Conditions: HIV-1 Infection
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 673
Healthy volunteers: no

Brief summary:
The multicenter, open label, randomized study will evaluate the safety and efficacy of a switch to MK-1439A (MK-1439 \[doravirine\] plus lamivudine and tenofovir disoproxil fumarate) in HIV-1-infected participants virologically suppressed on a protocol-specified antiretroviral regimen. The primary hypothesis is that a switch to doravirine, tenofovir, lamivudine will be non-inferior to continuation of the regimen at Screening for 24 weeks, as assessed by the proportion of participants maintaining HIV-1 ribonucleic acid (RNA) \<50 copies/mL. The Base Study results will be based on the first 48 weeks of this ongoing study.

Detailed description:
Three optional study extensions are planned. Study Extension 1 will evaluate safety of the switch to doravirine, tenofovir, lamivudine for an additional 2 years beyond the Base Study. Study Extensions 2 and 3 will evaluate safety of the switch to doravirine, tenofovir, lamivudine until doravirine, tenofovir, lamivudine becomes locally available, or 4 years beyond Study Extension 1, whichever comes first.

Arms:
arm 1: Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for \>=6 months with undetectable HIV-1 RNA will switch on Day 1 to doravirine, tenofovir, lamivudine single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions arm 2: Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for \>=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to doravirine, tenofovir, lamivudine single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions

Interventions: intervention 1: Doravirine, Tenofovir, Lamivudine intervention 2: Baseline regimen of ritonavir- or cobicistat-boosted protease inhibitor intervention 3: Baseline regimen of cobicistat-boosted elvitegravir intervention 4: Baseline regimen of a non-nucleoside reverse transcriptase inhibitor intervention 5: Baseline regimen of two nucleoside reverse transcriptase inhibitors
Intervention descriptions: intervention 1: Single tablet containing MK-1439 (doravirine) 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg intervention 2: Baseline regimen of antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) administered according to the product circular intervention 3: Baseline regimen of antiretroviral therapy with cobicistat-boosted elvitegravir administered according to the product circular intervention 4: Baseline regimen of antiretroviral therapy with a NNRTI (efavirenz, nevirapine, or rilpivirine) administered according to the product circular intervention 5: Baseline regimen of antiretroviral therapy with two NRTIs administered according to the product circular

Protocol document:
Prot_SAP_001.pdf: 
Official Protocol Title: 
NCT number: 
NCT02397096 
Document Date: 
31-Oct-2022
A Phase III Multicenter, Open-Label, Randomized Study to Evaluate 
a Switch to MK-1439A in HIV-1-Infected Subjects Virologically 
Suppressed on a Regimen of a Ritonavir-boosted Protease Inhibitor 
and Two Nucleoside Reverse Transcriptase Inhibitors (NRTIs)


