AN INTERNATIONAL, MULTICENTER, PROSPECTIVE OBSERVATIONAL STUDY OF THE SAFETY OF MARAVIROC USED WITH OPTIMIZED BACKGROUND THERAPY IN TREATMENT-EXPERIENCED HIV-1 INFECTED PATIENTS
Conditions: Human Immunodeficiency Virus
Sponsor: ViiV Healthcare

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AN INTERNATIONAL, MULTICENTER, PROSPECTIVE OBSERVATIONAL 
STUDY OF THE SAFETY OF MARAVIROC USED WITH OPTIMIZED 
BACKGROUND THERAPY IN TREATMENT-EXPERIENCED HIV-1 INFECTED 
PATIENTS
Compound:
UK-427,857
Compound Name:
Maraviroc
Protocol Number:
A4001067
Phase:
4
European Clinical Trial 
Database (EudraCT) Number:
2007-006148-24
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Document History
Document
Version Date
Summary of Changes
Protocol Amendment #3
29 November 2010
This amendment outlines the 
change from enrolling 2000 
maraviroc-exposed and 
1000 maraviroc-unexposed patients 
to enrolling 1500 patients in 
each arm. 
AND
To amend the procedures for 
ascertaining survival status of 
patients “switching to non-
participating physicians" (Protocol 
Section 6.5). 
Protocol Amendment #2
12 August 2010
See Appendix 5
Protocol Amendment #1
23 March 2009
See Appendix 4
Original protocol
16 January 2008
N/A
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EPIDEMIOLOGY STUDY PROTOCOL
MARAVIROC
PROTOCOL NUMBER: A4001067
Sponsoring Group:
ViiV Healthcare Ltd
Pfizer Epidemiologist:
 MBBS, MHS, PhD
235 East 42  Street,  MS 150/3/1
New York, NY 10017
Pfizer 
:
 MD
235 East 42  Street  MS 219/8/02
New York, NY 10017
Pfizer Statistician:
 MS
NYO-219-08-02
219 East 42nd Street
New York, NY 10017
Name and Title of Persons 
 ScD
Authorized to Sign for the Sponsor:
235 East 42  Street,  MS 150/3/72
New York, NY 10017
 MD
 
235 East 42  Street,  MS 219/8/30
New York, NY 10017
C
CI
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
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TABLE OF CONTENTS
LIST OF TABLES...........................................................................................................................6
1. INTRODUCTION .......................................................................................................................7
1.1. Indication.........................................................................................................................7
1.2. Background and Rationale ..............................................................................................7
1.2.1. HIV Infection: Epidemiology and Treatment.....................................................7
1.2.2. HIV Tropism.......................................................................................................7
1.2.3. CCR5 Antagonists ..............................................................................................8
1.2.4. Safety Concerns with CCR5 Antagonists...........................................................8
1.2.4.1. Hepatotoxicity...................................................................................8
1.2.4.2. Infections and malignancies..............................................................8
1.2.4.3. Myocardial Infarction........................................................................9
1.2.4.4. Rhabdomyolysis..............................................................................10
1.2.5. Study Rationale.................................................................................................10
2. STUDY OBJECTIVES AND ENDPOINTS.............................................................................11
2.1. Objectives......................................................................................................................11
2.2. Endpoints.......................................................................................................................11
3. STUDY DESIGN.......................................................................................................................12
4. SUBJECT SELECTION............................................................................................................12
4.1. Study Population ...........................................................................................................12
4.2. Inclusion Criteria...........................................................................................................13
4.3. Exclusion Criteria..........................................................................................................14
5. STUDY TREATMENTS...........................................................................................................14
5.1. Drug administration and dosing ....................................................................................14
5.2. Concomitant medication(s) ...........................................................................................15
5.3. HIV Tropism Assay ......................................................................................................15
6. STUDY PROCEDURES ...........................................................................................................15
6.1. Study Period ..................................................................................................................15
6.2. Follow-up Visits............................................................................................................15
6.3. Follow-up of patients discontinuing maraviroc.............................................................15
6.4. Patients lost to follow-up...............................................................................................16
6.5. Follow-up of patients switched to non-participating physicians...................................16
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6.6. Termination of follow-up..............................................................................................16
6.7. Subject Withdrawal.......................................................................................................17
6.8. Transfer of Study Data ..................................................................................................17
7. BASELINE AND FOLLOW-UP DATA COLLECTION ........................................................17
7.1. Collection of Data .........................................................................................................17
7.2. Baseline Data.................................................................................................................18
7.3. Follow-up Data..............................................................................................................19
7.4. Endpoint Evaluation......................................................................................................20
8. ADVERSE EVENT REPORTING............................................................................................21
8.1. ADVERSE EVENTS ....................................................................................................21
8.2. Reporting Period ...........................................................................................................22
8.3. Definition of an Adverse Event.....................................................................................22
8.4. Abnormal Test Findings................................................................................................23
8.5. Serious Adverse Events.................................................................................................23
8.6. Hospitalization ..............................................................................................................24
8.7. Causality Assessment....................................................................................................24
8.8. Exposure During Pregnancy..........................................................................................24
8.8.1. Medication Error...............................................................................................25
8.9. Reporting Requirements................................................................................................25
8.9.1. Serious Adverse Event Reporting Requirements .............................................25
8.9.2. Non-serious Adverse Event Reporting Requirement .......................................26
8.10. Communication of Issues............................................................................................26
9. DATA ANALYSIS/STATISTICAL METHODS.....................................................................26
9.1. Sample Size...................................................................................................................26
9.2. Analysis of Study Endpoint...........................................................................................28
10. QUALITY CONTROL AND QUALITY ASSURANCE.......................................................28
11. DATA HANDLING AND RECORD KEEPING ...................................................................29
11.1. Questionnaires.............................................................................................................29
11.2. Record Retention.........................................................................................................29
12. ETHICS....................................................................................................................................30
12.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ..................30
12.2. Ethical Conduct of the Study ......................................................................................30
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12.3. Subject Information, Consent and Confidentiality......................................................30
13. SPONSOR DISCONTINUATION CRITERIA ......................................................................31
14. COMMUNICATION AND PUBLICATION OF STUDY RESULTS...................................31
15. OVERSIGHT COMMITTEES................................................................................................33
15.1. Scientific Steering Committee ....................................................................................33
15.2. Endpoint Committee ...................................................................................................33
16. REFERENCES ........................................................................................................................34
LIST OF TABLES
Table 1.
Enrollment targets by country ....................................................................................13
Table 2.
Minimum detectable relative rates using a two sided test, α =0.05, and a 
power of 80%..............................................................................................................27
APPENDICES
Appendix 1. 1993 Revised Classification System for HIV Infection and Expanded 
Surveillance Case Definition for AIDS among Adolescents and Adults ...................36
Appendix 2. Enrollment procedure................................................................................................38
Appendix 3. Calculation of person-time expected to be accrued in the study...............................39
Appendix 4. Clinical Protocol Amendment #1..............................................................................41
Appendix 5. Clinical Protocol Amendment #2..............................................................................46
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1. INTRODUCTION
1.1. Indication
Maraviroc, in combination with other antiretroviral medicinal products, is indicated for 
treatment-experienced adult patients infected with only CCR5-tropic HIV-1 detectable.
1.2. Background and Rationale
1.2.1. HIV Infection: Epidemiology and Treatment
AIDS has killed more than 25 million people since it was first recognized in 1981, making it 
one of the most destructive epidemics in recorded history. As of December 2006, 
WHO/UNAIDS estimated that there were 39.5 million (34.1–47.1 million) people living with 
HIV/AIDS.  4.3 million (3.6–6.6 million) people were newly infected with the virus in 2005.1
At present the only means of slowing HIV disease progression is the use of highly active 
antiretroviral therapy (HAART), with the preferred initial regimen containing a three or 
four-drug regimens consisting of a non-nucleoside reverse transcriptase inhibitor (NNRTI) or 
a ritonavir-boosted protease inhibitor (PI/r) plus two nucleoside reverse transcriptase 
inhibitors (NRTIs).  Subsequent regimens frequently require more drugs, and become 
increasingly complex due to difficulty with adherence, tolerability due to adverse events and 
drug interactions with other required medications and the development of resistance to drugs 
in the failed regimen(s) or acquired resistant virus and class cross-resistance.2-4  In the 
developed world, where antiretroviral drugs have been available since 1987, the unmet 
medical need is for new antiretroviral medications with unique resistance profiles, improved 
short- and long-term safety profiles, and convenient dosing to treat patients who have not 
achieved treatment success with multiple treatment regimens due to drug resistance, side 
effects, incomplete adherence, or some combination of these factors.  Drugs that target novel 
steps of the HIV-1 life cycle are needed, as they do not share cross-resistance with currently 
available antiretroviral therapy. 
1.2.2. HIV Tropism
An essential, early step in the replication cycle of HIV-1 is attachment to the CD4 receptor 
and to one of the chemokine coreceptors, CCR5 or CXCR4.  Generally, sexually transmitted 
HIV uses CCR5 exclusively during primary infection.  However, HIV that can use CXCR4 
to enter CD4+ T lymphocyte cells can be detected in about 15% of treatment naïve patients 
and up to 50% of patients with late HIV disease or antiretroviral treatment experience in the 
developed world where Clade B virus predominates. In most cases the CXCR4-using 
HIV (X4 HIV) is present with CCR5-using virus (R5 HIV) as a single virus that can use 
either receptor (dual tropic) or a mixture of R5 and X4 HIV (mixed tropic).  Infections with 
HIV-1 that exclusively use CXCR4 to enter CD4+ T lymphocyte cells are rare, and represent 
approximately 1% of treatment naïve and approximately 2-4% of treatment-experienced 
patients.5, 6
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1.2.3. CCR5 Antagonists
Maraviroc is a member of a new class of antiretroviral compounds known as small molecule 
CCR5 antagonists that block R5 HIV-1 entry into CD4+ T lymphocyte cells.  This group of 
molecules binds non-competitively to CCR5, causing a conformational change in the 
extracellular loops of CCR5 that renders it unrecognizable to wild type R5 HIV-1. 
1.2.4. Safety Concerns with CCR5 Antagonists
1.2.4.1. Hepatotoxicity
The development program for aplaviroc (GSK 873140), another CCR5 antagonist, was 
terminated due to severe drug-induced hepatotoxicity. For a third drug in this class, 
vicriviroc, no severe hepatic-related adverse events have been reported in the ongoing 
clinical trials to date.
The clinical data to date do not indicate that maraviroc causes abnormalities in hepatic 
function relative to placebo. No clinically relevant difference in severity or nature of hepatic 
dysfunction was observed among the two active and the placebo control treatment arms in 
the Phase 2b/3 program of maraviroc. There was a slight difference in rates of hepatic 
adverse events which was driven by events related to laboratory abnormalities but this 
difference was not evident when the overall laboratory data were analysed. Based on the 
available data, including those observed with maraviroc in short and long-term studies, it 
appears that the hepatotoxicity observed with aplaviroc is most likely drug-specific and not a 
class effect. 
1.2.4.2. Infections and malignancies
When a CCR5 antagonist binds to the CCR5 receptor on the surface of CD4+ T lymphocyte, 
it blocks the natural function of the CCR5 molecule, which is primarily associated with 
retention of mononuclear cells in areas of inflammation and injury. Individuals who are born 
with two copies of a mutant CCR5 gene (CCR5Δ32) (ie, homozygous for CCR5Δ32) and do 
not express CCR5 on the surface of their CD4+ T lymphocyte cells represent 1% of 
Caucasians of European descent. They appear to be essentially resistant to HIV-1 infection 
and have apparently normal immune function.  Individuals with one normal CCR5 gene and 
one copy of the CCR5Δ32 gene (ie, heterozygous for CCR5Δ32), who comprise 10-15% of 
Caucasians of European descent, have a reduced concentration of CCR5 molecules on the 
surface of their CD4+ T lymphocyte cells and have essentially normal immune function. 
Relative to HIV-infected patients with two copies of the normal gene, the CCR5Δ32 
heterozygote individuals have delayed CD4+ T lymphocyte decline, delayed progression to 
AIDS, and longer survival once infected.7-10 However, whether blocking the CCR5 receptors 
in adults, who have had functioning CCR5 molecules throughout life, will have the same 
biologic effects as those observed in homozygotes or heterozygotes for CCR5Δ32 is unclear. 
It is theoretically possible that blocking CCR5 molecules after a critical period in immune 
development could result in increased or decreased immune surveillance, leading to 
increased frequency or severity of infections or malignancies.
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Infection with West Nile Virus (WNV) is of particular scientific and clinical interest. Elderly 
and immunocompromised individuals have increased susceptibilityto WNV, but genetic risk 
factors and immunologic control mechanisms have not been fully delineated. The monocyte 
and T lymphocyte chemokine receptor CCR5 have recently been identified as a key factor in 
viral clearance and survival in a mouse model of WNV encephalitis, in which the mechanism 
involved trafficking of leukocytes into the infected brain. Consistent with this, WNV induces 
expression of CCR5 ligands in WNV-infected mouse brain.  To test whether this receptor is 
also protective in man, Glass and colleagues determined the frequency of CCR5Δ32, in two 
independent cohorts of patients, one from Arizona and the other from Colorado, who had 
laboratory-confirmed, symptomatic WNV infection.11 The distribution of CCR5Δ32 in a 
control population of healthy United States Caucasian random blood donors was in
Hardy-Weinberg equilibrium and CCR5Δ32 homozygotes represented 1.0% of the total 
group (n = 1,318). In contrast, CCR5Δ32 homozygotes represented 4.2% of Caucasians in 
the Arizona cohort (odds ratios [OR] = 4.4 [95% confidence interval [CI], 1.6–11.8], P
=0.0013) and 8.3% of Caucasians in the Colorado cohort (OR = 9.1 [95% CI, 3.4–24.8], 
P <0.0001). CCR5Δ32 homozygositywas significantly associated with fatal outcome in the 
Arizona cohort (OR = 13.2 [95% CI, 1.9–89.9], P = 0.03). These authors concluded that
CCR5 mediates resistance to symptomatic WNV infection.  These findings may have 
important implications for the effect of CCR5-blocking agents on the incidence and severity 
of WNV infection.
