 
employees.  Data generated by this trial will be considered confidential by the investigator, 
except to the extent that it is included in a publication as provided in the Publications section 
of this protocol.
Confidentiality of Subject Records
By signing this protocol, the investigator agrees that the Sponsor (or Sponsor representative), 
IRB/ERC, or regulatory authority representatives may consult and/or copy trial documents in 
order to verify worksheet/case report form data.  By signing the consent form, the subject 
agrees to this process.  If trial documents will be photocopied during the process of verifying 
worksheet/case report form information, the subject will be identified by unique code only; 
full names/initials will be masked prior to transmission to the Sponsor.
By signing this protocol, the investigator agrees to treat all subject data used and disclosed in 
connection with this trial in accordance with all applicable privacy laws, rules and 
regulations.
Confidentiality of Investigator Information
By signing this protocol, the investigator recognizes that certain personal identifying 
information with respect to the investigator, and all subinvestigators and trial site personnel, 
may be used and disclosed for trial management purposes, as part of a regulatory 
submissions, and as required by law.  This information may include:
1. name, address, telephone number and e-mail address;
2. hospital or clinic address and telephone number;
3. curriculum vitae or other summary of qualifications and credentials; and
4. other professional documentation.
Consistent with the purposes described above, this information may be transmitted to the 
Sponsor, and subsidiaries, affiliates and agents of the Sponsor, in your country and other 
countries, including countries that do not have laws protecting such information.  
Additionally, the investigator’s name and business contact information may be included 
08K3V5

Product:  MK-1439A 
104
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
when reporting certain serious adverse events to regulatory authorities or to other 
investigators.  By signing this protocol, the investigator expressly consents to these uses and 
disclosures.
If this is a multicenter trial, in order to facilitate contact between investigators, the Sponsor 
may share an investigator’s name and contact information with other participating 
investigators upon request.
Confidentiality of IRB/IEC Information
The Sponsor is required to record the name and address of each IRB/IEC member that 
reviews and approves this trial.  The Sponsor is also required to document that each IRB/IEC 
meets regulatory and ICH GCP requirements by requesting and maintaining records of the 
names and qualifications of the IRB/IEC members and to make these records available for 
regulatory agency review upon request by those agencies.
Compliance with Financial Disclosure Requirements
Financial Disclosure requirements are outlined in the US Food and Drug Administration 
Regulations, Financial Disclosure by Clinical Investigators (21 CFR Part 54).  It is the 
Sponsor's responsibility to determine, based on these regulations, whether a request for 
Financial Disclosure information is required.  It is the investigator's/subinvestigator's 
responsibility to comply with any such request.  
The investigator/subinvestigator(s) agree, if requested by the Sponsor in accordance with 21 
CFR Part 54, to provide his/her financial interests in and/or arrangements with the Sponsor to 
allow for the submission of complete and accurate certification and disclosure statements.  
The investigator/subinvestigator(s) further agree to provide this information on a 
Certification/Disclosure Form, commonly known as a financial disclosure form, provided by 
the Sponsor or through a secure password-protected electronic portal provided by the 
Sponsor.  The investigator/subinvestigator(s) also consent to the transmission of this 
information to the Sponsor in the United States for these purposes.  This may involve the 
transmission of information to countries that do not have laws protecting personal data.
Compliance with Law, Audit and Debarment
By signing this protocol, the investigator agrees to conduct the trial in an efficient and 
diligent manner and in conformance with this protocol; generally accepted standards of Good 
Clinical Practice (e.g., International Conference on Harmonization of Technical 
Requirements for Registration of Pharmaceuticals for Human Use Good Clinical Practice: 
Consolidated Guideline and other generally accepted standards of good clinical practice); and 
all applicable federal, state and local laws, rules and regulations relating to the conduct of the 
clinical trial.
The Code of Conduct, a collection of goals and considerations that govern the ethical and 
scientific conduct of clinical investigations sponsored by MSD, is provided in Section 12.1 -
Code of Conduct for Clinical Trials.
08K3V5

Product:  MK-1439A 
105
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
The investigator also agrees to allow monitoring, audits, IRB/ERC review and regulatory 
authority inspection of trial-related documents and procedures and provide for direct access 
to all trial-related source data and documents.
The investigator agrees not to seek reimbursement from subjects, their insurance providers or 
from government programs for procedures included as part of the trial reimbursed to the 
investigator by the Sponsor.
The investigator shall prepare and maintain complete and accurate trial documentation in 
compliance with Good Clinical Practice standards and applicable federal, state and local 
laws, rules and regulations; and, for each subject participating in the trial, provide all data, 
and, upon completion or termination of the clinical trial, submit any other reports to the 
Sponsor as required by this protocol or as otherwise required pursuant to any agreement with 
the Sponsor.
Trial documentation will be promptly and fully disclosed to the Sponsor by the investigator 
upon request and also shall be made available at the trial site upon request for inspection, 
copying, review and audit at reasonable times by representatives of the Sponsor or any 
regulatory authorities.  The investigator agrees to promptly take any reasonable steps that are 
requested by the Sponsor as a result of an audit to cure deficiencies in the trial documentation 
and worksheets/case report forms.
The investigator must maintain copies of all documentation and records relating to the 
conduct of the trial in compliance with all applicable legal and regulatory requirements.  This 
documentation includes, but is not limited to, the protocol, worksheets/case report forms, 
advertising for subject participation, adverse event reports, subject source data, 
correspondence with regulatory authorities and IRBs/ERCs, consent forms, investigator’s 
curricula vitae, monitor visit logs, laboratory reference ranges, laboratory certification or 
quality control procedures and laboratory director curriculum vitae.  By signing this protocol, 
the investigator agrees that documentation shall be retained until at least 2 years after the last 
approval of a marketing application in an ICH region or until there are no pending or 
contemplated marketing applications in an ICH region or until at least 2 years have elapsed 
since the formal discontinuation of clinical development of the investigational product.  
Because the clinical development and marketing application process is variable, it is 
anticipated that the retention period can be up to 15 years or longer after protocol database 
lock. The Sponsor will determine the minimum retention period and notify the investigator 
when documents may be destroyed.  The Sponsor will determine the minimum retention 
period and upon request, will provide guidance to the investigator when documents no longer 
need to be retained.  The sponsor also recognizes that documents may need to be retained for 
a longer period if required by local regulatory requirements. All trial documents shall be 
made available if required by relevant regulatory authorities. The investigator must consult 
with and obtain written approval by the Sponsor prior to destroying trial and/or subject files.  
ICH Good Clinical Practice guidelines recommend that the investigator inform the subject’s 
primary physician about the subject’s participation in the trial if the subject has a primary 
physician and if the subject agrees to the primary physician being informed.
08K3V5

Product:  MK-1439A 
106
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
The investigator will promptly inform the Sponsor of any regulatory authority inspection 
conducted for this trial.
Persons debarred from conducting or working on clinical trials by any court or regulatory 
authority will not be allowed to conduct or work on this Sponsor’s trials.  The investigator 
will immediately disclose in writing to the Sponsor if any person who is involved in 
conducting the trial is debarred or if any proceeding for debarment is pending or, to the best 
of the investigator’s knowledge, threatened.
In the event the Sponsor prematurely terminates a particular trial site, the Sponsor will 
promptly notify that trial site’s IRB/IEC.
According to European legislation, a Sponsor must designate an overall coordinating 
investigator for a multi-center trial (including multinational).  When more than one trial site 
is open in an EU country, MSD, as the Sponsor, will designate, per country, a national 
principal coordinator (Protocol CI), responsible for coordinating the work of the principal 
investigators at the different trial sites in that Member State, according to national 
regulations.  For a single-center trial, the Protocol CI is the principal investigator.  In 
addition, the Sponsor must designate a principal or coordinating investigator to review the 
trial report that summarizes the trial results and confirm that, to the best of his/her 
knowledge, the report accurately describes the conduct and results of the trial [Clinical Study 
Report (CSR) CI].  The Sponsor may consider one or more factors in the selection of the 
individual to serve as the Protocol CI and or CSR CI (e.g., availability of the CI during the 
anticipated review process, thorough understanding of clinical trial methods, appropriate 
enrollment of subject cohort, timely achievement of trial milestones).  The Protocol CI must 
be a participating trial investigator.
Compliance with Trial Registration and Results Posting Requirements
Under the terms of the Food and Drug Administration Amendments Act (FDAAA) of 2007 
and the European Medicines Agency (EMA) clinical trial Directive 2001/20/EC, the Sponsor 
of the trial is solely responsible for determining whether the trial and its results are subject to 
the 
requirements 
for 
submission 
to 
http://www.clinicaltrials.gov, 
www.clinicaltrialsregister.eu or other local registries.  MSD, as Sponsor of this trial, will 
review this protocol and submit the information necessary to fulfill these requirements. MSD
entries are not limited to FDAAA or the EMA clinical trial directive mandated trials.  
Information posted will allow subjects to identify potentially appropriate trials for their 
disease conditions and pursue participation by calling a central contact number for further 
information on appropriate trial locations and trial site contact information.  
By signing this protocol, the investigator acknowledges that the statutory obligations under 
FDAAA, the EMA clinical trials directive or other locally mandated registries are that of the 
Sponsor and agrees not to submit any information about this trial or its results to those 
registries.
08K3V5

