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)

A5324, Version 2.0 LOA #4 (10/23/20) 
IND Number: 126,854 
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ACTG NETWORK COORDINATING CENTER 
Social & Scientific Systems, Inc., a DLH Company 
 
 
 
 
8757 Georgia Avenue, 12th Floor 
Silver Spring, MD  20910-3714  
 
 
 
 
 
 
Phone: 301-628-3000 
Fax: 301-628-3302 
 
 
 
LETTER OF AMENDMENT 
 
DATE:  
October 23, 2020 
 
TO: 
 
ACTG CTU Principal Investigators, CRS Leaders, and CTU/CRS Coordinators 
 
FROM:  
A5324 Protocol Team  
 
SUBJECT: 
Letter of Amendment #4 for Protocol A5324 
 
 
The following information affects the A5324 study and must be forwarded to each site’s 
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 the IRB/EC before 
implementation.  
 
The following information may also affect the Sample Informed Consent. The site 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 file. 
 
This LOA is being implemented for the following reasons: 
• 
To update the protocol team roster.  
• 
To incorporate the instructions for alternate study product dispensing and completion of post-entry 
evaluations that were provided through A5324 Version 2.0 Clarification Memo (CM) #3 for participant 
and site staff safety and flexibility to complete study visits during the ongoing COVID-19 pandemic. 
• 
To update the sample informed consent (SIC) to include information for participants about 
adjustments that may be made to their study visits during the ongoing COVID-19 pandemic.  
 
The following are changes (noted in bold or strikethrough) to A5324, Version 2.0, 08/25/20, titled “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.” These changes will be included in the next version of the 
A5324 protocol if it is amended at a future date. Changes that have already been made (either by LOA or 
by CM) have been incorporated in the excerpted text shown below (and are no longer presented in bold 
or strikethrough).  
 
1. A Protocol Signature Page (PSP) is appended for submission to DAIDS Protocol Registration System 
(DPRS) as part of the LOA registration packet. 
 

A5324, Version 2.0 LOA #4 (10/23/20) 
IND Number: 126,854 
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2. In the Protocol Team Roster, the following updates have been made: 
 
Data Manager 
Thomas Miller, BS 
Frontier Science & Technology Research Foundation, Inc. 
4033 Maple Road 
Amherst, NY 14226 
Phone: 716-834-0900 
E-mail: tmiller@fstrf.org 
Dave Rusin, MT (ASCP), CCRP 
Frontier Science & Technology Research Foundation, Inc.  
4033 Maple Road  
Amherst, NY  14226-1056 
Phone: 716-834-0900 x7333  
FAX: 716-834-8432 
E-Mail: rusin.david@fstrf.org 
 
DAIDS Pharmacist 
Justine Beck, PharmD 
Pharmaceutical Affairs Branch 
DAIDS, NIAID, NIH 
5601 Fishers Lane, Room 9D39 
Rockville, MD 20852 
Phone: 301-761-5288 
Fax: 240-627-3112 
E-mail: justine.beck@nih.gov 
Nayri Khairalla, PharmD, BS 
Pharmaceutical Affairs Branch 
DAIDS, NIAID, NIH 
5601 Fishers Lane, 9D35 
Rockville, MD 20852 
Phone: 301-761-6659 
FAX: 240-627-3112 
E-Mail: nayri.khairalla@nih.gov 
 
Neuropsychologist 
Robert H. Paul, PhD 
University of Missouri, St. Louis 
Missouri Institute of Mental Health 
ITE Building 
4633 World Parkway Circle 
Berkeley, MO 63134 
Phone: 314-516-8403 
Fax: 636-544-8522 
E-mail: robert.paul@mimh.edu 
 
NIMH Representative 
Deborah Ann Colosi, PhD 
Division of AIDS Research 
National Institute of Mental Health/NIH  
6001 Executive Boulevard 
NSC 6115D-9619 
Bethesda, MD 20892  
Phone: 301-443-8542 
E-Mail: Deborah.Colosi@nih.gov 
 

A5324, Version 2.0 LOA #4 (10/23/20) 
IND Number: 126,854 
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Laboratory Data Manager 
Kacey Matecki, BS 
Frontier Science & Technology Research Foundation, Inc. 
4033 Maple Road 
Amherst, NY 14226 
Phone: 716-834-0900, Ext. 7272 
E-mail: matecki@frontierscience.org 
Andee Fox, MPH 
Frontier Science & Technology Research Foundation 
4033 Maple Road 
Amherst, NY 14226 
Phone: 716-834-0900 Ext. 7276 
E-Mail: fox@fstrf.org 
 
3. In section 5.1.2, Administration and Dispensing, the following paragraph has been added as the last 
paragraph in this section, below item number 5.1.2.2: 
 
For rare instances or emergency cases, the Pharmacy Guidelines and Instructions for DAIDS 
Clinical Trials Networks permits shipment by mail or courier of study product from the site 
directly to participants. This method should only be used on a short-term basis and if 
permissible by the site’s institution. If this method is to be implemented, each site’s 
Pharmacist of Record (PoR) must develop appropriate procedures for the shipment or courier 
of study product to identified participants in accordance with these guidelines, and document 
chain of custody. Prior to implementation, the site PoR must coordinate with site clinic staff to 
determine the appropriateness of this method for applicable protocols and participants. 
 