On March 3, 2006 Schering-Plough announced that five cases of malignancy (four cases of 
lymphoma and one case of gastric adenocarcinoma) had been reported in 118 heavily 
pretreated patients participating in a Phase 2b clinical study of vicriviroc, AIDS Clinical Trial 
Group (ACTG) trial, A5211.  The National Institute of Allergy and Infectious Disease 
(NIAID) Therapeutic DSMB overseeing the trial concluded that a causal association between 
vicriviroc and the lymphoma cases could not be established at that time.  This experience is 
in contrast to findings of a 1999 article that reported a reduced risk of AIDS-associated 
lymphoma in HIV-infected CCR5Δ32 gene heterozygotes when compared to individuals 
without the polymorphism.12 Currently, the data from clinical studies in treatment-
experienced HIV-1 infected patients do not indicate a clinically meaningful alteration in the 
frequency or severity of infections or malignancy related to the use of maraviroc. In the 
phase 2b/3 trials of maraviroc (MOTIVATE 1, MOTIVATE 2) at 48 weeks no difference in 
rates of lymphoma was demonstrated between maraviroc and placebo treatment arms, despite 
the much longer exposure in the maraviroc treated patients.
1.2.4.3. Myocardial Infarction
Metabolic abnormalities associated with HIV-1 infection, including glucose homeostasis 
disturbances and dyslipidemia, are increasingly prevalent, and there is concern about the 
possibility of an association with accelerated cardiovascular disease. In addition, recent 
results from the D:A:D Study, an international collaboration of 11 cohorts following 
23,468 HIV-infected patients prospectively in 21 countries situated in Europe, the USA, and 
Australia, indicated that the incidence of myocardial infarction (MI) increased by 26% per 
year of exposure to combination antiretroviral treatment, consistent with the hypothesis that 
atherosclerosis is a side-effect of combination antiretroviral treatment, generally attributed to 
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PIs dosed simultaneously with NRTIs.13 The data from the Phase 2b/3 studies of maraviroc 
indicated a rate of MI and ischemic heart disease in keeping with that expected from the 
studied population. However there was an imbalance, with all the events occurring on 
maraviroc, most likely due to the design of the study and the limited follow up time in the 
placebo arm. Due to the relatively small data it is currently unknown whether the addition of 
maraviroc will modify the rate of MI occurrence in HIV-1 infected patients receiving 
HAART.
1.2.4.4. Rhabdomyolysis
Rhabdomyolysis is a condition associated with the injury of skeletal muscle. 
Rhabdomyolysis was initially described as a complication of traumatic injury particularly 
crush injuries however infections and most notably certain classes of drugs such as statins 
have been associated with this disorder. Myopathy has also been associated with nucleoside 
reverse transcriptase inhibitors (NRTIs), most notably zidovudine, which are commonly used 
in the treatment of patients with HIV. In the phase 2b/3 trials of maraviroc (MOTIVATE 1, 
MOTIVATE 2) subjects receiving maraviroc had a higher median change in creatine kinase 
compared to placebo. There was also a higher incidence of creatine kinase abnormalities 
(>2x ULN) in subjects receiving maraviroc: 30% and 29% on maraviroc QD and BID 
respectively, compared to 20% on placebo. Three patients in the MOTIVATE 1 and 
2 studies reported adverse events of rhabdomyolysis or myositis and discontinued study drug. 
Two further patients receiving maraviroc QD in the MOTIVATE 2 study discontinued due to 
myalgia. 
1.2.5. Study Rationale
There is limited information about the safety of long-term treatment with maraviroc. No 
signal for increased risk of hepatotoxicity, malignancy or infection has been observed in the 
clinical development program for maraviroc through 48 weeks of therapy. However, the 
concern that hepatotoxicity is a CCR5 antagonist class effect and the theoretical risk of 
altered immune function leading to altered rates or severity of malignancy or infections, 
including opportunistic infections (OI) remain to be fully addressed. Given the imbalance in 
the incidence of myocardial ischemic events in the ongoing clinical trials of maraviroc, data 
on long-term follow-up for MI and myocardial ischemia incidence in patients receiving 
maraviroc along with HAART would more fully characterize this potential safety risk. As 
most of these patients receive lipid-lowering agents that may be associated with a heightened 
risk of rhabdomyoloysis, it is of interest to examine the incidence of this event.  All-cause 
mortality will also provide information regarding any possible long term implications of 
treatment with maraviroc.
The objective of this international, multicenter, prospective observational comparative study 
is to monitor the safety of long term use of maraviroc in a larger and more diverse patient 
population than that in which the phase 2b/3 clinical trials were conducted. By providing 
additional data regarding long-term use of maraviroc, this study will help further characterize 
the safety profile of the drug. This is a post-approval safety study (PASS) and is a 
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commitment to the U.S. Food and Drug Administration (FDA) and the European Medicines 
Agency (EMA). 
2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Objectives
1. To estimate the incidence rates of: (a) Centers for Disease Control and Prevention 
category C AIDS-defining opportunistic infections (OI), (b) viral encephalitis,
(c) liver failure, and (d) rhabdomyolysis in treatment-experienced HIV-1 infected 
patients receiving maraviroc during time of use and for up to six months following 
discontinuation of maraviroc treatment, up to a total of five years since entry into the 
study.
2. To estimate the incidence rates of (a) myocardial infarction (MI) or ischemia, 
(b) all malignancies, (c) all cause mortality, and (d) liver related deaths in treatment-
experienced HIV-1 infected patients receiving maraviroc for up to five years after 
entry into the study regardless of the actual duration of maraviroc use.
3. To compare the rates of the study endpoints in patients receiving maraviroc to those 
observed in an internal comparator group of treatment-experienced, HIV-1 infected 
patients not receiving maraviroc.
4. To compare the observed rates of the study endpoints in patients receiving maraviroc
in this study to those observed in HIV-1 infected patients not receiving maraviroc in 
an appropriate external comparator cohort (eg, EuroSIDA). 
2.2. Endpoints
The study endpoints are:
1. Centers for Disease Control and Prevention Category C AIDS-defining opportunistic 
infections (Appendix 1);
2. Viral encephalitis;
3. All malignancies;
4. Liver failure;
5. Myocardial infarction or ischemia;
6. Rhabdomyolysis;
7. Death from liver-related cause;
8. Death from any cause.
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The operational diagnostic criteria of each endpoint are described in the endpoint 
adjudication manual for this study.
3. STUDY DESIGN
This is an international, multicenter, open-label, comparative, prospective observational 
epidemiologic study. 
4. SUBJECT SELECTION
4.1. Study Population
The study will enroll 1500 HIV-1 infected, treatment-experienced adult patients who have 
been prescribed maraviroc along with an optimized background antiretroviral therapy (OBT)
regimen in usual clinical practice following the approved local label of maraviroc.  
The internal comparator group will consist of 1500 HIV-1 infected, treatment-experienced 
adult patients receiving OBT who received an HIV-1 tropism assay as a screening test for 
eligibility to receive maraviroc in usual clinical practice but were not prescribed maraviroc. 
This group may include patients infected with dual/mixed tropic or CXCR4 tropic HIV-1 as 
well as patients infected with CCR5 tropic HIV-1.
The subject enrollment scheme is presented in Appendix 2.
The study will be conducted at approximately 300 sites in multiple countries. Participating 
countries were chosen on the basis of extensive feasibility assessments and include: Belgium,
Brazil, Canada, France, Germany, Greece, Italy, Portugal, Spain, United Kingdom, and 
United States. If required, additional countries may be added and some countries in this 
initially proposed list may be dropped. Countries will participate only after maraviroc is 
approved by Health Authorities in that country and is commercially available.  Enrollment 
will be competitive and recruitment of subjects will terminate after the global target sample 
size is achieved. The expected numbers of subjects in the participating countries are 
provided in Table 1. Initial enrollment goals set for each country will be redistributed if 
necessary.  Barring unforeseen circumstances (eg, significant delays in marketing 
authorization approval in countries, marked delays in regulatory approvals of the study 
protocol in countries, etc.), enrollment is expected to commence in 1Q2008 and is anticipated 
to continue for approximately 30 months. The enrollment status will be continuously 
monitored by the Sponsor and the external Scientific Steering Committee overseeing the 
study. If required, the enrollment period will be extended to enroll the necessary sample size.
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Table 1.
Enrollment targets by country
Countries
Expected number of study 
subjects
Projected launch date for 
commercial Maraviroc
Belgium
80
March 2008
France
200
April 2008
Germany
223
October 2007
Greece
40
March 2008
Italy
140
March 2008
Portugal
35
April 2008
Spain
250
May 2008
UK
161
November 2007
USA
1700
August 2007
Canada
80
October 2007
Brazil
91
May 2008
4.2. Inclusion Criteria
Subjects (male or female) must meet the following inclusion criteria to be eligible for 
enrollment into the study:
1. The subject is antiretroviral treatment experienced and is currently being considered 
for treatment with maraviroc; 
2. Receive an appropriate HIV-1 tropism assay as a screening for eligibility to receive 
maraviroc within 14 weeks prior to enrollment (The 14-week window does not apply 
to patients who started maraviroc as participants of A4001050 or A4001063);   
3. Provide signed and dated informed consent to enrolling physician indicating that the 
patient (or, legally acceptable representative) has been informed of all pertinent 
aspects of the study;
4. Of 18 years of age or older (or, minimum age as determined by local regulatory 
authorities or as dictated by local law) at the time of screening;
5. Provide signed and dated informed consent to allow the enrolling physician access to 
medical, hospital and vital statistics records as appropriate;
6. Provide information on at least one alternate contact person (preferably the legal next 
of kin) who can be contacted regarding the patient’s whereabouts and survival status, 
should the patient be lost-to-follow-up over the course of the study;
7. Acknowledge that in case of his or her death, the next of kin may be approached for 
a medical records release form if needed;
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8. Provide Social Security Number (applicable to U.S. participants) or other national 
identification number or national health insurance number, as available and allowed 
by local law. This information will only be used to search appropriate national 
or regional cancer and vital status registries for incidences of malignancies and 
deaths.
4.3. Exclusion Criteria
1. Pregnant or lactating;
2. Unable to provide informed consent;
3. Recipient of a small molecule CCR5 inhibitor other than maraviroc;
4. Previously enrolled in this study.
5. Already exposed to maraviroc (Except patients who started maraviroc as participants 
of either study A4001050 or study A4001063 and are still continuing the drug).
These patients may constitute up to 15% of the target sample size in the 
maraviroc-exposed arm).
5. STUDY TREATMENTS
5.1. Drug administration and dosing
Patients receiving maraviroc:
All patients will receive maraviroc per the approved local label in combination with an 
optimized background antiretroviral therapy (OBT) regimen, composed of appropriate 
antiretroviral drugs prescribed by the enrolling physician according to the local standard of 
care of HIV infected patients. Enrolling physicians should refer to the local package 
insert for maraviroc administration information. There are no study-related restrictions 
on dose or OBT regimen prescribed by the physician. 
Patients will obtain commercially available maraviroc as they would in routine clinical 
practice.
Patients not receiving maraviroc:
Subjects in the comparator group will receive appropriate antiretroviral drugs prescribed by 
the enrolling physician, according to the local standard of care of HIV infected patients. 
There are no study-related restrictions on dose or regimen prescribed by the physician. 
However, patients receiving any other CCR5 inhibitor are ineligible to participate. 
Patients will obtain commercially available drugs as they would in routine clinical practice.
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5.2. Concomitant medication(s)
All concomitant therapy as prescribed by the treating physicians is allowed as per the 
approved local label of maraviroc, with the exception of other CCR5 inhibitors.
5.3. HIV Tropism Assay
The Sponsor will cover the cost of tropism assay performed by the Monogram Biosciences, 
Inc., USA as a screening test for eligibility to receive maraviroc.  The details of the sample 
collection, processing and shipping information will be made available to participating study 
sites as a separate document.
6. STUDY PROCEDURES
6.1. Study Period
All subjects will be followed for up to 5 years after enrollment in the study. The estimated 
length of time needed to complete the entire study, from enrollment of the first subject to 
completion of five years of observation of the last subject, is approximately 7.5 years, 
assuming enrollment will be complete in 2.5 years.
6.2. Follow-up Visits
There will be no protocol-mandated patient visits or laboratory tests in this 
observational, non-interventional study. Data on subject’s vital status, continued use of 
maraviroc, and study endpoints will be obtained through follow-up with the treating 
physician according to the local HIV/AIDS treatment guidelines and routine medical 
practice. Medical records and other documentation, where applicable, will be obtained to 
adjudicate study endpoints according to the endpoint adjudication manual. 
6.3. Follow-up of patients discontinuing maraviroc
If a patient discontinues maraviroc, the enrolling physician will record information on the 
date of and primary reason for discontinuation. Discontinuation of maraviroc due to adverse 
events should be distinguished from discontinuation due to insufficient response, and any 
serious adverse events (SAE) should be reported immediately to Pfizer, as the Sponsor’s 
designated representative. A change in any of the components of OBT will not be considered 
as treatment discontinuation if the patient continues to receive maraviroc, but these changes 
in regimen will be recorded on patient questionnaires by enrolling physicians. Follow-up 
will continue after a patient discontinues maraviroc up to a total period of 5 years since 
enrollment, and safety data will be collected and reported for a total of 5 years following 
enrollment as well.