Product:  MK-1439A 
107
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Quality Management System
By signing this protocol, the Sponsor agrees to be responsible for implementing and 
maintaining a quality management system with written development procedures and 
functional area standard operating procedures (SOPs) to ensure that trials are conducted and 
data are generated, documented, and reported in compliance with the protocol, accepted 
standards of Good Clinical Practice, and all applicable federal, state, and local laws, rules and 
regulations relating to the conduct of the clinical trial.
Data Management
The investigator or qualified designee is responsible for recording and verifying the accuracy 
of subject data.  By signing this protocol, the investigator acknowledges that his/her 
electronic signature is the legally binding equivalent of a written signature.  By entering 
his/her electronic signature, the investigator confirms that all recorded data have been 
verified as accurate.
Detailed information regarding Data Management procedures for this protocol will be 
provided separately.
Publications
This trial is intended for publication, even if terminated prematurely. Publication may include 
any or all of the following: posting of a synopsis online, abstract and/or presentation at a 
scientific conference, or publication of a full manuscript.  The Sponsor will work with the 
authors to submit a manuscript describing trial results within 12 months after the last data 
become available, which may take up to several months after the last subject visit in some 
cases such as vaccine trials.  However, manuscript submission timelines may be extended on 
OTC trials.  For trials intended for pediatric-related regulatory filings, the investigator agrees 
to delay publication of the trial results until the Sponsor notifies the investigator that all 
relevant regulatory authority decisions on the trial drug have been made with regard to 
pediatric-related regulatory filings. MSD will post a synopsis of trial results for approved 
products on www.clinicaltrials.gov by 12 months after the last subject's last visit for the 
primary outcome, 12 months after the decision to discontinue development, or product 
marketing (dispensed, administered, delivered or promoted), whichever is later.
These timelines may be extended for products that are not yet marketed, if additional time is 
needed for analysis, to protect intellectual property, or to comply with confidentiality 
agreements with other parties.  Authors of the primary results manuscript will be provided 
the complete results from the Clinical Study Report, subject to the confidentiality agreement. 
When a manuscript is submitted to a biomedical journal, the Sponsor's policy is to also 
include the protocol and statistical analysis plan to facilitate the peer and editorial review of 
the manuscript.  If the manuscript is subsequently accepted for publication, the Sponsor will 
allow the journal, if it so desires, to post on its website the key sections of the protocol that 
are relevant to evaluating the trial, specifically those sections describing the trial objectives 
and hypotheses, the subject inclusion and exclusion criteria, the trial design and procedures, 
08K3V5

Product:  MK-1439A 
108
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
the efficacy and safety measures, the statistical analysis plan, and any amendments relating to 
those sections.  The Sponsor reserves the right to redact proprietary information.
For multicenter trials, subsequent to the multicenter publication (or after public disclosure of 
the results online at www.clinicaltrials.gov if a multicenter manuscript is not planned), an 
investigator and his/her colleagues may publish their data independently.  In most cases, 
publication of individual trial site data does not add value to complete multicenter results, 
due to statistical concerns.  In rare cases, publication of single trial site data prior to the main 
paper may be of value.  Limitations of single trial site observations in a multicenter trial 
should always be described in such a manuscript.
Authorship credit should be based on 1) substantial contributions to conception and design, 
or acquisition of data, or analysis and interpretation of data; 2) drafting the article or revising 
it critically for important intellectual content; and 3) final approval of the version to be 
published. Authors must meet conditions 1, 2 and 3.  Significant contributions to trial 
execution may also be taken into account to determine authorship, provided that 
contributions have also been made to all three of the preceding authorship criteria.  Although 
publication planning may begin before conducting the trial, final decisions on authorship and 
the order of authors’ names will be made based on participation and actual contributions to 
the trial and writing, as discussed above. The first author is responsible for defending the 
integrity of the data, method(s) of data analysis and the scientific content of the manuscript.
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.
LIST OF REFERENCES
1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of 
antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and 
Human 
Services. 
November 
3, 
2008; 
1-139. 
Available 
at 
http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.
2. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing 
HIV infection - recommendations for a public health approach.
3. Anderson M, Gilmartin J, Cilissen C, etc., Safety, Tolerability, and Pharmacokinetics of 
Single and Multiple Doses of MK-1439, a Novel HIV Non-Nucleoside Reverse 
Transcriptase Inhibitor, in Healthy Subjects, Abstract presented at Conference on 
Retroviruses and Opportunistic Infections, March 3 – 6, 2014, Boston, MA
08K3V5

Product:  MK-1439A 
109
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
4. Gatell1 JM, Morales-Ramirez JO, Hagins DP, Thompson M, Arastéh K, Hoffmann C, 
Rugina S, Osiyemi O, Erscoiu S, Dretler R, Harvey C, Xu X, Teppler H. 48 week 
Efficacy and Safety and Early CNS tolerability of Doravirine, a novel NNRTI, with 
TDF/FTC in ART-Naïve HIV Infected patients. Presented at the Conference on HIV 
Drug Therapy, Glasgow, Nov. 2 – 6, 2014.
5. Miettinen OS, Nurminen M. Comparative analysis of two rates. Statistics in Medicine 
1985; 4:213-226.
6. Farrington CP, Manning G. Test statistics and sample size formulae for comparative 
binomial trials with null hypothesis of non-zero risk difference or non-unity relative risk. 
Statistics in Medicine 1990; 9: 1447-54.
7. Clopper CJ, Pearson ES. The use of confidence or fiducial limits illustrated in the case 
of binomial. Biometrika 1934; 26: 404-13.
08K3V5

Product:  MK-1439A 
110
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
APPENDICES
Code of Conduct for Clinical Trials
Merck Sharp & Dohme LLC, Rahway, NJ, USA (MSD)
Code of Conduct for Interventional Clinical Trials
I.
Introduction
A. Purpose
MSD, through its subsidiaries, conducts clinical trials worldwide to evaluate the safety and effectiveness of our 
products. As such, we are committed to designing, implementing, conducting, analyzing, and reporting these trials in 
compliance with the highest ethical and scientific standards. Protection of participants in clinical trials is the 
overriding concern in the design and conduct of clinical trials. In all cases, MSD clinical trials will be conducted in 
compliance with local and/or national regulations (including all applicable data protection laws and regulations), and 
International Council for Harmonisation Good Clinical Practice (ICH-GCP), and also in accordance with the ethical 
principles that have their origin in the Declaration of Helsinki.
B. Scope
Highest ethical and scientific standards shall be endorsed for all clinical interventional investigations sponsored by 
MSD irrespective of the party (parties) employed for their execution (e.g., contract research organizations, 
collaborative research efforts). This Code is not intended to apply to trials that are observational in nature, or which 
are retrospective. Further, this Code does not apply to investigator-initiated trials, which are not under the full control 
of MSD.
II. Scientific Issues
A. Trial Conduct
1. Trial Design
Except for pilot or estimation trials, clinical trial protocols will be hypothesis-driven to assess safety, efficacy 
and/or pharmacokinetic or pharmacodynamic indices of MSD or comparator products. Alternatively, MSD may 
conduct outcomes research trials, trials to assess or validate various endpoint measures, or trials to determine 
patient preferences, etc.
The design (i.e., participant population, duration, statistical power) must be adequate to address the specific 
purpose of the trial and shall respect the data protection rights of all participants, trial site staff and, where 
applicable, third parties. All trial protocols are and will be assessed for the need and capability to enroll 
underrepresented groups. Participants must meet protocol entry criteria to be enrolled in the trial.
2. Site Selection
MSD’s clinical trials are conducted globally in many different countries and in diverse populations, including 
people of varying age, race, ethnicity, gender, and accounting for other potential disease related factors. MSD 
selects investigative sites based on medical expertise, access to appropriate participants, adequacy of facilities and 
staff, previous performance in clinical trials, as well as budgetary considerations. Prior to trial initiation, sites are 
evaluated by MSD personnel (or individuals acting on behalf of MSD) to assess the ability to successfully conduct 
the trial.
Where appropriate, and in accordance with regulatory authority guidance, MSD will make concerted efforts to 
raise awareness of clinical trial opportunities in various communities. MSD will seek to engage underrepresented 
groups and those disproportionately impacted by the disease under study. MSD will support clinical trial 
investigators to enroll underrepresented groups and expand access to those who will ultimately use the products 
under investigation.
3. Site Monitoring/Scientific Integrity
Investigative trial sites are monitored to assess compliance with the trial protocol and Good Clinical Practice 
(GCP). MSD reviews clinical data for accuracy, completeness, and consistency. Data are verified versus source 
documentation according to standard operating procedures. Per MSD policies and procedures, if potential fraud, 
scientific/research misconduct, privacy incidents/breaches or Clinical Trial-related Significant Quality Issues are 
reported, such matters are investigated. When necessary, appropriate corrective and/or preventative actions are 
defined and regulatory authorities and/or ethics review committees are notified.
08K3V5

