A Randomized, Double-Blinded, Placebo-Controlled Trial Comparing Antiretroviral Intensification With Maraviroc and Dolutegravir With No Intensification or Intensification With Dolutegravir Alone for the Treatment of Cognitive Impairment in HIV
Phase: PHASE4
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

ACTG Network Coordinating Center 
Social & Scientific Systems, Inc. 
 
 
 
 
Telephone: 301-628-3000 
8757 Georgia Avenue, 12th Floor 
 
 
 
 
Fax: 
301-628-3302 
Silver Spring, MD  20910 
 
 
LETTER OF AMENDMENT 
 
 
DATE:  
March 29, 2018 
 
TO: 
 
ACTG CTU Principal Investigators, CRS Leaders, and CTU/CRS Coordinators 
 
FROM: 
A5324 Protocol Team  
 
SUBJECT: 
Letter of Amendment #1 for Protocol A5324, Version 2.0, 08/25/17, entitled “A 
Randomized, Double-Blinded, Placebo-Controlled Trial Comparing Antiretroviral 
Intensification with Maraviroc and Dolutegravir with No Intensification or 
Intensification with Dolutegravir Alone for the Treatment of Cognitive Impairment 
in HIV” 
 
 
The following information impacts the A5324 study and must be forwarded to your 
institutional review board (IRB)/ethics committee (EC) as soon as possible for their 
information and review. This Letter of Amendment (LOA) must be approved by your 
IRB/EC before implementation.  
 
The following information may also impact the Sample Informed Consent. Your IRB/EC is 
responsible for determining the process of informing participants of the contents of this 
LOA. 
 
Upon receiving final IRB/EC and any other applicable regulatory entity approvals for this 
LOA, sites should implement the LOA immediately. Sites are still required to submit an 
LOA registration packet to the DAIDS Protocol Registration Office (PRO) at the 
Regulatory Support Center. Sites will receive a registration notification for the LOA once 
the DAIDS PRO verifies that all required LOA registration documents have been received 
and are complete. An LOA registration notification from the DAIDS PRO is not required 
prior to implementing the LOA. A copy of the LOA registration notification, along with 
this letter and any IRB/EC correspondence, should be retained in the site’s regulatory 
files. 
 
 
 
 

 
 
 
A5324 Version 2.0, LOA #1 (03/29/18) 
IND Number: 126,854 
 
 
Page 2 of 7 
 
Page 
TABLE OF CONTENTS 
 
1. 
Section 5.1.2 ....................................................................................................................... 3 
2. 
Section 6.1 .......................................................................................................................... 3 
3. 
Section 6.2.4 ....................................................................................................................... 3 
4. 
Section 6.3 .......................................................................................................................... 3 
5. 
Section 6.3.5 ....................................................................................................................... 4 
6. 
Section 6.3.11 ..................................................................................................................... 4 
7. 
Section 6.3.15 ..................................................................................................................... 4 
8. 
Section 10.2.1 ..................................................................................................................... 4 
9. 
Section 10.2.2 ..................................................................................................................... 4 
10. Section 11.3.2 ..................................................................................................................... 5 
11. Section 12.2 ........................................................................................................................ 5 
12. Sample Informed Consent, WHAT DO I HAVE TO DO IF I AM IN THIS STUDY? .............. 5 
13. Sample Informed Consent, WHAT ARE THE RISKS OF THE STUDY? ............................. 5 
14. Sample Informed Consent, WHAT ABOUT CONFIDENTIALITY? ....................................... 6 
15. Protocol Signature Page ..................................................................................................... 6 
 
 
 

 
 
 
A5324 Version 2.0, LOA #1 (03/29/18) 
IND Number: 126,854 
 
 
Page 3 of 7 
 
The specific updates that are being made via this LOA #1 to A5324, Version 2.0, 08/25/17, 
are listed below. An italicized statement provides the location of the update within the identified 
section of the protocol. New text resulting from this LOA appears in bold; deleted text is shown 
in strikethrough. Changes that were made in the excerpted text shown below when the protocol 
was amended to Version 2.0 are no longer presented in bold. 
 
1. Section 5.1.2 
 
The paragraph below is being added as the second paragraph in this section. 
 
At study entry, dispense either a 12-week supply of study medication or a sufficient 
quantity to last until the participant’s next visit. Refer to section 6.3.11 for the study 
medication dispensing schedule. 
 