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6.4. Patients lost to follow-up
A patient will be categorized as lost to follow-up if there has not been any contact with the 
patient for six months since last contact and attempts to reach the patient and/or his/her 
secondary contact person(s) fail.
In the situation where neither the patient nor the secondary contact person(s) can be reached, 
attempts will be made to ascertain the vital status of the patient by searching the appropriate 
national or regional vital status registry or other relevant databases, where available and 
allowable by local law. Depending on the local law, this search will be conducted by a 
designated CRO, or a professional search firm, or the enrolling physician or his/her designee 
at the study site. Medical records of these patients cannot be obtained or reviewed for 
adjudication of any death event.  Therefore, the supplemental data on the un-adjudicated 
mortality events will not be included in the primary analyses of the study. It should be noted 
that there is usually a lag between calendar time of death and the time that data are available 
from vital status registries, due to the additional time necessary for government agencies to 
collate information from regional death registries and to check these data for accuracy. In the 
U.S. National Death Index, the delay is approximately 18 months.
6.5. Follow-up of patients switched to non-participating physicians
If for any reason (eg, relocation, insurance change) a patient switches to a physician who is 
not participating in the study, the patient will be discontinued from the study. The enrolling 
physician will complete a follow up questionnaire with the last available clinical data and the 
subject summary module of the questionnaire. If the patient does not withdraw consent to 
participate in the study, an attempt will be made to ascertain the vital status of the patient as 
mentioned in Section 6.4 for patients lost to follow up. 
6.6. Termination of follow-up
Follow-up will terminate at the earliest of any of the following events:
•
Withdrawal of consent by the patient;
•
Death of the patient;
•
Completion of five years since entry into the study;
•
Switching to another CCR5 inhibitor medication (Applicable for maraviroc 
recipients);
•
If a patient in the maraviroc-unexposed comparator group commences treatment with 
a CCR5 inhibitor other than maraviroc, study follow-up will terminate. If a patient in 
the maraviroc-unexposed comparator group commences treatment with maraviroc, 
the follow-up will continue as usual. However, the follow-up experience after 
commencement of maraviroc will be attributed to the maraviroc-exposed group;
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•
Discontinuation of the study by the Sponsor.
This study may be terminated or suspended by the Sponsor at any time.  If the study is 
terminated or suspended, the Sponsor will promptly inform the enrolling 
physicians/institutions and the regulatory authorities.  The IRB/IEC will be promptly 
informed and provided the reason(s) for the termination or suspension by the enrolling 
physician/institution, as specified by applicable regulatory requirement(s).
6.7. Subject Withdrawal
Subjects may withdraw their consent from study participation at any time at their own 
request, or they may be withdrawn at any time at the discretion of the enrolling physician or 
the Sponsor for behavioral or administrative reasons.  If a subject does not return for a 
scheduled visit, every effort should be made by the enrolling physician or site staff to contact 
the subject and his/her alternate contacts, as provided by the subject.  In any circumstance, 
every effort should be made to document subject outcome, if possible.  The enrolling 
physician should inquire about the reason for withdrawal, request the subjects to return for a 
final visit, if applicable, and follow-up with the subject regarding any unresolved serious 
adverse events and study endpoints.
The enrolling physician should determine the primary reason for withdrawal of consent, as 
well as any contributory factors, and record this information on the follow-up questionnaire.  
Withdrawal must be reported immediately if it is due to a serious adverse event.
If the subject withdraws from the study and also withdraws consent for disclosure of future 
information, no further evaluations should be performed and no additional data should be 
collected.  The sponsor may retain and continue to use any data collected before such 
withdrawal of consent.
6.8. Transfer of Study Data
The study sites will report data without any personal identifiers other than the study 
identification number using an electronic data capture system.
Copies of all external documents (eg, hospital discharge certificates, death certificates, EKG 
tracings etc.) collected by the enrolling physician at the study sites will be de-identified, 
labeled with the patient’s study identification number, and forwarded to a CRO designated by 
Sponsor. After ensuring that no personal identifiers are present, the CRO will forward the 
copies to the endpoint adjudication committee for validation of study end points. 
7. BASELINE AND FOLLOW-UP DATA COLLECTION
7.1. Collection of Data
Several questionnaire forms will be used to collect information in this study.  The Informed 
Consent and Alternate Contact Information forms will be completed by the subject at the 
time of screening.  All other forms will be completed by the enrolling physician (or his/her 
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qualified representative), including the  screening, enrollment and follow-up questionnaires, 
final disposition forms, adverse event monitoring forms, and endpoint notification forms.
7.2. Baseline Data
Once a patient has signed informed consent, baseline data will be collected at Screening and 
Enrollment visits.  The enrolling physician will collect data from the patient interview and 
from relevant medical and laboratory records and will electronically complete baseline 
questionnaire pages without any personal identifiers. Data elements on the questionnaire 
pages will include but are not limited to:
•
Study ID number;
•
Date of birth;
•
Sex;
•
Race/ethnicity;
•
Risk behavior(s) for HIV exposure;
•
Duration of HIV infection;
•
Diagnosis date and type of any current or past CDC category C AIDS-defining event;
•
General medical history and relevant family history with specific emphasis on:
•
Malignancies: history of malignancies specifying the type and site;
•
Opportunistic infections: history of any opportunistic infection;
•
Past history of myocardial infarction (MI), ischemia and cardiovascular risk 
factors in general, including smoking history, family history and any 
significant EKG (ECG) finding if available;
•
History of any acute or chronic liver disease including viral hepatitis, 
alcoholic liver disease and alcohol use.
•
Height, weight, systolic and diastolic blood pressure;
•
Co-medications: including lipid-lowering agents, anti-hypertensive medication, 
anti-platelet medications, treatment for HCV/HBV, agents for OI treatment and 
prophylaxis and any potentially hepatotoxic medication;
•
Components of OBT, including start dates and dose of each;
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•
Prior antiretroviral medication history with particular focus on the total duration of all 
antiretroviral therapy and number of failed regimens;
•
Laboratory data: total, LDL and HDL-Cholesterol; serum triglycerides, liver 
enzymes: ALT, AST, bilirubin; Hepatitis B & C serology; CD4+ T lymphocyte cell 
count; nadir CD4+ T lymphocyte cell count; levels of HIV-1 RNA, HCV RNA from 
the most recent tests done per routine clinical care will be collected when available. 
During the screening and enrollment visits, historical data will be accepted for 
laboratory records up to 120 days prior to the visit date.  (Please note: historical data 
on tests for viral hepatitis will be accepted up to 1 year prior to the visit date.)  There 
are no study mandated laboratory tests.
•
Result from the screening HIV-1 tropism assay;
•
Starting date and dose of maraviroc;
•
For the maraviroc non-user comparator group, the anchor drug in the OBT regimen 
will be identified according to the following hierarchy: 
•
Raltegravir or other integrase inhibitor > Enfuvirtide or other fusion 
inhibitor >Etravirine or other 2nd generation NNRTI > Darunavir or other 
protease inhibitor.
•
For subjects who participated in other studies involving maraviroc (eg, the Maraviroc 
Expanded Access Program, A4001050 or study A4001063), the name and/or protocol 
number of the study and the subject ID in that study will be collected.
In addition to these clinical data, the following information will be recorded on a separate 
form and stored separately from the questionnaire data. 
•
Contact information of primary care physician (if appropriate);
•
Contact information of next of kin or other contacts (eg, primary care physician) who 
may be contacted if the patient is lost to follow-up;
•
Social security number, national identifying number or national health insurance 
number as appropriate and allowed by local law to search national and state cancer 
and vital status registries to ascertain incidences of malignancies and death.
7.3. Follow-up Data
Follow-up information on the study outcomes, adverse events, laboratory tests, medication 
use, other relevant clinical information and the patient’s vital status will be abstracted on 
follow-up questionnaires by the enrolling physician or a designated member of the clinical 
team from medical records and charts as well as from the patient, where applicable.
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The complete follow-up questionnaires will be electronically submitted after a patient returns
for follow-up according to local HIV treatment guidelines and routine medical practice 
(usually 3-4 monthly), and at least once every 6 months. At these visits, the physician will 
treat the patient per standard clinical practice and will conduct laboratory investigations as 
appropriate. There will be no study-mandated tests or interventions. Data on the 
patient’s medications, recent laboratory test results and the study endpoints since the last 
visit/report will be recorded in the follow-up questionnaires based on the source medical 
records. 
If a patient does not return for follow-up within six months from last contact, the enrolling 
physician will make at least three attempts to contact the patient to return for routine 
follow-up.  If these initial attempts to directly contact the patient fail, the alternate contact 
person(s) recorded on file will be contacted to ascertain the whereabouts and survival status 
of the patient. 
7.4. Endpoint Evaluation
At each visit after enrollment, the enrolling physician/investigator or designee will report all 
study endpoints for the subjects using an endpoint notification form.  These endpoints may 
be identified by the enrolling physician at a follow-up visit or reported to the enrolling 
physician by other treating physicians or health care facilities. For subjects lost to follow-up, 
survival status may be identified through standard measures used in cohort studies, such as 
alternate contacts and tracking mechanisms (eg, national or regional death certificate data)
however, endpoints will not be collected for adjudication.  
When any of the study endpoints are identified or diagnosed, the enrolling physician will 
report the occurrence using an endpoint notification form and obtain the relevant medical 
records necessary to adjudicate the endpoint.  The enrolling physician may request hospital 
discharge forms and medical records or their summary as needed.  Where necessary and 
applicable, subjects will be contacted by the physician to assist in obtaining medical or 
hospital records.
These documents will be forwarded by the enrolling physician to the designated CRO for 
review by the Endpoint Committee (EC) in a de-identified format with the subject’s study 
number added.  The detailed process and timeframe for this endpoint data collection is 
described in the study Endpoint Manual.
De-identified copies of records, with translations into English where necessary, will be 
collated by the CRO for EC review. The EC will adjudicate the endpoint based on a review 
of the copies of relevant medical and hospital records. Two committee members will review 
each set of records individually and classify them according to the diagnostic algorithms 
described in the Endpoint Manual for the study. If the two adjudicators differ in their 
opinion, a third adjudicator will be assigned.  The operational case definitions of the study 
endpoints as well as the operational aspects of the adjudication process are described in the 
study Endpoint Manual. 
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Study endpoints that are closely temporally related to drug exposures ie, CDC category C 
opportunistic infections, viral encephalitis, rhabdomyolysis and liver failure will cease to be 
adjudicated as study endpoints after six months following discontinuation of maraviroc.  For 
patients in the maraviroc unexposed comparator group, adjudication of these events will 
cease after six months following discontinuation of the anchor drug in their OBT as
identified at baseline (Section 7.2).  If these events are diagnosed after this cut-off period,
they will be considered as any other adverse event and reported per the Adverse Event 
Reporting guidelines described in Section 8, which requires the collection and reporting of all 
serious adverse events (SAE) and all adverse reactions. Occurrence of myocardial infarction 
or ischemia, malignancies, and death (all-cause and liver-related) will be reported and 
adjudicated as study endpoints for up to five years following enrollment.
The follow-up duration for malignancies may be extended beyond five years if, based on 
emerging safety data, the Scientific Steering Committee (SSC) overseeing the study 
recommends a longer period of observation. Due to the potentially prolonged time required 
for a malignancy to become clinically apparent, a search of national and state cancer and 
death registries will be performed to look for all episodes of malignancy within 10 years of 
study entry for all subjects in countries where such registries are available, are accessible for 
research purposes and where such search is allowed by local law. Active study participation 
of subjects will be for only 5 years, but informed consent will be obtained at enrollment 
allowing for passive subject follow-up beyond the 5 years of active participation through this 
additional search of cancer and vital status registries. This search will be conducted by a 
designated CRO or professional search firm using appropriate national identifiers collected at 
enrollment. The investigators will not have to do the search.
8. ADVERSE EVENT REPORTING
ViiV is the Sponsor of the study.  Pfizer will conduct the study on behalf of ViiV.  All 
adverse event reporting under this section will be to Pfizer, as the Sponsor’s designated 
representative, using forms provided by Pfizer.
8.1. ADVERSE EVENTS
All observed or volunteered serious adverse events (SAE) regardless of treatment group or
suspected causal relationship to maraviroc and all non-serious adverse events suspected by 
the investigator to be related to maraviroc (ie, adverse reactions) will be recorded on the 
adverse event page(s) of the case report form (CRF) as follows.
For all adverse events, the investigator must pursue and obtain information adequate both to 
determine the outcome of the adverse event and to assess whether it meets the criteria for 
classification as a serious adverse event (see section "Serious Adverse Events”) requiring 
immediate notification to Pfizer as the Sponsor’s designated representative. For all adverse 
events, sufficient information should be obtained by the investigator to determine the 
causality of the adverse event. The investigator is required to assess causality. For adverse 
events with a causal relationship to maraviroc, follow-up by the investigator is required until 
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the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer on behalf of the Sponsor concurs with that assessment.
8.2. Reporting Period
For serious adverse events, the reporting period to Pfizer, as the Sponsor’s designated
representative begins from the time that the subject provides informed consent or signed data 
privacy statement, which is obtained prior to the subject’s participation in the study to 
60 months from enrollment in the study regardless of the actual duration of the use of the 
study drug.