Product:  MK-1439A 
111
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
B. Publication and Authorship
Regardless of trial outcome, MSD commits to publish the primary and secondary results of its registered trials of 
marketed products in which treatment is assigned, according to the pre-specified plans for data analysis. To the extent 
scientifically appropriate, MSD seeks to publish the results of other analyses it conducts that are important to patients, 
physicians, and payers. Some early phase or pilot trials are intended to be hypothesis-generating rather than 
hypothesis testing; in such cases, publication of results may not be appropriate since the trial may be underpowered 
and the analyses complicated by statistical issues such as multiplicity.
MSD’s policy on authorship is consistent with the recommendations published by the International Committee of 
Medical Journal Editors (ICMJE). In summary, authorship should reflect significant contribution to the design and 
conduct of the trial, performance or interpretation of the analysis, and/or writing of the manuscript. All named authors 
must be able to defend the trial results and conclusions. MSD funding of a trial will be acknowledged in publications.
III. Participant Protection
A. Regulatory Authority and Ethics Committee Review (Institutional Review Board [IRB]/Independent Ethics 
Committee [IEC])
All protocols and protocol amendments will be submitted by MSD for regulatory authority acceptance/authorization 
prior to implementation of the trial or amendment, in compliance with local and/or national regulations.
The protocol, protocol amendment(s), informed consent form, investigator’s brochure, and other relevant trial 
documents must be reviewed and approved by an IRB/IEC before being implemented at each site, in compliance with 
local and/or national regulations. Changes to the protocol that are required urgently to eliminate an immediate hazard 
and to protect participant safety may be enacted in anticipation of ethics committee approval. MSD will inform 
regulatory authorities of such new measures to protect participant safety, in compliance with local and/or national 
regulations.
B. Safety
The guiding principle in decision-making in clinical trials is that participant welfare is of primary importance. 
Potential participants will be informed of the risks and benefits of, as well as alternatives to, trial participation. At a 
minimum, trial designs will take into account the local standard of care.
All participation in MSD clinical trials is voluntary. Participants enter the trial only after informed consent is obtained. 
Participants may withdraw from an MSD trial at any time, without any influence on their access to, or receipt of, 
medical care that may otherwise be available to them.
C. Confidentiality
MSD is committed to safeguarding participant confidentiality, to the greatest extent possible, as well as all applicable 
data protection rights. Unless required by law, only the investigator, Sponsor (or individuals acting on behalf of 
MSD), ethics committee, and/or regulatory authorities will have access to confidential medical records that might 
identify the participant by name.
D. Genomic Research
Genomic research will only be conducted in accordance with a protocol and informed consent authorized by an ethics 
committee.
IV.Financial Considerations
A. Payments to Investigators
Clinical trials are time- and labor-intensive. It is MSD’s policy to compensate investigators (or the sponsoring 
institution) in a fair manner for the work performed in support of MSD trials. MSD does not pay incentives to enroll 
participants in its trials. However, when enrollment is particularly challenging, additional payments may be made to 
compensate for the time spent in extra recruiting efforts.
MSD does not pay for participant referrals. However, MSD may compensate referring physicians for time spent on 
chart review and medical evaluation to identify potentially eligible participants.
B. Clinical Research Funding 
Informed consent forms will disclose that the trial is sponsored by MSD, and that the investigator or sponsoring 
institution is being paid or provided a grant for performing the trial. However, the local ethics committee may wish 
to alter the wording of the disclosure statement to be consistent with financial practices at that institution. As noted 
above, all publications resulting from MSD trials will indicate MSD as a source of funding.
08K3V5

Product:  MK-1439A 
112
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
C. Funding for Travel and Other Requests
Funding of travel by investigators and support staff (e.g., to scientific meetings, investigator meetings, etc.) will be 
consistent with local guidelines and practices.
V. Investigator Commitment
Investigators will be expected to review MSD’s Code of Conduct as an appendix to the trial protocol, and in signing 
the protocol, agree to support these ethical and scientific standards.
08K3V5

Product:  MK-1439A 
113
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Collection and Management of Specimens for Future Biomedical Research
1. Definitions
a.
Biomarker:  A biological molecule found in blood, other body fluids, or tissues that is 
a sign of a normal or abnormal process or of a condition or disease. A biomarker may 
be used to see how well the body responds to a treatment for a disease or condition.1
b. Pharmacogenomics:  The investigation of variations of DNA and RNA characteristics 
as related to drug/vaccine response.2
c.
Pharmacogenetics:  A subset of pharmacogenomics, pharmacogenetics is the 
influence of variations in DNA sequence on drug/vaccine response.2
d. DNA:  Deoxyribonucleic acid.
e.
RNA:  Ribonucleic acid.
2. Scope of Future Biomedical Research
The specimens collected in this trial as outlined in Section 7.1.3.8 – Future Biomedical 
Research will be used to study various causes for how subjects may respond to a 
drug/vaccine. Future biomedical research specimen(s) will be stored to provide a resource 
for future trials conducted by MSD focused on the study of biomarkers responsible for 
how a drug/vaccine enters and is removed by the body, how a drug/vaccine works, other 
pathways a drug/vaccine may interact with, or other aspects of disease. The specimen(s) 
may be used for future assay development and/or drug/vaccine development.
It is now well recognized that information obtained from studying and testing clinical 
specimens offers unique opportunities to enhance our understanding of how individuals 
respond to drugs/vaccines, enhance our understanding of human disease and ultimately 
improve public health through development of novel treatments targeted to populations 
with the greatest need. All specimens will be used by MSD or designees and research will 
be monitored and reviewed by a committee of our scientists and clinicians.
3. Summary of Procedures for Future Biomedical Research
a.
Subjects for Enrollment
All subjects enrolled in the clinical trial will be considered for enrollment in future 
biomedical research.
b. Informed Consent
Informed consent for specimens (i.e., DNA, RNA, protein, etc.) will be obtained 
during screening for protocol enrollment from all subjects or legal guardians, at a trial 
visit by the investigator or his or her designate.  Informed consent for Future 
Biomedical Research should be presented to the subjects on Visit 1.  If delayed, 
present consent at next possible Subject Visit. Informed consent must be obtained 
prior to collection of all Future Biomedical Research specimens.  Consent forms 
signed by the subject will be kept at the clinical trial site under secure storage for 
regulatory reasons.  Information contained on the consent form alone cannot be traced 
08K3V5