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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 Guatemala, Mexico, Peru, Australia, 
New Zealand, Russia, Spain.
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, Open-Label, Randomized Study to Evaluate a Switch to MK-1439A 
in HIV-1-Infected Subjects Virologically Suppressed on a Regimen of a Ritonavir-boosted 
Protease Inhibitor and Two Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
SUBTITLE: Amendment to Include Switches From Additional Antiretroviral Regimens 
IND NUMBER:  124,997
EudraCT NUMBER:  2014-005550-18
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TABLE OF CONTENTS
DOCUMENT HISTORY ..................................................................................................... 10
SUMMARY OF CHANGES................................................................................................ 14
1.0
TRIAL SUMMARY.................................................................................................. 16
2.0
TRIAL DESIGN........................................................................................................ 17
Trial Design ........................................................................................................... 17
Trial Diagram........................................................................................................ 20
3.0
OBJECTIVE(S) & HYPOTHESIS(ES).................................................................. 20
Primary Objective(s) & Hypothesis(es).............................................................. 20
Secondary Objective(s) & Hypothesis(es)........................................................... 21
Exploratory Objectives......................................................................................... 23
4.0
BACKGROUND & RATIONALE.......................................................................... 24
Background ........................................................................................................... 24
Pharmaceutical and Therapeutic Background .................................................... 24
Rationale................................................................................................................ 26
Rationale for the Trial and Selected Subject Population .................................... 26
Rationale for Expansion of Subject Population (Amendment 06)............... 27
Rationale for Dose Selection/Regimen............................................................... 28
Rationale for Endpoints ...................................................................................... 30
Efficacy Endpoints....................................................................................... 30
Safety Endpoints.......................................................................................... 30
Pharmacokinetic Endpoints ......................................................................... 31
Patient Reported Outcome Endpoints.......................................................... 31
Planned Exploratory Biomarker .................................................................. 32
Future Biomedical Research........................................................................ 32
Rationale for Study Extensions........................................................................... 32
Benefit/Risk ........................................................................................................... 33
5.0
METHODOLOGY ................................................................................................... 33
Entry Criteria........................................................................................................ 33
Diagnosis/Condition for Entry into the Trial...................................................... 33
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Subject Inclusion Criteria.................................................................................... 33
Subject Exclusion Criteria .................................................................................. 39
Trial Treatment(s) ................................................................................................ 40
Dose Selection .................................................................................................... 42
Dose Selection (Preparation) ....................................................................... 42
Dose Modification/Interruption ................................................................... 42
Timing of Dose Administration.......................................................................... 42
Trial Blinding/Masking....................................................................................... 43
Randomization or Treatment Allocation............................................................ 43
Stratification.......................................................................................................... 43
Concomitant Medications/Vaccinations (Allowed & Prohibited).................... 44
Rescue Medications & Supportive Care............................................................. 49
Diet/Activity/Other Considerations..................................................................... 49
Subject Withdrawal/Discontinuation Criteria................................................... 49
Subject Replacement Strategy............................................................................. 51
Beginning and End of the Trial ........................................................................... 51
Clinical Criteria for Early Trial Termination ................................................... 51
6.0
TRIAL FLOW CHART ........................................................................................... 52
7.0
TRIAL PROCEDURES ........................................................................................... 59
Trial Procedures ................................................................................................... 59
Administrative Procedures.................................................................................. 59
Informed Consent......................................................................................... 59
7.1.1.1.1
General Informed Consent.................................................................... 59
7.1.1.1.2
Consent and Collection of Specimens for Future Biomedical 
Research................................................................................................ 60
Inclusion/Exclusion Criteria ........................................................................ 60
Subject Identification Card .......................................................................... 60
Medical History ........................................................................................... 60
Prior and Concomitant Medications Review............................................... 61
7.1.1.5.1
Prior Medications.................................................................................. 61
7.1.1.5.2
Concomitant Medications..................................................................... 61
Assignment of Screening Number............................................................... 61
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Assignment of Randomization Number....................................................... 61
Trial Compliance (Medication/Diet/Activity/Other)................................... 61
Patient-Reported Outcomes ......................................................................... 62
Clinical Procedures/Assessments........................................................................ 63
Physical Examination................................................................................... 63
Height Assessment....................................................................................... 64
Vital Signs and Weight................................................................................ 64
12-Lead ECG (performed locally)............................................................... 64
Adverse Events ............................................................................................ 64
Toxicity Management .................................................................................. 65
Birth Control Confirmation.......................................................................... 65
Laboratory Procedures/Assessments .................................................................. 65
Serum /Urine Pregnancy Test...................................................................... 66
Laboratory Safety Evaluations (Hematology, Chemistry and Urinalysis) .. 66
HIV/ Hepatitis Screening............................................................................. 68
Virology Test ............................................................................................... 68
Viral Resistance Testing .............................................................................. 68
CD4 Cell Counts.......................................................................................... 68
Pharmacokinetic/Pharmacodynamic Evaluations........................................ 68
Future Biomedical Research........................................................................ 69
Other Procedures................................................................................................. 69
Withdrawal/Discontinuation........................................................................ 69
7.1.4.1.1
Withdrawal From Future Biomedical Research ................................... 70
Blinding/Unblinding .................................................................................... 70
Calibration of Critical Equipment................................................................ 70
Visit Requirements.............................................................................................. 70
Screening...................................................................................................... 70
Treatment Visits (Visit 2 to Visit 26) .......................................................... 71
Post-Trial...................................................................................................... 77
Assessing and Recording Adverse Events .......................................................... 77
Definition of an Overdose for This Protocol and Reporting of Overdose to 
the Sponsor.......................................................................................................... 78
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Reporting of Pregnancy and Lactation to the Sponsor ....................................... 78
Immediate Reporting of Adverse Events to the Sponsor.................................... 79
Serious Adverse Events ............................................................................... 79
Events of Clinical Interest............................................................................ 80
Evaluating Adverse Events................................................................................. 81
Sponsor Responsibility for Reporting Adverse Events ...................................... 84
TRIAL GOVERNANCE AND OVERSIGHT................................................... 84
Scientific Advisory Committee........................................................................... 84
8.0
STATISTICAL ANALYSIS PLAN ........................................................................ 84
Statistical Analysis Plan Summary ..................................................................... 84
Responsibility for Analyses/In-House Blinding ................................................. 87
Hypotheses/Estimation......................................................................................... 88
Analysis Endpoints ............................................................................................... 88
Efficacy/Pharmacokinetics Endpoints ................................................................ 88
Efficacy Endpoints....................................................................................... 88
Safety Endpoints ................................................................................................. 89
Analysis Populations............................................................................................. 90
Efficacy Analysis Populations ............................................................................ 90
Safety Analysis Populations ............................................................................... 90
Statistical Methods................................................................................................ 90
Statistical Methods for Efficacy Analyses.......................................................... 91
Statistical Methods for Safety Analyses ............................................................. 97
Summaries of Baseline Characteristics, Demographics, and Other Analyses.... 98
Demographic and Baseline Characteristics ................................................. 98
Interim Analyses ................................................................................................... 99
Multiplicity ............................................................................................................ 99
Sample Size and Power Calculations .................................................................. 99
Sample Size and Power for Efficacy Analyses................................................... 99
Sample Size and Power for Safety Analyses .................................................... 100
Overall Power ................................................................................................... 102
Subgroup Analyses and Effect of Baseline Factors ......................................... 103
Compliance (Medication Adherence)................................................................ 103
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Extent of Exposure.............................................................................................. 104
9.0
LABELING, PACKAGING, STORAGE AND RETURN OF CLINICAL 
SUPPLIES ............................................................................................................... 104
Investigational Product ...................................................................................... 104
Packaging and Labeling Information ............................................................... 104
Clinical Supplies Disclosure............................................................................... 105
Storage and Handling Requirements................................................................ 105
Returns and Reconciliation................................................................................ 105
Standard Policies................................................................................................. 105
10.0
ADMINISTRATIVE AND REGULATORY DETAILS..................................... 105
Confidentiality..................................................................................................... 105
Confidentiality of Data ..................................................................................... 105
Confidentiality of Subject Records................................................................... 106
Confidentiality of Investigator Information...................................................... 106
Confidentiality of IRB/IEC Information........................................................... 106
Compliance with Financial Disclosure Requirements..................................... 107
Compliance with Law, Audit and Debarment ................................................. 107
Compliance with Trial Registration and Results Posting Requirements...... 109
Quality Management System............................................................................. 109
Data Management............................................................................................... 109
Publications ......................................................................................................... 110
11.0
LIST OF REFERENCES....................................................................................... 111
12.0
APPENDICES......................................................................................................... 113
Code of Conduct for Clinical Trials.................................................................. 113
Collection and Management of Specimens for Future Biomedical 
Research............................................................................................................... 116
Understanding the Intent, Scope and Public Health Benefits of 
Exploratory Biomarker Research: A Guide for IRBs/IECs and 
Investigational Site Staff .................................................................................... 122
Approximate Blood Volumes Drawn/Collected by Trial Visit and by 
Sample Types....................................................................................................... 133
Plasma Assay—Sample Collection, Handling, Labeling, Storage, and 
Shipment.............................................................................................................. 135
List of Abbreviations and Acronyms ................................................................ 136
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Guidelines for Grading Severity of Laboratory Adverse Experiences for 
Toxicity Management......................................................................................... 138
13.0
SIGNATURES......................................................................................................... 145
Sponsor's Representative ................................................................................... 145
Investigator.......................................................................................................... 145
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LIST OF TABLES
Table 1
Treatment Regimens During Base Study........................................................... 41
Table 2
Treatment Regimen During Study Extensions .................................................. 41
Table 3
Stratification....................................................................................................... 43
Table 4
Laboratory Tests ................................................................................................ 67
Table 5
Pharmacokinetic Sampling Timepoints............................................................. 69
Table 6
Evaluating Adverse Events................................................................................ 82
Table 7
Definition of Study Timepoint........................................................................... 92
Table 8
Summary of the Two Approaches to Handle Missing Values........................... 93
Table 9
Analysis Strategy for Key Efficacy Variables................................................... 96
Table 10
Analysis Strategy for Safety Parameters............................................................ 98
Table 11
Power (%) Under Various Assumptions (With 440 Subjects Randomized in 
Immediate Switch Group and 220 Subjects Randomized in the Delayed 
Switch Group).................................................................................................. 100
Table 12
Estimate of Incidence of AEs and 95% Upper Confidence Bound Based on 
Hypothetical Numbers of Subjects with AEs Among 440 Subjects 
Randomized to the Immediate Switch Group and 220 Subjects Randomized 
to the Delayed Switch Group........................................................................... 101
Table 13
Differences in Incidences of AEs (Immediate Switch Group minus Delayed 
Switch Group) That Can Be Ruled Out With 440 Subjects Randomized to 
the Immediate Switch Group and 220 Subjects Randomized to the Delayed 
Switch Group ................................................................................................... 102
Table 14
Product Descriptions........................................................................................ 104
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LIST OF FIGURES
Figure 1
Trial Design ....................................................................................................... 20
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DOCUMENT HISTORY
Document
Date of Issue
Overall Rationale
Amendment 10
31-OCT-2022
This is a country-specific amendment for Guatemala, Mexico, Peru, Australia, 
New Zealand, Russia, 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.
Amendment 10 supersedes Amendment 09.
Amendment 09
29-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 09 was not released to sites.
Amendment 08
13-DEC-2019
-
The trial is being extended 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.
Amendment 07
14-DEC-2017
-
Added open-label study extension 2 to provide continued access to 
DOR/3TC/TDF until the drug is available locally in countries participating in 
the trial or for  an additional 2 years (whichever comes first)
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Document
Date of Issue
Overall Rationale
Amendment 06
26-MAY-2016
-
Added text to expand subject population by allowing enrollment of 
participants on InSTIs (specifically, EVG) and NNRTIs (specifically, EFV, 
NVP, or RPV) and use of cobicistat as a booster for PIs in order to better reflect 
the real-world use of various antiretroviral agents and current HIV treatment 
guidelines.
-
Updated text to specify that newly added EVG-based regimens require 
baseline genotyping, while NNRTI based regimens do not.
-
Clarified the plan of visits for resistance testing in both base study and 
study extension 1 and for participants who discontinue for reasons other than 
virologic failure to ensure that comprehensive resistance testing is done 
-
Expanded the list of prohibited concomitant medications to account for 
additional therapies permitted in the study.
Amendment 05
16-MAR-2016
-
Added open-label study extension 1 for 2 years to collect long-term 
efficacy and safety data.
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Document
Date of Issue
Overall Rationale
Amendment 04
03-NOV-2015
-
A secondary objective was added to evaluate the antiretroviral activity 
of an immediate switch to DOR/3TC/TDF on Study Day 1 compared with 
continuation of a ritonavir-boosted PI based-regimen for 24 weeks, as measured 
by the proportion of participants with HIV-1 RNA ≥50 copies/mL (ie, viral 
rebound) at Study Week 48 in the ISG and at Study Week 24 in the DSG based 
on the FDA snapshot approach. Viral rebound is of particular interest in the 
virologically-suppressed patient population entering a switch trial.
-
Removed rosuvastatin from the prohibited medication list, thereby 
allowing coadministration of DOR and rosuvastatin. This change was made 
after a drug–drug interaction study conducted with atorvastatin (which, similar 
to rosuvastatin, is a substrate for both OAT1B1 and BCRP) found no clinically 
meaningful changes in atorvastatin PK with DOR co-administration.
Amendment 03
31-JUL-2015
-
Added text to explain the rationale for the selected doses of the 
lamivudine and TDF components of DOR/3TC/TDF. These dose levels have 
demonstrated efficacy and safety in treatment-naive participants, and no 
antagonism was observed between DOR and either of these drugs in in vitro 
studies.
-
Added text to provide examples of medical conditions that might cause 
an investigator to discontinue a subject to ensure consistency with the 3TC and 
TDF prescribing information.
-
Added text to instruct investigators to monitor participants for 
symptoms of hyperlactatemia due to the use of 3TC and TDF in this trial and to 
ensure consistency with the 3TC and TDF prescribing information.
-
Clarified that sites would receive the calculated creatinine clearance in 
the laboratory reports from the central laboratory.
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Document
Date of Issue
Overall Rationale
Amendment 02
22-MAY-2015
-
Changed the PK/PD evaluation from an exploratory objective to a 
secondary objective given its importance in supporting the assessment of the 
exposure-response relationship for safety and efficacy in long-term use of 
DOR/3TC/TDF.
-
Added a baseline hemoglobin threshold ( ≥9.0 g/dL, if female; ≥10.0 
g/dL if male) to the inclusion criterion #9c to ensure that patients can safely 
undergo study-related laboratory procedures.
-
Added exclusion criterion #10 to exclude participants with severe 
hepatic impairment.
-
Specified additional visits for the collection of plasma for potential viral 
resistance testing to ensure that resistance testing can be done on the on-
treatment sample at the time of virologic failure, should this occur.
Amendment 01
23-MAR-2015
-
Modified exclusion criterion #4b to include the mutations D67N and 
K70R in the list of excluded mutations as these 2 mutations confer decreased 
susceptibility to NRTIs. 
-
Clarified single mutations or components of double or triple mutations 
in the DOR resistance mutation list.
Original protocol
14-JAN-2015
Not applicable.
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SUMMARY OF CHANGES
PRIMARY REASON(S) FOR THIS AMENDMENT:
Section Number (s)
Section Title(s)
Description of Change (s)
Rationale
Title Page 
Guatemala, Mexico, Peru, 
Australia, New Zealand, 
Russia, and Spain were added 
to the Title Page.
This is a country-specific 
amendment for Guatemala, 
Mexico, Peru, Australia, New 
Zealand, Russia, 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.  
The following changes were made in Amendment 09; however, Amendment 09 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 09.
To align with the current 
standard text for Code of 
Conduct.
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ADDITIONAL CHANGE(S) FOR THIS AMENDMENT:
No additional changes.
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1.0 TRIAL SUMMARY
Abbreviated Title
Switch to MK-1439A from PI-, EVG- or NNRTI-based regimen for HIV-1
infection
Trial Phase
Phase III
Clinical Indication
Treatment of HIV-1 infection (therapy switch in virologically-suppressed 
subjects).
Trial Type
Interventional
Type of control
Active control without placebo
Route of administration
Oral
Trial Blinding
Unblinded Open-label
Treatment Groups
Immediate Switch Group: Immediate Switch (at Study Day 1) to MK-1439A 
from a stable antiretroviral baseline regimen of a ritonavir- or cobicistat-
boosted protease inhibitor (PI), specifically, atazanavir, darunavir, or 
lopinavir, or cobicistat-boosted elvitegravir, or a non-nucleoside reverse 
transcriptase inhibitor (NNRTI), specifically, efavirenz, nevirapine, or 
rilpivirine, each administered with  2 nucleoside/nucleotide
reverse 
transcriptase inhibitors (NRTIs).  
Delayed Switch Group: Delayed Switch (at Study Week 24) to MK-1439A 
from a baseline regimen as described above.
Number of trial subjects
Approximately 660 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
For subjects who participate in the base study but do not continue into study 
extension 1, these subjects will participate in the trial for approximately 55
weeks, from the time they sign the Informed Consent Form (ICF) through 
the final contact.  For subjects who continue into study extension 1 but who 
do not continue into study extension 2, these subjects will participate for 
approximately 151 weeks (approximately 3 years total) from the time the 
subject signs the ICF in the base study through the final contact. For 
subjects who continue into study extension 2, these subjects will participate 
for approximately 247 weeks (approximately 5 years total) from the time 
they sign the ICF in the base study through the final contact.  For subjects 
who continue into study extension 3, these subjects will participate for 
approximately 343 weeks (approximately 7 years total) from the time they 
sign the ICF in the base study through the final contact.  
After a screening phase of up to 30 days, each subject will be receiving 
assigned treatment for approximately 48 weeks in the base study. For 
subjects who continue into study extension 1, study treatment will continue 
for an additional 96 weeks, approximately, through a total of approximately 
144 weeks of treatment.  For subjects who continue into study extension 2, 
study treatment with MK-1439A will continue until locally available or for 
an additional 96 weeks (whichever comes first), through a maximum of 
approximately 240 weeks of total treatment. For subjects who continue into 
study extension 3, study treatment with MK-1439A will continue until 
locally available or for an additional 96 weeks (whichever comes first), 
through a maximum of approximately 336 weeks of total treatment. After
the end of treatment, each subject will be followed for 14 days.  
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Randomization Ratio
2:1 with ~440 subjects in the Immediate Switch Group to MK-1439A on 
Study Day 1 and ~220 subjects in the Delayed Switch Group to MK-1439A 
at Study Week 24.
A list of abbreviations used in this document can be found in Section 12.6.
2.0 TRIAL DESIGN
Trial Design
This is a multicenter, open-label, randomized, active-controlled study to evaluate a switch 
from a stable antiretroviral regimen of a ritonavir- or cobicistat-boosted protease inhibitor 
(PI) (specifically, atazanavir, darunavir, or lopinavir), or cobicistat-boosted elvitegravir (an 
integrase strand transfer inhibitor [InSTI]), or a non-nucleoside reverse transcriptase inhibitor 
(NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine), each administered with two 
nucleoside/nucleotide
reverse 
transcriptase 
inhibitors 
(NRTIs) 
to 
MK-1439A 
in 
virologically-suppressed, human immunodeficiency virus type 1 (HIV-1)-infected subjects. 
The study consists of a 48-week base study, followed by a 96-week open-label study 
extension (study extension 1) in which all subjects receive MK-1439A. Subjects who have 
completed the base study and are considered eligible for entering study extension 1 must 
provide consent in order to enroll in study extension 1. Subjects who have completed study 
extension 1 and are considered eligible for entering study extension 2 must provide consent 
in order to enroll in study extension 2.  For subjects who continue into study extension 2, 
study treatment with MK-1439A will continue for an additional 96 weeks or until 
commercially available once approved in the local country (whichever comes first).  Subjects 
who have completed study extension 2 and are considered eligible for entering study 
extension 3 must provide consent in order to enroll in study extension 3.  For subjects who 
continue into study extension 3, study treatment with MK-1439A will continue for an 
additional 96 weeks or until commercially available once approved in the local country 
(whichever comes first).  The study is to be conducted in conformance with Good Clinical 
Practice. 
MK-1439A is a single-tablet fixed-dose regimen (FDR) that combines MK-1439, an 
investigational NNRTI, with lamivudine (3TC) and tenofovir disoproxil fumarate (TDF), 2 
approved and commercially-available NRTIs.  A single tablet of MK-1439A contains a full 
daily HIV treatment regimen of MK-1439 100 mg + lamivudine 300 mg + tenofovir 
disoproxil fumarate 300 mg.  
Subjects who have been virologically suppressed for at least 6 months and have HIV-1 RNA
below the limit of quantification (BLoQ) by the Abbott RealTime HIV-1 Assay 
(<40 copies/mL) at screening on a stable antiretroviral regimen consisting of one of the
ritonavir- or cobicistat-boosted PIs or one of the NNRTIs specified above, or cobicistat-
boosted elvitegravir, each on a backbone of 2 NRTIs, will be eligible for enrollment, 
provided they have no prior history of virologic failure on any regimen or resistance to the 
components of MK-1439A. 
For the purpose of historical documentation of virologic 
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suppression, undetectable HIV-1 RNA is considered a result below the level of quantification 
using a validated (local) assay with lower limit of quantification of 50 copies/mL or less.  
Subjects should be on their first or second antiretroviral regimen prior to enrollment. 
Subjects who complete the base study, as specified below, will be eligible to enter study 
extension 1 and if they remain eligible at the end of study extension 1, will be eligible to 
enroll in study extension 2.  If subjects remain eligible at the end of study extension 2, they 
will be eligible to enroll in study extension 3 and continue until MK-1439A becomes locally 
available or up to approximately 2 years beyond the second extension (whichever comes 
first). 
Approximately 660 subjects will be stratified in the base study by their regimen at screening
(one of the PIs specified above boosted with ritonavir vs. one of the PIs specified above 
boosted with cobicistat vs. elvitegravir boosted with cobicistat or one of the NNRTIs 
specified above); subjects in the ritonavir-boosted PI stratum will be further stratified by use 
of lipid-lowering therapy at Study Day 1 (yes/no). Subjects will be randomized in a 2:1 ratio 
to an immediate switch to MK-1439A on Study Day 1 (Immediate Switch Group) or delayed 
switch to MK-1439A at Study Week 24 (Delayed Switch Group).  The Delayed Switch 
Group will continue their baseline regimen until the time of the switch to MK-1439A at 
Study Week 24.  
At Study Week 48, subjects who meet the following criteria will be eligible to enter study 
extension 1: (1) completed the Week 48 study visit, (2) considered by the investigator to have 
derived benefit from study participation, (3) further treatment with MK-1439A is considered 
clinically appropriate by the investigator, and (4) have provided informed consent to continue 
into the study extension, thus continuing for approximately 2 years beyond the base study.
Similarly, at Study Week 144, subjects who meet the following criteria will be eligible to 
enter study extension 2: (1) completed the Week 144 study visit, (2) considered by the 
investigator to have derived benefit from treatment with MK-1439A, (3) further treatment 
with MK-1439A is considered clinically appropriate by the investigator, and (4) have 
provided informed consent, thus continuing until MK-1439A becomes locally available or up 
to approximately 2 years beyond the first extension (whichever comes first).  
At Study Week 240, subjects who meet the following criteria will be eligible to enter study 
extension 3: (1) completed the Week 240 study visit, (2) considered by the investigator to 
have derived benefit from treatment with MK-1439A, (3) further treatment with MK-1439A 
is considered clinically appropriate by the investigator, and (4) have provided informed 
consent, thus continuing until MK-1439A becomes locally available or up to approximately 2 
years beyond the second extension (whichever comes first).  
The total duration of treatment for a given subject in the base study is 48 weeks; for subjects 
who continue into study extension 1, the total duration of treatment is 144 weeks. For 
subjects who continue into study extension 2, the total duration is dependent on when MK-
1439A becomes locally available, with a maximum total duration of treatment of 240 weeks.  
For subjects who continue into study extension 3, the total duration is dependent on when 
MK-1439A becomes locally available, with a maximum total duration of treatment of 336
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weeks from the beginning of the study.  Subjects should discontinue at the next scheduled 
visit after MK-1439A becomes locally available in the market.