8.3. Definition of an Adverse Event
An adverse event is any untoward medical occurrence in a clinical investigation subject 
administered a product or medical device; the event need not necessarily have a causal 
relationship with the treatment or usage.  Examples of adverse events include but are not 
limited to:  
•
Abnormal test findings;
•
Clinically significant symptoms and signs;
•
Changes in physical examination findings;
•
Hypersensitivity;
•
Progression/worsening of underlying disease.
Additionally, they may include the signs or symptoms resulting from:
•
Drug overdose;
•
Drug withdrawal;
•
Drug abuse;
•
Drug misuse;
•
Drug interactions;
•
Drug dependency;
•
Extravasation;
•
Exposure in during pregnancy;
•
Exposure during breast feeding;
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•
Medication error.
8.4. Abnormal Test Findings
The criteria for determining whether an abnormal objective test finding should be reported as 
an adverse event are as follows: 
•
Test result is associated with accompanying symptoms; and/or
•
Test result requires additional diagnostic testing or medical/surgical intervention;
and/or
•
Test result leads to a change in study dosing or discontinuation from the study,
significant additional concomitant drug treatment, or other therapy; and/or
•
Test result is considered to be an adverse event by the investigator or the sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an adverse event.  Any abnormal test result that is determined to be an error does 
not require reporting as an adverse event.
8.5. Serious Adverse Events
A serious adverse event is any untoward medical occurrence at any dose that:
•
Results in death;
•
Is life-threatening (immediate risk of death);
•
Requires inpatient hospitalization or prolongation of existing hospitalization;
•
Results in persistent or significant disability/incapacity;
•
Results in congenital anomaly/birth defect.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other adverse event outcomes, 
the important medical event should be reported as serious.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse.
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8.6. Hospitalization
Adverse events reported from studies associated with hospitalization or prolongations of 
hospitalization are considered serious.  Any initial admission (even if less than 24 hours) to a 
healthcare facility meets these criteria.  Admission also includes transfer within the hospital 
to an acute/intensive care unit (eg, from the psychiatric wing to a medical floor, medical floor 
to a coronary care unit, neurological floor to a tuberculosis unit).
8.7. Causality Assessment
The investigator’s assessment of causality must be provided for all serious adverse events 
and non-serious adverse reactions. The investigator must record the causal relationship in the 
CRF, as appropriate, and report such an assessment in accordance with the serious adverse 
reporting requirements if applicable.  An investigator's causality assessment is the 
determination of whether there exists a reasonable possibility that maraviroc caused or 
contributed to an adverse event.  If the investigator's final determination of causality is 
unknown and the investigator does not know whether maraviroc caused the event, then the 
event will be handled as related to maraviroc for reporting purposes.  If the investigator’s 
causality assessment is unknown but not related to maraviroc this should be clearly 
documented in the CRF.
8.8. Exposure During Pregnancy
An exposure during pregnancy (also referred to as exposure in-utero [EIU]) occurs if:
1. A female becomes, or is found to be, pregnant either while receiving or having been
directly exposed to (eg, environmental exposure) maraviroc, or the female becomes, or is 
found to be, pregnant after discontinuing and/or being directly exposed to maraviroc
(maternal exposure);
2. A male has been exposed, either due to treatment or environmental, to maraviroc prior to 
or around the time of conception and/or is exposed during his partner’s pregnancy 
(paternal exposure).
If any study subject or study subject’s partner becomes or is found to be pregnant during the
study subject’s treatment with maraviroc, the investigator must submit this information to 
Pfizer, as the Sponsor’s designated representative, within 24 hours of awareness of 
pregnancy, irrespective of whether an adverse event has occurred.
Follow-up is conducted to obtain pregnancy outcome information on all Exposure in Utero
reports with an unknown outcome. The investigator will follow the pregnancy until 
completion or until pregnancy termination (eg, induced abortion) and then notify Pfizer, as 
the Sponsor’s designated representative, of the outcome. The investigator will provide this 
information as a follow up to the initial Exposure in Utero Form.
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8.8.1. Medication Error
A medication error is any preventable event that may cause or lead to inappropriate 
medication use or patient harm while the medication is in the control of the health care 
professional, patient, or consumer.  Such events may be related to professional practice, 
health care products, procedures, and systems including: prescribing; order communication; 
product labeling, packaging, and nomenclature; compounding; dispensing; distribution; 
administration; education; monitoring; and use.  
Medication errors include:
•
near misses, involving or not involving a patient directly (eg, inadvertent/erroneous 
administration, which is the accidental use of a product outside of labeling or 
prescription on the part of the healthcare provider or the patient/consumer).
•
confusion with regard to invented name (eg, trade name, brand name).
The investigator must submit the following medication errors to Pfizer within 24 hours of 
awareness, irrespective of whether an adverse event occurred:
•
Medication errors involving patient exposure to the product, whether or not the 
medication error is accompanied by an AE.
•
Medication errors including potential medication errors or near misses that do not 
involve a patient directly.  When a medication error does not involve patient exposure 
to the product the following minimum criteria constitute a medication error report:
•
An identifiable reporter;
•
A suspect product;
•
A medication error including potential medication error or near miss.
8.9. Reporting Requirements
Each adverse event is to be assessed to determine if it meets the criteria for serious adverse 
event. If a serious adverse event occurs, expedited reporting will follow local and 
international regulations, as appropriate. 
8.9.1. Serious Adverse Event Reporting Requirements
If a serious adverse event occurs, Pfizer is to be notified within 24 hours of awareness of the
event by the investigator. In particular, if the serious adverse event is fatal or life-
threatening, notification to Pfizer must be made immediately, irrespective of the extent of 
available adverse event information.  This timeframe also applies to additional new 
information (follow-up) on previously forwarded serious adverse event reports as well as to 
the initial and follow-up reporting of exposure during pregnancy cases.
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In the rare event that the investigator does not become aware of the occurrence of a serious 
adverse event immediately (eg, if an outpatient study subject initially seeks treatment 
elsewhere), the investigator is to report the event within 24 hours after learning of it and 
document the time of his/her first awareness of the adverse event.
For all serious adverse events, the investigator is obligated to pursue and provide information 
to Pfizer in accordance with the timeframes for reporting specified above. In addition, an 
investigator may be requested by Pfizer to obtain specific additional follow-up information in 
an expedited fashion. This information collected for serious adverse events is more detailed 
than that captured on the adverse event case report form. In general, this will include a 
description of the adverse event in sufficient detail to allow for a complete medical 
assessment of the case and independent determination of possible causality. Information on 
other possible causes of the event, such as concomitant medications and illnesses must be 
provided.  In the case of a subject death, a summary of available autopsy findings must be 
submitted as soon as possible to the Sponsor or its designated representative.
8.9.2. Non-serious Adverse Event Reporting Requirement
Non-serious adverse events are to be reported if they are suspected to be related to maraviroc 
(ie, adverse reaction) on the adverse event page, which is to be submitted to Pfizer, as the 
Sponsor’s designated representative.
8.10. Communication of Issues
In the event of any prohibition or restriction imposed (eg, clinical hold) by an applicable
Competent Authority in any area of the World, or if the investigator is aware of any new
information which might influence the evaluation of the benefits and risks of maraviroc, 
Pfizer, as the Sponsor’s designated representative, should be informed immediately.
In addition, the investigator will inform Pfizer, as the Sponsor’s designated representative,
immediately of any urgent safety measures taken by the investigator to protect the study 
subjects against any immediate hazard, and of any serious breaches of this non-interventional 
study protocol that the investigator becomes aware of.
9. DATA ANALYSIS/STATISTICAL METHODS
Detailed methodology for summary and statistical analyses of data collected in this study will 
be documented in a Statistical Analysis Plan, which will be dated, filed, and maintained by 
the sponsor.  This document may modify the plans outlined in the protocol; however, any 
major modifications of the primary endpoint definition and/or its analysis will also be 
reflected in a protocol amendment.
9.1. Sample Size 
The sample size for the study was determined based on an extensive feasibility assessment in 
28 countries, input from Pfizer country offices, and in consultation with the regulators.  This 
number was estimated to be 3,000 subjects (1,500 patients receiving maraviroc and 
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1,500 patients not receiving maraviroc) to allow calculations of reliable and precise risk 
estimates.
Malignancies, myocardial ischemia or infarction and deaths (liver-related and all cause) 
occurring at any time during the 5-year follow-up period will be adjudicated and analyzed as 
study endpoints.  Assuming up to 10% annual loss to follow-up, the 1,500 patients each 
receiving maraviroc or the anchor drug will contribute 5,836 person-years of observation for 
these study endpoints over a 5-year period (See Scenario 1 in Appendix 3 for details) in each 
treatment arm.  It is assumed that the expected incidence rates are 12.7 per 1000 person-years 
for malignancies,14 3.5 per 1,000 person-years for myocardial infarction,13 2.35 per 1,000 
person-years  for liver-related deaths,15 and 16 per 1,000 person-years for all cause 
mortality15 in the internal comparator group of patients not receiving maraviroc.
CDC category C AIDS-defining opportunistic infections, viral encephalitis, rhabdomyolysis 
and liver failure will be adjudicated and analyzed as study endpoints if they occur during the 
use of maraviroc or the anchor drug in the OBT arm or within 6 months following maraviroc 
or anchor drug discontinuation.  Accounting for the expected rates of drug discontinuation in 
the two treatment arms over time and a 10% annual loss to follow-up, each study arm will 
accrue 2,875 person-years of observation for these study endpoints (See Scenario 2 in 
Appendix 3 for details). It is assumed that the expected incidence rates are 3.5 per 
1,000 person-years for liver failure,16 and 160 per 1,000 person-years for AIDS-defining 
opportunistic infections17 in the internal comparator group of patients not receiving 
maraviroc.
Based on these assumptions of equal person years of contribution in the maraviroc exposed 
and unexposed groups, using a two-tailed test with α=0.05, and a power of 80%, the 
minimum detectable relative rates for various study end points are reported in Table 2.18
Table 2.
Minimum detectable relative rates using a two sided test, α =0.05, and a 
power of 80%
End Point
Expected number of 
events in the unexposed 
internal comparator
group
Detectable Relative 
rates
Malignancies
74
1.572
AIDS-defining opportunistic infections
460
1.1955
Myocardial infarction
20
2.136
Liver failure
10
2.760
Liver-related deaths
14
2.410
All cause mortality
93
1.464
For example, results from Table 2 suggest that the study has 80% power to detect a relative 
risk of ≥1.527 for malignancies and ≥1.196 for AIDS-defining opportunistic infections, 
respectively for the patients receiving maraviroc.  Similar conclusions can be drawn for other 
end points as well.
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9.2. Analysis of Study Endpoint
This study is intended to provide descriptive and comparative data on the incidence rates of 
the selected study endpoints in the two study groups. 
1. Descriptive statistics (ie, frequency, percent, mean, median, standard deviation as 
appropriate depending on data type) will be used to summarize baseline 
characteristics (clinical and demographic) of patients enrolled in the study.  
(Potential variables include but are not limited to age, gender, weight, BMI, race, 
smoking, alcohol consumption, HIV-1 RNA level, CD4+ T lymphocyte counts, 
duration of antiretroviral therapy, duration of HIV infection, number of failed 
regimens etc).
2. Cumulative incidence rates and incidence-density rates of the study endpoints in the 
two groups will be reported along with respective 95% confidence intervals. 
3. Subject discontinuation, loss to follow-up and total person-time of follow-up accrued 
in the study will be summarized. 
4. Depending on data availability, subgroup analyses may be performed to further 
describe the rates of the study endpoints stratified by age group, gender, baseline 
CD4+ cell counts, baseline viral load, hepatitis C/hepatitis B serology, duration of 
maraviroc use, total duration of antiretroviral use, components of OBT etc. 
5. In addition to the selected study endpoints, SAEs and adverse reactions reported 
during the study will be summarized in summary tables and listings. 
6. Crude and adjusted rate ratios with 95% confidence intervals will be calculated for 
each study endpoint comparing maraviroc-exposed patients to maraviroc-unexposed 
patients. Multivariate analysis techniques, including recurrent event analyses 
techniques, will also be used as appropriate to account for the baseline difference in 
the two study groups and recurrent events if any for a given subject, respectively.
In addition, incidence rates in patients receiving maraviroc in this study may be compared to 
those reported in comparable patients not using maraviroc in other HIV-1 infected cohort(s) 
such as EuroSIDA. The baseline characteristics of the patients (eg, number of failed 
regimens, CD4+ T lymphocyte counts) in this study will be used to identify comparable 
subjects from the external cohort(s).
10. QUALITY CONTROL AND QUALITY ASSURANCE
During study conduct, Pfizer or Sponsor will conduct periodic monitoring visits of sites at 
least once a year to ensure that the protocol is being followed.  The monitors may review 
source documents to confirm that the data recorded on questionnaire pages is accurate.  The 
enrolling physician and institution will allow the Sponsor or its designated representatives 
and appropriate regulatory authorities direct access to source documents to perform this 
verification.
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The study site may be subject to review by the Institutional Review Board (IRB)/Independent 
Ethics Committee (IEC), and/or to quality assurance audits performed by the Sponsor or its 
designated representative, and/or to inspection by appropriate regulatory authorities.
It is important that the enrolling physician(s) and their relevant personnel are available during 
the monitoring visits and possible audits or inspections and that sufficient time is devoted to 
the process. 
11. DATA HANDLING AND RECORD KEEPING
11.1. Questionnaires
As used in this protocol, the term questionnaire refers to either a paper form or an electronic 
data record or both, depending on the data collection method used in this study.
Baseline (screening and enrollment), follow-up, and final disposition questionnaires are 
required and should be completed for each included subject.  The completed original 
questionnaires are the sole property of the Sponsor and should not be made available in any 
form to third parties, except for authorized representatives of the Sponsor or appropriate 
regulatory authorities, without written permission from the Sponsor.