Product:  MK-1439A 
114
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
to any specimens, test results, or medical information once the specimens have been 
rendered de-identified
A template of each trial site’s approved informed consent will be stored in the 
Sponsor’s clinical document repository.  Each consent will be assessed for 
appropriate specimen permissions.  
Each informed consent approved by an ethics committee is assigned a unique tracking 
number.  The tracking number on this document will be used to assign specimen 
permissions for each specimen into the Entrusted Keyholder’s Specimen Database.
c.
eCRF Documentation for Future Biomedical Research Specimens
Documentation of participant consent for future biomedical research will be captured 
in the eCRFs. Any specimens for which such an informed consent cannot be verified 
will be destroyed.
d. Future Biomedical Research Specimen Collections
Blood specimens for DNA or RNA isolation will usually be obtained at a time when 
the subject is having blood drawn for other trial purposes. Specimens like tissue and 
bone marrow will usually be obtained at a time when the subject is having such a 
procedure for clinical purposes.
Specimens will be collected and sent to the laboratory designated for the trial where 
they will be processed (e.g., DNA or RNA extraction, etc) following the MSD
approved policies and procedures for specimen handling and preparation.
4. Confidential Subject Information for Future Biomedical Research 
In order to optimize the research that can be conducted with Future Biomedical Research 
specimens, it is critical to link subject' clinical information with future test results. In fact 
little or no research can be conducted without connecting the clinical trial data to the 
specimen. The clinical data allow specific analyses to be conducted. Knowing subject 
characteristics like gender, age, medical history and treatment outcomes are critical to 
understanding clinical context of analytical results.
To maintain privacy of information collected from specimens obtained for Future 
Biomedical Research, MSD has developed secure policies and procedures.  All 
specimens will be de-identified as described below. 
At the clinical trial site, unique codes will be placed on the Future Biomedical Research 
specimens for transfer to the storage facility.  This first code is a random number which 
does not contain any personally identifying information embedded within it. The link (or 
key) between subject identifiers and this first unique code will be held at the trial site.  No 
personal identifiers will appear on the specimen tube.  
This first code will be replaced with a second code at a MSD designated storage/lab 
facility.  The second code is linked to the first code via a second key. The specimen is 
now double coded.  Specimens with the second code are sometimes referred to as de-
identified specimens. The use of the second code provides additional confidentiality and 
08K3V5

Product:  MK-1439A 
115
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
privacy protection for subjects over the use of a single code.  Access to both keys would 
be needed to link any data or specimens back to the subject's identification.
The second code is stored separately from the first code and all associated personal 
specimen identifiers.  A secure link, the second key, will be utilized to match the second 
code to the first code to allow clinical information collected during the course of the trial 
to be associated with the specimen.  This second key will be transferred under secure 
procedures by the MSD designated facility to an Entrusted Keyholder at MSD.  The 
second code will be logged into the primary biorepository database at MSD and, in this 
database, this identifier will not have identifying demographic data or identifying clinical 
information (i.e., race, sex, age, diagnosis, lab values) associated with it. The specimen 
will be stored in a designated biorepository site with secure policies and procedures for 
specimen storage and usage.
The second key can be utilized to reconstruct the link between the results of future 
biomedical research and the clinical information, at the time of analysis.  This linkage 
would not be possible for the scientist conducting the analysis, but can only be done by 
the MSD Entrusted Keyholder under strict security policies and procedures.  The MSD
Entrusted Keyholder will link the information and then issue a de-identified data set for 
analysis.  The only other circumstance by which future biomedical research data would 
be directly linked to the full clinical data set would be those situations mandated by 
regulatory authorities (e.g., EMEA, FDA), whereby this information would be directly 
transferred to the regulatory authority.
5. Biorepository Specimen Usage
Specimens obtained for the Sponsor will be used for analyses using good scientific 
practices. Analyses utilizing the future biomedical research specimens may be performed 
by the Sponsor, or an additional third party (eg, a university investigator) designated by 
the Sponsor. The investigator conducting the analysis will follow the Sponsor’s privacy 
and confidentiality requirements. Any contracted third party analyses will conform to the 
specific scope of analysis outlined in future biomedical research protocol and consent. 
Future biomedical research specimens remaining with the third party after specific 
analysis is performed will be reported to the Sponsor.
6. Withdrawal From Future Biomedical Research 
Subjects may withdraw their consent for Future Biomedical Research and have their 
specimens and all derivatives destroyed.   Subjects may withdraw consent at any time by 
contacting the principal investigator for the main trial.  If medical records for the main 
trial are still available, the investigator will contact MSD using the designated mailbox 
(clinical.specimen.management@MSD.com) and a form will be provided by MSD to 
obtain appropriate information to complete specimen withdrawal.  Subsequently, the 
subject's specimens will be removed from the biorepository and be destroyed. A letter 
will be sent from MSD to the investigator confirming the destruction. It is the 
responsibility of the investigator to inform the subject of completion of destruction.  Any 
analyses in progress at the time of request for destruction or already performed prior to 
the request being received by the Sponsor will continue to be used as part of the overall 
08K3V5

Product:  MK-1439A 
116
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
research trial data and results. No new analyses would be generated after the request is 
received.
In the event that the medical records for the main trial are no longer available (e.g., if the 
investigator is no longer required by regulatory authorities to retain the main trial 
records) or the specimens have been completely anonymized, there will no longer be a 
link between the subject’s personal information and their specimens. In this situation, the 
request for specimen destruction can not be processed. 
7. Retention of Specimens 
Future Biomedical Research specimens will be stored in the biorepository for potential 
analysis for up to 20 years from acquisition.  Specimens may be stored for longer if a 
regulatory or governmental authority has active questions that are being answered.  In 
this special circumstance, specimens will be stored until these questions have been 
adequately addressed.
Specimens from the trial site will be shipped to a central laboratory and then shipped to 
the MSD designated biorepository.  The specimens will be stored under strict supervision 
in a limited access facility which operates to assure the integrity of the specimens.  
Specimens will be destroyed according to MSD policies and procedures and this 
destruction will be documented in the biorepository database.
8. Data Security
Databases containing specimen information and test results are accessible only to the 
authorized Sponsor representatives and the designated study administrator research 
personnel and/or collaborators. Database user authentication is highly secure, and is 
accomplished using network security policies and practices based on international 
standards to protect against unauthorized access.
9. Reporting of Future Biomedical Research Data to Subjects
There is no definitive requirement in either authoritative ethical guidelines or in relevant 
laws/regulations globally that research results have to be, in all circumstances, returned to 
the trial participant.  Some guidelines advocate a proactive return of data in certain 
instances.  No information obtained from exploratory laboratory studies will be reported 
to the subject or family, and this information will not be entered into the clinical database 
maintained by MSD on subjects.  Principle reasons not to inform or return results to the 
subject include: lack of relevance to subject health, limitations of predictive capability, 
concerns of misinterpretation and absence of good clinical practice standards in 
exploratory research typically used for diagnostic testing.
If any exploratory results are definitively associated with clinical significance for subjects 
while the clinical trial is still ongoing, investigators will be contacted with information as 
to how to offer clinical diagnostic  testing (paid for by MSD) to subjects enrolled and will 
be advised that counseling should be made available for all who choose to participate in 
this diagnostic testing. 
If any exploratory results are definitively associated with clinical significance after 
completion of a clinical trial, MSD will publish the results without revealing specific 
08K3V5

Product:  MK-1439A 
117
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
subject information, inform all trial sites who participated in the MSD clinical trial and 
post anonymized results on our website or other accredited website(s) that allow for 
public access (e.g., disease societies who have primary interest in the results) in order that 
physicians and patients may pursue clinical diagnostic testing if they wish to do so.
10. Gender, Ethnicity and Minorities
Although many diagnoses differ in terms of frequency by ethnic population and gender, 
every effort will be made to recruit all subjects diagnosed and treated on MSD clinical 
trials for future biomedical research.  When trials with specimens are conducted and 
subjects identified to serve as controls, every effort will be made to group specimens 
from subjects and controls to represent the ethnic and gender population representative of 
the disease under current investigation.
11. Risks Versus Benefits of Future Biomedical Research 
For future biomedical research, risks to the subject have been minimized. Risks include 
those associated with venipuncture to obtain the whole blood specimen. This specimen 
will be obtained at the time of routine blood specimens drawn in the main trial. 
MSD has developed strict security, policies and procedures to address subject data 
privacy concerns.  Data privacy risks are largely limited to rare situations involving 
possible breach of confidentiality.  In this highly unlikely situation there is risk that the 
information, like all medical information, may be misused.
It is necessary for subject-related data (i.e., ethnicity, diagnosis, drug therapy and dosage, 
age, toxicities, etc.) to be re-associated to double coded specimens at the time of data 
analysis.  These subject data will be kept in a separate, secure MSD database, and all 
specimens will be stripped of subject identifiers.  No information concerning results 
obtained from future biomedical research will be entered into clinical records, nor will it 
be released to outside persons or agencies, in any way that could be tied to an individual 
subject.
12. Self-Reported Ethnicity
Subjects who participate in future biomedical research will be asked to provide self-
reported ethnicity.  Subjects who do not wish to provide this data may still participate in 
future biomedical research.
13. Questions
Any questions related to the future biomedical research should be e-mailed directly to 
clinical.specimen.management@ MSD.com.
14. References
1. National Cancer Institute: http://www.cancer.gov/dictionary/?searchTxt=biomarker
2. International Conference on Harmonization: DEFINITIONS FOR GENOMIC 
BIOMARKERS, PHARMACOGENOMICS, PHARMACOGENETICS, GENOMIC 
DATA 
AND 
SAMPLE 
CODING 
CATEGORIES 
-
E15; 
http://www.ich.org/LOB/media/MEDIA3383.pdf
08K3V5