The primary endpoint is the proportion of subjects maintaining HIV-1 RNA <50 copies/mL
by the Abbott RealTime HIV-1 Assay at Study Week 48 in the Immediate Switch Group and 
the proportion of subjects with HIV-1 RNA <50 copies/mL by the Abbott RealTime HIV-1 
Assay at Study Week 24 in the Delayed Switch Group.
Thus, in the primary efficacy 
assessment, the Immediate Switch Group will have received MK-1439A for 48 weeks, and 
the Delayed Switch Group will have received their baseline regimen for 24 weeks on-study
(though they will have received the same regimen for at least 6 months prior to the study 
[note that the primary endpoint will be assessed before the Delayed Switch Group switches to 
MK-1439A]).  This endpoint compares the ability of MK-1439A to maintain virologic 
suppression for 48 weeks in previously suppressed subjects with the ability of the continued 
PI-based, elvitegravir-based, or NNRTI-based treatment regimen, as specified above, to 
maintain suppression for at least 24 weeks in previously-suppressed subjects (who will have 
received their baseline regimen for ≥48 weeks in total at the time of the primary assessment).  
Long-term efficacy data will be collected during study extension 1 and summarized 
descriptively.  Efficacy data will not be collected for study extension 2 or study extension 3.
The open-label design of the study will reduce complexity and allow observation of the 
simplicity and acceptability of a complete fixed-dose regimen as an aspect of switching 
therapy.  Because the study, by design, allows a switch from multiple ART regimens, 
including multiple backbone agents, blinding of all of these agents would be operationally
challenging.
Randomized subjects who meet virologic failure criteria during the study (base study or 
study extension 1) (see Section 4.2.3.1) will return to the site for repeat viral RNA testing 
between 1 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 criterion for resistance testing 
(>400 copies/mL) in the base study or study extension 1, viral resistance testing will be 
performed.  For subjects in the base study with confirmed virologic failure, plasma samples
collected for resistance testing from the virologic failure visit and from the confirmation visit 
will be sent for resistance testing.  For subjects in study extension 1 with confirmed virologic 
failure, the plasma sample from the virologic failure confirmation visit will be sent for 
resistance testing.  In addition, plasma samples for resistance testing collected at the 
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. (Note that if a 
sample from the discontinuation visit is not available, a sample from the most recent previous 
visit [if available] will be sent.)
Pharmacokinetic (PK) samples to be assayed for MK-1439 plasma concentrations will be 
collected in all subjects in both treatment groups at Study Day 1 (randomization visit) as a 
pre-drug sample and at Study Week 48.  In addition, blood samples for PK will also be 
collected from subjects in the Immediate Switch Group at Study Weeks 4, 12, and 24. 
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During study extension 1, subjects will continue to be monitored for safety, including fasting 
lipids, and maintenance of virologic suppression.  Long-term safety data will be collected 
during study extension 1 and summarized.  During study extension 2 and study extension 3, 
serious adverse events (SAEs) and pregnancy for female subjects will be monitored and 
collected.  
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.  
Figure 1
Trial Design
3.0 OBJECTIVE(S) & HYPOTHESIS(ES)
Primary Objective(s) & Hypothesis(es)
In HIV-1 positive subjects who have been virologically suppressed for at least 6 months and 
have HIV-1 RNA below the limit of quantification (BLoQ) by the Abbott RealTime HIV-1 
Assay (<40 copies/mL) at screening on a stable antiretroviral regimen of a ritonavir- or 
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cobicistat-boosted PI (specifically, atazanavir, darunavir, or lopinavir), or cobicistat-boosted 
elvitegravir, or an NNRTI (specifically, efavirenz, nevirapine, or rilpivirine), each 
administered with 2 NRTIs:
1) Objective:  To evaluate the non-inferior antiretroviral activity of an immediate 
switch to MK-1439A on Study Day 1 compared with continuation of a ritonavir- or 
cobicistat-boosted PI-based or cobicistat-boosted elvitegravir-based or NNRTI-based 
regimen for 24 weeks, as measured by the proportion of subjects maintaining HIV-1 
RNA <50 copies/mL by the Abbott RealTime HIV-1 Assay at Study Week 48 in the 
Immediate Switch Group and at Study Week 24 in the Delayed Switch Group.
Hypothesis:  An immediate switch to MK-1439A on Study Day 1 is non-inferior to 
continuation of a ritonavir- or cobicistat-boosted PI-based or cobicistat-boosted 
elvitegravir-based or NNRTI-based regimen for 24 weeks, as assessed by the 
proportion of subjects maintaining HIV-1 RNA <50 copies/mL by the Abbott 
RealTime HIV-1 Assay at Study Week 48 in the Immediate Switch Group and at 
Study Week 24 in the Delayed Switch Group. A margin of 8 percentage points is 
used to define non-inferiority.
Secondary Objective(s) & Hypothesis(es)
In HIV-1 positive subjects who have been virologically suppressed for at least 6 months and 
have HIV-1 RNA below the limit of quantification (BLoQ) by the Abbott RealTime HIV-1 
Assay (<40 copies/mL) at screening on a stable antiretroviral regimen of a ritonavir-boosted 
PI administered with 2 NRTIs:
1) Objective:  To evaluate the effect on fasting LDL-C of an immediate switch to MK-
1439A on Study Day 1 compared with continuation of a ritonavir-boosted, PI-based 
regimen for 24 weeks, as measured by mean change from baseline at Study Week 24 
in each treatment group.
Hypothesis:  An immediate switch to MK-1439A on Study Day 1 is superior to the 
continuation of a ritonavir-boosted, PI-based regimen for 24 weeks, as assessed by 
the mean change from baseline in fasting LDL-C at Study Week 24 in each treatment 
group.
2) Objective:  To evaluate the effect on fasting non-HDL-C of an immediate switch to 
MK-1439A on Study Day 1 compared with continuation of a ritonavir-boosted, PI-
based regimen for 24 weeks, as measured by mean change from baseline at Study 
Week 24 in each treatment group.
Hypothesis: An immediate switch to MK-1439A on Study Day 1 is superior to the 
continuation of a ritonavir-boosted, PI-based regimen for 24 weeks, as assessed by 
the mean change from baseline in fasting non-HDL-C at Study Week 24 in each 
treatment group. 
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In HIV-1 positive subjects who have been virologically suppressed for at least 6 months and 
have HIV-1 RNA below the limit of quantification (BLoQ) by the Abbott RealTime HIV-1 
Assay (<40 copies/mL) at screening on a stable antiretroviral regimen of a ritonavir- or 
cobicistat-boosted PI (specifically, atazanavir, darunavir, or lopinavir), or cobicistat-boosted 
elvitegravir, or an NNRTI (specifically, efavirenz, nevirapine, or rilpivirine), each 
administered with 2 NRTIs:
3) Objective: To evaluate the non-inferior antiretroviral activity of an immediate switch 
to MK-1439A on Study Day 1 compared with continuation of a ritonavir- or 
cobicistat-boosted PI-based or cobicistat-boosted elvitegravir-based or NNRTI-based 
regimen for 24 weeks, as measured by the proportion of subjects maintaining HIV-1 
RNA <50 copies/mL by the Abbott RealTime HIV-1 Assay at Study Week 24 in each 
treatment group.
Hypothesis:  An immediate switch to MK-1439A on Study Day 1 is non-inferior to 
the continuation of a ritonavir- or cobicistat-boosted PI-based or cobicistat-boosted 
elvitegravir-based or NNRTI-based regimen for 24 weeks, as assessed by the 
proportion of subjects maintaining HIV-1 RNA <50 copies/mL by the Abbott 
RealTime HIV-1 Assay at Study Week 24 in each treatment group. A margin of 
8 percentage points is used to define non-inferiority.
4) Objective:  To evaluate the superior antiretroviral activity of an immediate switch to 
MK-1439A on Study Day 1 compared with continuation of a ritonavir- or cobicistat-
boosted PI-based or cobicistat-boosted elvitegravir-based or NNRTI-based regimen 
for 24 weeks, as measured by the proportion of subjects maintaining HIV-1 RNA 
<50 copies/mL by the Abbott RealTime HIV-1 Assay at Study Week 48 in the 
Immediate Switch Group and at Study Week 24 in the Delayed Switch Group.  
Hypothesis:  An immediate switch to MK-1439A on Study Day 1 is superior to 
continuation of a ritonavir- or cobicistat-boosted PI-based or cobicistat-boosted 
elvitegravir-based or NNRTI-based regimen for 24 weeks, as assessed by the 
proportion of subjects maintaining HIV-1 RNA <50 copies/mL by the Abbott 
RealTime HIV-1 Assay at Study Week 48 in the Immediate Switch Group and at 
Study Week 24 in the Delayed Switch Group. 
5) Objective: To evaluate the superior antiretroviral activity of an immediate switch to 
MK-1439A on Study Day 1 compared with continuation of a ritonavir- or cobicistat-
boosted PI-based or cobicistat-boosted elvitegravir-based or NNRTI-based regimen 
for 24 weeks, as measured by the proportion of subjects maintaining HIV-1 RNA 
<50 copies/mL by the Abbott RealTime HIV-1 Assay at Study Week 24 in each 
treatment group
Hypothesis:  An immediate switch to MK-1439A on Study Day 1 is superior to the 
continuation of a ritonavir- or cobicistat-boosted PI-based or cobicistat-boosted 
elvitegravir-based or NNRTI-based regimen for 24 weeks, as assessed by the 
proportion of subjects maintaining HIV-1 RNA <50 copies/mL by the Abbott 
RealTime HIV-1 Assay at Study Week 24 in each treatment group. 
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6) Objective:
To evaluate the antiretroviral activity of an immediate switch to MK-
1439A on Study Day 1 compared with continuation of a ritonavir- or cobicistat-
boosted PI-based or cobicistat-boosted elvitegravir-based or NNRTI-based regimen
for 24 weeks, as measured by the proportion of subjects maintaining HIV-1 RNA 
below the limit of quantification (BLoQ) by the Abbott RealTime HIV-1 Assay 
(<40 copies/mL) at Study Week 48 in the Immediate Switch Group vs Study Week 
24 in the Delayed Switch Group and at Study Week 24 in both treatment groups.
7) Objective:  To evaluate the immunological effect of an immediate switch to MK-
1439A on Study Day 1 compared with continuation of a ritonavir- or cobicistat-
boosted PI-based or cobicistat-boosted elvitegravir-based or NNRTI-based regimen 
for 24 weeks, as measured by the change from baseline in CD4 cell count at Study 
Week 48 in the Immediate Switch Group and at Study Week 24 in the Delayed 
Switch Group.
8) Objective:  To evaluate the immunological effect of an immediate switch to MK-
1439A on Study Day 1 compared with continuation of a ritonavir- or cobicistat-
boosted PI-based or cobicistat-boosted elvitegravir-based or NNRTI-based regimen 
for 24 weeks, as measured by the change from baseline in CD4 cell count at Study 
Week 24 in each treatment group.
9) Objective: To evaluate the safety and tolerability of an immediate switch to MK-
1439A on Study Day 1 compared with continuation of a ritonavir- or cobicistat-
boosted PI-based or cobicistat-boosted elvitegravir-based or NNRTI-based regimen 
for 24 weeks, as assessed by review of the accumulated safety data by Study Week 24
in each treatment group.
10) 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.
11) Objective:  To evaluate the antiretroviral activity of an immediate switch to MK-
1439A on Study Day 1 compared with continuation of a ritonavir- or cobicistat-
boosted PI-based or cobicistat-boosted elvitegravir-based or NNRTI-based regimen
for 24 weeks, as measured by the proportion of subjects with HIV-1 RNA 
≥50 copies/mL at Study Week 48 in the Immediate Switch Group and at Study 
Week 24 in the Delayed Switch Group based on the FDA snapshot approach.
Exploratory Objectives
In HIV-1 positive subjects who have been virologically suppressed for at least 6 months and 
have HIV-1 RNA below the limit of quantification (BLoQ) by the Abbott RealTime HIV-1 
Assay (<40 copies/mL) at screening on a stable antiretroviral regimen of a ritonavir- or 
cobicistat-boosted PI (specifically, atazanavir, darunavir, or lopinavir), or cobicistat-boosted 
elvitegravir, or an NNRTI (specifically, efavirenz, nevirapine, or rilpivirine), each 
administered with 2 NRTIs.
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1) Objective:  To describe patient-reported outcomes related to health-related quality of 
life, self-reported HIV symptoms, work productivity/activity impairment and 
gastrointestinal symptoms at Study Day 1, Study Weeks 24 and 48 in subjects who 
switch to MK-1439A at Study Day 1 relative to those who continue a ritonavir- or 
cobicistat-boosted PI-based or cobicistat-boosted elvitegravir-based or NNRTI-based 
regimen for 24 weeks.
2) Objective: To assess the development of resistance to MK-1439 in subjects who 
have virologic failure.
3) 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.  
4) Objective:  To assess data on long-term efficacy and safety of MK-1439A 
administered for up to 144 weeks in subjects enrolled in study extension 1 of the 
study.  
4.0 BACKGROUND & RATIONALE
Background
Refer to the Investigator’s Brochure (IB) for detailed background information on MK-
1439A.
Pharmaceutical and Therapeutic Background
HIV infection, which causes Acquired Immunodeficiency Syndrome (AIDS) and for many 
years was associated with substantial morbidity and mortality, has now become a chronic 
disease that can be controlled through life-long combination antiretroviral therapy (cART) or 
Highly Active Antiretroviral Therapy (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 five distinct mechanistic classes known as reverse transcriptase 
inhibitors [nucleos(t)ide reverse transcriptase inhibitors (N(t)RTIs) and non-nucleoside 
reverse transcriptase inhibitors (NNRTIs)], protease inhibitors (PIs), fusion inhibitors, entry 
inhibitors (CCR5 co–receptor antagonists), and integrase strand transfer inhibitors (InSTIs).  
Successful combinations of 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 noncompliance 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 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 
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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 still highly desirable.
Currently available therapies for HIV infection include PIs, a diverse class of potent agents 
with a high genetic barrier to resistance, but generally requiring boosting by ritonavir or 
cobicistat to achieve appropriate drug exposure.  As a class, PIs are highly efficacious, and 
several are recommended as preferred agents for first-line therapy for treatment-naïve HIV-
infected subjects; however, they are also associated with a variety of toxicities including 
gastrointestinal adverse experiences (AEs) (especially diarrhea), serum lipid abnormalities, 
and lipodystrophy, which are of particular concern in view of the need for lifelong HIV 
therapy.  Based on preclinical and clinical data to date, MK-1439 is not expected to have 
similar safety concerns.  Therefore, MK-1439A could be a valuable treatment option for 
subjects switching from a PI-containing regimen, providing that virologic suppression can be 
maintained on the new regimen after the switch. 
Elvitegravir boosted with cobicistat, in the InSTI mechanistic class, is recommended as a 
fixed-dose combination with two NRTIs for treatment of ART-naïve patients, as long as their 
CrCl is ≥70 mL/min [1], and as a single agent, combined with a ritonavir-boosted PI and 
other antiretroviral drugs, in ART-experienced patients.  As with PIs, elvitegravir requires 
boosting by ritonavir or cobicistat to achieve appropriate drug exposure; the most frequently 
reported AEs are nausea and diarrhea.
For initiation of combination antiretroviral therapy for HIV infection, currently available 
NNRTIs constitute an important option for use as anchor agents, along with two NRTIs.
Efavirenz and rilpivirine have been 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/µL.  
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. Furthermore, 
supratherapeutic doses of rilpivirine (≥75 mg QD) have been shown to prolong the QTc 
interval [3]. 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.
MK-1439 is a novel NNRTI being studied for treatment of HIV-1 infection in antiretroviral-
naïve HIV-infected subjects.  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 
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(NHS). 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 potency against viruses containing the double mutant K103N +
Y181C is 33nM.  The preclinical toxicity profile of MK-1439 is favorable in rats up to 
6 months in duration at 3, 30, and 450 mg/kg/day, and in dogs up to 9 months in duration at 
1, 10, and 1000 mg/kg/day.  Clinical pharmacology studies indicate that MK-1439 can be 
dosed once daily, without regard to food, and MK-1439 is not a metabolic inducer or 
inhibitor, reducing the likelihood of significant drug-drug interactions.  Furthermore, the 
available data from a Phase 2 study in treatment-naive HIV-infected patients demonstrate 
that MK-1439 in combination with TDF/emtricitabine has 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).  This need is further driven by 
the necessity for life-long treatment of HIV infection as many HIV patients become 
increasingly older with co-morbid diseases/conditions.
Recent advances in HIV therapeutics have included the development of complete fixed-dose 
regimen pills.  HIV-infected patients who are suppressed on complex, multi-pill regimens 
may benefit from treatment simplification.  This strategy is supported in recent iterations of 
treatment guidelines which recommend regimen simplification to improve a patient’s quality 
of life, increase medication adherence, reduce the likelihood of virologic non-suppression, 
and improve tolerability [1].  The key principles of regimen switch in this setting are to 
maintain viral suppression without compromising future options and to consider a patient’s 
prior treatment history and responses to ART, resistance profiles, and drug tolerance when 
contemplating a regimen switch.
With current antiretroviral therapy (ART) regimens, HIV-infected patients have a high 
likelihood of achieving and maintaining undetectable HIV RNA levels, however it is 
estimated that 25% of those patients receiving ART are not virologically suppressed.  Drug 
adverse effects and toxicities, food requirements, high pill burden and/or dosing frequency 
and drug-drug interactions with concomitant medications are among the reasons cited for 
virologic failure due to ART regimens.  Earlier patient cohorts suggested that suboptimal 
adherence and drug intolerance/toxicity accounted for 28% to 40% of virologic failure and 
regimen discontinuations [4].  These are the same reasons patients and prescribers consider 
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switching components of a patient’s antiretroviral therapy in the setting of viral suppression, 
before failure occurs. 
With the aging of the HIV-infected population, it is anticipated that switches will become 
even more common with increased concerns for the risks of long-term toxicity, drug-drug 
interactions and co-morbid conditions (i.e. neuropsychiatric, cardiovascular).
MK-1439 has the potential to be an ideal agent in the switch setting due to its favorable 
efficacy and safety profile, anticipated lack of food requirements, and favorable drug-drug 
interaction profile observed to date.
Rationale for Expansion of Subject Population (Amendment 06) 
Amendment 06 allows individuals to enter the study whose ART regimens at screening 
include a third agent from either of two mechanistic classes (InSTIs and NNRTIs) in addition 
to the originally allowed PI class; it also allows individuals with a baseline PI regimen using
cobicistat as a boosting agent in addition to the originally allowed ritonavir.  
The expansion of the subject population in this amendment better reflects the real-world use 
of antiretroviral agents and current HIV treatment guidelines.  Initial ART regimens are now 
less likely to be PI-based.  For example, the most recent update of the US Department of 
Health and Human Services (DHHS) guideline for ART in adults and adolescents, released 
while this study was ongoing, includes multiple InSTI-based regimens, with PI-based 
regimens moved into the alternative category [1].  A majority of patients whose initial ART 
regimen was PI-based and who had tolerability issues have already switched to another 
regimen that is more tolerable.  Those patients remaining on PI-based regimens are now less 
likely to switch.  Recently completed and ongoing switch studies of other HIV-1 therapies 
have also allowed multiple mechanistic classes as a third agent.  Note that the primary 
hypothesis, non-inferiority of MK-1439A to baseline regimens with regard to antiretroviral 
activity, remains unchanged and applies to the expanded list of baseline regimens.  All other 
hypotheses and objectives also apply to all baseline regimens with the following exception: 
the two secondary hypotheses that a switch to MK-1439A is superior to maintenance of 
baseline regimen with respect to fasting LDL-C and fasting non-HDL-C, respectively, apply
only to regimens of a ritonavir-boosted PI, as in the original protocol. The rationale for 
restricting the lipid-related objectives to this subset of subjects is the known adverse effect of 
ritonavir-boosted PIs, as a class, on lipid profiles, and the expectation that relatively few 
subjects on a cobicistat-boosted PI regimen will be enrolled compared with the number of 
already-enrolled subjects on a ritonavir-boosted PI, such that statistical analysis of these 
subjects would not be feasible.
For individuals whose regimen at screening is based on an NNRTI, the inclusion criterion 
requiring documentation of pre-treatment HIV genotyping has been removed.  This is
because individuals who are virologically suppressed on a regimen of an NNRTI plus 
2 NRTIs are unlikely to have major drug resistance mutations to the NRTI components, since 
NNRTI monotherapy is not sufficient to maintain complete suppression.  Therefore, for 
individuals to be suppressed on an NNRTI-based regimen at screening, NRTI efficacy would 
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need to be robust, indicating lack of NRTI resistance, such that absence of baseline genotype 
information would not increase the risk of failure on MK-1439A due to NRTI resistance.
Documentation of pre-treatment HIV genotype in subjects on a regimen at screening of a 
ritonavir- or cobicistat-boosted PI or cobicistat-boosted elvitegravir is required since these 
drugs in combination with NRTIs may mask the presence of NRTI resistance that could 
potentially affect the activity and efficacy of MK-1439A.  Boosted-PI regimens are 
commonly used as second-line regimens, even in the presence of resistance to emtricitabine 
or lamivudine, due to the potency of PIs.  Cobicistat-boosted elvitegravir is also a potent 
third agent with the potential to mask the presence of NRTI resistance. 
Rationale for Dose Selection/Regimen
The investigational FDR, MK-1439A, contains 100 mg of MK-1439, a potent investigational 
NNRTI, and standard doses of 2 commercially-available and commonly used NRTIs, 
lamivudine (300 mg) and TDF (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.
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 
vRNA 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 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 [5, 6]).  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 
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these efficacy data strongly support that the dose range studied (25-200 mg daily) was on the 
plateau of the dose response curve.   
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 24week 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 CNS 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).    
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 
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 G190A 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 CNS AE was reported in 22.2% of the MK1439 group and 43.5% of the EFV group 
(p<0.001).  The most commonly-reported CNS 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). 
The rationale for selection of the 100 mg daily dose of MK-1439 in treatment-naïve HIV-1 
infected subjects is considered to also be applicable to subjects eligible for the current study, 
since they are required to be virologically suppressed for at least 6 months prior to entry, to 
have no history of prior virologic failure, and, where applicable depending on the regimen at 
screening (see inclusion criteria in Section 5.1.2), to have documented pre-treatment HIV 
resistance testing showing no resistance mutations to any of the components of the 
MK-1439A regimen.  The 100-mg dose is expected to provide sufficient coverage for 
subjects entering this study whose pre-treatment HIV resistance testing shows those NNRTI 
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mutations that confer < 3-fold increase in IC95 to MK-1439; therefore these subjects will be 
permitted to enroll in this study, as specified in Section 5.1.2, inclusion criterion 7. 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.
There is no dose modification for MK-1439A permitted in this study. 
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 hypothesis of this study compares the proportion of subjects maintaining HIV-1
RNA <50 copies/mL at Study Week 48 in the Immediate Switch Group with the proportion 
of subjects maintaining HIV-1 RNA <50 copies/mL at Study Week 24 in the Delayed Switch 
Group.  Note that the time points for the assessment of the primary efficacy hypothesis are 
defined as per agreement with regulatory agencies. It is acknowledged that the longer
assessment period in the Immediate Switch Group may lead to more non-treatment related 
dropouts in that group. Therefore, an additional efficacy comparison will be performed 
based on Study Week 24 assessments for both groups, as this represents the last available 
time point at which the immediate switch to MK-1439A can be directly compared to those 
subjects continuing on their previous ART regimen with the same follow-up time for each 
treatment group.  
Secondary and exploratory measurements for efficacy include the proportion of subjects 
maintaining HIV-1 RNA <40 copies/ mL (BLoQ), the proportion of subjects with HIV-1 
RNA ≥50 copies/mL based on the FDA snapshot approach, change from baseline in CD4 cell 
counts, time to loss of virologic response (TLVOR), and viral resistance for subjects who 
meet the virologic failure criteria and whose virus can be amplified.
Protocol-defined virologic failure (PDVF) is defined as subjects who have two consecutive 
measurements of HIV-1 RNA ≥50 copies/mL at least one week apart. Subjects should be 
discontinued, regardless of compliance to study therapy, if they meet the protocol defined 
virologic failure criteria.
Safety Endpoints
Key safety endpoints include change from baseline in fasting serum lipids, clinical and 
laboratory adverse experiences and predefined limits of change in laboratory parameters.  
While lipid data will be evaluated as part of the general safety assessment for all subjects 
(through predefined limits of change or summary of laboratory values), primary analyses 
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related to change from baseline in fasting lipids will include data only from subjects whose 
regimen at screening is a ritonavir-boosted PI (see Table 10).
Safety evaluations in the base study will include physical examinations (including vital signs) 
and laboratory tests (blood) performed at the screening visit, randomization (Study Day 1), 
Study Weeks 4, 12, 24, 28, 36, 48, a virologic failure confirmation visit (no physical exam or 
vital signs), an early discontinuation visit (for subjects who discontinue the study early), and, 
for subjects who do not enter study extension 1, a 14-day follow-up visit.  For subjects who 
continue into study extension 1, safety evaluations will be performed at each of the study 
visits in the extension (Study Weeks 64, 80, 96, 112, 128 and 144 and, if applicable, an early 
discontinuation visit and/or a virologic failure confirmation visit) and at a 14-day follow-up 
visit.  Adverse experiences 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.
During study extension 2 and study extension 3, SAEs and pregnancies will be collected at 
each study visit (study extension 2:  Week 160, 176, 192, 208, 224, and 240, as applicable; 
study extension 3:  Week 256, 272, 288, 304, 320, and 336, as applicable, depending on 
when MK-1439A is available locally, and, if applicable, at early discontinuation and 14-day 
follow-up visits).  
Pharmacokinetic Endpoints
Pharmacokinetic (PK) samples to be assayed for MK-1439 plasma concentrations will be 
collected in all subjects in both treatment groups at the Study Day 1 (randomization) visit as 
a pre-drug sample and at Study Week 48. In addition, blood samples for PK will also be 
collected from subjects in the Immediate Switch Group at Study Weeks 4, 12, and 24. 
At Study Day 1 and Study Week 4 the samples must be collected predose.  At Study Weeks 
24 and 48, the samples must be collected predose and within 0.5 to 2 hours postdose
(subjects should remain fasting until post dose sample is collected); at Study Week 12, the 
samples 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 4 patient-reported outcome questionnaires at Study Day 1, Study
Weeks 4, 24, 28, 48 and/or the discontinuation visit.  The questionnaires are designed to 
capture patient-reported assessments for health domains that may be affected by the use of 
currently available PIs: 1) general quality of life, 2) symptoms associated with HIV and its 
treatment, 3) the impact of health conditions on productivity and 4) gastrointestinal-related 
impact on quality of life. The specific questionnaires to be used are the Irritable Bowel
Syndrome-Quality of Life (IBS-QOL) questionnaire, the HIV Symptom Index (HIV-SI or 
SDM) questionnaire, Work Productivity and Activity Impairment Questionnaire (WPAI) and
the EuroQol five dimensional descriptive system, five level version (EQ-5D-5L).
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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.
Future Biomedical Research
The Sponsor will conduct Future Biomedical Research on DNA (blood) and plasma
specimens collected during this clinical trial.  This research may include genetic analyses 
(DNA), gene expression profiling (RNA), proteomics, metabolomics (serum, plasma) and/or 
the measurement of other analytes.
Such research is for biomarker testing to address emergent questions not described elsewhere 
in the protocol (as part of the main trial) and will only be conducted on specimens from 
appropriately consented subjects. The objective of collecting specimens for Future 
Biomedical Research is to explore and identify biomarkers that inform the scientific 
understanding of diseases and/or their therapeutic treatments. For instance, exploratory 
pharmacogenetic (PGt) studies may be performed if significant Pharmacokinetic/
Pharmacodynamic (PK/PD) relationships are observed or adverse events are identified.  
Genomic markers of disease may also be investigated.  Such retrospective pharmacogenetic 
studies will be conducted with appropriate biostatistical design and analysis and compared to 
PK/PD results or clinical outcomes. Any significant PGt relationships to outcome would 
require validation in future clinical trials. The overarching goal is to use such information to 
develop safer, more effective drugs/vaccines, and/or to ensure that subjects receive the 
correct dose of the correct drug/vaccine at the correct time.  The details of this Future 
Biomedical Research sub-trial are presented in Section 12.2 - Collection and Management of 
Specimens for Future Biomedical Research.  Additional informational material for 
institutional review boards/ethics committees (IRBs/ERCs) and investigational site staff is 
provided in Section 12.3.
Rationale for Study Extensions
Because HIV infection is chronic, with treatment generally lasting for years, collection of 
long-term safety and efficacy data in study extension 1 will provide useful information, 
although these data will not be subject to inferential analyses.  
The rationale for study extension 2 and study extension 3 is to avoid interruption of treatment 
by providing continued study drug, until it becomes locally available, for subjects who are 
eligible and deemed by the investigator to have benefited from treatment with study drug.  
An additional rationale is that any change from a successfully suppressive and tolerated 
cART regimen carries with it a well-recognized but small risk of treatment failure on a new 
regimen.
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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/tolerability
concerns associated with boosted PIs or boosted elvitegravir, the neuropsychiatric effects 
associated with EFV, or the food requirements of rilpivirine.  Therefore, MK-1439 could 
represent a valuable addition to the HIV armamentarium as a treatment which could be used 
in patients who are virologically suppressed on a regimen containing a ritonavir- or 
cobicistat-boosted PI, cobicistat-boosted elvitegravir, or a traditional NNRTI, but needing a 
switch due to tolerability-based considerations.
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. Thus, the fixed dose regimen, MK-1439A, may improve quality of life.
Additional details regarding specific benefits and risks for subjects participating in this 
clinical trial may be found in the accompanying Investigator’s Brochure (IB) and Informed 
Consent documents.
5.0 METHODOLOGY
Entry Criteria
Diagnosis/Condition for Entry into the Trial
Male/female subjects 18 years of age or older who are HIV-1 positive and who, at study 
entry, have had HIV RNA at an undetectable level for at least 6 months on a stable 
antiretroviral regimen consisting of a ritonavir- or cobicistat-boosted PI (specifically,
atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or an NNRTI 
(specifically, efavirenz, nevirapine, or rilpivirine) on a backbone of 2 NRTIs 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.  
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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. have plasma HIV-1 RNA levels BLoQ (<40 copies/mL by the Abbott RealTime HIV-
1 Assay as determined by the central laboratory) at the screening visit.
4. have been receiving antiretroviral therapy with a ritonavir- or cobicistat-boosted PI 
(specifically atazanavir, darunavir or lopinavir) or cobicistat-boosted elvitegravir or 
an NNRTI (specifically, efavirenz, nevirapine or rilpivirine), each given in 
combination with 2 NRTIs (and no other ART) continuously with HIV-1 RNA at 
undetectable levels for ≥6 months prior to the screening visit (as measured at ≥2 
sequential time points) and have no history of prior virologic failure.  See table in 
inclusion criterion (5).
Note: The more recent of the 2 sequential time points must be within the 6 months 
immediately prior to screening. 
Note: For the purpose of historical documentation of virologic suppression, 
undetectable HIV-1 RNA is considered a result below the level of quantification 
using a validated (local) assay with lower limit of quantification of 50 copies/mL or 
less.
5. be receiving his/her first or second antiretroviral regimen
Note: 