The enrolling physician has ultimate responsibility for the accuracy and authenticity of all 
clinical, safety, laboratory data entered on the questionnaires.  The questionnaires must be 
signed by the enrolling physician or by an authorized staff member to attest that the data 
contained on the questionnaires is true.  In most cases, the source documents are the 
hospital's or the physician's subject chart.  In these cases data collected on the questionnaires 
must match the data in those charts. 
In some cases, the questionnaire, or part of the questionnaire, may also serve as source 
documents.  In these cases, a document should be available at the enrolling physician’s site 
as well as at the Sponsor and clearly identify those data that will be recorded in the 
questionnaire, and for which the questionnaire will stand as the source document.
11.2. Record Retention
To enable evaluations and/or audits from regulatory authorities or the Sponsor, the enrolling 
physician agrees to keep records, including the identity of all participating subjects 
(sufficient information to link records, eg, questionnaires and hospital records), all original 
signed informed consent forms, copies of all questionnaires, serious adverse event forms, 
source documents, and detailed records of treatment disposition.  After the end of the study 
the records should be retained by the enrolling physician according to local regulations or as 
specified in the Clinical Study Agreement, whichever is longer.
If the enrolling physician relocates, retires, or for any reason withdraws from the study, 
Pfizer, as the Sponsor’s designee should be prospectively notified.  The study records must 
be transferred to an acceptable designee, such as another enrolling physician, another 
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institution, or to Pfizer.  The enrolling physician must obtain Pfizer's written permission 
before disposing of any records, even if retention requirements have been met.
12. ETHICS
12.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
It is the responsibility of the enrolling physician to have prospective approval of the study 
protocol, protocol amendments, informed consent forms, and other relevant documents, eg, 
advertisements, if applicable, from the IRB/IEC.  All correspondence with the IRB/IEC 
should be retained in the Enrolling Physician File.  Copies of IRB/IEC approvals should be 
forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/IEC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In 
that event, the enrolling physician must notify the IRB/IEC and the Study Team in writing 
within 5 working days after the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with the International Conference on 
Harmonization (ICH) guidelines.  In addition, the study will be conducted in accordance with 
the protocol, the International Society for Pharmacoepidemiology’s Good 
Pharmacoepidemiology Practices, and applicable local regulatory requirements and laws.
12.3. Subject Information, Consent and Confidentiality
All personal study subject data collected and processed for the purposes of this study will be 
managed by the enrolling physician and his/her staff with adequate precautions to ensure the 
confidentiality of those data, and in accordance with applicable national and/or local laws 
and regulations on personal data protection.
Only the enrolling physician and his/her designee, authorized agents of Pfizer, Inc., or of a 
CRO designated by Pfizer Inc. following the guidelines proposed by the ethics committees 
approving this research, will be granted direct access to the study subjects’ original medical 
and hospital records for verification of study procedures and/or data, without violating the 
confidentiality of the subjects, to the extent permitted by the law and regulations. The 
Sponsor. will not have access to the study subject’s address, phone number, social security 
number or any other national identification number or alternate contact information collected 
for the purpose of this study. 
All parties will ensure protection of subject personal data and will not include subject names 
on any sponsor forms, reports, publications, or in any other disclosures.  In case of data 
transfer, Pfizer and Sponsor will maintain high standards of confidentiality and protection of 
subject personal data. 
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Informed consent must take place prior to enrollment of subjects in the study. Written, 
signed and dated informed consent will be obtained from each subject in accordance with 
local regulatory and legal requirements.
The informed consent form must be agreed to by the Sponsor or designee and the IRB/IEC 
and must be in compliance with local regulatory requirements and legal requirements. 
The consent document will be available in English and in all applicable local languages 
depending on the site and country.
The completed and signed consent forms will be stored in a locked file cabinet at the study 
site. A separate document will include the secondary contact information provided by the 
subject and, where allowed by law, the social security number or any other national 
identification number or national insurance number. One copy of this contact form will be 
stored in a locked file cabinet at the study site. In countries where the CRO is allowed to 
contact the secondary contact person or the patient, a second copy of this contact form will 
be stored at the designated CRO office, separate from other data, and in locked file cabinets 
to insure confidentiality.
The enrolling physician must ensure that each study subject, or his/her legally acceptable 
representative, is fully informed about the nature and objectives of the study and possible 
risks associated with participation.  The enrolling physician, or a person designated by the 
enrolling physician, will obtain written informed consent from each subject or the subject's 
legally acceptable representative before any study-specific activity is performed.  The 
informed consent form used in this study, and any changes made during the course of the 
study, must be prospectively approved by both the IRB/IEC and the Sponsor before use.  The 
enrolling physician will retain the original of each subject's signed consent form.
If the consent form is revised during the course of the study, it is the enrolling physician’s 
responsibility to ensure that an amended consent receives approval/favorable opinion by the 
local IRB/IEC, and signed by all patients subsequently participating in the study.  
13. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/IEC, drug safety problems, or at the discretion of the Sponsor.  
If a study is prematurely terminated or discontinued, the Sponsor or designee will promptly 
notify the enrolling physician.  After notification, the enrolling physician must contact all 
participating subjects within one month.  As directed by Pfizer, all study materials must be 
collected and all questionnaires completed to the greatest extent possible.
14. COMMUNICATION AND PUBLICATION OF STUDY RESULTS
Publication of study results is discussed in the Clinical Study Agreement.
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Communication of Results 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report.  The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a Sponsor site or other 
mutually-agreeable location.
Sponsor will also provide the investigator with the full summary of the study results.  The 
investigator is encouraged to share the summary results with the study subjects, as 
appropriate.
The results summary will be posted to an internet-based study register at the time of the first 
regulatory approval or within 12 months of study completion or of any decision to terminate 
development.  In addition, a manuscript will be submitted to a peer-reviewed journal for 
publication within 12 months of the first regulatory approval or within 12 months of study 
completion or of any decision to terminate development.  When manuscript publication in a 
peer-reviewed journal is not feasible, further study information will be posted to an 
internet-based study register to supplement the results summary.
Publications by Investigators
ViiV Healthcare has no objection to publication by Investigator of any information collected 
or generated by Investigator, whether or not the results are favorable to the Investigational 
Drug.  However, to ensure against inadvertent disclosure of Confidential Information or 
unprotected Inventions, Investigator will provide ViiV Healthcare and/or designee an 
opportunity to review any proposed publication or other type of disclosure before it is 
submitted or otherwise disclosed.
Investigator will provide manuscripts, abstracts, or the full text of any other intended 
disclosure (poster presentation, invited speaker or guest lecturer presentation, etc.) to ViiV 
Healthcare /and/or designee at least 30 days before they are submitted for publication or 
otherwise disclosed.  If any patent action is required to protect intellectual property rights, 
Investigator agrees to delay the disclosure for a period not to exceed an additional 60 days.
Investigator will, on request, remove any previously undisclosed Confidential Information 
(other than the Study results themselves) before disclosure.
If the Study is part of a multi-centre study, Investigator agrees that the first publication is to 
be a joint publication covering all centers.  However, if a joint manuscript has not been 
submitted for publication within 12 months of completion or termination of the Study at all 
participating sites, Investigator is free to publish separately, subject to the other requirements 
of this Section.
For all publications relating to the Study, Institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
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Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors. 
Publication of study results is also provided for in the Clinical Study Agreement between 
Pfizer and the Institution.  In this section entitled Publications by Investigators, the defined 
terms shall have the meanings given to them in the Clinical Study Agreement.
15. OVERSIGHT COMMITTEES
15.1. Scientific Steering Committee
The Scientific Steering Committee (SSC) is an external group of epidemiology, biostatistics, 
infectious disease/HIV medicine, hepatology, cardiology, and oncology experts that will 
serve two roles: (1) to safeguard the interests of study participants and (2) to monitor study 
conduct, in conjunction with the sponsor study team.  The remit of the SSC will be described 
in the charter for the SSC. In summary, the role of the SSC will be to periodically monitor 
the progress of the study, including logistical and operational aspects, to establish acceptable 
performance criteria (eg, acceptable rates of withdrawn consent and loss to follow-up), to 
evaluate the quality of the data being collected in the study, and to assist the sponsor in the 
development of any remedial plans of action as necessary. The SSC may propose changes to 
the study design and conduct including follow-up duration, as the committee deems 
necessary based on emerging safety data.  In the event of recommendations for a significant 
change by the SSC, the Sponsor will notify regulatory agencies where necessary, as per legal 
or regulatory requirements.
15.2. Endpoint Committee
The Endpoint Committee will review all study endpoints occurring over the course of the 
study.  The EC will be comprised of an independent group of infectious disease specialists, 
hepatologists, cardiologists and oncologists experienced in the treatment of HIV-1 infection 
and/or the study of HIV in large observational study settings.  The members of the EC will 
receive de-identified data gathered on subjects who are suspected to have experienced a 
study outcome and will be responsible for adjudicating and coding the endpoints as described 
in Section 7.4.
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16. REFERENCES
1.
UNAIDS, AIDS Epidemic Update.  
http://data.unaids.org/pub/EpiReport/2006/2006_EpiUpdate_en.pdf, 2006.
2.
McNicholl, I.R. and J.J. McNicholl, On the horizon: promising investigational 
antiretroviral agents. Curr Pharm Des, 2006. 12(9): p. 1091-103.
3.
Maeda, K., et al., Structural and molecular interactions of CCR5 inhibitors with CCR5.
J Biol Chem, 2006. 281(18): p. 12688-98.
4.
Yeni, P.G., et al., Treatment for adult HIV infection: 2004 recommendations of the 
International AIDS Society-USA Panel.  Jama, 2004. 292(2): p. 251-65.
5.
Moyle, G.J., et al., Epidemiology and predictive factors for chemokine receptor use in 
HIV-1 infection.  J Infect Dis, 2005. 191(6): p. 866-72.
6.
Brumme, Z.L., et al., Molecular and clinical epidemiology of CXCR4-using HIV-1 in a 
large population of antiretroviral-naive individuals.  J Infect Dis, 2005. 192(3):
p.466-74.
7.
Dean, M., et al., Genetic restriction of HIV-1 infection and progression to AIDS by a 
deletion allele of the CKR5 structural gene.  Hemophilia Growth and Development 
Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San 
Francisco City Cohort, ALIVE Study. Science, 1996. 273(5283): p. 1856-62.
8.
Eugen-Olsen, J., et al., Heterozygosity for a deletion in the CKR-5 gene leads to 
prolonged AIDS-free survival and slower CD4 T-cell decline in a cohort of 
HIV-seropositive individuals. Aids, 1997. 11(3): p. 305-10.
9.
Huang, Y., et al., The role of a mutant CCR5 allele in HIV-1 transmission and disease 
progression. Nat Med, 1996. 2(11): p. 1240-3.
10.
Michael, N.L., et al., The role of CCR5 and CCR2 polymorphisms in HIV-1 
transmission and disease progression. Nat Med, 1997. 3(10): p. 1160-2.
11.
Glass, W.G., et al., CCR5 deficiency increases risk of symptomatic West Nile virus 
infection. J Exp Med, 2006. 203(1): p. 35-40.
12.
Dean, M., et al., Reduced risk of AIDS lymphoma in individuals heterozygous for the 
CCR5-delta32 mutation. Cancer Res, 1999. 59(15): p. 3561-4.
13.
Friis-Moller, N., et al., Combination antiretroviral therapy and the risk of myocardial 
infarction.  N Engl J Med, 2003. 349(21): p. 1993-2003.
14.
Highly active antiretroviral therapy and incidence of cancer in human 
immunodeficiency virus-infected adults.  J Natl Cancer Inst, 2000. 92(22): p. 1823-30.
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15.
Weber, R., et al., Liver-related deaths in persons infected with the human 
immunodeficiency virus: the D:A:D study.  Arch Intern Med, 2006. 166(15):
p. 1632-41.
16.
Friis-Moller, N., Kirk O, Reiss P, Safety of non-nucleoside reverse transcriptase 
therapy: data from the EuroSIDA study [abstract 24].  In: Abstracts of the 5th 
International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV (Paris).  
Antiviral Ther, 2003. 8: p. L20.
17.
Kaplan, J.E., et al., Epidemiology of human immunodeficiency virus-associated 
opportunistic infections in the United States in the era of highly active antiretroviral 
therapy. Clin Infect Dis, 2000. 30 Suppl 1: p. S5-14.
18.
McMahon, A.D. and T.M. MacDonald, Sample size for cohort studies in 
pharmacoepidemiology. Pharmacoepidemiol Drug Saf, 1997. 6(5): p. 331-5.
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Appendix 1.   1993 Revised Classification System for HIV Infection and Expanded 
Surveillance Case Definition for AIDS among Adolescents and Adults
Category C AIDS-defining events
Category C includes the clinical conditions listed below. For classification purposes, once a 
Category C condition has occurred, the person will remain in Category C. 