2. Section 6.1 
 
In this section, Stored Plasma is being deleted from the Confirmation of VF visit as shown 
below. 
 
Evaluation Screening 
Pre-
Entry  Entry 
Post-Entry Evaluations 
(Weeks) 
Confirmation 
of VF 
Premature 
Study/Treatment 
Discontinuation 
2 
4 12 24 36 48 60 72 84 96 
Stored 
Plasma 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
3. Section 6.2.4 
 
In this section, the Premature Treatment Discontinuation Evaluations sub-section is being 
updated as shown below. 
 
Premature Treatment Discontinuation Evaluations  
Participants who discontinue the study medications before the end of the study should have 
the premature treatment discontinuation evaluations done within 14 days after stopping 
study medications. Participants will be followed off study treatment/on study. They should be 
encouraged to continue to attend all study visits and receive study evaluations as per 
section 6.1, with the exception of the adherence questionnaires PK studies, and optional 
lumbar puncture, through completion of the study. 
 
4. Section 6.3 
 
The first paragraph in this section is being updated as shown below. 
 
All clinical and laboratory information required by this protocol is to be present in the source 
documents. Sites must refer to the Source Document Guidelines on the DAIDS website for 
information about what must be included in the source document: 
https://www.niaid.nih.gov/sites/default/files/sourcedocappndx.pdf 
https://www.niaid.nih.gov/sites/default/files/daids-sourcedocpolicy.pdf. 

 
 
 
A5324 Version 2.0, LOA #1 (03/29/18) 
IND Number: 126,854 
 
 
Page 4 of 7 
 
 
5. Section 6.3.5 
 
In this section, height measurement at week 12 is being removed from the Targeted 
Physical Exam sub-section. 
 
Targeted Physical Exam 
After screening, a targeted physical examination, including height (at entry and week 12 
only), weight, and vital signs (temperature, pulse, and blood pressure) should be per section 
6.1, along with additional assessments based upon previously identified findings, diagnoses, 
or new signs or symptoms since the last visit. 
 
6. Section 6.3.11 
 
This section is being updated as shown below. 
 
At study entry and thereafter, dispense either a 12-week supply of study medication or a 
sufficient quantity to last until the participant’s next visit. Beginning with the week 12 
visit, study medications will be dispensed every 12 weeks. At weeks 36, 60, and 84, 
participants will return for study medication dispensing only. No other study evaluations will 
be performed. 
 
7. Section 6.3.15 
 
In this section, the second paragraph in the Plasma sub-section is being deleted.  
 
Plasma  
Plasma will be collected and stored for single copy assay (SCA).   
 
Plasma collected at the confirmation of VF visit will be stored for resistance and tropism 
testing if VF is confirmed (see sections 6.3.19 and 6.3.20). 
 
8. Section 10.2.1 
 
In this section, the sentence below is being added to the end of the first paragraph. 
 
The last three doses of study medication taken before the PK sample collection will 
be recorded on the CRF. 
 
9. Section 10.2.2 
 
In this section, the sentence below is being added to the end of the first paragraph. 
 
The last three doses of study medication taken before the trough sample collection 
will be recorded on the CRF. 
 

 
 
 
A5324 Version 2.0, LOA #1 (03/29/18) 
IND Number: 126,854 
 
 
Page 5 of 7 
 
10. Section 11.3.2 
 
This section is being updated as shown below. 
 
The site investigator will make study documents (eg, consent forms, drug distribution forms, 
CRFs) and pertinent hospital or clinic records readily available for inspection by the local 
IRB/EC, the site monitors, the FDA, the NIAID, the OHRP, and the industry supporter(s) or 
designee, and other local, US, and international regulatory entities for confirmation of 
the study data. 
 
11. Section 12.2 
 
This section is being updated as shown below. 
 
All laboratory specimens, evaluation forms, reports, and other records that leave the site will 
be identified by coded number only to maintain participant confidentiality. All records will be 
kept locked. All computer entry and networking programs will be done with coded numbers 
only. Clinical information will not be released without written permission of the participant, 
except as necessary for monitoring by the ACTG, IRB/EC, FDA, NIAID, OHRP, other 
government agencies local, US, or international regulatory authorities as part of their 
duties, or the industry supporter(s) or designee. 
 
12. Sample Informed Consent, WHAT DO I HAVE TO DO IF I AM IN THIS STUDY? 
 
In this section, the first paragraph in the Virologic Failure sub-section is being updated as 
shown below. 
 