Subjects receiving an NNRTI-based regimen must be on their first antiretroviral 
regimen.

Subjects receiving a boosted PI-based or boosted elvitegravir-based regimen may 
be on their first or second antiretroviral regimen.  If subjects are on their second 
regimen, HIV-1 RNA must have been below the limit of quantification (BLoQ) at 
the time of the first change in antiretroviral agents.  See table below.

A change in NRTI background therapy due to tolerability or toxicity while 
virologically suppressed prior to enrollment in the trial will not be considered an 
additional regimen change.
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Mechanistic 
Class
Permitted as first regimen (in 
combination w/2 NRTIs)
Permitted as second regimen 
(in combination w/2 NRTIs)a
PIs
ATV/r, ATV/c
DRV/r, DRV/c
LPV/r
ATV/r, ATV/c
DRV/r, DRV/c
LPV/r
NNRTIs
EFZ
NVP
RPV
None
InSTIs
EVG/c only
EVG/c only
Abbreviations: 
PIs = protease inhibitors: ATV = atazanavir; DRV = darunavir; LPV = lopinavir; /c = boosted with 
cobicistat; /r = boosted with ritonavir.
NNRTIs = non-nucleoside reverse transcriptase inhibitors: EFZ = efavirenz; NVP = nevirapine; RPV = 
rilpivirine.
InSTIs = integrase strand transfer inhibitors: EVG = elvitegravir.
a If a subject is on a second regimen, he/she must have had HIV-1 RNA at a level below the limit of 
quantification (BLoQ) before the second regimen was begun.
6. have no history of using any experimental NNRTI for any length of time.
Note: No history of use is defined as having received no (0 days of) NNRTI therapy 
for the treatment of HIV infection.
7. have had a genotype prior to starting his/her initial antiretroviral regimen and have no 
known resistance to any of the study agents (MK-1439, TDF, or lamivudine).  
Note: Subjects on their first NNRTI-based regimen are not required to have 
documentation of pre-treatment HIV genotyping. 
If, however, a subject on an
NNRTI-based regimen has had documented HIV genotyping at any time before or 
during treatment, and if any subject on another ART regimen has had additional 
documented genotyping after beginning initial treatment, the same criteria apply, i.e., 
the subject must have no known resistance to any of the study agents: MK-1439, 
TDF, or lamivudine.
Note: Subjects with selected NNRTI-class mutations that confer resistance to other 
NNRTIs, but are considered susceptible to MK-1439, are eligible for the study. 
Reverse transcriptase mutations K103N, Y181C, and G190A as well as the 
K103N+Y181C double-mutant constitute the majority of transmitted NNRTI-
resistant variants.  Each of these mutations confers less than a 3-fold reduction in 
sensitivity to MK-1439, and PK/PD modeling indicates that the 100mg q.d. dose 
of MK-1439 should be able to inhibit these variants in vivo.  Therefore, a subject 
whose virus harbors any of these mutations would be eligible for the study.
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8. be on either no lipid-lowering therapy or on a stable dose of lipid-lowering therapy at 
the time of enrollment
9. have the following laboratory values at screening within 30 days prior to the 
treatment phase of this study:  
a) Alkaline phosphatase ≤ 3.0 x upper limit of normal (ULN) 
b) AST (SGOT) and ALT (SGPT) ≤ 5.0 x ULN 
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.
10. have a calculated creatinine clearance at the time of screening ≥50 mL/min, based on 
the Cockcroft-Gault equation which is as follows:
For Men: 
Clcr (mL/min) =
(140-age) x weight (in kg)
72 x serum creatinine (mg/dL)
For Women:
Clcr (mL/min) =
(140-age) x weight (in kg)
X    0.85
72 x serum creatinine (mg/dL)
11. 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).
12. 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 
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for 14 days after the last dose of study drug 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:
Single method (one of the following is acceptable):
•
intrauterine device (IUD)
•
vasectomy of a female subject’s male partner 
•
contraceptive rod‡ implanted into the skin (not acceptable for the subjects 
in the Delayed Switch Group until they switch to MK-1439A at Study 
Week 24)
Combination method (requires use of two 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, 
or subcutaneous contraceptive injection (not acceptable for the subjects in 
the Delayed Switch Group until they switch to MK-1439A at Study Week 
24)
*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. In 
addition, more restrictive contraceptive methods must be used if required by local 
ethics or regulatory authorities.
If a contraceptive method listed above is restricted by local standard of 
care/guidelines, then it does not qualify as an acceptable method of contraception 
for subjects participating at sites in this country/region.
↑Use of barrier methods of contraception is strongly encouraged to reduce the risk 
of HIV-1 transmission during sexual contact.
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‡Contraceptives containing ethinyl estradiol (including contraceptive rods and 
hormonal contraceptives) cannot be used as a method of birth control for subjects 
who are taking ritonavir in this study (applicable to subjects in the Delayed Switch 
Group until they switch to MK-1439A at Study Week 24) due to an interaction 
between ethinyl estradiol and ritonavir that may reduce the effectiveness of the 
contraceptives. 
Therefore, it is recommended that a condom or other non-
hormonal method of contraception should be used instead.  
In order to be eligible for participation in study extension 1 at the Week 48 visit, the subject 
must:
13. have completed the Week 48 visit.
14. be considered, in the opinion of the investigator, to have derived benefit from study 
participation through Week 48.
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 the study extension and provide written informed 
consent to enter study extension 1, 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 
144 visit the subject must:
17. have completed the Week 144 visit.
18. be considered, in the opinion of the investigator, to have derived benefit from MK-
1439A by Week 144 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 the study extension and have provided written informed 
consent to enter study extension 2, thus continuing until MK-1439A is locally 
available 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 
240 visit the subject must: 
21. have completed the Week 240 visit.
22. be considered, in the opinion of the investigator, to have derived benefit from MK-
1439A by Week 240 of the study.
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23. 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.
24. understand the procedures in the study extension and have provided written informed 
consent to enter study extension 3, thus continuing until MK-1439A is locally 
available or for up to approximately 2 years (whichever comes first) beyond study 
extension 2.  
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,
emtricitabine, entecavir, lamivudine or tenofovir.  
Note: Subjects may be enrolled if treatment occurred prior to the diagnosis of HIV or 
in the context of a complete regimen for HIV
4. has documented or known resistance to study drugs including MK-1439, lamivudine, 
and/or tenofovir, as defined below:
a.
Resistance to MK-1439 for the purpose of this study is considered to include the 
following NNRTI mutations (as single mutations or components of double or 
triple mutations): L100I, K101E, K101P, K103S, V106A, V106I, V106M, V108I, 
E138A, E138G, E138K, E138Q, E138R, V179L, Y181I, Y181V, Y188C, 
Y188H, Y188L, G190S, H221Y, L234I, P225H, F227C, F227L, F227V, M230L, 
M230I.   
b. Resistance to 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.
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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).
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 Child-Pugh Class C score or Pugh-Turcotte (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 (at any time during the study).
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).
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 Study Day 1 procedures and confirmation of eligibility, the site 
will contact the IVRS/IWRS for assignment of the drug to be administered.  For subjects in 
the Immediate Switch Group, the study drug will be MK-1439A.  For subjects assigned to 
the Delayed Switch Group, study treatment consists of maintaining therapy with the baseline 
regimen until a switch to MK-1439A at Study Week 24.  Trial treatment for the Immediate 
Switch Group should begin on the day of randomization.  Sites should not contact
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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 Study Day 1.  The two treatment 
regimens/groups to be used in this trial are outlined in Table 1.
Table 1
Treatment Regimens During Base Study
Immediate Switch 
Group
n = ~440
MK-1439A PO q.d.†
Delayed Switch 
Group 
n = ~220
Ritonavir-
or 
cobicistat-boosted 
PI 
(specifically, 
atazanavir, 
darunavir, or lopinavir) or cobicistat-boosted elvitegravir or an 
NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) each 
administered with 2 NRTIs from Study Day 1 to Study Week 24 and
MK-1439A PO q.d. † from Study Week 24 to Study Week 48
† MK-1439A is a single-tablet FDR containing MK-1439 100 mg, lamivudine 300 mg and TDF 300 mg.
Table 2
Treatment Regimen During Study Extensions
Immediate Switch 
Group
n = ~440
MK-1439A PO q.d.† 
Delayed Switch 
Group 
n = ~220
† MK-1439A is a single-tablet FDR containing MK-1439 100 mg, lamivudine 300 mg and TDF 300 mg.
For subjects in the Immediate Switch Group, the first dose of study treatment (MK-1439A) 
should be taken on Study Day 1 (Visit 2).  Subsequent dosing will be performed once daily 
by the subject at approximately the same time each day. 
Subjects in the Delayed Switch Group will continue their baseline regimen (provided by the 
trial site) until the switch to MK-1439A at the Study Week 24 visit.  The first dose of MK-
1439A study treatment for this Group should be taken on the day of Study Week 24 visit 
(Visit 5).  Subsequent dosing will be performed once daily by the subject at approximately 
the same time each day. 
MK-1439A is to be taken once daily without regard to food at approximately the same time 
each day. 
Please refer to the product circulars for all allowed ART therapies for recommendations 
regarding the administration of these agents.
MK-1439A for the base study and for the extensions (provided that development of 
MK-1439A is continuing) will be provided centrally by the Sponsor.  The PIs, ritonavir, 
cobicistat, elvitegravir, NNRTIs and NRTIs used during the trial in subjects randomized to 
the Delayed Switch Group will be provided by the trial site.
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All supplies indicated in Table 1 and Table 2 above will be provided centrally by the Sponsor 
or locally by the trial site, subsidiary or designee, depending on local country operational or 
regulatory requirements.
For any commercially available product that is provided by the trial site, subsidiary or 
designee every attempt will be made to source these supplies from a single lot/batch number. 
The trial site will be responsible for recording the lot number, manufacturer and expiry date 
of any locally purchased 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 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.
Dose Modification/Interruption
Dose Modification:
No dose modification is allowed during the study or the extensions.  
Dose Interruption:
Consideration should be given to interrupting study therapy for toxicity management.
For subjects in the Delayed Switch Group, during the 1st 24 weeks of the study while subjects 
are continuing on their baseline regimens, if study therapy is interrupted, all ARTs should be 
interrupted to minimize the risk of resistance, and, if appropriate, should be restarted 
concurrently at full dose.
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
Subjects will be instructed to take one MK-1439A tablet once a day (q.d.) orally with or 
without food at approximately the same time each day.
Please refer to the product circulars for all allowed ART therapies for recommendations 
regarding the administration of these agents.
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If a subject misses a dose of study drug (MK-1439A) 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
This is an open-label trial; therefore, the Sponsor, investigator and subject will know the 
treatment administered.
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 2:1 ratio to an immediate switch to MK-1439A on Study Day 1 (Immediate 
Switch Group) or a delayed switch to MK-1439A at Study Week 24 (Delayed Switch 
Group).  With ~660 subjects enrolled, ~440 and ~220 will be randomized to the Immediate 
Switch Group and the Delayed Switch Group, respectively.
Subjects will be assigned randomly according to a computer-generated allocation schedule.
Stratification
Randomization will be stratified according to the following factors:
1. The ART class used in the subject’s regimen at screening (a ritonavir-boosted PI vs.
cobicistat-boosted PI vs. cobicistat-boosted elvitegravir or an NNRTI)
2. For subjects whose regimen at screening includes a ritonavir-boosted PI: Use of lipid-
lowering therapy at Study Day 1 (yes/no)
Thus, IVRS/IWRS will randomize subjects within 4 strata as outlined in Table 3.
Table 3
Stratification
Stratum
I
Ritonavir-boosted PI 
with the use of lipid-lowering therapy at Study Day 1
II
Ritonavir-boosted PI 
without the use of lipid-lowering therapy at Study Day 1
III
Cobicistat-boosted PI 
IV
Cobicistat-boosted elvitegravir or an NNRTI 
Note: Allowed protease inhibitors (PIs) are atazanavir, darunavir, or lopinavir.
Note: Allowed non-nucleoside reverse transcriptase inhibitors (NNRTIs) are efavirenz, nevirapine, or 
rilpivirine.
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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 prior to the start of treatment in this 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 Medication/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 all applicable study 
therapies being administered to a given subject, i.e., the PIs atazanavir, darunavir, or 
lopinavir, elvitegravir, the NNRTIs efavirenz, nevirapine, or rilpivirine), the boosting agents 
ritonavir or cobicistat, and the appropriate NRTIs.
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 
is not allowed during the course of the study.  Important exceptions to this rule include:

Short courses of corticosteroids and inhaled corticosteroids (e.g., in the setting of 
exacerbation of chronic respiratory ailments or for prophylaxis for these ailments) are 
allowed. 

Intralesional or localized electron beam therapy for cutaneous Kaposi’s sarcoma is 
permitted. 
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
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.  
Depending on the type of chemotherapy, study medication may need to be interrupted 
until completion of the chemotherapy.

If a subject requires interferon-based treatment for hepatitis C after randomization, 
the subject may receive treatment and remain in the study if, in the opinion of the 
investigator, the benefits outweigh the risks.  If it is possible, interferon-based therapy 
should be deferred until the completion of the study.  
Antiretroviral therapies other than those used in the study (MK-1439A and the specific 
baseline regimens used by patients in the Delayed Switch Group) are also not permitted 
during the course of the study.  
Investigational agents must be discontinued for 30 days prior to treatment in this study and
are also 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 (cytochrome)3A-mediated oxidation. 
The medications and/or substances below are prohibited in this study because they are 
moderate or potent inducers of CYP3A, and their coadministration 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 MK1439 Interaction
Carbamazepine
Oxcarbazepine
Rifapentine
Phenobarbital
Phenytoin
Rifabutin
Rifampin
St. John’s Wort
Modafinil
Bosentan
Nafcillin
Enzalutamide
Mitotane
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Prohibited Concomitant Therapy Due to Potential Interactions with PIs, Ritonavir, 
Cobicistat, Elvitegravir or NNRTIs
The following medications are prohibited for subjects in the Delayed Switch Group, while 
receiving baseline medication, because competition for CYP3A4 by a PI (including ritonavir
used as a boosting agent), cobicistat, elvitegravir or an NNRTI could result in inhibition of 
metabolism of these drugs and create the potential for serious and/or life-threatening adverse 
events.  For complete information, refer to the most recent package circulars for all allowed 
ART therapies (as appropriate).
Prohibited Medication/
Therapy Due to PI Interaction
Alfuzosin
Amiodarone
Astemizole
Bepridil
Cisapride
Dronedarone
Ergot alkaloids (eg, ergotamine, ergonovine)
Irinotecan
Lidocaine, systemic
Lovastatin
Midazolam administered orally
Pimozide
Quetiapine
Quinidine
Ranolazine
Rifampin/Rifampicin 
Sertindole
Sildenafil (for treatment of pulmonary arterial 
hypertension)
Simvastatin
St. John’s Wort
Terfenadine
Ticagrelor
Triazolam
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Prohibited Medication/ 
Therapy Due to Ritonavir or Cobicistat Interaction
Prohibited Due to 
Ritonavir Interaction
(see combined list below)
Astemizole
Avanafil
Bepridil
Clorazepate
Clozapine
Diazepam
Eletriptan
Encainide
Estazolam
Flecainide
Flurazepam
Fusidic acid
Pethidine
Piroxicam
Propafenone
Propoxyphene
Quetiapine
Rifabutin
Terfenadine
Vardenafil
Voriconazole
Prohibited Due to 
Cobicistat Interaction
(see combined list below)
Carbamazepine
Dronedarone
Irinotecan
Phenobarbital
Phenytoin
Rifampin/Rifampicin
Prohibited Due to Ritonavir and Cobicistat 
Interaction
Alfuzosin 
Amiodarone
Cisapride 
Ergot alkaloids (eg, ergotamine, ergonovine)
Lovastatin
Midazolam administered orally
Pimozide
Quinidine 
Rivaroxaban
Simvastatin
St. John’s Wort
Sildenafil (for treatment of pulmonary arterial 
hypertension)
Triazolam administered orally
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Prohibited Medication/
Therapy Due to Elvitegravir Interaction
Carbamazepine
Phenobarbital
Phenytoin
Rifampin/Rifampicin
St. John’s Wort
Prohibited Medication/
Therapy Due to NNRTI Interaction
Astemizole
Bepridil
Boceprevir
Carbamazepine
Cisapride
Dexamethasone (if >1 dose)
Ergot derivatives (eg, ergotamine, ergonovine)
Itraconazole
Ketoconazole
Midazolam
Oxcarbazepine
Phenobarbital
Phenytoin
Pimozide
Proton pump inhibitors (eg, omeprazole, pantoprazole)
Rifampin/Rifampicin
Rifapentine
St. John’s Wort
Telaprevir
Triazolam
Voriconazole
It is the responsibility of the investigator to review the current product circulars for the 
NRTIs used in his/her patients to ensure that contraindicated and prohibited medications are 
not concomitantly administered.  
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 product circulars for all allowed ART therapies
(i.e., the PIs atazanavir, darunavir, or lopinavir, elvitegravir, the NNRTIs efavirenz, 
nevirapine, or rilpivirine, the boosting agents ritonavir or cobicistat, and the relevant NRTIs)
for drugs that are permitted in the protocol but that should be used with caution because they 
have established drug interactions with any of these agents.
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Lipid Lowering Therapy
For subjects requiring initiation or modification to lipid-lowering therapy due to toxicity, a 
fasting blood sample should be drawn prior to initiation or modification. This could be done 
via an unscheduled visit. 
Rescue Medications & Supportive Care
No rescue or supportive medications are specified to be used in this trial.
Diet/Activity/Other Considerations
Diet:
MK-1439A can be taken without regard to food and should generally be taken at 
approximately the same time each day.
Please refer to the product circulars for all allowed ART therapies for recommendations 
regarding the diet requirements for administration of these agents.
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.
Note:  Please provide additional detail for the reason the subject withdrew consent on 
the Subject Disposition eCRF.
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
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).

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.

The subject has a creatinine clearance of <50 mL/min (confirmed by repeat 
measurement) based on the following 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)

Subject has serum phosphorous < 0.32 mmol/L.