•
Candidiasis of bronchi, trachea, or lungs 
•
Candidiasis, esophageal 
•
Cervical cancer, invasive 
•
Coccidioidomycosis, disseminated or extrapulmonary 
•
Cryptococcosis, extrapulmonary 
•
Cryptosporidiosis, chronic intestinal (greater than 1 month's duration) 
•
Cytomegalovirus disease (other than liver, spleen, or nodes) 
•
Cytomegalovirus retinitis (with loss of vision) 
•
Encephalopathy, HIV-related 
•
Herpes simplex: chronic ulcer(s) (greater than 1 month's duration); or bronchitis, 
pneumonitis, or esophagitis 
•
Histoplasmosis, disseminated or extrapulmonary 
•
Isosporiasis, chronic intestinal (greater than 1 month's duration) 
•
Kaposi's sarcoma 
•
Lymphoma, Burkitt's (or equivalent term) 
•
Lymphoma, immunoblastic (or equivalent term) 
•
Lymphoma, primary, of brain 
•
Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary 
•
Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary) 
•
Mycobacterium, other species or unidentified species, disseminated or 
extrapulmonary 
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•
Pneumocystis carinii pneumonia 
•
Pneumonia, recurrent 
•
Progressive multifocal leukoencephalopathy 
•
Salmonella septicemia, recurrent 
•
Toxoplasmosis of brain 
•
Wasting syndrome due to HIV
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Appendix 2.   Enrollment procedure
Based on history, clinical features and laboratory results 
physician considers patient a candidate for maraviroc
Physician informs patient about the possibility of using maraviroc and invites 
the patient to participate in the study and obtains written informed consent
Tropism assay performed
Patient infected with 
CCR5 tropic HIV
Patient infected with CXCR4 
tropic or dual/mixed tropic HIV
Patient prescribed 
maraviroc along with 
optimized background 
therapy
Patient not prescribed 
maraviroc or declines 
maraviroc and receives 
only optimized 
background therapy
Patient not eligible to 
receive maraviroc and 
receives only optimized 
background therapy
Patient participates in the 
maraviroc exposed group
Patient participates in the maraviroc 
unexposed comparator group
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Appendix 3. Calculation of person-time expected to be accrued in the study
Scenario 1
Endpoints: All cause mortality, Liver-related death, Malignancies, Myocardial ischemia and 
infarction
Expected person-time of observation in maraviroc exposed and unexposed groups:
These events occurring at anytime during the 5-year follow up period will be adjudicated and 
analyzed as study endpoints. It is assumed that each year 10% patients will be lost to 
follow-up and that on average these losses will occur at the midpoint of the 12 months 
period.
Person-time accrual in the maraviroc exposed and unexposed groups for all cause mortality, Liver-
related death, Malignancies, Myocardial ischemia and infarction
n at the 
beginning of 
period
Lost to follow-up midway 
of the period
(provide 6 months of 
follow-up)
n at the end of the 
period
(provide 12 months of 
follow-up)
Person-Years 
accrued
Year 1
1500
150
1350
1425.0
Year 2
1350
135
1215
1282.5
Year 3
1215
122
1093
1154.0
Year 4
1094
109
984
1038.5
Year 5
984
98
886
935.0
Total person-years
5835.0
Based on the above assumptions, both these groups will accrue 5835 person-years of 
follow-up during the study for the assessment of all cause mortality, Liver-related death, 
Malignancies, Myocardial ischemia and infarction.
Scenario 2:  
Endpoints: CDC category C AIDS-defining opportunistic infection, viral encephalitis, liver 
failure, rhabdomyolysis
Expected person-time of observation in:
These events will be adjudicated and analyzed as study endpoints if they occur during use of 
maraviroc or the anchor drug in the OBT, or within 6 months following their discontinuation
•
Based on clinical experience, it is assumed that the rate of drug discontinuation will 
be higher in the earlier part of the study and will gradually decrease over time.  To 
obtain a conservative estimate, it is assumed based on the observations from the 
48-week clinical development program of maraviroc that the rate of discontinuation 
will be approximately 30% during the first 6 months of therapy, 25% between the 7th
and 12th month, 20% between the 13th and 18th months and 15% in each 6 month 
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period thereafter.  For the purpose of this calculation it is assumed that on average 
discontinuation occurs at the midpoint of each 6-month period.  
•
It is assumed that 5% of the patients (either continuing maraviroc or during the 
6 months post discontinuation follow-up) will be lost every 6 months and on average 
these losses will occur at the midpoint of the 6-month period.  
•
Patients lost to follow-up during any 6-month period (either on or off maraviroc) will 
contribute only 3 months of follow-up time during that period.  Patients who are 
being actively followed up at the end of each 6-month period will contribute 6 months 
of follow-up time.
Based on the above assumptions, both these groups will accrue 2875 person-years of 
follow-up during the study for the assessment of AIDS-defining OI, viral encephalitis, 
rhabdomyolysis and liver failure.
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Appendix 4. Clinical Protocol Amendment #1
Current Amendment:
Amendment No.
1
Date
23 March 2009
Country (ies)
All
Site(s)
All
SUMMARY
Reason(s) for Amendment
The A4001067 protocol is being revised to reflect the following administrative changes:
1. To update the list of countries participating in the study.
2. To modify the process of searching and establishing the survival status of patients 
who may have switched to a physician not participating in A4001067, or of patients 
who are lost to follow-up as defined in the protocol. 
3. To include study A4001063 in addition to A4001050 in the examples of other Pfizer 
clinical studies where the patients may have started Maraviroc.
The protocol section(s) that have been amended and the details of the changes are 
summarized in the following sections.
Protocol Section(s) Amended
The protocol sections that were amended are detailed below.  The format is as follows:
•
The “change from” section represents the current text in the protocol.  Bolded text is used 
to indicate the addition of information to the current text, and strike-out of text (eg, text) 
is used to show the deletion of information from the current text.
•
The “change to” section represents the revised text, with the revisions shown in the 
“change from” section in normal text.
1. SECTION 4.1. Study Population; Paragraph 4 (Sentences 1-3) and Table 1:
CHANGE FROM
The study will be conducted at approximately 300 sites in 13 multiple countries.  
Participating countries were chosen on the basis of extensive feasibility assessments and 
include: Australia, Belgium, Brazil, Canada, France, Germany, Greece, Italy, Malaysia, 
Mexico, Portugal, Spain, United Kingdom, and United States.  If required, additional 
countries may be added and some countries in this list may be dropped.
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Table 1: Enrollment Targets by Country
Countries
Expected number of study 
subjects
Projected launch date for 
commercial Maraviroc
Australia
30
December 2008
Belgium
80
March 2008
France
200
April 2008
Germany
175 223
October 2007
Greece
40
March 2008
Italy
140
March 2008
Portugal
35
April 2008
Spain
250
May 2008
UK
200 161
November 2007
USA
1540 1700
August 2007
Canada
160 80
October 2007
Malaysia
102
January 2009
Mexico
80
June 2008
Brazil
91
May 2008
CHANGE TO
The study will be conducted at approximately 300 sites in multiple countries.  Participating 
countries were chosen on the basis of extensive feasibility assessments and include: Belgium, 
Brazil, Canada, France, Germany, Greece, Italy, Portugal, Spain, United Kingdom, and 
United States.  If required, additional countries may be added and some countries in this list 
may be dropped.
Table 1: Enrollment Targets by Country
Countries
Expected number of study 
subjects
Projected launch date for 
commercial Maraviroc
Belgium
80
March 2008
France
200
April 2008
Germany
223
October 2007
Greece
40
March 2008
Italy
140
March 2008
Portugal
35
April 2008
Spain
250
May 2008
UK
161
November 2007
USA
1700
August 2007
Canada
80
October 2007
Brazil
91
May 2008
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2. SECTION 6.4. Patients lost to follow-up; Paragraph 2:
CHANGE FROM
In the situation where neither the patient nor the secondary contact person(s) can be reached, 
attempts will be made to ascertain the vital status of the patient by searching the appropriate
a national or regional vital status registry or other relevant databases, where available and 
allowable by local law, by a designated CRO or a professional search firm.  Depending on 
the local law, this search will be conducted by a designated CRO, or a professional 
search firm, or the enrolling physician or his/her designee at the study site. It should be 
noted that there is usually a lag between calendar time of death and the time that data are 
available from vital status registries, due to the additional time necessary for government 
agencies to collate information from regional death registries and to check these data for 
accuracy. In the U.S. National Death Index, the delay is approximately 18 months.
CHANGE TO
In the situation where neither the patient nor the secondary contact person(s) can be reached, 
attempts will be made to ascertain the vital status of the patient by searching the appropriate 
national or regional vital status registry or other relevant databases, where available and 
allowable by local law.  Depending on the local law, this search will be conducted by a 
designated CRO, or a professional search firm, or the enrolling physician or his/her designee 
at the study site.  It should be noted that there is usually a lag between calendar time of death 
and the time that data are available from vital status registries, due to the additional time 
necessary for government agencies to collate information from regional death registries and 
to check these data for accuracy. In the U.S. National Death Index, the delay is 
approximately 18 months.
3. SECTION 6.5. Follow-up of patients switched to non-participating physicians:
CHANGE FROM
If for any reason (eg, relocation, insurance change) a patient switches to a physician who is 
not participating in the study, the enrolling physician will complete a questionnaire with the 
last available clinical data.  If the patient does not withdraw consent to participate in the 
study, the patient or his/her current physician will be contacted the designated CRO will 
directly contact the patient (or the secondary contact person(s) if needed) by telephone or 
mail every six months to ascertain survival status provided the local regulations allow such 
contact. This communication will be conducted by the CRO or the enrolling
physician or his/her designee at the study site as allowed by local law. Where such 
contact is not allowed, attempts will be made to ascertain the vital status of the patient by 
searching a national vital status registry, where available and allowable by local law as 
mentioned in Section 6.4 for patients lost to follow up.  Information on the occurrence of the 
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other study events (eg, MI, OI etc.) will not be sought, since patient-reported
endpoints are not verifiable and are unable to be adjudicated by medical records
in this situation.  Therefore, in the analyses of the study endpoints except all cause mortality, 
such patients will be censored at the date of last clinical encounter with the enrolling 
physician.
CHANGE TO
If for any reason (eg, relocation, insurance change) a patient switches to a physician who is 
not participating in the study, the enrolling physician will complete a questionnaire with the 
last available clinical data.  If the patient does not withdraw consent to participate in the 
study, the patient or his/her current physician will be contacted by telephone or mail every 
six months to ascertain survival status provided the local regulations allow such contact.  
This communication will be conducted by the CRO or the enrolling physician or his/her 
designee at the study site as allowed by local law.  Where such contact is not allowed,
attempts will be made to ascertain the vital status of the patient as mentioned in Section 6.4
for patients lost to follow up.  Information on the occurrence of the other study events (eg, 
MI, OI etc.) will not be sought, since patient-reported endpoints are not verifiable and are 
unable to be adjudicated by medical records in this situation.  Therefore, in the analyses of 
the study endpoints except all cause mortality, such patients will be censored at the date of 
last clinical encounter with the enrolling physicians.
4. SECTION 7.2. Baseline Data; List bullet 23:
CHANGE FROM
•
For subjects who participated in other studies involving maraviroc (eg, the 
Maraviroc Expanded Access Program, A4001050 or study A4001063), the 
name and/or protocol number of the study and the subject ID in that study will 
be collected.
CHANGE TO
•
For subjects who participated in other studies involving maraviroc (eg, the 
Maraviroc Expanded Access Program (A4001050 or study A4001063), the 
name and/or protocol number of the study and the subject ID in that study will 
be collected.
5. SECTION 12.3. Subject Information, Consent and Confidentiality; Paragraphs 
2 and 7:
CHANGE FROM
Only the enrolling physician and his/her designee, authorized agents of Pfizer, Inc., or of a 
CRO designated by Pfizer Inc. following the guidelines proposed by the ethics committees 
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approving this research, will be granted direct access to the study subjects’ original medical 
and hospital records for verification of study procedures and/or data, without violating the 
confidentiality of the subjects, to the extent permitted by the law and regulations. Pfizer, Inc. 
will not have access to the study subject’s address, phone number, social security number or 
any other national identification number or alternate contact information collected for the 
purpose of this study. 
The completed and signed consent forms will be stored in a locked file cabinet at the study 
site.  A separate document will include the secondary contact information provided by the 
subject and, where allowed by law, the social security number or any other national 
identification number or national insurance number.  One copy of this contact form will be 
stored in a locked file cabinet at the study site.  In countries where the CRO is allowed to 
contact the secondary contact person or the patient, a A second copy of this contact form 
will be stored at the designated CRO office, separate from other data, and in locked file 
cabinets to insure confidentiality.
CHANGE TO
Only the enrolling physician and his/her designee, authorized agents of Pfizer, Inc., or of a 
CRO designated by Pfizer Inc. following the guidelines proposed by the ethics committees 
approving this research, will be granted direct access to the study subjects’ original medical 
and hospital records for verification of study procedures and/or data, without violating the 
confidentiality of the subjects, to the extent permitted by the law and regulations. Pfizer, Inc. 
will not have access to the study subject’s address, phone number, social security number or 
any other national identification number or alternate contact information collected for the 
purpose of this study.
The completed and signed consent forms will be stored in a locked file cabinet at the study 
site.  A separate document will include the secondary contact information provided by the 
subject and, where allowed by law, the social security number or any other national 
identification number or national insurance number.  One copy of this contact form will be 
stored in a locked file cabinet at the study site.  In countries where the CRO is allowed to 
contact the secondary contact person or the patient, a second copy of this contact form will 
be stored at the designated CRO office, separate from other data, and in locked file cabinets 
to insure confidentiality.
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Appendix 5. Clinical Protocol Amendment #2
Current Amendment:
Amendment 
No.
2
Date
12 August 2010
Country 
(ies)
All
Site(s)
All
Previous Amendments:
Amendment 
No.
1
Date
23 March 2009
Country 
(ies)
All
Site(s)
All
SUMMARY
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Reason(s) for Amendment
The A4001067 protocol is being revised to reflect the following changes:
•
To reflect the change of sponsor for this study from Pfizer Inc, to ViiV 
Healthcare.  ViiV Healthcare as the sponsor (“ViiV” or “Sponsor”) will 
continue to use Pfizer and Pfizer’s designated agents (“Pfizer”) to conduct the 
study.