Product:  MK-1439A 
118
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Understanding the Intent, Scope and Public Health Benefits of Exploratory Biomarker Research: A Guide for 
IRBs/IECs and Investigational Site Staff
08K3V5

Product:  MK-1439A 
119
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
08K3V5

Product:  MK-1439A 
120
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
08K3V5

Product:  MK-1439A 
121
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
08K3V5

Product:  MK-1439A 
122
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
08K3V5

Product:  MK-1439A 
123
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
08K3V5

Product:  MK-1439A 
124
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
08K3V5

Product:  MK-1439A 
125
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
08K3V5

Product:  MK-1439A 
126
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
08K3V5

Product:  MK-1439A 
127
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
08K3V5

Product:  MK-1439A 
128
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
08K3V5

Product:  MK-1439A 
129
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Approximate Blood Volumes Drawn/Collected by Trial Visit and by Sample Types
Base Study
Visit Number/Title:
1
2
Random-
ization
3
4
5
6
7
8
9
10
11
12
U (Virologic 
Failure 
Confirmation)
U (Early 
Discon-
tinuation
99
Trial Period
Screen-
ing
Treatment
Post 
treatment
Trial Procedures
Screen
Fastinga
Day 1a
WK
4
WK
8
WK
16
Fast-
inga
WK 
24
WK 
36
Fast-
inga
WK 
48
WK
60
WK 
72
WK 
84
Fast-
inga
WK 
96
>1week after 
initial virologic 
failure
At time 
of Discon
Post-
study 
14-day 
follow-up
Laboratory 
Procedures/Assessments
Total 
Volume
Hematology
2
2
2
2
2
2
2
2
2
2
2
2
2
2
28
Serum Pregnancy Testc
29
Collect Blood for Safety Laboratory 
Tests (Chemistry)
7a
7
7
7
7a
7
7
7
7
7
7a
3.5h
7
7
123.5
HIV/Hepatitis Screenb
Hemostatic Function Testd
4.5
4.5
Virology Test Plasma HIV viral 
RNA quantification test (Abbott 
Real Time HIV-1)
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
150
Collect Blood for CD4 Cell Count
2
2
2
2
2
2
2
14
Collect Blood for MK-1439 PKe
4
4
4
8
8
28
Collect Plasma for Viral Resistance 
Test
14
14
14
14
14
14
14
14
14
14
14
14
14g
182
Collect Blood (DNA) for Genetic 
Analysisb
8.5
8.5
Collect Plasma for Future 
Biomedical Researchb
10
10
10
30
Total (mL)
61.5
43.5
37
39
33
43
33
53
33
35
33
45
27.5 
33
19
568.5 
Total (tablespoons)
4.1
2.9
2.5
2.6
2.2
2.9
2.2
3.5
2.2
2.3
2.2
3.0
1.8
2.2
1.3
~37.9
08K3V5

Product:  MK-1439A 
130
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Visit Number/Title:
1
2
Random-
ization
3
4
5
6
7
8
9
10
11
12
U (Virologic 
Failure 
Confirmation)
U (Early 
Discon-
tinuation
99
Trial Period
Screen-
ing
Treatment
Post 
treatment
Trial Procedures
Screen
Fastinga
Day 1a
WK
4
WK
8
WK
16
Fast-
inga
WK 
24
WK 
36
Fast-
inga
WK 
48
WK
60
WK 
72
WK 
84
Fast-
inga
WK 
96
>1week after 
initial virologic 
failure
At time 
of Discon
Post-
study 
14-day 
follow-up
a. Fasting is required at these visits for lipids measurement.
b. Includes Enzyme Immunoassay HIV Antibody Screen, Serum Hepatitis B Surface Antigen, Serum Hepatitis B Surface Antibody, Serum Hepatitis B e-Antigen and Serum 
Hepatitis C Antibody. A plasma Hepatitis C virus PCR quantitative test (an additional ~6 ml= 0.4 tablespoon of blood) will be performed if the Hepatitis C antibody test is 
positive.
c. For women of childbearing potential.
d. Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) and International Normalized Ratio (INR).
e. At Study Day 1 and Study Week 4, sample must be collected predose. At Study Week 12, the sample may be collected irrespective of time of dose. At Study Weeks 24 and 
48, samples must be collected predose, and within 0.5 to 2 hours postdose (subjects should remain fasting until postdose PK sample is collected).
f. One Tablespoon = 15 mL.
g. If viral failure or relapse is confirmed (with a confirmatory HIV-1 RNA at least one week later), and the decision is made to discontinue the subject, plasma for resistance needs 
not be collected again at the discontinuation visit.
h. For creatinine clearance only.
08K3V5

Product:  MK-1439A 
131
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Week 100 Through Week 192 Including Post-Study 14-Day Follow-up (Study Extension 1)
Week (Visit)
100
(V13)
116
(V14)
132
(V15)
Fasting
148
(V16)a
164
(V17)
180
(V18)
Fasting
192
(V19)a
Viral Failure 
Confirmation
(U)
Early 
Discontinuation
(U)
Post-Study
14-Day 
Follow-up 
(99)
Total Vol. 
in Study 
Extension 1b
Hematology
2
2
2
2
2
2
2
2
2
18
Collect Blood for CD4 
Cell Count
2
2
2
6
Collect Blood for Safety 
Laboratory Tests 
(Chemistry)
7
7
7
7
7
7
7
3.5c
7
7
66.5
Virology Test Plasma 
HIV viral RNA 
quantification test 
(Abbott Real Time 
HIV-1)
10
10
10
10
10
10
10
10
10
10
100
Collect Plasma for Viral 
Resistance
14
14d
28 
TOTAL for visit (mL)
21
19
19
21
19
19
21
27.5
33
19
218.5
Total (tablespoons)e
1.4
1.3
1.3
1.4
1.3
1.3
1.4
1.8
2.2
1.2
~14.5
a Fasting is required at these visits for lipids measurement.
b These samples are in addition to those collected during the base study. Because an early discontinuation visit could potentially happen during the base study or study extension
1, but not both, and because there is no post-study follow-up visit after the base study for subjects who continue into study extension 1, the total volume for the base study and
study extension 1 could be less than the sum.
c For creatinine clearance only.
d Early Discontinuation Visit sample should be collected only if not done at Viral Failure Confirmation Visit.
e One tablespoon = 15 mL.
08K3V5

Product:  MK-1439A 
132
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Plasma Assay—Sample Collection, Handling, Labeling, Storage, and Shipment
See Laboratory Manual.
08K3V5

Product:  MK-1439A 
133
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
List of Preferred Neuropsychiatric Adverse Events
Category
Active PTs in MedDRA version 17.0
Dizziness
Dizziness
Sleep Disorders and Disturbances
Behavioural insomnia of childhood
Hyposomnia
Initial insomnia
Insomnia
Middle insomnia
Terminal insomnia
Breathing-related sleep disorder
Dyssomnia
Hypnagogic hallucination
Hypnopompic hallucination
Sleep attacks
Abnormal dreams
Abnormal sleep-related event
Confusional arousal
Loss of dreaming
Nightmare
Parasomnia
Rapid eye movements sleep abnormal
Sleep inertia
Sleep sex
Sleep talking
Sleep terror
Sleep-related eating disorder
Somnambulism
Sleep disorder due to a general medical condition
Sleep disorder due to general medical condition, hypersomnia type
Sleep disorder due to general medical condition, insomnia type
Sleep disorder due to general medical condition, mixed type
Sleep disorder due to general medical condition, parasomnia type
Hypersomnia-bulimia syndrome
Sleep disorder
Sopor
Hypersomnia related to another mental condition
Insomnia related to another mental condition
Altered Sensorium
Altered state of consciousness
Apallic syndrome
Consciousness fluctuating
Depressed level of consciousness
Hyperglycaemic unconsciousness
Lethargy
Loss of consciousness
Neonatal oversedation
Post-injection delirium sedation syndrome
Postictal state
Preictal state
08K3V5