Subjects who participate in study extension 2 or study extension 3 should be 
discontinued at next scheduled visit after MK-1439A becomes locally available.
Subjects should be discontinued regardless of compliance to study therapy, if they meet the 
protocol-defined virologic failure criteria in Section 4.2.3.1.
Subjects who require discontinuation of any component of the study therapy must be 
discontinued from the trial.
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Subjects who discontinue study therapy prior to the last scheduled treatment visit should 
have an Early Discontinuation visit and 14 day follow up visit conducted.
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.  
Note that 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.  Likewise, 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).
Clinical Criteria for Early Trial Termination
Early trial termination will be the result of the criteria specified below:
There are no pre-specified criteria for terminating the trial early. 
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.
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6.0 TRIAL FLOW CHART
Flow chart A applies to the base study from screening through follow-up after the Week 48 visit, flow chart B applies to those subjects 
continuing into study extension 1 from Week 48 through follow-up after the Week 144 visit, flowchart C applies to those subjects 
continuing into study extension 2 from Week 160 through follow-up after the Week 240 visit, and flowchart D applies to those 
subjects continuing into study extension 3 from Week 256 through follow-up after the last extension 3 treatment visit.
Flow Chart A: Screening Through Week 48 Plus 14 Days Follow-up (Base Study)
Visit Number/Title:
1
2
Randomization
3
4
5
6
7
8
U
(Virologic
Failure
Confirmation)
U
(Early
Discontinuation)
99
Trial Period:
Screening
Treatmentp
Post-
treatmentq
TRIAL PROCEDURES
Screen
Fasting
Day 1 a
WK 
4
WK 
12
Fasting
WK 24
WK 
28
WK 
36
Fasting
WK 48
1 to 4 weeks
after initial
virologic failure
At time of
Discontinuation
14 Day
Follow-up
Administrative Procedures
Informed Consent
x
x r
Informed Consent for Future Biomedical 
Research b
x
Inclusion/Exclusion Criteria
x
x
Medical History c
x
Provide Subject Identification Card
x
Concomitant Medication Review
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
Dispense Study Therapyd
x e
x e
x e
x
x
x
x r
Provide/Review Study Medication Diary
x
x
x
x
x
x
x
x
Clinical Procedures/Assessments
Full Physical Examination
x
Directed Physical Examination
x
x
x
x
x
x
x
x
x
Height
x
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Visit Number/Title:
1
2
Randomization
3
4
5
6
7
8
U
(Virologic
Failure
Confirmation)
U
(Early
Discontinuation)
99
Trial Period:
Screening
Treatmentp
Post-
treatmentq
TRIAL PROCEDURES
Screen
Fasting
Day 1 a
WK 
4
WK 
12
Fasting
WK 24
WK 
28
WK 
36
Fasting
WK 48
1 to 4 weeks
after initial
virologic failure
At time of
Discontinuation
14 Day
Follow-up
Vital Signs (including pulse rate, blood 
pressure, respiratory rate, and body 
temperature) and weight
x
x
x
x
x
x
x
x
x
x
Adverse Events Monitoring
x
x
x
x
x
x
x
x
x
Birth Control Confirmation
x
x
x
x
x
x
x
x
x
x
12-Lead Electrocardiogram (ECG) (local)
x f o
Patient Reported Outcomes g
x
x
x
x
x
x
Assess Subject Eligibility for Extension 1 r
x
Laboratory Procedures/Assessments
Collect Blood for Safety Laboratory Tests 
(Hematology/Chemistry) h
x
x i
x
x
x i
x
x
x i
x
x
x
Serum Pregnancy Test j
x
Urine Pregnancy Test (if applicable) j
x f
x
x
x
x
x
x
x
x
Hemostatic Function Test k
x
HIV/Hepatitis Screen l
x
Virology Test Plasma HIV viral RNA 
quantification test (Abbott Real Time HIV-
1)
x
x
x
x
x
x
x
x
x
x
x
Collect Blood for CD4 Cell Count
x
x
x
x
x
Viral Resistance Test (Plasma)
x
x
x
x
x
x
x
x
x m
Collect Blood for MK1439 PK n
x
x
x
x
x
Collect Blood for Geneticsb
x
Collect Plasma for Future Biomedical 
Research b
x
x
x
a. Prior to the first dose on Day 1.
b. 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 FBR consent.  Plasma samples for FBR should be collected at Study Day 1, and Study Weeks 24 and 48.
c. Includes smoking history, pretreatment HIV RNA, and, for subjects whose regimen at screening includes a boosted PI or cobicistat-boosted elvitegravir, historical 
genotype.
d. IVRS/IWRS will be used to allocate drug and to manage distribution of MK-1439A. 
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Visit Number/Title:
1
2
Randomization
3
4
5
6
7
8
U
(Virologic
Failure
Confirmation)
U
(Early
Discontinuation)
99
Trial Period:
Screening
Treatmentp
Post-
treatmentq
TRIAL PROCEDURES
Screen
Fasting
Day 1 a
WK 
4
WK 
12
Fasting
WK 24
WK 
28
WK 
36
Fasting
WK 48
1 to 4 weeks
after initial
virologic failure
At time of
Discontinuation
14 Day
Follow-up
e. For the subjects in the Delayed Switch Group IVRS/IWRS will be called to register the subject’s visit; no MK-1439A will be dispensed at these visits since they will 
continue on their ongoing baseline regimen.
f.
Results of test must be available prior to randomization and prior to the subject’s first dose of medication.
g. Patient Reported Outcomes will be done on Study Day 1, Study Weeks 4, 24, 28, 48 and at discontinuation (if applicable) for all subjects (Immediate and Delayed Switch 
Treatment Groups). There are a total of four questionnaires in the study (IBS-QOL, HIV-SI, WPAI and EuroQol EQ-5D-5L). Only at sites in the United States (US), 
subjects, whose native language is either English or Spanish, will be eligible to complete all four questionnaires. At all other sites outside the US, subjects will be eligible 
to complete the questionnaires only if language translations are available in the subject’s native language for all four questionnaires. The questionnaires will be 
administered in the following sequential order: IBS-QOL, HIV-SI, WPAI and EuroQol EQ-5D-5L.
h. Refer to Table 4 for listing of specific blood safety tests.
i.
Fasting for at least 8 hours. Fasting is required at these visits for lipids measurement. For subjects requiring initiation or modification to lipid lowering therapy due to 
toxicity, a fasting blood sample should be also drawn prior to initiation or modification via an unscheduled visit. 
j.
For women of childbearing potential.
k. Hemostatic Function Test includes: Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) and International Normalized Ratio (INR).
l.
HIV/Hepatitis Screening Tests include: 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.
m. 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 
need not be collected again at the discontinuation visit. All other early discontinuation tests should be performed at the early discontinuation visit.
n. Blood samples will be collected from all subjects in both treatment groups at Randomization (Study Day 1) and at Study Week 48. In addition, blood samples for PK will 
also be collected from subjects in the Immediate Switch Group at Study Weeks 4, 12, and 24. 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).
o. 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). 
p. Visit window periods are approximately +/- 3 days for the Week 4 to Week 28 visits and approximately +/- 7 days for the Week 36 and Week 48 visits.  The timing of each 
visit is relative to the randomization (Day 1) visit.  Every attempt must be made to keep subjects on schedule.
q.
The visit window period for the Post study 14 day follow up visit is approximately – 2 to 0 days.  This follow-up assessment applies only to subjects who complete (or 
discontinue from) the base study and do not enter study extension 1.
r.
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,
immediately enter study extension 1 and be dispensed MK-1439A.
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Flow Chart B: Week 64 Through Week 144 Plus 14 Days Follow-up (Study Extension 1)
Visit Number/Title:
9 a
10
11
12
13
14
U
(Virologic
Failure
Confirmation)
U
(Extension
Early
Discontinuation)
99
Trial Period:
Extension: Treatment b
Post-
Treatment c
TRIAL PROCEDURES
Wk 64
Wk 80
Fasting 
Wk 96
Wk 112
Wk 128
Fasting 
Wk 144
1 to 4 weeks 
after initial 
virologic failure
At time of
Discontinuation
14 Day
Follow-up
Administrative Procedures
Informed Consent
x d
Concomitant Medication Review
x
x
x
x
x
x
x
x
Register Study Visit via Interactive Voice/Web 
Response System (IVRS/IWRS)
x
x
x
x
x
x
x
Dispense Study Therapy e
x
x
x
x
x
x
Provide/Review Study Medication Diary
x
x
x
x
x
x
x
Assess Subject Eligibility for Study Extension 2 d
x 
Clinical Procedures/Assessments
Directed Physical Examination
x
x
x
x
x
x
x
x
Vital Signs (including pulse rate, blood pressure, 
respiratory rate, and body temperature) and 
weight
x
x
x
x
x
x
x
x
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
Collect Blood for Safety Laboratory Tests 
(Hematology/Chemistry) f
x
x 
x g
x
x
x g
x
x
x
Urine Pregnancy Test (if applicable) h
x
x
x
x
x
x
x
x
Virology Test Plasma HIV viral RNA 
quantification test (Abbott Real Time HIV-1)
x
x
x
x
x
x
x
x
x
Collect Blood for CD4 Cell Count
x
x
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Visit Number/Title:
9 a
10
11
12
13
14
U
(Virologic
Failure
Confirmation)
U
(Extension
Early
Discontinuation)
99
Trial Period:
Extension: Treatment b
Post-
Treatment c
TRIAL PROCEDURES
Wk 64
Wk 80
Fasting 
Wk 96
Wk 112
Wk 128
Fasting 
Wk 144
1 to 4 weeks 
after initial 
virologic failure
At time of
Discontinuation
14 Day
Follow-up
Viral Resistance Test (Plasma)
x
x i
a. Subjects who enter study extension 1 are considered enrolled in the extension upon providing written informed consent at the Week 48 study visit.
b.
The visit windows are approximately +/- 14 days for all visits from Week 64 through Week 144.  The timing of each visit is relative to the randomization (Day 1) visit.  
Every attempt must be made to keep subjects on schedule.
c. The visit window for the post-study 14-day follow-up visit is approximately – 2 to 0 days.
d. 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.
e. IVRS/IWRS will be used to allocate drug and to manage distribution of MK-1439A.
f.
Refer to Table 4 for listing of specific blood safety tests.
g. Fasting for at least 8 hours. Fasting is required at these visits for lipids measurement. For subjects requiring initiation or modification to lipid-lowering therapy due to 
toxicity, a fasting blood sample should be also drawn prior to initiation or modification via an unscheduled visit.
h. For women of childbearing potential.
i.
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 
need not be collected again at the discontinuation visit. All other early discontinuation tests should be performed at the early discontinuation visit.
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Flow Chart C: Week 160 Through Week 240 a Plus 14 Days Follow-up (Study Extension 2)
Visit Number/Title:
15 b
16
17
18
19
20
U
(Extension
Early
Discontinuation)
99
Trial Period:
Extension: Treatment c
Post-
Treatment d
TRIAL PROCEDURES
Wk 160
Wk 176
Wk 192
Wk 208
Wk 224
Wk 240
At time of
Discontinuation
14 Day
Follow-up
Administrative Procedures
Informed Consent
xe
Register Study Visit via Interactive Voice/Web 
Response System (IVRS/IWRS)
x
x
x
x
x
x
x
Dispense Study Therapy f
x
x
x
x
x
xe
Assess Subject Eligibility for Study Extension 
3e
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 Test (if applicable) g
x
x
x
x
x
x
x
x
a. The total duration is dependent on when MK-1439A becomes locally available, with a maximum total duration of treatment of 240 weeks.  Subjects should discontinue at 
the next scheduled visit after MK-1439A becomes locally available in the market.
b. Subjects who enter study extension 2 are considered enrolled in the extension upon providing written informed consent at the Week 144 study visit.
c. The visit windows are approximately +/- 14 days for all visits from Week 160 through Week 240.  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. 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 at 
the Week 240 study visit, immediately enter study extension 3 and be dispensed MK-1439A.
f.
IVRS/IWRS will be used to allocate drug and to manage distribution of MK-1439A.
g. For women of childbearing potential.
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Flow Chart D: Week 256 Through Week 336 a Plus 14 Days Follow-up (Study Extension 3)
Visit Number/Title:
21 b
22
23
24
25
26
U
(Extension
Early
Discontinuation)
99
Trial Period:
Extension: Treatment c
Post-
Treatment d
TRIAL PROCEDURES
Wk 256
Wk 272
Wk 288
Wk 304
Wk 320
Wk 336
At time of
Discontinuation
14 Day
Follow-up
Administrative Procedures
Register Study Visit via Interactive Voice/Web 
Response System (IVRS/IWRS)
x
x
x
x
x
x
x
Dispense Study Therapy 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 Test (if applicable) f
x
x
x
x
x
x
x
x
a.
The total duration is dependent on when MK-1439A becomes locally available, with a maximum total duration of treatment of 336 weeks.  Subjects should discontinue at 
the next scheduled visit after MK-1439A becomes locally available in the market.
b.
Subjects who enter study extension 3 are considered enrolled in the extension upon providing written informed consent at the Week 240 study visit.
c.
The visit windows are approximately +/- 14 days for all visits from Week 256 through Week 336.  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 MK-1439A.
f.
For women of childbearing potential.
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7.0 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.
7.1.1.1.1 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.
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7.1.1.1.2 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 the Future Biomedical Research sub-trial.  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 (13 to 16, Section 5.1.2) are 
to be reviewed at the Week 48 study visit.  For subjects who wish to continue into study 
extension 2, the additional inclusion criteria (17 to 20, Section 5.1.2) are to be reviewed at 
the Week 144 study visit.  For subjects who wish to continue into study extension 3, the 
additional inclusion criteria (21 to 24, Section 5.1.2) are to be reviewed at the Week 240 
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 Acquired Immunodeficiency Syndrome (if applicable) and the year diagnosed.  
If the subject has been previously diagnosed with any Acquired Immunodeficiency 
Syndrome (AIDS) defining conditions, or CD4 <200, the condition as well as a 
corresponding medical history of Acquired Immunodeficiency Syndrome must be reported.  
Additionally, the subject’s pre-treatment HIV viral load (RNA) and historical genotypes (for 
those subjects whose ART regimen at screening is a boosted PI or cobicistat-boosted 
elvitegravir) should be documented, and the subject’s history of smoking should be obtained 
and recorded on the appropriate eCRF.
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Prior and Concomitant Medications Review
7.1.1.5.1 Prior Medications
The investigator or qualified designee will review prior medication use, record all prior 
medication taken by the subject within 30 days before starting the trial and all prior 
antiretroviral agents taken for treatment of HIV infection.
Investigational agents must be discontinued for 30 days prior to receiving study therapy.
7.1.1.5.2 Concomitant Medications
The investigator or qualified designee will record medication, if any, taken by the subject 
during the trial.
Lipid Lowering Therapy
For subjects requiring initiation or modification to lipid-lowering therapy due to toxicity or 
improvement, a fasting blood sample should be drawn prior to initiation or modification. 
This could be done via an unscheduled visit.
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 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 Medication Diary 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 study medication diary to 
be completed during the study period. The study coordinator will be responsible for entering 
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the subject’s identification (screening and randomization number) before giving the study 
medication diary to the subject. The subject should follow the instructions on the study 
medication diary for recording all study drugs.  Aside from the initial information entered by 
the study coordinator, only the subject should enter information on the study medication 
diary.  The subject is to return the completed study medication diary at each scheduled visit.  
The study coordinator will be responsible for reviewing the study medication diary for 
completeness and accuracy with the subject.  Only the subject shall make any changes to the 
entries on the diary.  The subject will initial the diary to confirm that the information is 
accurate.  The study coordinator will be responsible for transferring the appropriate 
information from the diary onto the appropriate case report form.
Rigorous monitoring is especially important during the early part of the study, specifically 
between the Day 1 and Study Week 4 visits to ascertain problems with non-compliance as 
early as possible, to assess whether subjects are 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 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 following 4 questionnaires at Study Day 1, Study Weeks 4, 24,
28, 48 or the Early Discontinuation visit if patient discontinues prior to Study Week 48:
1) Irritable Bowel Syndrome - Quality Of Life (IBS-QoL)
The IBS-QoL is a self-administered questionnaire, initially developed and validated for use 
in patients with IBS, that has been used in HIV-infected patients where it has been shown to 
offer specificity for identifying GI-related QoL measures.  The IBS-QoL questionnaire 
consists of 34 items, used to derive an overall score, plus eight sub-scale scores relating to 
categories of dysphoria, interference with activity, body image, health worry, food 
avoidance, social reaction, sexual issues, and relationships.  The IBS-QOL has been 
previously been used to measure the impact of gastrointestinal (GI) complications of 
treatment on patient QoL as related to the effects of boosted protease inhibitor (PI)-based 
antiretroviral regimens.
2) HIV Symptom Index (HIV-SI or SDM)
The HIV-SI is a validated, self-administered, 20-item health-state questionnaire for use in 
clinical care and research among patients with HIV infection in order to identify and address 
common and bothersome symptoms associated with HIV and its treatment.  The index was 
developed based upon prior reports of symptom frequency and bother and expert opinion and 
has a four-week recall period.
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3) Work Productivity and Activity Impairment Questionnaire (WPAI)
The 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.
4) EuroQol Five Dimensional Descriptive System, Five Level Version (EQ-5D-5L)
The EuroQol EQ-5D-5L is a validated, standardized 5-item health-state questionnaire 
applicable to a wide range of health conditions and treatments and used to assess health 
outcomes [7, 8].  The five health state dimensions include: mobility, self-care, usual 
activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no 
problems, slight problems, moderate problems, severe problems, and extreme problems.
Administration
Subjects are to complete the questionnaires on their own at the site using an electronic data 
capture tool at the beginning of the appropriate study visit (see study 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.  Only at sites in the United States (US), subjects, whose native language is 
either English or Spanish, will be eligible to complete all four questionnaires: IBS-QOL, 
HIV-SI, WPAI and EQ-5D-5L. At sites outside the US, subjects will be eligible to complete 
the questionnaires only if language translations are available in the subject’s native language 
for all four of these questionnaires.  The questionnaires will be administered in the following 
sequential order: IBS-QoL, HIV-SI, WPAI, EQ-5D-5L.
Clinical Procedures/Assessments
Physical Examination
All physical examinations should be performed as indicated in the study flow chart 
(Section 6.0). All physical examinations must be performed by the principal investigator or 
sub-investigator (physician, physician assistant or nurse practitioner). 
A complete (full) physical examination (including vital signs [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, 
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 
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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 study 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, 
should be assessed as indicated in the study flow chart (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 study flow chart 
(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.
Adverse Events
If a subject has been diagnosed with an AIDS defining condition following randomization, 
the condition must also be reported as an AE.
Due to the use of lamivudine and tenofovir in this trial, subjects should be monitored for 
symptoms of hyperlactatemia.
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Details on assessing and recording adverse events can be found in Section 7.2.
Toxicity Management
Guidelines grading the severity of laboratory adverse events based on Division of Acquired 
Immunodeficiency Syndrome (DAIDS) criteria for grading severity of adverse events 
(Appendix 12.7). 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 re-challenge 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 re-challenge consent is needed prior to re-
initiation of study therapy.  If advance approval of re-challenge is not required by local 
regulations, the Independent Ethics Committee/Institutional Review Board 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. In general, when a clinical or laboratory adverse 
event occurs which requires interruption of study therapy, all study drugs should be 
interrupted to avoid having a subject receive suboptimal therapy which may predispose them 
to the development of resistance. In general, all study medications should be restarted 
concomitantly at full dose. 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.
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. 
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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 Study Day 1 visit prior to randomization.  Urine 
pregnancy tests must also be subsequently done at each study visit, including the 
Discontinuation and 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 Urinalysis)
Laboratory tests (hematology, chemistry and other) which are to be performed during the
base study and study extension 1 of the trial are specified in Table 4.
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Table 4
Laboratory Tests
Hematology
Chemistry
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 antigen 3
Erythrocyte Mean 
corpuscular volume
Total Bilirubin  
Hepatitis B Virus surface antibody 3
CD4% and Absolute CD4/ 
Lymphocytes
Direct Bilirubin
Hepatitis B e-Antigen 3
CD8% and Absolute 
CD8/Lymphocytes
Indirect Bilirubin
Hepatitis C Antibody 3
CD4/CD8 ratio
Amylase
Plasma hepatitis C virus PCR quantitative4
White Blood cell Count
Lipase
Enzyme immunoassay HIV antibody (with 
confirmation WB)3
WBC Differential 
Leukocytes
Glucose, Fasting 1
HIV viral RNA Quantification
Glucose, Non-Fasting 2
Serum -human chorionic gonadotropin 
(hCG) test5
Blood Urea Nitrogen
Urine -human chorionic gonadotropin 
(hCG) test6
Creatinine8
HIV Viral resistance7
Calcium
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 (Study Day 1) and the Study Weeks 24 and 48 visits and, for subjects who continue into 
study extension 1, at the Week 96 and 144 visits. Subjects should be fasting for at least 8 hours. 
2.
Perform at the Screening visit and the Study Weeks 4, 12, 28 and 36 visits and, in study extension 1, at the Study 
Week 64, 80, 112 and 128 visits. 
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.
Perform at Day 1, all scheduled study visits (except the Screening and Post-study 14-day follow up visits), the 
Virologic Failure Confirmation and the Early Discontinuation visit (if not collected at Virologic Failure Confirmation 
visit).
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.
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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 HIV viral resistance testing at the Study Day 1 visit, at 
all scheduled study visits in the base study (except the Screening and Post-Study 14-day 
follow up visits), and at the Virologic Failure Confirmation visit or the Early Discontinuation 
Visit (if not already obtained at Virologic Failure Confirmation visit) in both the base study 
and study extension 1.  Baseline (Day 1) samples will be analyzed in cases of virologic 
failure and/or discontinuation, provided the viral load meets the criterion for resistance 
testing (>400 copies/mL).  Amplifiable virus to screen for resistance would not be expected 
for subjects whose viral load was BLoQ at entry.  All resistance testing in the base study and 
in study extension 1 will be performed by a central laboratory.
CD4 Cell Counts
CD4 cell count (absolute and percentage) will be determined at Study Day 1, and at Study 
Weeks 12, 24, 36 and 48; for subjects who continue into study extension 1, CD4 cell count 
will also be determined at the Study Week 96 and 144 visits.  Testing 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 (MK-1439A) 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 (MK-1439A) prior to the 
collection of the PK sample will also be recorded on the appropriate eCRF.
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)
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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:  For subjects in the Immediate Switch Group at Study Week 24 (Visit 5) and for both 
treatment groups at Study Week 48 (Visit 8), two 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 study drug (MK-1439A) 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.  
Table 5
Pharmacokinetic Sampling Timepoints
Visit 
Number
Study Day/Week
Time Relative to MK1439-A dose
2
Day 1
(for all subjects)
Sample to be collected predose
3
Week 4
(for subjects in the Immediate 
Switch group only)
Sample to be collected predose
4
Week 12
(for subjects in the Immediate 
Switch group only)
Sample to be collected pre or postdose
5
Week 24
(for subjects in the Immediate 
Switch group only)
Sample to be collected predose and within 0.5 to 2 hours 
postdose (Patient should remain fasting until postdose PK 
sample is collected).
8
Week 48
(for all subjects)
Sample to be collected predose and within 0.5 to 2 hours 
postdose (Patient should remain fasting until 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 research