You will be tested for virologic failure at weeks 12, 24, 48, 72, and 96. Virologic failure is 
when your anti-HIV drugs are not fully suppressing HIV in the blood. If the study staff sees 
that your viral load has gone up, you will be asked to have another viral load test done within 
30 days. About 2 teaspoons (10mL) of blood will be drawn for the viral load test. We will also 
draw an additional 1-2 about 4 teaspoons (20mL) (6mL) of blood that will be used for tests 
that check which anti-HIV drugs have stopped working on the HIV in your blood (resistance 
test) and if a specific type of anti-HIV drug will be able to control your HIV (tropism test) if the 
repeat viral load test shows that your viral load is still up. We will also ask you to fill out a 
questionnaire about how well you are taking your current anti-HIV drugs. 
 
13. Sample Informed Consent, WHAT ARE THE RISKS OF THE STUDY? 
 
In this section, the list of other side effects of dolutegravir (DTG) under the Risks of DTG 
(Tivicay) sub-section is being updated as shown below. 
 
Other side effects of DTG include: 
• 
Changes in liver test results, more common in people with hepatitis B or C 
• 
Trouble sleeping 
• 
Abnormal dreams 
• 
Tiredness 

 
 
 
A5324 Version 2.0, LOA #1 (03/29/18) 
IND Number: 126,854 
 
 
Page 6 of 7 
 
• 
Headache 
• 
Anxiety 
• 
Dizziness 
• 
Abdominal pain 
• 
Flatulence 
• 
Nausea, vomiting 
• 
Muscle and joint aches 
 
14. Sample Informed Consent, WHAT ABOUT CONFIDENTIALITY? 
 
The following updates are being made in this section: 
 
a. The second paragraph in the For Sites in the US sub-section is being updated as 
shown below. 
 
People who may review your records include the ACTG, U.S. Office for Human 
Research Protections (OHRP) or other government agencies as part of their duties, 
U.S. Food and Drug Administration (FDA), or other local, U.S., and international 
regulatory entities as part of their duties, (insert name of site) Institutional Review 
Board (a group that protects the rights and well-being of people in research), 
National Institutes of Health (NIH), study staff, study monitors, the drug company 
supporting this study, and its designees. Having a Certificate of Confidentiality does 
not prevent you from releasing information about yourself and your participation in 
the study. 
 
b. The second paragraph in the For Sites outside the US sub-section is being updated 
as shown below. 
 
Your records may be reviewed by the ACTG, U.S. Office for Human Research 
Protections (OHRP), U.S. Food and Drug Administration (FDA), or other local, 
U.S., and international regulatory entities as part of their duties, (insert name of 
site) IRB Institutional Review Board or Ethics Committee (a committee that 
protects the rights and safety of participants in research), National Institutes of 
Health (NIH), study staff, study monitors, and drug company supporting this study, 
and their designees. 
 
15. Protocol Signature Page 
 
Per a new regulatory requirement by the Division of AIDS (DAIDS), a Protocol Signature 
Page (PSP) is appended for submission to the DAIDS Protocol Registration System (DPRS) 
as part of the LOA registration packet. 
 
 
The information above will be incorporated into the next protocol version as necessary if the 
protocol is amended.

 
 
 
A5324 Version 2.0, LOA #1 (03/29/18) 
IND Number: 126,854 
 
 
Page 7 of 7 
 
 
 
 
A Randomized, Double-Blinded, Placebo-Controlled Trial Comparing Antiretroviral 
Intensification with Maraviroc and Dolutegravir with No Intensification or Intensification 
with Dolutegravir Alone for the Treatment of Cognitive Impairment in HIV 
Version 2.0, 08/25/17  
 
SIGNATURE PAGE 
 
 
I will conduct the study in accordance with the provisions of this protocol and all applicable 
protocol-related documents. I agree to conduct this study in compliance with United States (US) 
Health and Human Service regulations (45 CFR 46); applicable U.S. Food and Drug 
Administration regulations; standards of the International Conference on Harmonization 
Guideline for Good Clinical Practice (E6); Institutional Review Board/Ethics Committee 
determinations; all applicable in-country, state, and local laws and regulations; and other 
applicable requirements (e.g., US National Institutes of Health, Division of AIDS) and 
institutional policies. 
 
 
 
 
 
Principal Investigator: _____________________________________________________ 
 
Print/Type 
 
 
 
 
 
Signed: _______________________________________________Date: _____________ 
 
Name/Title