ViiV Healthcare was formed in November of 2009.  ViiV Healthcare is a global 
specialist HIV company established by GlaxoSmithKline and Pfizer to deliver 
advances in treatment and care for people living with HIV.  The purpose of this 
amendment is to outline the changes that are relevant to ongoing clinical studies.
On June 16th 2010, sponsorship of all maraviroc clinical trials including A4001067, 
was transferred from Pfizer Inc to ViiV Healthcare (980 Great West Road, 
Brentford, Middlesex, TW8 9GS. UK).  There have been no changes to the study 
conduct or study team related to this transfer.  Pfizer will continue to conduct 
maraviroc clinical trials on ViiV’s behalf.  Safety reporting procedures will continue 
to be managed as was done previously, and all AEs, SAEs and deaths must continue 
to be reported to Pfizer Inc.
The protocol section(s) that have been amended and the details of the changes are 
summarized in the following sections.
Protocol Section(s) Amended
The protocol sections that were amended are detailed below.  The format is as follows:
•
The “change from” section represents the current text in the protocol.  Bolded text is 
used to indicate the addition of information to the current text, and strike-out of text 
(eg, text) is used to show the deletion of information from the current text.
•
The “change to” section represents the revised text, with the revisions shown in the 
“change from” section in normal text.
1. Entire Protocol; Footer
Change From
Pfizer — Company Confidential
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Change To
Confidential
2. Cover page
Change From
Change To
3. Contact Information
Change From
PFIZER INC
EPIDEMIOLOGY STUDY PROTOCOL
MARAVIROC
PROTOCOL NUMBER: A4001067
Sponsoring Group:
ViiV Healthcare Ltd
Pfizer Inc. 
Safety and Risk Management
Epidemiology
235 East 42nd Street
New York, NY 10017
Pfizer Epidemiologist:
 MBBS, MHS, PhD
PPD
PPD
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235 East 42nd Street,  MS 150/3/72
New York, NY 10017
Pfizer 
:
 MD
235 East 42  Street    MS 219/8/02
New York, NY 10017
 MD
235 East 42  Street    MS 235/3/38
New York, NY 10017
Pfizer Statistician:
 MS
NYO-219-08-02
219 East 42nd Street
New York, NY 10017
 PhD 
235 East 42  Street, MS 685/11/16
New York, NY 10017
Name and Title of Persons 
 ScD
Authorized to Sign for the Sponsor:
235 East 42  Street,  MS 150/3/72
New York, NY 10017
 MD
 
235 East 42  Street,  MS 219/8/30
New York, NY 10017
 MD
235 East 42  Street,  MS 235/3/38
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
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New York, NY 10017
Change To
EPIDEMIOLOGY STUDY PROTOCOL
MARAVIROC
PROTOCOL NUMBER: A4001067
Sponsoring Group:
ViiV Healthcare Ltd
Pfizer Epidemiologist:
 MBBS, MHS, PhD
235 East 42  Street,  MS 150/3/72
New York, NY 10017
Pfizer 
:
 MD
235 East 42  Street    MS 219/8/02
New York, NY 10017
Pfizer Statistician:
 MS
NYO-219-08-02
219 East 42nd Street
New York, NY 10017
Name and Title of Persons 
 ScD
Authorized to Sign for the Sponsor:
235 East 42  Street,  MS 150/3/72
New York, NY 10017
 MD
 
235 East 42  Street,  MS 219/8/30
New York, NY 10017
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
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4. Section 5.3; HIV Tropism Assay
Change From
Paragraph
Pfizer The Sponsor will cover the cost of tropism assay to determine the viral tropism as a 
screening test for eligibility to receive maraviroc.  The details of the sample collection, 
processing and shipping information will be made available to participating study sites as a 
separate document.
Change To
The Sponsor will cover the cost of a tropism assay performed by the Monogram Biosciences, 
Inc., USA as a screening test for eligibility to receive maraviroc.  The details of the sample 
collection, processing and shipping information will be made available to participating study 
sites as a separate document.
5. Section 6.7; Subject Withdrawal
Change From
1st paragraph
Subjects may withdraw their consent from study participation at any time at their own 
request, or they may be withdrawn at any time at the discretion of the enrolling physician or 
the Sponsor for behavioral or administrative reasons.  If a subject does not return for a 
scheduled visit, every effort should be made by the enrolling physician or site staff to 
contact the subject and his/her alternate contacts, as provided by the subject.  In any 
circumstance, every effort should be made to document subject outcome, if possible.  The 
enrolling physician should inquire about the reason for withdrawal, request the subjects to 
return for a final visit, if applicable, and follow-up with the subject regarding any unresolved 
serious adverse events and study endpoints.
Change To
Subjects may withdraw their consent from study participation at any time at their own 
request, or they may be withdrawn at any time at the discretion of the enrolling physician or 
the Sponsor for behavioral or administrative reasons.  If a subject does not return for a 
scheduled visit, every effort should be made by the enrolling physician or site staff to contact 
the subject and his/her alternate contacts, as provided by the subject.  In any circumstance, 
every effort should be made to document subject outcome, if possible.  The enrolling 
physician should inquire about the reason for withdrawal, request the subjects to return for a 
final visit, if applicable, and follow-up with the subject regarding any unresolved serious 
adverse events and study endpoints.
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6. Section 6.8; Transfer of Study Data
Change From
2nd paragraph
Copies of all external documents (eg, hospital discharge certificates, death certificates, EKG 
tracings etc.) collected by the enrolling physician at the study sites will be de-identified, 
labeled with the patient’s study identification number, and forwarded to a CRO designated by 
Pfizer Sponsor.  After ensuring that no personal identifiers are present, the CRO will forward 
the copies to the endpoint adjudication committee for validation of study end points. 
Change To
Copies of all external documents (eg, hospital discharge certificates, death certificates, EKG 
tracings etc.) collected by the enrolling physician at the study sites will be de-identified, 
labeled with the patient’s study identification number, and forwarded to a CRO designated by 
Sponsor.  After ensuring that no personal identifiers are present, the CRO will forward the 
copies to the endpoint adjudication committee for validation of study end points. 
7. Section 8; Adverse Events
Change From
Paragraph added
Change To
ViiV is the Sponsor of the study.  Pfizer will conduct the study on behalf of ViiV.  All 
adverse event reporting under this section will be to Pfizer, as the Sponsor’s designated 
representative, using forms provided by Pfizer.
8. Section 8.1; Adverse Events
Change From
2nd paragraph
For all reportable adverse events, the investigator must pursue and obtain information 
adequate both to determine the outcome of the adverse event and to assess whether it meets 
the criteria for classification as a serious adverse event (see section "Serious Adverse 
Events”) requiring immediate notification to Pfizer or a Pfizer-designated representative as 
the Sponsor’s designated representative.. For all reportable adverse events, sufficient 
information should be obtained by the investigator to determine the causality of the adverse 
event. The investigator is required to assess causality. For adverse events with a causal 
relationship to maraviroc, follow-up by the investigator is required until the event or its 
sequelae resolve or stabilize at a level acceptable to the investigator, and Pfizer on behalf of 
the sponsor concurs with that assessment.
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Change To
For all reportable adverse events, the investigator must pursue and obtain information 
adequate both to determine the outcome of the adverse event and to assess whether it meets 
the criteria for classification as a serious adverse event (see section "Serious Adverse 
Events”) requiring immediate notification to Pfizer or a Pfizer-designated representative. For 
all reportable adverse events, sufficient information should be obtained by the investigator to 
determine the causality of the adverse event. The investigator is required to assess causality. 
For adverse events with a causal relationship to maraviroc, follow-up by the investigator is 
required until the event or its sequelae resolve or stabilize at a level acceptable to the 
investigator, and Pfizer on behalf of the sponsor concurs with that assessment.
9. Section 8.2; Reporting Period
Change From
Paragraph
For serious adverse events, the reporting period to Pfizer, or its as the Sponsor’s designated 
representative, begins from the time that the subject provides informed consent or signed data 
privacy statement, which is obtained prior to the subject’s participation in the study to 
60 months from enrollment in the study regardless of the actual duration of the use of the 
study drug.
Change To
For serious adverse events, the reporting period to Pfizer, as the Sponsor’s designated 
representative, begins from the time that the subject provides informed consent or signed data 
privacy statement, which is obtained prior to the subject’s participation in the study to 
60 months from enrollment in the study regardless of the actual duration of the use of the 
study drug.
10. Section 8.4; Abnormal Test Findings
Change From
Last bullet
•
Test result is considered to be an adverse event by the investigator or sponsor the Study
Team.
Change To
•
Test result is considered to be an adverse event by the investigator or the Study Team.
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11. Section 8.8; Exposure in Utero
Change From
From 2nd paragraph
If any study subject or study subject’s partner becomes or is found to be pregnant during the
study subject’s treatment with maraviroc, the investigator must submit this the required
information to Pfizer, as the Sponsor’s designated representative, irrespective of whether 
an adverse event has occurred and within 24 hours of awareness of the pregnancy. 
Follow-up is conducted to obtain pregnancy outcome information on all Exposure in Utero
reports with an unknown outcome. The investigator will follow the pregnancy until 
completion or until pregnancy termination (eg, induced abortion) and then notify Pfizer, as 
the Sponsor’s designated representative, of the outcome. The investigator will provide 
this information as a follow up to the initial Exposure in Utero Form.
Change To
If any study subject or study subject’s partner becomes or is found to be pregnant during the
study subject’s treatment with maraviroc, the investigator must submit the required 
information to Pfizer, as the Sponsor’s designated representative, irrespective of whether an 
adverse event has occurred and within 24 hours of awareness of the pregnancy. 
Follow-up is conducted to obtain pregnancy outcome information on all Exposure in Utero
reports with an unknown outcome. The investigator will follow the pregnancy until 
completion or until pregnancy termination (eg, induced abortion) and then notify Pfizer, as 
the Sponsor’s designated representative, of the outcome. The investigator will provide this 
information as a follow up to the initial Exposure in Utero Form.
12. Section 8.9.1; Serious Adverse Event Reporting Requirements
Change From
Last paragraph, last sentence
. . . In the case of a subject death, a summary of available autopsy findings must be submitted 
as soon as possible to Pfizer the Sponsor or its designated representative.
Change To
. . . In the case of a subject death, a summary of available autopsy findings must be submitted 
as soon as possible to the Sponsor or its designated representative.
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13. Section 8.9.2; Non-serious Adverse Event Reporting Requirement
Change From
Paragraph
Non-serious adverse events are to be reported if they are suspected to be related to maraviroc 
(ie, adverse reaction) on the adverse event page, which is to be submitted to Pfizer, as the 
Sponsor’s designated representative.
Change To
Non-serious adverse events are to be reported if they are suspected to be related to maraviroc 
(ie, adverse reaction) on the adverse event page, which is to be submitted to Pfizer, as the 
Sponsor’s designated representative.
14. Section 8.10; Communication of Issues
Change From
From 1st paragraph
In the event of any prohibition or restriction imposed (eg, clinical hold) by an applicable
Competent Authority in any area of the World, or if the investigator is aware of any new
information which might influence the evaluation of the benefits and risks of maraviroc, 
Pfizer, as the Sponsor’s designated representative, should be informed immediately.
In addition, the investigator will inform Pfizer, as the Sponsor’s designated representative,
immediately of any urgent safety measures taken by the investigator to protect the study 
subjects against any immediate hazard, and of any serious breaches of this observational plan 
that the investigator becomes aware of.
Change To
In the event of any prohibition or restriction imposed (eg, clinical hold) by an applicable
Competent Authority in any area of the World, or if the investigator is aware of any new
information which might influence the evaluation of the benefits and risks of maraviroc, 
Pfizer, as the Sponsor’s designated representative, should be informed immediately.
In addition, the investigator will inform Pfizer, as the Sponsor’s designated representative,
immediately of any urgent safety measures taken by the investigator to protect the study 
subjects against any immediate hazard, and of any serious breaches of this observational plan 
that the investigator becomes aware of.
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15. Section 10; Quality Control and Quality Assurance
Change From
First 2 paragraphs
During study conduct, Pfizer or its agent Sponsor will conduct periodic monitoring visits of 
sites at least once a year to ensure that the protocol is being followed.  The monitors may 
review source documents to confirm that the data recorded on questionnaire pages is 
accurate.  The enrolling physician and institution will allow Pfizer monitors or their agents
the Sponsor or its designated representatives and appropriate regulatory authorities direct 
access to source documents to perform this verification.
The study site may be subject to review by the Institutional Review Board (IRB)/Independent 
Ethics Committee (IEC), and/or to quality assurance audits performed by Pfizer the Sponsor 
or its designated representative, and/or to inspection by appropriate regulatory authorities.
Change To
During study conduct, Pfizer or Sponsor will conduct periodic monitoring visits of sites at 
least once a year to ensure that the protocol is being followed.  The monitors may review 
source documents to confirm that the data recorded on questionnaire pages is accurate.  The 
enrolling physician and institution will allow the Sponsor or its designated representatives 
and appropriate regulatory authorities direct access to source documents to perform this 
verification.
The study site may be subject to review by the Institutional Review Board (IRB)/Independent 
Ethics Committee (IEC), and/or to quality assurance audits performed by the Sponsor or its 
designated representative, and/or to inspection by appropriate regulatory authorities.
16. Section 11.1; Questionnaires
Change From
2nd paragraph; 1st sentence
Baseline (screening and enrollment), follow-up, and final disposition questionnaires are 
required and should be completed for each included subject.  The completed original 
questionnaires are the sole property of the Sponsor Pfizer and should not be made available 
in any form to third parties, except for authorized representatives of the Sponsor Pfizer or 
appropriate regulatory authorities, without written permission from the Sponsor Pfizer.