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 
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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.
7.1.4.1.1 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 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
This is an open label trial; there is no blinding for this trial.
Calibration of Critical 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 trial 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 
trial site.
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 
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discuss with each potential subject the study, its requirements, and its restrictions.  The study 
screening period is 30 days.

All procedures listed for the Screening visit (Visit 1) in the Study Flow Chart  (Section 
6.0) must be completed and the subject’s eligibility confirmed by the investigator prior to 
the subject’s randomization and drug administration on Study Day 1.

Blood will be collected for safety laboratory evaluations, HIV-1 RNA quantification, 
hemostatic function test and hepatitis screening.  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.

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 (Visit 2 to Visit 26)
Randomization - Study Day 1 (Visit 2)

Procedures listed for Study Day 1 (Visit 2) on the Study Flow Chart (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 pretreatment (Day 1) testing/procedures will be 
performed.  If the urine pregnancy test result is positive, the subject must not be 
randomized. 

Blood will be collected for safety laboratory evaluations, HIV-1 RNA quantification, 
CD4 cell counts, HIV viral resistance and PK measurements.  Subjects will be required to 
fast for at least 8 hours prior to the study visit.  These samples will be sent to the 
appropriate central laboratory(ies) following the procedure(s) set forth in the manual(s).

Blood and plasma samples for future biomedical research will be also collected from all 
subjects from whom appropriate consent has been obtained. 

Following completion of the Study Day 1 pretreatment procedures and confirmation of 
eligibility, the site pharmacist or study coordinator will access the IVRS/IWRS for 
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assignment of the drug to be administered. Site staff should not access 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.

Subjects randomized to the Immediate Switch Group will receive a 4-week supply of 
study medication on Day 1 (Visit 2). Subjects will be instructed to take their first dose of 
study medication on the same day as the Day 1 study visit. 

Subjects randomized to the Delayed Switch Group will not receive study medication on 
Day 1. They will continue their ongoing baseline regimen and will receive study drug at 
Study Week 24.  

The investigator/study coordinator will give a study medication diary to all subjects in 
both treatment groups. Subjects will start completion of the diary on Day 1 and continue 
throughout the treatment period.  The subjects in the Delayed Switch group will also 
complete a study medication diary to include their ongoing baseline regimen. The site 
must ensure that the subject is properly trained and comfortable with completing the 
medication diary prior to leaving the clinic.
Drug Administration
Only subjects in the Immediate Switch Group will be dispensed study drug, MK-1439A at 
this visit. 
Subjects will be instructed to take the study medication as follows:
Subjects randomized to the Immediate Switch Group will be instructed to take one tablet 
from the study medication (MK-1439A) bottle once a day (q.d.) orally, with or without food 
at approximately the same time each day.  Tablets must be kept in the bottle prior to taking 
study medication since the formulation being used in this study is moisture sensitive.
Note: In general study medication should be taken directly from the study bottle.  
Subjects randomized to the Delayed Switch Group will continue their baseline regimen as 
usual.
Week 4 (Visit 3) and Week 12 (Visit 4)

All procedures for Study Week 4 (Visit 3) and Study Week 12 (Visit 4) listed on the 
Study Flow Chart (Section 6.0) should be performed. 

Blood will be collected for safety laboratory evaluations, HIV-1 RNA quantification, 
HIV viral resistance and CD4 cell counts (only at Study Week 12 visit) at the time points 
specified on the Study Flow Chart.  These samples will be sent to the appropriate central 
laboratory(ies) following the procedure(s) set forth in the manual(s).
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
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. 

For subjects in the Immediate Switch Group a blood sample for PK measurement will 
also be collected. 

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.  
The primary source of adherence data, however, will be the subjects study medication 
diary.

Site staff will access the IVRS/IWRS for assignment of the drug to be administered and 
for registration of visits. Subjects randomized to the Immediate Switch Group will
receive an 8-week supply of study drug at Study Week 4 (Visit 3); and a 12-week supply 
at Study Week 12 (Visit 4).

At each treatment visit the study coordinator and subject will review the study medication 
diary information. 
Week 24 (Visit 5):
Subjects in the Delayed Switch Group, who have been on the ongoing baseline regimen, will 
be switched to MK-1439A at this visit. 

All procedures for Study Week 24 (Visit 5) listed on the Study Flow Chart (Section 6.0) 
should be performed. 

Blood will be collected for safety laboratory evaluations, HIV-1 RNA quantification, 
HIV viral resistance and CD4 cell counts at the time points specified on the Study Flow 
Chart.  Subjects will be required to fast for at least 8 hours prior to the study visit.  These 
samples will be sent to the appropriate central laboratory(ies) following the procedure(s) 
set forth in the manual(s).

A plasma sample for future biomedical research will be also collected from all subjects.

For subjects in the Immediate Switch Group a blood sample for PK measurement will 
also be collected. 

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.  
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The primary source of adherence data, however, will be the subject’s study medication 
diary.

Site staff will access the IVRS/IWRS for assignment of the drug to be administered and 
for registration of visits. 
Subjects randomized to both treatment groups will receive a 4-week supply of study 
medication (MK-1439A) at this visit. Subjects in the Delayed Switch Group will be 
instructed to take one tablet from the study medication bottle once a day (q.d.) orally, 
with or without food at approximately the same time each day.  Tablets must be kept in 
the bottle prior to taking study medication since the formulation being used in this study 
is moisture sensitive. 
Note: In general study medication should be taken directly from the study bottle.  

Study coordinator and subject will review the study medication diary information.
Week 28 (Visit 6), Week 36 (Visit 7) and Week 48 (Visit 8)

All procedures for Study Week 28 (Visit 6), Week 36 (Visit 7) and Week 48 (Visit 8) 
listed on the Study Flow Chart (Section 6.0) should be performed. 

Blood will be collected for safety laboratory evaluations, HIV-1 RNA quantification and
HIV viral resistance at the time points specified on the Study Flow Chart.  Sample for 
CD4 counts will also be collected at Study Weeks 36 and 48 visits. Subjects will be 
required to fast for at least 8 hours prior to Study Week 48 study visit.  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. 

For all subjects (in both treatment groups) blood samples for PK measurements will be 
collected on Study Week 48 visit (see Section 7.1.3.7 for details). 

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.  
The primary source of adherence data, however, will be the subjects study medication 
diary.

Site staff will access the IVRS/IWRS for assignment of the drug to be administered and 
for registration of visits. Subjects will receive an 8-week supply of study drug at Study 
Week 28 (Visit 6), a 12-week supply at Study Week 36 (Visit 7) and, for subjects who 
are considered eligible and elect to enter study extension 1, a 16-week supply at Study 
Week 48 (Visit 8).
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
At each study visit the study coordinator and subject will review the study medication 
diary information. 
Week 64 (Visit 9) Through Week 144 (Visit 14)

All procedures for Study Week 64 (Visit 9), Week 80 (Visit 10), Week 96 (Visit 11),
Week 112 (Visit 12), Week 128 (Visit 13), and Week 144 (Visit 14) listed on the Study 
Flow Chart (Section 6.0) should be performed. 

Blood will be collected for safety laboratory evaluations and HIV-1 RNA quantification 
at the time points specified in the Study Flow Chart.  Samples for CD4 counts will also 
be collected at the Study Week 96 and 144 visits.  Subjects will be required to fast for at 
least 8 hours prior to the Study Week 96 and 144 visits.  Samples for HIV viral resistance 
will be collected only at the virologic failure confirmation visit or, for subjects who 
discontinue due to any other reason, at the discontinuation visit.  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. 

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.  
The primary source of adherence data, however, will be the subject’s study medication 
diary.

Site staff will access the IVRS/IWRS for registration of visits. Subjects will receive a
16-week supply of study drug at each study visit through Week 128.

At each study visit the study coordinator and subject will review the study medication 
diary information. 
Week 160 (Visit 15) Through Week 240 (Visit 20)

All procedures for Study Week 160 (Visit 15), Week 176 (Visit 16), Week 192 (Visit 17), 
Week 208 (Visit 18), Week 224 (Visit 19), and Week 240 (Visit 20) listed on the Study 
Flow Chart (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.
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
Site staff will access the IVRS/IWRS for registration of visits.  Subjects will receive a 
16-week supply of study drug at each study visit through Week 224.

For subjects who continue into study extension 3, a 16-week supply of study drug will be
dispensed at Week 240.
Week 256 (Visit 21) Through Week 336 (Visit 26)

All procedures for Study Week 256 (Visit 21), Week 272 (Visit 22), Week 288 (Visit 23), 
Week 304 (Visit 24), Week 320 (Visit 25), and Week 336 (Visit 26) listed on the Study 
Flow Chart (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.  Subjects will receive a 
16-week supply of study drug at each study visit through Week 320.
Virologic Failure Confirmation Visit (Baseline 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 Study Flow Chart should be performed.
Protocol-defined virologic failure (PDVF) is defined as subjects who have two consecutive 
measurements of HIV-1 RNA ≥ 50 copies/mL at least one week apart.
The virologic failure confirmation visit should be done between one and four weeks (≥1 to 
≤4) 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 (Baseline 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 Study Flow Chart should be performed.
At a minimum, the following information should be collected when a subject 
discontinues:  
o
The reason the subject discontinued
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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
o
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. 
Post-Trial

Following the completion of study therapy (in the base study or study extensions) 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 Study Flow Chart (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.
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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 
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 of study medication higher than two times 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 
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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.
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 6 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 
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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. 
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).
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Evaluating Adverse Events
An investigator who is a qualified physician will evaluate all adverse events with respect to 
the elements outlined in Table 6.  The investigator’s assessment of causality is required for 
each adverse event.  Refer to Table 6 and Appendix 12.7 for additional instructions for
evaluating adverse events.
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Table 6
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
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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.)
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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.
8.0 STATISTICAL ANALYSIS PLAN
This section outlines the statistical analysis strategy and procedures for the study.  If, after 
the study has begun, but prior to the database lock, 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 the 
database lock, will be documented in a supplemental Statistical Analysis Plan (sSAP) and 
referenced in the Clinical Study Report (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.  
Statistical Analysis Plan Summary
Key elements of the statistical analysis plan (SAP)
are summarized below; the 
comprehensive plan is provided in Sections 8.2 through 8.12.  Analysis of data from the 
study extensions does not require changes to the SAP.  All data from study extension 1 will 
be summarized descriptively only and will be described in the sSAP.  These data will be 
summarized separately from data generated from the base study. Serious adverse event data 
from study extension 2 and study extension 3 will be summarized separately.
Study Design Overview
A Phase 3 Multicenter, Open-Label, Randomized Study to Evaluate a Switch 
to MK-1439A in HIV-1-Infected Subjects who are Virologically Suppressed 
on a Regimen of a Ritonavir-boosted Protease Inhibitor and 2 Nucleoside 
Reverse Transcriptase Inhibitors (NRTIs); Amendment to Include Switches 
From Additional Antiretroviral Regimens
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Treatment Assignment
Approximately 660 subjects will be stratified by the ART class used in their 
regimen
at screening
(a ritonavir-boosted PI, specifically atazanavir, 
darunavir, or lopinavir vs. a cobicistat-boosted PI vs. cobicistat-boosted 
elvitegravir or an NNRTI, specifically, efavirenz, nevirapine, or rilpivirine) 
and, for subjects whose regimen at screening includes a ritonavir-boosted PI,
by use of lipid lowering therapy at Study Day 1.  The 4 strata are: ritonavir-
boosted PI with lipid-lowering therapy at Day 1, ritonavir-boosted PI 
without
lipid-lowering therapy at Day 1, cobicistat-boosted PI, and 
cobicistat-boosted elvitegravir or an NNRTI. Subjects will be randomized in 
a 2:1 ratio to an immediate switch to MK-1439A on Study Day 1 (Immediate 
Switch Group) or delayed switch to MK-1439A at Study Week 24 (Delayed 
Switch Group).  The Delayed Switch group will continue their baseline 
regimen until the time of switch to MK-1439A at Study Week 24.  The total 
duration of treatment for a given subject who does not continue into study 
extension 1 is 48 weeks, for subjects who continue into study extension 1, 
144 weeks, for subjects who continue into study extension 2, 240 weeks, and 
for subjects who continue into study extension 3, a maximum of 336 weeks.
Analysis Populations
Efficacy: Treatment Full Analysis Set (FAS)
Safety: All Subjects as Treated (ASaT)
Primary Endpoint(s)
Proportion of subjects maintaining HIV-1 RNA <50 copies/mL by the Abbott 
RealTime HIV-1 Assay at Study Week 48 in the Immediate Switch Group 
and at Study Week 24 in the Delayed Switch Group
Key Secondary Endpoints
For subjects with a regimen at screening of a ritonavir-boosted PI: Change 
from baseline in fasting LDL-C at Study Week 24
Change from baseline in fasting non-HDL-C at Study Week 24
For all subjects: Proportion of subjects maintaining HIV-1 RNA <50
copies/mL by the Abbott RealTime HIV-1 Assay at Study Week 24 in 
both treatment groups
Proportion of subjects maintaining HIV-1 RNA BLoQ by the Abbott 
RealTime HIV-1 Assay (<40 copies/mL) at Study Week 48 in the 
Immediate Switch Group vs Study Week 24 in the Delayed Switch Group 
and at Study Week 24 in both treatment groups
Change from baseline in CD4 cell counts at Study Week 48 in the 
Immediate Switch Group and at Study Week 24 in the Delayed Switch 
Group
Change from baseline in CD4 cell counts at Study Week 24 in both 
treatment groups
General safety and tolerability by Study Week 24
PK of MK-1439 and the PK/PD association
Proportion of subjects with HIV-1 RNA ≥50 copies/mL by the Abbott 
RealTime HIV-1 Assay at Study Week 48 in the Immediate Switch Group 
and at Study Week 24 in the Delayed Switch Group
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Statistical Methods for Key 
Efficacy Analyses
The primary hypothesis will be assessed based on the proportion of subjects 
maintaining HIV-1 RNA <50 copies/mL by the Abbott RealTime HIV-1 
Assay at Study Week 48 in the Immediate Switch Group and at Study Week 
24 in the Delayed Switch Group. 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 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. Only 2 strata will be used for 
this analysis: ritonavir-boosted or cobicistat-boosted PI vs. cobicistat-boosted 
elvitegravir or NNRTI as a component of the baseline regimen. The use of 
lipid-lowering therapy is not expected to be associated with virologic 
response; therefore, stratification by use of lipid lowering therapy will not be 
included in the analyses of virologic response.
For the primary hypothesis, an immediate switch to MK-1439A on Study 
Day 1 will be concluded non-inferior to continuation of the baseline regimen, 
if the lower bound of the two-sided 95% CI for the difference in the 
proportion of subjects maintaining HIV-1 RNA <50 copies/mL by the Abbott 
RealTime HIV-1 Assay (Immediate Switch Group minus Delayed Switch 
Group) is greater than -8 percentage points. It can be further concluded that 
an immediate switch to MK-1439A is superior to continuation of the baseline 
regimen if the lower bound of the two-sided 95% CI for the difference in 
response rates (Immediate Switch Group minus Delayed Switch Group) 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 Study Week 24 for both 
treatment groups.
Statistical Methods for Key 
Safety Analyses
Tier I: Lipids (secondary safety hypothesis):
For subjects on a stable antiretroviral regimen of a ritonavir-boosted PI + 
2 NRTIs at screening, the change from baseline in fasting lipids (total 
cholesterol, LDL-C, non-HDL-C, and triglycerides) at Study Week 24 will be 
analyzed using ANCOVA models adjusted by baseline lipid level, use of 
lipid-lowering therapy at Study Day 1 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) by Study Week 24: (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 1% of subjects in at 
least one treatment group. These analyses will be performed using the 
Miettinen and Nurminen method [9], an unconditional, asymptotic method.
Interim Analyses
No interim analyses are planned for this study.  
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Multiplicity
The following hypotheses will be tested sequentially at the one-sided Type 1 
error rate of 2.5% in the following order:  
1)
Primary efficacy hypothesis testing non-inferiority at Study Week 48 for 
the Immediate Switch Group vs Study Week 24 for the Delayed Switch 
Group
2)
Secondary safety hypothesis for LDL-C
3)
Secondary safety hypothesis for non-HDL-C
4)
Secondary efficacy hypothesis testing superiority at Study Week 48 for 
the Immediate Switch Group vs Study Week 24 for the Delayed Switch 
Group.
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 Study Week 24 for both treatment groups are only supportive to 
the primary and secondary efficacy hypotheses at Study Week 48 for the 
Immediate Switch Group and Study Week 24 for the Delayed Switch Group 
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 
The planned sample size is 660 subjects to be randomized in a 2:1 ratio to 
either an immediately switch to MK-1439A (Immediate Switch Group) or a 
delayed switch to MK-1439A after continuation of a ritonavir- or cobicistat-
boosted PI-based or cobicistat-boosted elvitegravir-based or NNRTI-based 
regimen for 24 weeks (Delayed Switch Group). The primary hypothesis will 
be assessed based on the proportion of subjects maintaining HIV-1 RNA <50
copies/mL by the Abbott RealTime HIV-1 Assay at Study Week 48 in the 
Immediate Switch Group and at Study Week 24 in the Delayed Switch 
Group. A margin of 8 percentage points is used to define the non-inferiority 
of an immediate switch to MK-1439A relative to continuation of the baseline
regimen for 24 weeks. The study will have 80% power to demonstrate that an 
immediate switch to MK-1439A is non-inferior to continuation of the 
baseline regimen for 24 weeks, at an overall one-sided 2.5% alpha level, as 
measured by the proportion of subjects maintaining HIV-1 RNA <50
copies/mL by the Abbott RealTime HIV-1 Assay at Study Week 48 in the 
Immediate Switch Group and at Study Week 24 in the Delayed Switch 
Group. The power calculation assumes a true response rate of 85% for both 
arms 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.
This trial is being conducted as an open-label study, i.e., subjects, investigators, and 
SPONSOR personnel will be aware of subject treatment assignments after each subject is 
enrolled and treatment is assigned.
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The Clinical Biostatistics department will generate the randomized allocation schedule(s) for 
study treatment assignment. Randomization will be implemented in an interactive voice 
response system (IVRS/IWRS).
Hypotheses/Estimation
Objectives and hypotheses of the study are stated in Section 3.0.
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 Maintaining HIV-1 RNA <50 copies/mL or <40 copies/mL 
The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) 
of 40 copies/mL, will be used to measure the HIV-1 RNA level in blood samples obtained at 
each visit. The proportions of subjects maintaining HIV-1 RNA <50 copies/mL or <40 
copies/mL will be estimated at each time point.  
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 Study Week 48 in the 
Immediate Switch Group and at Study Week 24 in the Delayed Switch Group. In the 
Immediate Switch Group, subjects will have received MK-1439A for 48 weeks; in the 
Delayed Switch Group, subjects will have received their baseline regimen for 24 weeks on-
study (though they will have received the same regimen for at least 6 months prior to the 
study [note that the primary endpoint will be assessed before the Delayed Switch Group 
switches to MK-1439A]).  Because there will be different lengths of study follow-up in the 2 
treatment groups at the time of the primary efficacy assessment, there is potentially a bias in 
favor of the Delayed Switch Group as the likelihood to discontinue is greater in the 
Immediate Switch Group simply due to the longer duration (48 weeks) on study as compared 
to the Delayed Switch Group (24 weeks).
Proportions of Subjects With HIV-1 RNA ≥50 copies/mL Based on the FDA Snapshot 
Approach 
The proportion of subjects with HIV-1 RNA ≥50 copies/mL based on the FDA snapshot 
approach (the second category of the virologic outcome; details in Section 8.6.1) at study 
Week 48 in the Immediate Switch Group and at Study Week 24 in the Delayed Switch Group 
will be analyzed. 
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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 Study Week 48 for the Immediate Switch Group 
and at Study Week 24 for the Delayed Switch Group. 
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 (PDVF)
Subjects with protocol defined virologic failure (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.
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.  Primary 
analyses of these endpoints will be applied only to subjects whose regimen at screening is a 
ritonavir-boosted PI (see Table 10).  The analysis is restricted to this subset of subjects 
(Strata 1 and 2) because:
1) Ritonavir-boosted PIs, as a class, are known to have adverse effects on lipid profiles.
2) Individuals on regimens other than a ritonavir-boosted PI are eligible to enter the 
study beginning only with Amendment 06, thus relatively few subjects on a 
cobicistat-boosted PI regimen are expected to be enrolled compared with the number 
of already-enrolled subjects on a ritonavir-boosted PI, such that statistical analysis of 
these subjects would not be feasible.
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.
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 Pre-Defined Limit of 
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Change (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 (Appendix 12.7). A listing of the subjects who meet the criteria 
will be provided.
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 (note that for subjects who were 
randomized to the Delayed Switch Group, study treatment also includes their ongoing
baseline regimen during Study Week 0 to Study Week 24),