Product:  MK-1439A 
134
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Category
Active PTs in MedDRA version 17.0
Sedation
Somnolence
Somnolence neonatal
Stupor
Syncope
Depression and suicide/self-injury
Activation syndrome
Adjustment disorder with depressed mood
Adjustment disorder with mixed anxiety and depressed mood
Agitated depression
Anhedonia
Antidepressant therapy
Childhood depression
Decreased interest
Depressed mood
Depression
Depression postoperative
Depressive symptom
Dysphoria
Dysthymic disorder
Electroconvulsive therapy
Feeling guilty
Feeling of despair
Feelings of worthlessness
Major depression
Menopausal depression
Post stroke depression
Postictal depression
Postpartum depression
Completed suicide
Depression suicidal
Intentional overdose
Intentional self-injury
Poisoning deliberate
Self-injurious behaviour
Self-injurious ideation
Suicidal behaviour
Suicidal ideation
Suicide attempt
Psychosis and psychotic disorders
Acute psychosis
Alcoholic psychosis
Alice in wonderland syndrome
Brief psychotic disorder with marked stressors
Brief psychotic disorder without marked stressors
Brief psychotic disorder, with postpartum onset
Charles Bonnet syndrome
Childhood psychosis
Clang associations
Cotard's syndrome
Delusion
Delusion of grandeur
08K3V5

Product:  MK-1439A 
135
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Category
Active PTs in MedDRA version 17.0
Delusion of reference
Delusion of replacement
Delusional disorder, erotomanic type
Delusional disorder, grandiose type
Delusional disorder, jealous type
Delusional disorder, mixed type
Delusional disorder, persecutory type
Delusional disorder, somatic type
Delusional disorder, unspecified type
Delusional perception
Delusions, mixed
Dementia of the Alzheimer's type, with delusions
Depressive delusion
Derailment
Epileptic psychosis
Erotomanic delusion
Flight of ideas
Hallucination
Hallucination, auditory
Hallucination, gustatory
Hallucination, olfactory
Hallucination, synaesthetic
Hallucination, tactile
Hallucination, visual
Hallucinations, mixed
Hypnagogic hallucination
Hypnopompic hallucination
Hysterical psychosis
Ideas of reference
Illusion
Jealous delusion
Loose associations
Neologism
Paranoia
Paranoid personality disorder
Parkinson's disease psychosis
Paroxysmal perceptual alteration
Persecutory delusion
Postictal psychosis
Post-injection delirium sedation syndrome
Posturing
Psychosis postoperative
Psychotic behaviour
Psychotic disorder
Psychotic disorder due to a general medical condition
Reactive psychosis
Rebound psychosis
Schizoaffective disorder
Schizoaffective disorder bipolar type
Schizoaffective disorder depressive type
Schizophrenia
08K3V5

Product:  MK-1439A 
136
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Category
Active PTs in MedDRA version 17.0
Schizophrenia simple
Schizophrenia, catatonic type
Schizophrenia, disorganised type
Schizophrenia, paranoid type
Schizophrenia, residual type
Schizophrenia, undifferentiated type
Schizophreniform disorder
Schizotypal personality disorder
Senile psychosis
Shared psychotic disorder
Somatic delusion
Somatic hallucination
Substance-induced psychotic disorder
Tangentiality
Thought blocking
Thought broadcasting
Thought insertion
Thought withdrawal
Transient psychosis
Waxy flexibility
08K3V5

Product:  MK-1439A 
137
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
List of Abbreviations and Acronyms
Abbreviation
Definition
3TC
Lamivudine
AE 
Adverse event / adverse experience
AIDS
Acquired Immune Deficiency Syndrome
ALT
Serum alanine aminotransferase
ANCOVA
Analysis of covariance
ART
Antiretroviral therapy
ASaT
All Subjects as Treated
AST
Serum aspartate aminotransferase
BLoQ
Below the limit of quantification
cART
Combination antiretroviral therapy
CCR5
Chemokine Receptor Type 5
CFR
Code of Federal Regulations
CI
Confidence Interval; or (as in section 10.3 only) Coordinating Investigator
Clcr
Creatinine Clearance
CPT
Child-Pugh Class C score or Pugh-Turcotte
CSR
Clinical Study Report
CYP
Cytochrome
DAIDS
Division of Acquired Immunodeficiency Syndrome
DMC
Data Monitoring Committee
DNA
Deoxyribonucleic Acid
ECG
Electrocardiogram
ECI
Event of clinical interest
eCRF
Electronic case report form
eDMC
External Data Monitoring Committee
EFV
Efavirenz
EOC
Executive Oversight Committee
ERC
Ethical Review Committee
EU
European Union
FAS
Full Analysis Set
FDA
Food and Drug Administration
FDR
Fixed Dose Regimen
FTC
Emtricitabine
GCP
Good Clinical Practice
HAART
Highly Active Antiretroviral Therapy
HBV
Hepatitis B Virus
HCV
Hepatitis C Virus
HDL-C
High Density Lipoprotein Cholesterol
HIV
Human Immunodeficiency Virus
HIV-1
Human Immunodeficiency Virus Type I
IB
Investigator Brochure
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
INR
International Normalized Ratio
InSTI
Integrase Strand Inhibitors
IRB
Institutional Review Board
IRIS
Immune Reconstitution Syndrome
IUD
Intrauterine Device
IVRS/IWRS
Interactive voice response system/Integrated web response system
LDL-C
Low-Density Lipoprotein Cholesterol
08K3V5

Product:  MK-1439A 
138
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
Abbreviation
Definition
MedDRA
Medical Dictionary for Regulatory Activities
MK-1439
Doravirine
MK-1439A
Doravirine/ Lamivudine/ Tenofovir disoproxil fumarate
N(t)RTI
Nucleotide Reverse transcriptase inhibitor
NC=F
Non-Completer = Failure
NNRTI
Non-Nucleoside Reverse transcriptase inhibitor
NRTI
Nucleoside Reverse transcriptase inhibitor
OF
Observed Failure
PCR
Polymerase Chain Reaction
PDLC
Pre-Defined Limit of Change
PDVF
Protocol-Defined Virologic Failure
PI
Protease Inhibitor
PK
Pharmacokinetic
PK/PD
Pharmacokinetic/Pharmacodynamic
PO
Per os
PT
Prothrombin Time
q.d.
Once Daily
RNA
Ribonucleic acid
SAC
Scientific Advisory Committee
SAE
Serious adverse event
(s)SAP
(supplemental) Statistical Analysis Plan
SAP
Statistical Analysis Plan
SGOT
serum glutamic-oxaloacetic transaminase
SGPT
serum glutamic-pyruvic transaminase
SOC
System Organ Class
TDF
Tenofovir disoproxil fumarate
TDF/FTC
Tenofovir disoproxil fumarate/ Emtricitabine (TRUVADA™)
TLOVR
Time to Loss of Virologic Response
U
Unscheduled
ULN
Upper Limit of Normal
US
United States
WPAI
Work Productivity and Activity Impairment Questionnaire
08K3V5

Product:  MK-1439A 
139
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
DIVISION OF AIDS TABLE FOR GRADING THE SEVERITY OF ADULT AND PEDIATRIC ADVERSE EVENTS 
VERSION 1.0, DECEMBER, 2004; CLARIFICATION AUGUST 2009
LABORATORY
PARAMETER
GRADE 1 
MILD
GRADE 2
MODERATE
GRADE 3
SEVERE
GRADE 4 
POTENTIALLY LIFE-
THREATENING
HEMATOLOGY Standard International Units are listed in italics 
Absolute CD4+ count – Adult and Pediatric >13 years 
(HIV NEGATIVE ONLY) 
300 – 400/mm3 
300 – 400/μL 
200 – 299/mm3 
200 – 299/μL 
100 – 199/mm3 
100 – 199/μL 
<100/mm3 
<100/μL 
Absolute lymphocyte count – Adult and Pediatric >13 years 
(HIV NEGATIVE ONLY) 
600 – 650/mm3 
0.600 x 109 – 0.650 x 
109/L 
500 – 599/mm3 
0.500 x 109 – 0.599 x 
109/L 
350 – 499/mm3 
0.350 x 109 – 0.499 x 
109/L 
<350/mm3 
<0.350 x 109/L 
Comment: Values in children ≤13 years are not given for the 2 parameters above because the absolute counts are variable. 
Absolute neutrophil count (ANC) 
Adult and Pediatric, >7 days 
1,000 – 1,300/mm3 
1.000 x 109 – 1.300 x 
109/L 
750 – 999/mm3 
0.750 x 109 – 0.999 x 
109/L 
500 – 749/mm3 
0.500 x 109 – 0.749 x 
109/L 
<500/mm3 
<0.500 x 109/L 
Fibrinogen, decreased 
100 – 200 mg/dL 
1.00 – 2.00 g/L OR 
0.75 – 0.99 x LLN 
75 – 99 mg/dL 
0.75 – 0.99 g/L OR 
0.50 – 0.74 x LLN 
50 – 74 mg/dL 
0.50 – 0.74 g/L OR 
0.25 – 0.49 x LLN 
<50 mg/dL 
<0.50 g/L OR 
<0.25 x LLN OR 
Associated with gross bleeding 
† Use age and sex appropriate values (e.g., bilirubin).
08K3V5