Change To
Baseline (screening and enrollment), follow-up, and final disposition questionnaires are 
required and should be completed for each included subject.  The completed original 
questionnaires are the sole property of the Sponsor and should not be made available in any 
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form to third parties, except for authorized representatives of the Sponsor or appropriate 
regulatory authorities, without written permission from the Sponsor.
17. Section 11.2; Record Retention
Change From
1st and 2nd paragraphs
To enable evaluations and/or audits from regulatory authorities or Pfizer the Sponsor, the 
enrolling physician agrees to keep records, including the identity of all participating subjects 
(sufficient information to link records, eg, questionnaires and hospital records), all original 
signed informed consent forms, copies of all questionnaires, serious adverse event forms, 
source documents, and detailed records of treatment disposition.  After the end of the study 
the records should be retained by the enrolling physician according to local regulations or as 
specified in the Clinical Study Agreement, whichever is longer.
If the enrolling physician relocates, retires, or for any reason withdraws from the study, 
Pfizer, as the Sponsor’s designee should be prospectively notified.  The study records must 
be transferred to an acceptable designee, such as another enrolling physician, another 
institution, or to Pfizer.  The enrolling physician must obtain Pfizer's written permission 
before disposing of any records, even if retention requirements have been met.
Change To
To enable evaluations and/or audits from regulatory authorities or the Sponsor, the enrolling 
physician agrees to keep records, including the identity of all participating subjects 
(sufficient information to link records, eg, questionnaires and hospital records), all original 
signed informed consent forms, copies of all questionnaires, serious adverse event forms, 
source documents, and detailed records of treatment disposition.  After the end of the study 
the records should be retained by the enrolling physician according to local regulations or as 
specified in the Clinical Study Agreement, whichever is longer.
If the enrolling physician relocates, retires, or for any reason withdraws from the study, 
Pfizer, as the Sponsor’s designee should be prospectively notified.  The study records must 
be transferred to an acceptable designee, such as another enrolling physician, another 
institution, or to Pfizer.  The enrolling physician must obtain Pfizer's written permission 
before disposing of any records, even if retention requirements have been met.
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18. Section 12.1; Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC)
Change From
2nd paragraph, last sentence
. . . In that event, the enrolling physician must notify the IRB/IEC and Pfizer the Study 
Team in writing within 5 working days after the implementation.
Change To
. . . In that event, the enrolling physician must notify the IRB/IEC and the Study Team in 
writing within 5 working days after the implementation.
19. Section 12.3; Subject Information, Consent and Confidentiality
Change From
From 2nd paragraph
Only the enrolling physician and his/her designee, authorized agents of Pfizer, Inc., or of a 
CRO designated by Pfizer Inc. following the guidelines proposed by the ethics committees 
approving this research, will be granted direct access to the study subjects’ original medical 
and hospital records for verification of study procedures and/or data, without violating the 
confidentiality of the subjects, to the extent permitted by the law and regulations. Pfizer, Inc.
The Sponsor will not have access to the study subject’s address, phone number, social 
security number or any other national identification number or alternate contact information 
collected for the purpose of this study. 
All parties will ensure protection of subject personal data and will not include subject names 
on any sponsor forms, reports, publications, or in any other disclosures.  In case of data 
transfer, Pfizer and Sponsor will maintain high standards of confidentiality and protection of 
subject personal data. 
Informed consent must take place prior to enrollment of subjects in the study.  Written, 
signed and dated informed consent will be obtained from each subject in accordance with 
local regulatory and legal requirements.
The informed consent form must be agreed to by Pfizer the Sponsor or designee and the 
IRB/IEC and must be in compliance with local regulatory requirements and legal 
requirements.  
8th paragraph
The enrolling physician must ensure that each study subject, or his/her legally acceptable 
representative, is fully informed about the nature and objectives of the study and possible 
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risks associated with participation.  The enrolling physician, or a person designated by the 
enrolling physician, will obtain written informed consent from each subject or the subject's 
legally acceptable representative before any study-specific activity is performed.  The 
informed consent form used in this study, and any changes made during the course of the 
study, must be prospectively approved by both the IRB/IEC and Pfizer the Sponsor before 
use.  The enrolling physician will retain the original of each subject's signed consent form.
Change To
From 2nd paragraph
Only the enrolling physician and his/her designee, authorized agents of Pfizer, Inc., or of a 
CRO designated by Pfizer Inc. following the guidelines proposed by the ethics committees 
approving this research, will be granted direct access to the study subjects’ original medical 
and hospital records for verification of study procedures and/or data, without violating the 
confidentiality of the subjects, to the extent permitted by the law and regulations.  The 
Sponsor will not have access to the study subject’s address, phone number, social security 
number or any other national identification number or alternate contact information collected 
for the purpose of this study. 
All parties will ensure protection of subject personal data and will not include subject names 
on any sponsor forms, reports, publications, or in any other disclosures.  In case of data 
transfer, Pfizer and Sponsor will maintain high standards of confidentiality and protection of 
subject personal data. 
Informed consent must take place prior to enrollment of subjects in the study.  Written, 
signed and dated informed consent will be obtained from each subject in accordance with 
local regulatory and legal requirements.
The informed consent form must be agreed to by the Sponsor or designee and the IRB/IEC 
and must be in compliance with local regulatory requirements and legal requirements.  
8th paragraph
The enrolling physician must ensure that each study subject, or his/her legally acceptable 
representative, is fully informed about the nature and objectives of the study and possible 
risks associated with participation.  The enrolling physician, or a person designated by the 
enrolling physician, will obtain written informed consent from each subject or the subject's 
legally acceptable representative before any study-specific activity is performed.  The 
informed consent form used in this study, and any changes made during the course of the 
study, must be prospectively approved by both the IRB/IEC and the Sponsor before use.  The 
enrolling physician will retain the original of each subject's signed consent form.
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20. Section 13; Sponsor Discontinuation Criteria
Change From
From 1st paragraph
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/IEC, drug safety problems, or at the discretion of Pfizer the 
Sponsor.  
If a study is prematurely terminated or discontinued, Pfizer the Sponsor or designee will 
promptly notify the enrolling physician.  After notification, the enrolling physician must 
contact all participating subjects within one month.  As directed by Pfizer, all study materials 
must be collected and all questionnaires completed to the greatest extent possible.
Change To
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/IEC, drug safety problems, or at the discretion of the Sponsor.  
If a study is prematurely terminated or discontinued, the Sponsor or designee will promptly 
notify the enrolling physician.  After notification, the enrolling physician must contact all 
participating subjects within one month.  As directed by Pfizer, all study materials must be 
collected and all questionnaires completed to the greatest extent possible.
21. Section 14; Communication and Publication of Study Results
Change From
Communication of results by Pfizer:
Pfizer fulfils its commitment to publicly disclose the results of studies through postings on 
ClinicalStudyResults.org.  Pfizer posts the results of studies that fall into either of the 
following categories:
•
Studies that Pfizer registered on www.clinicaltrials.gov, (ClinicalTrials.gov) 
regardless of the reason for registration; OR
•
All other studies for which the results have scientific or medical importance as 
determined by Pfizer.
For studies involving a Pfizer product, the timing of the posting depends on whether the 
Pfizer product is approved for marketing in any country at the time the study is completed.
•
For studies involving products already approved in any country and for studies 
that do not involve a Pfizer product, Pfizer posts results within one year after 
study completion, defined as last subject, last visit (LSLV);
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•
For studies involving products that are not yet approved in any country, Pfizer 
posts the results of already-completed studies within one year after the first 
regulatory approval of the product;
•
For studies involving products whose drug development is discontinued before 
approval, Pfizer posts the results of already-completed studies within one year 
after such discontinuation.
Pfizer's posting on ClinicalStudyResults.org includes the following elements:
•
Protocol title, study phase, and indication;
•
A link to approved product labeling, if applicable;
•
The synopsis of study results;
•
Citations of known study publications;
•
Legal disclaimer.
If posting of study results to ClinicalStudyResults.org jeopardizes a planned publication of 
the study results, a Pending Full Publication notice is substituted for the synopsis until the 
study results publication has issued or two years have elapsed, whichever occurs first. 
Pfizer posts citations only for publications that are accessible in recognized (searchable) 
publication databases.  Single-centre results publications for a multi-centre study are 
generally not posted because they may not accurately reflect the results of the study.
Publication of study results is discussed in the Clinical Study Agreement.
Communication of Results 
Where required by applicable regulatory requirements, an investigator signatory will 
be identified for the approval of the clinical study report.  The investigator will be 
provided reasonable access to statistical tables, figures, and relevant reports and will 
have the opportunity to review the complete study results at a Sponsor site or other 
mutually-agreeable location.
Sponsor will also provide the investigator with the full summary of the study results.  
The investigator is encouraged to share the summary results with the study subjects, as 
appropriate.
The results summary will be posted to an internet-based study register at the time of 
the first regulatory approval or within 12 months of study completion or of any decision 
to terminate development.  In addition, a manuscript will be submitted to a peer-
reviewed journal for publication within 12 months of the first regulatory approval or 
within 12 months of study completion or of any decision to terminate development.  
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When manuscript publication in a peer-reviewed journal is not feasible, further study 
information will be posted to an internet-based study register to supplement the results 
summary.
Publications by Investigators
ViiV Healthcare has no objection to publication by Investigator of any information 
collected or generated by Investigator, whether or not the results are favorable to the 
Investigational Drug.  However, to ensure against inadvertent disclosure of Confidential 
Information or unprotected Inventions, Investigator will provide ViiV Healthcare 
and/or designee an opportunity to review any proposed publication or other type of 
disclosure before it is submitted or otherwise disclosed.
Investigator will provide manuscripts, abstracts, or the full text of any other intended 
disclosure (poster presentation, invited speaker or guest lecturer presentation, etc.) to 
ViiV Healthcare /and/or designee at least 30 days before they are submitted for 
publication or otherwise disclosed.  If any patent action is required to protect 
intellectual property rights, Investigator agrees to delay the disclosure for a period not 
to exceed an additional 60 days.
Investigator will, on request, remove any previously undisclosed Confidential 
Information (other than the Study results themselves) before disclosure.
If the Study is part of a multi-centre study, Investigator agrees that the first publication 
is to be a joint publication covering all centers.  However, if a joint manuscript has not 
been submitted for publication within 12 months of completion or termination of the 
Study at all participating sites, Investigator is free to publish separately, subject to the 
other requirements of this Section.
For all publications relating to the Study, Institution will comply with recognized 
ethical standards concerning publications and authorship, including Section II -
“Ethical Considerations in the Conduct and Reporting of Research” of the Uniform 
Requirements for Manuscripts Submitted to Biomedical Journals, 
http://www.icmje.org/index.html#authorship, established by the International 
Committee of Medical Journal Editors. 
Publication of study results is also provided for in the Clinical Study Agreement 
between Pfizer and the Institution.  In this section entitled Publications by 
Investigators, the defined terms shall have the meanings given to them in the Clinical 
Study Agreement.
Change To
Publication of study results is discussed in the Clinical Study Agreement.
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Communication of Results 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report.  The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a Sponsor site or other 
mutually-agreeable location.
Sponsor will also provide the investigator with the full summary of the study results.  The 
investigator is encouraged to share the summary results with the study subjects, as 
appropriate.
The results summary will be posted to an internet-based study register at the time of the first 
regulatory approval or within 12 months of study completion or of any decision to terminate 
development.  In addition, a manuscript will be submitted to a peer-reviewed journal for 
publication within 12 months of the first regulatory approval or within 12 months of study 
completion or of any decision to terminate development.  When manuscript publication in a 
peer-reviewed journal is not feasible, further study information will be posted to an 
internet-based study register to supplement the results summary.
Publications by Investigators
ViiV Healthcare has no objection to publication by Investigator of any information collected 
or generated by Investigator, whether or not the results are favorable to the Investigational 
Drug.  However, to ensure against inadvertent disclosure of Confidential Information or 
unprotected Inventions, Investigator will provide ViiV Healthcare and/or designee an 
opportunity to review any proposed publication or other type of disclosure before it is 
submitted or otherwise disclosed.
Investigator will provide manuscripts, abstracts, or the full text of any other intended 
disclosure (poster presentation, invited speaker or guest lecturer presentation, etc.) to ViiV 
Healthcare /and/or designee at least 30 days before they are submitted for publication or 
otherwise disclosed.  If any patent action is required to protect intellectual property rights, 
Investigator agrees to delay the disclosure for a period not to exceed an additional 60 days.
Investigator will, on request, remove any previously undisclosed Confidential Information 
(other than the Study results themselves) before disclosure.
If the Study is part of a multi-centre study, Investigator agrees that the first publication is to 
be a joint publication covering all centers.  However, if a joint manuscript has not been 
submitted for publication within 12 months of completion or termination of the Study at all 
participating sites, Investigator is free to publish separately, subject to the other requirements 
of this Section.
For all publications relating to the Study, Institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 
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Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors. 
Publication of study results is also provided for in the Clinical Study Agreement between 
Pfizer and the Institution.  In this section entitled Publications by Investigators, the defined 
terms shall have the meanings given to them in the Clinical Study Agreement.
22. Section 15.1; Scientific Steering Committee
Change From
Last sentence
. . . In the event of recommendations for a significant change by the SSC, Pfizer the Sponsor
will notify regulatory agencies where necessary, as per legal or regulatory requirements.
Change To
. . . In the event of recommendations for a significant change by the SSC, the Sponsor will 
notify regulatory agencies where necessary, as per legal or regulatory requirements
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