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 populations.  Details on the approach to handling 
missing data are provided in Section 8.6 Statistical Methods.
Safety Analysis Populations
The All Subjects as Treated (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 
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issues of multiplicity, sample size, etc.  Unless otherwise stated, all statistical tests will be 
conducted at the α=0.025 (1-sided) level.
Subjects in the Immediate Switch Group will receive MK-1439A throughout the treatment 
period in the base study. Subjects in the Delayed Switch Group will continue their baseline 
regimen from Study Day 1 through Study Week 24 and then receive MK-1439A from Study 
Week 24 through Study Week 48 in the base study.  Subjects in both treatment groups who 
continue into the study extensions will receive MK-1439A throughout the extension periods.
Between-treatment comparisons that address key efficacy and safety objectives will be 
limited to data from the Immediate Switch Group and data collected from the Delayed 
Switch Group BEFORE the switch in the base study. Efficacy and safety data from Study 
Week 24 through 48 for the Delayed Switch Group will be summarized separately. In 
addition, the safety data from Study Week 24 to 48 for the Delayed Switch Group will be 
combined with the Immediate Switch Group safety data for descriptive summaries. 
Demography, efficacy and safety data from study extension 1, for those subjects who 
continue into study extension 1, will be summarized separately using descriptive statistics 
only. Serious 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 7 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.
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Table 7
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
Treatment
Week 4
2 and 56
29
Week 4
Week 12
57 and 126
85
Week 12
Week 24
For DSG, 127 and 
last day of baseline 
regimen treatment 
period
For ISG, 127 and 
reported Week 24 
visit date for subject 
completed Week 24 
visit or last day of 
treatment period for 
subject discontinued 
before having Week 24 
visit
169
Week 24
Week 28
For DSG, first day of 
MK-1439A treatment 
and  224
For ISG, first day 
after reported Week 24 
visit date and  224
197
Week 28
Week 36
225 and 294
253
Week 36
Week 48
295 and last day of 
base study treatment 
period
337
Week 48
Treatment
Extension 1
Week 64
first day of Extension 
1 treatment period and 
504
449
Week 64
Week 80
505 and 616
561
Week 80
Week 96
617 and 728
673
Week 96
Week 112
729 and 840
785
Week 112
Week 128
841 and 952
897
Week 128
Week 144
953 and last day of 
Extension 1 treatment 
period
1009
Week 144
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.
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;
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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 8). The primary approach for 
the analysis of the proportion of subjects maintaining HIV-1 RNA <50 copies/mL is the 
Non-Completer=Failure (NC=F) approach as defined by the FDA “snapshot” approach [13]. 
Under this approach, only those subjects who 1) are on study-assigned treatment; 2) have 
HIV-1 RNA measurement(s) within the time window specified in Table 7; and 3) have the 
measurement closest to the target date of the time point <50 copies/mL, can be classified as 
virologic success at that time point. The other subjects, either with 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 maintaining HIV-1 RNA <50 copies/mL at that timepoint.
A second approach, the Observed Failure (OF) approach will be performed as a sensitivity 
analysis for the proportion of subjects maintaining HIV-1 RNA <50 copies/mL at Study 
Week 48 in the Immediate Switch Group and at Study Week 24 in the Delayed Switch 
Group.
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 copies/mL.
Table 8
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 Maintaining HIV-1 RNA <50 copies/mL 
The proportion of subjects maintaining HIV-1 RNA <50 copies/mL will be summarized by 
treatment group at each time point, with primary interest at Study Week 48 in the Immediate 
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Switch Group and at Study Week 24 in the Delayed Switch Group. 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 (ART class included in baseline regimen: ritonavir- or cobicistat-boosted PI vs. 
cobicistat-boosted elvitegravir or NNRTI). Although the study has two stratification factors,
ART class use in baseline regimen and use of lipid-lowering therapy at Study Day 1, the use
of lipid-lowering therapy is not expected to be associated with virologic response; therefore, 
stratification by use of lipid-lowering therapy 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 maintaining virologic 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 within the time window with reasons of 
1) discontinued study due to an AE, 2) discontinued study for other reasons (includes 
withdrawal of consent, loss to follow-up, moved, etc.), or 3) on study but missing data in 
window. The full categorization of virologic outcome at Study Week 24 and Study Week 48 
will be summarized by treatment group.
A sensitivity analysis will be performed using the Observed Failure (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 and secondary timepoints only (i.e., the 
proportion of subjects maintaining HIV-1 RNA <50 copies/mL at Study Week 24 and Study 
Week 48).
For the evaluation of primary and secondary hypotheses, a margin of 8 percentage points is 
used to define the non-inferiority of an immediate switch to MK-1439A at Day 1 to
continuation of the baseline regimen for 24 weeks. An immediate switch to MK-1439A on 
Day 1 will be concluded non-inferior to continuation of the baseline regimen for 24 weeks, if 
the lower bound of the two-sided 95% CI for the difference in the proportion of subjects 
maintaining HIV-1 RNA <50 copies/mL (Immediate Switch Group minus Delayed Switch 
Group) is greater than -8 percentage points. It can be further concluded that an immediate 
switch to MK-1439A is superior to continuation of the baseline regimen for 24 weeks if the 
lower bound of the two-sided 95% CI for the difference in response rates (Immediate Switch 
Group minus Delayed Switch Group) 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.
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Proportions of Subjects With HIV-1 RNA ≥50 copies/mL Based on the FDA Snapshot 
Approach 
The full categorization of virologic outcome at a timepoint by the FDA snapshot approach 
includes 1) HIV-1 RNA <50 copies/mL, 2) HIV-1 RNA ≥50 copies/mL, and 3) having no 
virologic data within the time window for reasons of a) discontinued study due to an AE, b) 
discontinued study for other reasons (includes withdrawal of consent, loss to follow-up, 
moved, etc.), or c) on study but missing data in window. The proportion of subjects with 
HIV-1 RNA ≥50 copies/mL based on the FDA snapshot approach (the second category of the 
virologic outcome) at study Week 48 in the Immediate Switch Group and at Study Week 24 
in the Delayed Switch Group will be analyzed. 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 (ART class used in baseline regimen: 
ritonavir- or cobicistat-boosted PI vs. cobicistat-boosted elvitegravir or NNRTI). A margin 
of 4 percentage points will be used to assess the non-inferiority of an immediate switch to 
MK-1439A at Day 1 to continuation of the baseline regimen for 24 weeks with respect to this 
endpoint as a measure of the strength of evidence for the treatment effect. (Note that the 
margin used to assess non-inferiority for this endpoint of  HIV-1 RNA ≥50 copies/mL is 
4 percentage points while the margin used for the endpoint of  HIV-1 RNA <50 copies/mL is 
8 percentage points.)  There will not be a multiplicity adjustment for this endpoint.  
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 Study Week 48 in the 
Immediate Switch Group and at Study Week 24 in the Delayed Switch Group. 
The treatment difference in changes from baseline in CD4 cell count at each time point will 
be estimated between the two 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 (PDVF)
The number of subjects with protocol defined virologic failure will be summarized for each 
treatment group.
Table 9 summarizes the key efficacy analyses.
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Table 9
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 
maintaining HIV-1 RNA <50
copies/mL at Study Week 48 in
the Immediate Switch Group 
and at Study Week 24 in the 
Delayed Switch Group
P
Stratum-adjusted 
Mantel-Haenszel‡
FAS
NC=F approach
Proportion 
of 
subjects 
maintaining HIV-1 RNA <50
copies/mL at Study Week 48 in
the Immediate Switch Group 
and at Study Week 24 in the 
Delayed Switch Group
S
Stratum-adjusted 
Mantel-Haenszel‡
FAS
OF approach
Secondary Objectives
Proportion 
of 
subjects 
maintaining HIV-1 RNA <50
copies/mL at Study Week 24 in
each treatment group
P
Stratum-adjusted 
Mantel-Haenszel‡
FAS
NC=F approach
Change from baseline in CD4 
cell counts at Study Week 48 in
the Immediate Switch Group 
and at Study Week 24 in the 
Delayed Switch Group
P
Two sample t-test
FAS
OF 
approach 
assuming 
baseline-
carried-forward
Change from baseline in CD4 
cell counts at Study Week 24 in
each treatment group
P
Two sample t-test
FAS
OF 
approach 
assuming 
baseline-
carried-forward
Proportion of subjects with HIV-
1 RNA ≥50 copies/mL at Study 
Week 48 in the Immediate 
Switch Group and at Study 
Week 24 in the Delayed Switch 
Group
S
Stratum-adjusted 
Mantel-Haenszel‡
FAS
FDA 
snapshot 
approach
  †
P=Primary approach; S=Supportive approach; OF = Observed Failure; NC=F = Non-completer=Failure.
  ‡
Stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of the sample size per 
arm for each stratum (ART class used in baseline regimen: ritonavir- or cobicistat-boosted PI vs. cobicistat-boosted 
elvitegravir or NNRTI).
The strategy to address multiplicity issues with regard to multiple endpoints, multiple 
timepoints, and/or interim analyses is described in Section 8.7, Interim Analyses and in 
Section 8.8, Multiplicity.
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Statistical Methods for Safety Analyses
Safety and tolerability will be assessed by clinical review of all relevant parameters including 
adverse experiences (AEs), laboratory tests, and vital signs.
The analysis of safety results will follow a tiered approach (Table 10).  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. 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.
Adverse experiences (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 1% of subjects in any treatment group exhibit the 
event; all other adverse experiences and predefined limits of change will belong to Tier 3.
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 Tier 1 events are the change from baseline in fasting LDL-C and non-
HDL-C at Study Week 24.  Change from baseline in other fasting lipids (total cholesterol, 
HDL-C, and triglycerides) will be Tier 2 events. These endpoints are evaluated based only 
on subjects whose regimen at screening consists of a ritonavir-boosted PI + 2 NRTIs.  The 
change from baseline in fasting lipids will be analyzed using ANCOVA models adjusted by 
baseline lipids level, use of lipid-lowering therapy at Study Day 1 and treatment group. The 
treatment differences and 95% confidence intervals will be provided for all lipid parameters, 
and p-values for the between treatment comparisons 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 lipid-lowering therapy use during the study, the last lipid 
measurement before modifying the lipid-lowering therapy use will be carried forward.
The percentages of subjects who modify lipid-lowering therapy use prior to Study Week 24
will be summarized by treatment group. 
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 
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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 (1985) [9], an unconditional, asymptotic method.
Table 10
Analysis Strategy for Safety Parameters
Safety Tier
Safety Endpoint†
p-Value
95% CI for 
Treatment 
Comparison
Descriptive 
Statistics
Tier 1
Change from baseline in fasting LDL-C, non-
HDL-C*
X
X
X
Tier 2
Change from baseline in other fasting lipids 
(total cholesterol, HDL-C, triglycerides)*
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 
≥1% of subjects in one of the treatment 
groups)
X
X
Tier 3
Specific AEs, SOCs or PDLCs‡ (incidence <1% 
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 subjects whose regimen at screening is a ritonavir-boosted PI + 2 NRTIs.
‡
Includes only those endpoints not pre-specified as Tier 1 or not already pre-specified as Tier-2 endpoints.
Note: SOC=System Organ Class; PDLC=Pre-Defined Limit of Change; X = results will be provided.
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 descriptive statistics.  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 using descriptive statistics for continuous or categorical variables, as appropriate.
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Interim Analyses
No interim analyses are planned for this study.
Multiplicity
The following hypotheses will be tested sequentially at the one-sided Type 1 error rate of 
2.5% in the following order:  
1) Primary efficacy hypothesis testing non-inferiority at Study Week 48 for the Immediate 
Switch Group vs Study Week 24 for the Delayed Switch Group
2) Secondary safety hypothesis for LDL-C
3) Secondary safety hypothesis for non-HDL-C
4) Secondary efficacy hypothesis testing superiority at Study Week 48 for the Immediate 
Switch Group vs Study Week 24 for the Delayed Switch Group
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 Study Week 
24 for both treatment groups are considered supportive of the primary and secondary efficacy 
hypotheses at Study Week 48 for the Immediate Switch Group and Study Week 24 for the 
Delayed Switch Group 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
This study will randomize 660 subjects in a 2:1 ratio to either an immediate switch to MK-
1439A at Study Day 1 (Immediate Switch Group, 440 subjects) or a delayed switch to MK-
1439A after continuation of a ritonavir- or cobicistat-boosted PI-based regimen or a
cobicistat-boosted elvitegravir-based regimen or an NNRTI-based regimen for 24 weeks 
(Delayed Switch Group, 220 subjects). The study will have 80% power to demonstrate the 
primary hypothesis that immediately switching to MK-1439A is non-inferior to continuing 
the baseline regimen for 24 weeks, at an overall one-sided 2.5% alpha level, as measured by 
the proportion of subjects maintaining HIV-1 RNA <50 copies/mL at Study Week 48 in the 
Immediate Switch Group and at Study Week 24 in the Delayed Switch Group using the 
Abbott RealTime HIV-1 Assay. The power calculation assumes a true response rate of 85% 
for both arms using the NC=F approach, as defined by the FDA “snapshot” approach. The 
assumed response rate for the delayed switch arm is based on the result from a similar switch 
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study (the SPIRIT study) but takes into consideration the different assay used in this study. 
A margin of 8 percentage points is used to define the non-inferiority of an immediate switch 
to MK-1439A at Study Day 1 to continuation of the baseline regimen for 24 weeks. Given 
the non-inferiority margin of 8%, the assumed response rates in the Delayed Switch Group,
and the chosen sample size, non-inferiority may be established when the observed difference 
in response rates (Immediate Switch Group minus Delayed Switch Group) is approximately -
2.1% or larger; superiority may be concluded when the observed difference in response rates 
is approximately 5.5% or larger contingent upon satisfying the multiplicity criteria. The 
power calculation is based on an asymptotic method proposed by Farrington and Manning 
(1990) [10] and is carried out using SAS v9.3. Table 11 summarizes the power for the 
primary comparison under various assumptions for the control response rate and underlying 
difference in response rates. 
Table 11
Power (%) Under Various Assumptions (With 440 Subjects Randomized in 
Immediate Switch Group and 220 Subjects Randomized in the Delayed Switch Group)
Response Rate (%) 
in Delayed Switch 
Group
Underlying Difference in Response Rates (%)
(Immediate Switch Group – Delayed Switch Group)
-3
-2
-1
0
1
2
3
83
37
51
64
76
86
93
97
85
41
55
69
80
89
95
98
87
45
60
74
85
93
97
99
90
53
69
83
92
97
99
>99
Note:  The power is calculated based on 440 subjects expected to be included in the analysis for 
the Immediate Switch Group and 220 subjects expected to be included in the analysis for the 
Delayed Switch Group.
Sample Size and Power for Safety Analyses
Lipids
Tier 1 events are evaluated based only on subjects whose regimen at screening is a ritonavir-
boosted PI + 2 NRTIs.  The change from baseline in fasting LDL-C and non-HDL-C at Study 
Week 24 will be analyzed using ANCOVA models adjusted by baseline lipid level, use of 
lipid-lowering therapy at Study Day 1 and treatment group. The primary hypothesis of non-
inferior efficacy must first be established before testing the hypothesis on lipids. An 
immediate switch to MK-1439A on Study Day 1 will be concluded to be superior to 
continuation of a ritonavir-boosted, PI-based regimen if the mean change from baseline in 
LDL-C in the Immediate Switch Group is significantly lower than that in the Delayed Switch 
Group (the one-sided p-value for the between-treatment comparison is less than 0.025). If 
superiority for LDL-C is established, sequential testing for non-HDL-C will be conducted at 
the same α level.
The estimated between-treatment differences in the mean changes in fasting LDL-C and non-
HDL-C, based on the results from a similar switch study (the SPIRIT study [12]), are 
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16 mg/dL and 21 mg/dL, respectively. It is expected that at least one half of enrolled 
subjects will, at screening, be on a regimen consisting of a ritonavir-boosted PI. With at least 
220 subjects in the Immediate Switch Group and at least 110 subjects in the Delayed Switch 
Group whose regimen at screening is based on a ritonavir-boosted PI, the study has >99% 
power to detect a between-treatment difference of 16 mg/dL for the mean change from 
baseline in LDL-C assuming a common standard deviation of 20 mg/dL. The study also has 
>99% power to detect a between-treatment difference of 21 mg/dL for the mean change from 
baseline in non-HDL-C assuming a common standard deviation of 25 mg/dL.
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 
98.8% and 89.0% chance of observing at least one adverse experience among the 440
subjects in the Immediate Switch Group and the 220 subjects in the Delayed Switch Group, 
respectively.  If no adverse experience of that type is observed among the 440 subjects in the 
Immediate Switch Group and 220 subjects in the Delayed Switch Group, this study will 
provide 95% confidence that the underlying percentage of subjects with that particular 
adverse experience is <0.8% for the Immediate Switch Group and <1.7% for the Delayed 
Switch 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 12.  These calculations are 
based on the exact binomial method proposed by Clopper and Pearson (1934) [11].
Table 12
Estimate of Incidence of AEs and 95% Upper Confidence Bound Based on 
Hypothetical Numbers of Subjects with AEs Among 440 Subjects Randomized to the 
Immediate Switch Group and 220 Subjects Randomized to the Delayed Switch Group
Hypothetical Number of 
Subjects 
With An Adverse Event
440 Subjects in Treatment Group
220 Subjects in Treatment Group
Estimate of 
Incidence
95% Upper Confidence 
Bound†
Estimate of 
Incidence
95% Upper 
Confidence Bound†
0
0.0%
0.8%
0.0%
1.7%
5
1.1%
2.6%
2.3%
5.2%
10
2.3%
4.1%
4.5%
8.2%
15
3.4%
5.6%
6.8%
11.0%
20
4.5%
6.9%
9.1%
13.7%
25
5.7%
8.3%
11.4%
16.3%
30
6.8%
9.6%
13.6%
18.9%
† Based on the two-tailed exact confidence interval for a binomial proportion (Clopper and Pearson, 1934).
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Table 13 gives the difference in the incidence of adverse experience (Immediate Switch 
Group minus Delayed Switch Group) that can be ruled out with different power levels and 
95% confidence when there are 440 subjects in the Immediate Switch Group and 220 
subjects in the Delayed Switch Group.  The underlying incidence of adverse experiences is 
assumed to be the same for the two treatment groups. For a reasonably common adverse 
experience which occurs in 20% of subjects either in the Immediate Switch Group or the 
Delayed Switch Group, the study has 90% power to declare with 95% confidence that the 
true difference between the treatment groups is no more than 10.7 percentage points. The 
calculations are based on an asymptotic method proposed by Farrington and Manning (1990) 
[10].
Table 13
Differences in Incidences of AEs (Immediate Switch Group minus Delayed 
Switch Group) That Can Be Ruled Out With 440 Subjects Randomized to the Immediate 
Switch Group and 220 Subjects Randomized to the Delayed Switch 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
6.9
9.3
10.6
11.3
11.6
85
7.4
9.9
11.3
12.1
12.4
90
8.0
10.7
12.3
13.1
13.4
95
8.9
11.9
13.6
14.6
14.9
†The upper bound of the two-sided 95% confidence interval (Farrington and Manning (1990) for the difference in AE
incidences (Immediate Switch Group minus Delayed Switch Group) assuming the incidences are the same.
Overall Power
The key efficacy and safety hypotheses of the study will be tested sequentially at the one-
sided Type 1 error rate of 2.5% in the following order:  
1) Primary efficacy hypothesis testing non-inferiority at Study Week 48 for the Immediate 
Switch Group vs. Study Week 24 for the Delayed Switch Group
2) Secondary safety hypothesis for LDL-C
3) Secondary safety hypothesis for non-HDL-C
4) Secondary efficacy hypothesis testing superiority at Study Week 48 for the Immediate 
Switch Group vs. Study Week 24 for the Delayed Switch Group.
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.
Based on the estimated power for each individual hypothesis, the probability of reaching 
steps 2 through 4 for statistical testing is approximately 80%, 79%, and 78%, respectively.
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Subgroup Analyses and Effect of Baseline Factors
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)