Product:  MK-1439A 
140
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
LABORATORY
PARAMETER
GRADE 1 
MILD
GRADE 2 
MODERATE
GRADE 3 
SEVERE
GRADE 4 
POTENTIALLY LIFE-
THREATENING
Hemoglobin (Hgb) 
Comment: The Hgb values in mmol/L have changed because the conversion factor used to convert g/dL to mmol/L has been changed from 0.155 to 0.6206 (the most commonly 
used conversion factor). For grading Hgb results obtained by an analytic method with a conversion factor other than 0.6206, the result must be converted to g/dL using the 
appropriate conversion factor for that lab. 
Adult and Pediatric ≥57 days 
(HIV POSITIVE ONLY) 
8.5 – 10.0 g/dL 
5.24 – 6.23 mmol/L 
7.5 – 8.4 g/dL 
4.62–5.23 mmol/L 
6.50 – 7.4 g/dL 
4.03–4.61 mmol/L 
<6.5 g/dL 
<4.03 mmol/L 
Adult and Pediatric ≥57 days 
(HIV NEGATIVE ONLY) 
10.0 – 10.9 g/dL 
6.18 – 6.79 mmol/L OR 
Any decrease 2.5 - 3.4 g/dL 
1.58 – 2.13 mmol/L 
9.0 – 9.9 g/dL 
5.55 - 6.17 mmol/L OR 
Any decrease 3.5 - 4.4 g/dL
2.14 – 2.78 mmol/L 
7.0 – 8.9 g/dL 
4.34 - 5.54 mmol/L OR 
Any decrease ≥4.5 g/dL
>2.79 mmol/L 
<7.0 g/dL 
<4.34 mmol/L 
Comment: The decrease is a decrease from baseline 
International Normalized Ratio of 
prothrombin time (INR) 
1.1 – 1.5 x ULN 
1.6 – 2.0 x ULN 
2.1 – 3.0 x ULN 
>3.0 x ULN 
Methemoglobin 
5.0 – 10.0% 
10.1 – 15.0% 
15.1 – 20.0% 
>20.0% 
Prothrombin Time (PT) 
1.1 – 1.25 x ULN 
1.26 – 1.50 x ULN 
1.51 – 3.00 x ULN 
>3.00 x ULN 
Partial Thromboplastin Time (PTT) 
1.1 – 1.66 x ULN 
1.67 – 2.33 x ULN 
2.34 – 3.00 x ULN 
>3.00 x ULN 
Platelets, decreased 
100,000 – 124,999/mm3 
100.000 x 109 – 124.999 x 109/L 
50,000 – 99,999/mm3 
50.000 x 109 – 99.999 x 109/L 
25,000 – 49,999/mm3 
25.000 x 109 - 49.999 x 109/L 
<25,000/mm3 
<25.000 x 109/L 
WBC, decreased 
2,000 – 2,500/mm3 
2.000 x 109 – 2.500 x 109/L 
1,500 – 1,999/mm3 
1.500 x 109 – 1.999 x 109/L 
1,000 – 1,499/mm3 
1.000 x 109 – 1.499 x 109/L 
<1,000/mm3 
<1.000 x 109/L 
* Values are for term infants. Preterm infants should be assessed using local normal ranges. 
† Use age and sex appropriate values (e.g., bilirubin).
08K3V5

Product:  MK-1439A 
141
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
LABORATORY
PARAMETER
GRADE 1 
MILD
GRADE 2 
MODERATE
GRADE 3 
SEVERE
GRADE 4 
POTENTIALLY LIFE-
THREATENING
CHEMISTRIES Standard International Units are listed in italics 
Acidosis 
NA 
pH <normal, but ≥7.3 
pH <7.3 without life-threatening consequences pH <7.3 with life-threatening consequences 
Albumin, serum, low 
3.0 g/dL – <LLN 
30 g/L – <LLN 
2.0 – 2.9 g/dL 
20 – 29 g/L 
<2.0 g/dL 
<20 g/L 
NA 
Alkaline Phosphatase 
1.25 – 2.5 x ULN† 
2.6 – 5.0 x ULN† 
5.1 – 10.0 x ULN† 
>10.0 x ULN† 
Alkalosis 
NA 
pH >normal, but ≤7.5 
pH >7.5 without life-threatening consequences pH >7.5 with life-threatening consequences 
ALT (SGPT) 
1.25 – 2.5 x ULN 
2.6 – 5.0 x ULN 
5.1 – 10.0 x ULN 
>10.0 x ULN 
AST (SGOT) 
1.25 – 2.5 x ULN 
2.6 – 5.0 x ULN 
5.1 – 10.0 x ULN 
>10.0 x ULN 
Bicarbonate, serum, low 
16.0 mEq/L – <LLN 
16.0 mmol/L – <LLN 
11.0 – 15.9 mEq/L 
11.0 – 15.9 mmol/L 
8.0 – 10.9 mEq/L 
8.0 – 10.9 mmol/L 
<8.0 mEq/L 
<8.0 mmol/L 
Comment: Some laboratories will report this value as Bicarbonate (HCO3) and others as Total Carbon Dioxide (CO2). These are the same tests; values should be graded 
according to the ranges for Bicarbonate as listed above. 
Bilirubin (Total) 
Adult and Pediatric >14 days 
1.1 – 1.5 x ULN 
1.6 – 2.5 x ULN 
2.6 – 5.0 x ULN 
>5.0 x ULN 
Calcium, serum, high 
Adult and Pediatric ≥7 days 
10.6 – 11.5 mg/dL 
2.65 – 2.88 mmol/L 
11.6 – 12.5 mg/dL 
2.89 – 3.13 mmol/L 
12.6 – 13.5 mg/dL 
3.14 – 3.38 mmol/L 
>13.5 mg/dL 
>3.38 mmol/L 
Calcium, serum, low 
Adult and Pediatric ≥7 days 
7.8 – 8.4 mg/dL 
1.95 – 2.10 mmol/L 
7.0 – 7.7 mg/dL 
1.75 – 1.94 mmol/L 
6.1 – 6.9 mg/dL 
1.53 – 1.74 mmol/L 
<6.1 mg/dL 
<1.53 mmol/L 
Comment: Do not adjust Calcium, serum, low or Calcium, serum, high for albumin 
† Use age and sex appropriate values (e.g., bilirubin).
08K3V5

Product:  MK-1439A 
142
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
LABORATORY
PARAMETER
GRADE 1 
MILD
GRADE 2 
MODERATE
GRADE 3 
SEVERE
GRADE 4 
POTENTIALLY LIFE-
THREATENING
Cardiac troponin I (cTnI) 
NA 
NA 
NA 
Levels consistent with myocardial infarction 
or unstable angina as defined by the manufacturer 
Cardiac troponin T (cTnT) 
NA 
NA 
NA 
≥0.20 ng/mL OR Levels consistent with myocardial infarction 
or unstable angina as defined by the manufacturer 
Cholesterol (fasting)
Adult ≥18 years 
200 – 239 mg/dL 
5.18- 6.19 mmol/L 
240 – 300 mg/dL 
6.20 - 7.77 mmol/L 
>300 mg/dL 
>7.77 mmol/L 
NA 
Pediatric <18 years 
170 – 199 mg/dL 
4.40 - 5.15 mmol/L 
200 – 300 mg/dL 
5.16 - 7.77 mmol/L 
>300 mg/dL 
>7.77 mmol/L 
NA 
Creatine Kinase 
3.0 - 5.9 x ULN† 
6.0 – 9.9 x ULN† 
10.0 - 19.9 x ULN† 
≥ 20.0 x ULN† 
Creatinine 
1.1 – 1.3 x ULN† 
1.4 – 1.8 x ULN† 
1.9 – 3.4 x ULN† 
≥ 3.5 x ULN† 
08K3V5