4. In section 6.1, Schedule of Evaluations, the visit window for weeks 36 to 96 has been changed 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 
Visit 
Windows 
 
 
 
± 1 
wk 
± 2 
wks 
- 4 wks, + 8 12 wks 
 
 
 
5. In section 6.2.3, Post-Entry Evaluations, the following instructions have been added to the On-
Treatment Evaluations subsection: 
 
Alternate Completion of Post-Entry Evaluations 
• 
If the participant’s visit is postponed within the extended visit window, the site should 
ensure that the participant has sufficient supply of the study products to last him or 
her to the point when he or she can come to the clinic. 
• 
If the participant does not have enough supply of study products to allow the visit to 
be postponed, the site must attempt to contact the participant by phone or other 
method available. 
− 
During the remote contact for visit week 72 or week 96, the site should conduct a 
safety follow-up (such as inquiring about signs and symptoms) to determine if any 
AEs or serious adverse events (SAEs) have occurred since the last visit and if the 
participant needs medical follow-up. Additionally, the site should complete the 
questionnaires and adherence assessment per section 6.3.9, section 6.3.10, and 
MOPS section 4. All other evaluations and stored samples that will be missing for 
the visits, and the reason why they are missing, must be documented in the 
participant’s study file. 
− 
At all visits except week 96, the site should confirm if the participant is able to 

A5324, Version 2.0 LOA #4 (10/23/20) 
IND Number: 126,854 
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receive a new supply of study medications if it is shipped via mail or sent via 
courier (see section 5.1.2). If a participant is unable to pick up or receive study 
medications via shipment or courier, the site should consult the study core team 
(actg.corea5324@fstrf.org) for further guidance. 
− 
If safety laboratory evaluations, and a pregnancy test for female participants of 
reproductive potential, cannot be performed, the continuation of study treatment is 
at the discretion of the Investigator of Record (IoR). The site should inform the 
study core team of the decision of the IoR. 
 
6. In section 6.2.4, Discontinuation Evaluations, the following instructions have been added to the 
Premature Treatment Discontinuation Evaluations subsection: 
 
Alternate Completion of Post-Entry Evaluations 
• 
The visit can be postponed within the extended visit window if needed to safely 
conduct a face-to-face clinic visit. If the participant can safely be seen in the clinic, the 
site should perform all the evaluations for the visit per the SOE in section 6.1, Letter of 
Amendment (LOA) #1, and LOA #2. 
• 
If the visit cannot be completed with a face-to-face visit despite the extended visit 
window, the site must attempt to contact the participant by phone or other method 
available. During the remote contact for visit week 72 or week 96, the site should 
conduct a safety follow-up (such as inquiring about signs and symptoms) to determine 
if any AEs or SAEs have occurred since the last visit and the participant needs 
medical follow-up. Additionally, the site should complete the questionnaires and 
adherence assessment per section 6.3.9, section 6.3.10, and MOPS section 4. All other 
evaluations and stored samples that will be missing for the visits, and the reason why 
they are missing, must be documented in the participant’s study file.  
 
7. In Appendix I, Sample Informed Consent (SIC), the following has been added as a new subsection, 
before the Optional Lumbar Puncture subsection, in the section WHAT DO I HAVE TO DO IF I AM IN 
THIS STUDY?: 
 
COVID-19 Pandemic Considerations 
During the ongoing COVID-19 pandemic, the following adjustments may be made to your 
study visits: 
• 
If there is an outbreak of COVID-19 in your community and you are unable to come to 
the study clinic, your study doctor or staff member will try to contact you by phone or 
other remote method if you have a study visit due. During this contact: 
− 
You will be asked about your health since your last study visit or contact. 
− 
If there are questionnaires to be completed for a particular study visit, you will be 
asked some questions about how you are feeling, how well you are able to perform 
your daily activities, your alcohol and drug use, and how well you are taking your 
current anti-HIV drugs. 
− 
If you did not have to stop taking the study medications early: 
o 
You will be asked if you are able to pick up your new supply of study 
medications from the study clinic. If you are not able to pick up the study 
medications, you will be asked if you can receive the study medications 
through the mail or a courier. You and your study doctor or staff member 
will decide on the best way to make sure you receive your new supply of 
study medications. 
o 
Your study doctor or staff member will inform you if you can continue 
taking the study medications. 
 

A5324, Version 2.0 LOA #4 (10/23/20) 
IND Number: 126,854 
Page 5 of 5 
 
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 
 
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 US 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