Chronic Hepatitis B or C status (HBV/HCV-infected or HBV/HCV-uninfected)

Baseline CD4 categories (<200 cells/mm3, ≥200 cells/mm3)

ART class used in baseline regimen (ritonavir- or cobicistat-boosted PI or cobicistat-
boosted elvitegravir or NNRTI) 

Duration of ART regimen (in use at screening) prior to enrollment (≥1 year, <1 year)

For subjects whose baseline regimen includes a ritonavir- or cobicistat-boosted PI or 
cobicistat-boosted elvitegravir, historical documentation of selected NNRTI-class 
mutations that confer resistance to other NNRTIs but are considered susceptible to MK-
1439 (K103N, Y181C, G190A and K103N + Y181C).  
The Observed Failure approach will be used to handle missing values in these subgroup 
analyses.
Compliance (Medication Adherence)
Study Medication Diary will be used to ensure and document the drug compliance in the base 
study and study extension 1.
For the main analysis of compliance in this 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.
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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
Summary statistics will be provided on percent compliance by treatment group for the FAS
population.
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 study extension 
3. 
Extent of Exposure
The extent of exposure to study therapy for all randomized and treated subjects will be 
evaluated by treatment group. 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.
9.0 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 14.
Table 14
Product Descriptions
Product Name & Potency
Dosage Form
MK-1439A 100 mg/ 300 mg/ 300 mg
Tablet
Packaging and Labeling Information
Clinical supplies will be affixed with a clinical label in accordance with regulatory 
requirements.
Subjects will receive open label monthly bottles. No kitting is required.
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Clinical Supplies Disclosure
This trial is open-label; therefore, the subject, the trial site personnel, the Sponsor and/or 
designee are not blinded. Treatment (name, strength or potency) is included in the label text; 
random code/disclosure envelopes or lists are not provided.
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.
10.0 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.
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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 
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.
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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.
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.
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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.
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 
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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.
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.
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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, 
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 
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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.
11.0 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.
28 
January 
2016; 
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. World Health Organization, 
June 2013.
3. European Medicines Agency. Summary of Product Characteristics (SmPC) for 
rilpivirine. 
 
Accessed 
13-April-2016. 
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/00226
4/human_med_001513.jsp&mid=WC0b01ac058001d124
4. Palella JF, Fisher, M, Tebas P, Gazzard B, Ruane P, Lunzen JV, Shamblaw D, Flamm J, 
Ebrahimi R, Porter D, White K, Hindman  J, Elbert E, De-Oertel S, Fralich,T: 
Simplification to rilpivirine/emtricitabine/tenofovir disoproxil fumarate from ritonavir-
boosted protease inhibitor antiretroviral therapy in a randomized trial of HIV-1 RNA-
suppressed participants. AIDS, 2014, 28: 335-344 
5. Morales-Ramirez JO, Gatel JM, Hagins DP, Thompson M, Arasteh K, Hoffman C, C. 
Harvey C, Xu X, Teppler H. Safety and antiviral effect of MK-1439, a novel NNRTI, 
(+Truvada®) in ART-Naïve HIV infected patients. 
Presented at Conference on 
Retrovirus and Opportunistic Infections (CROI) March 3-6, 2014
6. Gatell 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 Conference on HIV Drug 
Therapy, Glasgow, November 2-6, 2014.
7. The EuroQol Group. EuroQol - a new facility for the measurement of health-related
quality of life. Health Policy 1990; 16:199-208.
8. Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, Bonsel G, Badia X.  
Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-
5L). Qual Life Res 2011 Dec; 20(10): 1727-36.
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9. Miettinen OS, Nurminen M. Comparative analysis of two rates. Statistics in Medicine 
1985; 4:213-226.
10. 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.
11. Clopper CJ, Pearson ES. The use of confidence or fiducial limits illustrated in the case of 
binomial. Biometrika 1934; 26: 404-13.
12. Tebas P, Palella F, Gazzard B, Ruane P, Shamblaw D, Flamm J, Fisher M, Van Lunzen J, 
Ebrahimi R, White K, Guyer B, Goodgame J, Fralich T, Graham H, Elbert E. SPIRIT 
Study: Switching boosted PI to Rilpivirine In-combination with Truvada as a Single-
Tablet Regimen Week 24 Results. Presented at 14th International Workshop on Co-
morbidities and Adverse Drug Reactions in HIV, Washington D.C., 2012.
13. Department of Health and Human Services, Food & Drug Administration, Center for 
Drug Evaluation & Research. Human Immunodeficiency Virus-1 Infection: Developing 
Antiretroviral Drugs for Treatment_Guidance for Industry. November 2015; 1-47.
Available 
at 
http://www.fda.gov/downloads/drugs/
guidancecomplianceregulatoryinformation/guidances/ucm355128.pdf.
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12.0 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.
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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.
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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.
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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 the 
Future Biomedical Research sub-trial.

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 
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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 both consent and acquisition of Future Biomedical Research 
specimens will be captured in the electronic Case Report Forms (eCRFs).  
Reconciliation of both forms will be performed to assure that only appropriately-
consented specimens are used for this sub-trial's research purposes. 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.
If specimens are collected for a specific genotype or expression analysis as an 
objective to the main trial, this analysis is detailed in the main body of this protocol 
(Section 8.0 – Statistical Analysis Plan).  These specimens will be processed, 
analyzed, and the remainder of the specimen will be destroyed.  The results of these 
analyses will be reported along with the other trial results.  A separate specimen will 
be obtained from properly-consented subjects in this protocol for storage in the 
biorepository for Future Biomedical Research.
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 
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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 
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 MSD Biorepository will be used for analyses using good 
scientific practices.  However, exploratory analyses will not be conducted under the 
highly validated conditions usually associated with regulatory approval of diagnostics.  
The scope of research performed on these specimens is limited to the investigation of the 
variability in biomarkers that may correlate with a clinical phenotype in subjects.
Analyses utilizing the Future Biomedical Research specimens may be performed by 
MSD, or an additional third party (e.g., a university investigator) designated by MSD.  
The investigator conducting the analysis will be provided with double coded specimens.  
Re-association of analysis results with corresponding clinical data will only be conducted 
by the MSD Entrusted Keyholder.  Any contracted third party analyses will conform to 
the specific scope of analysis outlined in this sub-trial.  Future Biomedical Research 
specimens remaining with the third party after the specific analysis is performed will be 
returned to the sponsor or destroyed and documentation of destruction will be reported to 
MSD.
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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 
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
Separate databases for specimen information and for results from the Future Biomedical 
Research sub-trial will be maintained by MSD.  This is done to separate the future 
exploratory test results (which include genetic data) from the clinical trial database 
thereby maintaining a separation of subject number and these results.  The separate 
databases are accessible only to the authorized Sponsor and the designated trial 
administrator research personnel and/or collaborators.  Database user authentication is 
highly secure, and is accomplished using network security policies and practices based in 
international standards (e.g., ISO17799) to protect against unauthorized access.  The 
MSD Entrusted Keyholder maintains control over access to all specimen data.  These 
data are collected for future biomedical research purposes only as specified in this sub-
trial will not be used for any other purpose.
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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 
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 
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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
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Understanding the Intent, Scope and Public Health Benefits of Exploratory Biomarker Research: A Guide for 
IRBs/IECs and Investigational Site Staff
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Approximate Blood Volumes Drawn/Collected by Trial Visit and by Sample Types
Table A: Approximate Blood Volume Drawn From Screening Through Week 48 Plus 14 Days Follow-up (Base Study)
Week (Visit)
Screen
(V1)
Randomization
Day 1
(V2)
WK 4
(V3)
WK 
12
(V4)
WK 
24
(V5)
WK 
28
(V6)
WK 
36
(V7)
WK 
48
(V8)
Virologic
Failure
Confirmation
(U)
Early
Discontinuation
(U)
14 Day
Follow-up
(Post 
Treatment)
(99)
Total
Volume
Hematology
2
2
2
2
2
2
2
2
2
2
2
22
Chemistry
29
7 a
7
7
7 a
7
7
7 a
7
7
7
99
HIV/Hepatitis Screen b
Serum Pregnancy Test c
Hemostatic Function 
Test d
4.5
4.5
Plasma for HIV Viral 
RNA
10
10
10
10
10
10
10
10
10
10
10
110
CD4 Cell Count
2
2
2
2
2
10 
Plasma for Viral 
Resistance
14
14
14
14
14
14
14
14
14g
126
Blood for MK1439 PK e
4
4
4
8
8
28
Blood for Genetics
8.5
8.5
Plasma for Future 
Biomedical Research
10
10
10
30
TOTAL (mL)
45.5
57.5
37
39
53
33
35
53
33
33 
19
438 
Total (tablespoons) f
3
3.8
2.5
2.6
3.5
2.2
2.3
3.5
2.2
2.2 
1.3
~29.1 
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 need 
not be collected again at the discontinuation visit.
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Table B: Approximate Blood Volume Drawn From Week 64 Through Week 144 Plus 14 Days Follow-up (Study Extension 1)
Week (Visit)
WK 64
(V 9)
WK 80
(V 10)
WK 96
(V 11)
WK 112
(V 12)
WK 128
(V 13)
WK 144
(V 14)
Virologic
Failure
Confirmation
(U)
Extension
Early
Discontinuation
(U)
14 Day
Follow-up
(Post Treatment)
(99)
Total
Volume
Hematology
2
2
2
2
2
2
2
2
2
18
Chemistry
7
7
7 a
7
7
7 a
7
7
7
63
Plasma for HIV Viral RNA
10
10
10
10
10
10
10
10
10
90
CD4 Cell Count
2
2
4
Plasma for Viral Resistance
14
14b
28
TOTAL (mL)
19
19
21
19
19
21
33
33
19
203
Total (tablespoons) c
1.3
1.3
1.4
1.3
1.3
1.4
2.2
2.2
1.3
~13.5
a.
Fasting is required at these visits for lipids measurement.
b.
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 need 
not be collected again at the discontinuation visit.
c.
One tablespoon = 15 mL.
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Plasma Assay—Sample Collection, Handling, Labeling, Storage, and Shipment
See Laboratory Manual.
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List of Abbreviations and Acronyms
3TC
Lamivudine
AE
Adverse Event
AIDS
Acquired Immunodeficiency Syndrome
ALT
Serum Alanine Aminotransferase
APTT
Activated Partial Thromboplastin Time
ART
Antiretroviral Therapy
ASaT
All Subjects as Treated
AST
Serum Aspartate Aminotransferase
BLoQ
Below the Limit of Quantification 
CCR5
Chemokine Receptor Type 5
CI
Confidence Interval or (as in section 10.3 only) Coordinating Investigator
Clcr
Creatinine Clearance
CNS
Central Nervous System
CSR
Clinical Study Report
CYP
Cytochrome
DAIDS
Division of Acquired Immunodeficiency Syndrome
DILI
Drug Induced Liver Injury
DNA
Deoxyribonucleic Acid
ECG
Electrocardiogram
ECI
Event of Clinical Interest
EFV
Efavirenz
EOC
Executive Oversight Committee
EQ-5D-5L
EuroQol Five Dimensional Descriptive System, Five Level Version
ERC
Ethical Review Committee
FAS
Full Analysis Set
FBR
Future Biomedical Research
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-1
Human Immunodeficiency Virus Type 1
HIV-SI
Human Immunodeficiency Virus - Symptom Index
IB
Investigator's Brochure
IBS-QoL
Irritable Bowel Syndrome - Quality Of Life
ICF
Informed Consent Form
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ICH
International Conference on Harmonization of Technical Requirements for Registration 
of Pharmaceuticals for Human Use
IEC
Independent Ethics Committee
INR
International Normalized Ratio 
InSTI
Integrase Strand Inhibitors
IRB
Institutional Review Board
IUD
Intrauterine Device
IVRS/IWRS
Interactive Voice Response System/Integrated Web Response System
LDL-C
Low-Density Lipoprotein Cholesterol
LOQ
Lower Limit of Quantification
MedDRA
Medical Dictionary for Regulatory Activities
N(t)RTI
Nucleotide Reverse Transcriptase Inhibitor
NC=F
Non-Completer = Failure
NHS
Normal Human Serum
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
PGt
Pharmacogenetic 
PI
Protease Inhibitors
PK
Pharmacokinetics
PK/PD
Pharmacokinetic/Pharmacodynamic
PO
Per os 
PT
Prothrombin Time 
QD
Once Daily
(v)RNA
(viral) Ribonucleic Acid
SAC
Scientific Advisory Committee
SOC
System Organ Class
(s)SAP
(supplemental) Statistical Analysis Plan
TDF
Tenofovir Disoproxil Fumarate
TDF/FTC
Tenofovir Disoproxil Fumarate/ Emtricitabine (TRUVADA™)
TLOVR
Time to Loss of Virologic Response
ULN
Upper Limit of Normal
US
United States
WPAI
Work Productivity and Activity Impairment Questionnaire
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Guidelines for Grading Severity of Laboratory Adverse Experiences for Toxicity Management
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 two 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).
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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).
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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).
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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† 
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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 
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 
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LABORATORY
PARAMETER
GRADE 1 MILD
GRADE 2 MODERATE
GRADE 3 SEVERE
GRADE 4 POTENTIALLY 
LIFE-THREATENING
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).
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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 RBC/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.
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13.0 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
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