Product:  MK-1439A 
143
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
LABORATORY
PARAMETER
GRADE 1 
MILD
GRADE 2 
MODERATE
GRADE 3 
SEVERE
GRADE 4 
POTENTIALLY LIFE-
THREATENING
Glucose, serum, high
Nonfasting 
116 – 160 mg/dL 
6.44 – 8.88 mmol/L 
161 – 250 mg/dL 
8.89 – 13.88 mmol/L 
251 – 500 mg/dL 
13.89 – 27.75 mmol/L 
>500 mg/dL 
>27.75 mmol/L 
Fasting 
110 – 125 mg/dL 
6.11 – 6.94 mmol/L 
126 – 250 mg/dL 
6.95 – 13.88 mmol/L 
251 – 500 mg/dL 
13.89 – 27.75 mmol/L 
>500 mg/dL 
>27.75 mmol/L 
Glucose, serum, low
Adult and Pediatric ≥1 month 
55 – 64 mg/dL 
3.05 – 3.55 mmol/L 
40 – 54 mg/dL 
2.22 – 3.06 mmol/L 
30 – 39 mg/dL 
1.67 – 2.23 mmol/L 
<30 mg/dL 
<1.67 mmol/L 
Infant*†, <1 month 
50 – 54 mg/dL 
2.78 – 3.00 mmol/L 
40 – 49 mg/dL 
2.22 – 2.77 mmol/L 
30 – 39 mg/dL 
1.67 – 2.21 mmol/L 
<30 mg/dL 
<1.67 mmol/L 
Lactate 
ULN - <2.0 x ULN without 
acidosis 
≥2.0 x ULN without 
acidosis 
Increased lactate with pH <7.3
without life-threatening 
consequences 
Increased lactate with pH <7.3
with life-threatening 
consequences 
Comment: Added ULN to Grade 1 parameter
LDL cholesterol (fasting)
Adult ≥18 years 
130 – 159 mg/dL 
3.37 – 4.12 mmol/L 
160 – 190 mg/dL 
4.13 – 4.90 mmol/L 
≥190 mg/dL 
≥4.91 mmol/L 
NA 
Pediatric >2 - <18 years 
110 – 129 mg/dL 
2.85 – 3.34 mmol/L 
130 – 189 mg/dL 
3.35 – 4.90 mmol/L 
≥190 mg/dL 
≥4.91 mmol/L 
NA 
Lipase 
1.1 – 1.5 x ULN 
1.6 – 3.0 x ULN 
3.1 – 5.0 x ULN 
>5.0 x ULN 
Magnesium, serum, low 
1.2 – 1.4 mEq/L 
0.60 – 0.70 mmol/L 
0.9 – 1.1 mEq/L 
0.45 – 0.59 mmol/L 
0.6 – 0.8 mEq/L 
0.30 – 0.44 mmol/L 
<0.60 mEq/L 
<0.30 mmol/L 
Pancreatic amylase 
1.1 – 1.5 x ULN 
1.6 – 2.0 x ULN 
2.1 – 5.0 x ULN 
>5.0 x ULN 
08K3V5

Product:  MK-1439A 
144
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
LABORATORY
PARAMETER
GRADE 1 
MILD
GRADE 2 
MODERATE
GRADE 3 
SEVERE
GRADE 4 
POTENTIALLY LIFE-
THREATENING
Phosphate, serum, low
Adult and Pediatric >14 years
2.5 mg/dL – <LLN 
0.81 mmol/L – <LLN 
2.0 – 2.4 mg/dL 
0.65 – 0.80 mmol/L 
1.0 – 1.9 mg/dL 
0.32 – 0.64 mmol/L 
<1.00 mg/dL 
<0.32 mmol/L 
Pediatric 1 year – 14 years 
3.0 – 3.5 mg/dL 
0.97 – 1.13 mmol/L 
2.5 – 2.9 mg/dL 
0.81 – 0.96 mmol/L 
1.5 – 2.4 mg/dL 
0.48 – 0.80 mmol/L 
<1.50 mg/dL 
<0.48 mmol/L 
Pediatric <1 year 
3.5 – 4.5 mg/dL 
1.13 – 1.45 mmol/L 
2.5 – 3.4 mg/dL 
0.81 – 1.12 mmol/L 
1.5 – 2.4 mg/dL 
0.48 – 0.80 mmol/L 
<1.50 mg/dL 
<0.48 mmol/L 
Potassium, serum, high 
5.6 – 6.0 mEq/L 
5.6 – 6.0 mmol/L 
6.1 – 6.5 mEq/L 
6.1 – 6.5 mmol/L 
6.6 – 7.0 mEq/L 
6.6 – 7.0 mmol/L 
>7.0 mEq/L 
>7.0 mmol/L 
Potassium, serum, low 
3.0 – 3.4 mEq/L 
3.0 – 3.4 mmol/L 
2.5 – 2.9 mEq/L 
2.5 – 2.9 mmol/L 
2.0 – 2.4 mEq/L 
2.0 – 2.4 mmol/L 
<2.0 mEq/L 
<2.0 mmol/L 
Sodium, serum, high 
146 – 150 mEq/L 
146 – 150 mmol/L 
151 – 154 mEq/L 
151 – 154 mmol/L 
155 – 159 mEq/L 
155 – 159 mmol/L 
≥160 mEq/L 
≥160 mmol/L 
Sodium, serum, low 
130 – 135 mEq/L 
130 – 135 mmol/L 
125 – 129 mEq/L 
125 – 129 mmol/L 
121 – 124 mEq/L 
121 – 124 mmol/L 
≤ 120 mEq/L 
≤ 120 mmol/L 
Triglycerides (fasting) 
NA 
500 – 750 mg/dL 
5.65 – 8.48 mmol/L 
751 – 1,200 mg/dL 
8.49 – 13.56 mmol/L 
>1,200 mg/dL 
>13.56 mmol/L 
† Use age and sex appropriate values (e.g., bilirubin).
08K3V5

Product:  MK-1439A 
145
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
LABORATORY
PARAMETER
GRADE 1 
MILD
GRADE 2 
MODERATE
GRADE 3 
SEVERE
GRADE 4 
POTENTIALLY LIFE-
THREATENING
Uric acid 
7.5 – 10.0 mg/dL 
0.45 – 0.59 mmol/L 
10.1 – 12.0 mg/dL 
0.60 – 0.71 mmol/L 
12.1 – 15.0 mg/dL 
0.72 – 0.89 mmol/L 
>15.0 mg/dL 
>0.89 mmol/L 
URINALYSIS Standard International Units are listed in italics
Hematuria (microscopic) 
6 – 10 Red Blood Cell/HPF 
>10 RBC/HPF 
Gross, with or without clots OR 
with RBC casts 
Transfusion indicated 
Proteinuria, random collection 
1 + 
2 – 3 + 
4 + 
NA 
Proteinuria, 24 hour collection
Adult and Pediatric ≥10 years 
200 – 999 mg/24 h 
0.200 – 0.999 g/d 
1,000 - 1,999 mg/24 h 
1.000 – 1.999 g/d 
2,000 – 3,500 mg/24 h 
2.000 – 3.500 g/d 
>3,500 mg/24 h 
>3.500 g/d 
Pediatric >3 mo - <10 years 
201 - 499 mg/m2/24 h 
0.201 – 0.499 g/d 
500 - 799 mg/m2/24 h 
0.500 – 0.799 g/d 
800 – 1,000 mg/m2/24 h
0.800 – 1.000 g/d 
>1,000 mg/ m2/24 h 
>1.000 g/d 
† Use age and sex appropriate values (e.g., bilirubin).
Adapted from DIVISION OF AIDS TABLE FOR GRADING THE SEVERITY OF 
ADULT AND PEDIATRIC ADVERSE EVENTS, 
PUBLISH DATE: 28 Dec-04/Clarification Aug 09 DECEMBER.
08K3V5

Product:  MK-1439A 
146
Protocol/Amendment No.: 021-09
MK-1439A-021-09 Final Protocol
02-Nov-2022
Confidential
SIGNATURES
Sponsor's Representative
TYPED NAME
TITLE
SIGNATURE
DATE SIGNED
Investigator
I agree to conduct this clinical trial in accordance with the design outlined in this protocol 
and to abide by all provisions of this protocol (including other manuals and documents 
referenced from this protocol).  I agree to conduct the trial in accordance with generally 
accepted standards of Good Clinical Practice.  I also agree to report all information or data in 
accordance with the protocol and, in particular, I agree to report any serious adverse events 
as defined in Section 7.0 – Assessing and Recording Adverse Events.  I also agree to handle 
all clinical supplies provided by the Sponsor and collect and handle all clinical specimens in 
accordance with the protocol.  I understand that information that identifies me will be used 
and disclosed as described in the protocol, and that such information may be transferred to 
countries that do not have laws protecting such information.  Since the information in this 
protocol and the referenced Investigator’s Brochure is confidential, I understand that its 
disclosure to any third parties, other than those involved in approval, supervision, or conduct 
of the trial is prohibited.  I will ensure that the necessary precautions are taken to protect such 
information from loss, inadvertent disclosure or access by third parties.
TYPED NAME
TITLE
SIGNATURE
DATE SIGNED
08K3V5