Phase III Study of the Virologic Efficacy and Safety of Dolutegravir-Containing Versus Efavirenz-Containing Antiretroviral Therapy Regimens in HIV-1-Infected Pregnant Women and Their Infants
Phase: PHASE3
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Letter of Amendment #3 
Page 1 of 5 
10 June 2020 
IMPAACT 2010 Protocol Version 2.0 
Letter of Amendment #3 for: 
 
IMPAACT 2010 
Phase III Study of the Virologic Efficacy and Safety of 
Dolutegravir-Containing versus Efavirenz-Containing Antiretroviral Therapy 
Regimens in HIV-1-Infected Pregnant Women and their Infants 
 
Version 2.0, dated 8 December 2017 
 
DAIDS Study ID #30129 
IND #133,438 
 
Letter of Amendment Date: 10 June 2020 
 
 
Table of Contents 
 
Information/Instructions to Study Sites from the Division of AIDS ............................................................ 1 
Letter of Amendment Signature Page ........................................................................................................... 2 
Summary of Modifications, Rationale, and Implementation ........................................................................ 3 
 
 
Information/Instructions to Study Sites from the Division of AIDS 
 
The information contained in this Letter of Amendment (LoA) affects the IMPAACT 2010 study and 
must be submitted to site Institutional Review Boards and/or Ethics Committees (IRBs/ECs) as soon as 
possible for their review and approval. Approval must also be obtained from other site regulatory entities 
if applicable per the policies and procedures of the regulatory entities. All applicable IRB/EC and 
regulatory entity requirements must be followed. 
 
This LoA incorporates the contents of protocol Clarification Memorandum (CM) #2, which was issued on 
31 March 2020 to safeguard the health and well-being of IMPAACT 2010 study participants in the 
context of circulating SARS-CoV-2 and the associated COVID-19 pandemic. Per the study Sponsor, sites 
were instructed to implement the guidance provided in CM #2 immediately. 
 
Upon obtaining IRB/EC approvals and any other applicable regulatory entity approvals, sites are required 
to submit an LoA registration packet to the DAIDS Protocol Registration Office (DAIDS PRO) at the 
Regulatory Support Center. Sites will receive a registration notification for the LoA after the DAIDS PRO 
verifies that all required registration documents have been received and are complete. Sites should not 
await this notification before implementing this LoA.  
 
Please file this LoA, all associated IRB/EC and regulatory entity correspondence, and all correspondence 
with the DAIDS PRO in your essential document files for IMPAACT 2010. 
 

Letter of Amendment #3 
Page 2 of 5 
10 June 2020 
IMPAACT 2010 Protocol Version 2.0 
IMPAACT 2010 
Phase III Study of the Virologic Efficacy and Safety of 
Dolutegravir-Containing versus Efavirenz-Containing Antiretroviral Therapy 
Regimens in HIV-1-Infected Pregnant Women and their Infants 
 
DAIDS Study ID #30129 
 
 
Version 2.0, Letter of Amendment #3 
Letter of Amendment Signature Page 
 
 
I will conduct this 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 Council 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. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator of Record 
  
 
Date 
 
 
 
 
 
 
 
 
 
 
Name of Investigator of Record  
 
(printed) 
 
 

Letter of Amendment #3 
Page 3 of 5 
10 June 2020 
IMPAACT 2010 Protocol Version 2.0 
Summary of Modifications, Rationale, and Implementation 
 
This LoA incorporates the contents of protocol Clarification Memorandum (CM) #2, which was issued on 
31 March 2020 to safeguard the health and well-being of study participants in the context of circulating 
SARS-CoV-2 and the associated COVID-19 pandemic. CM #2 provided operational flexibility for 
conducting study visits and procedures when needed to ensure ongoing access to maternal study drug and 
to prioritize the conduct of clinically and scientifically important maternal and infant evaluations when 
possible.    
 
Consistent with the instructions provided in CM #2, implementation of this LoA is expected to be time-
limited in relation to the COVID-19 pandemic. In consultation with IMPAACT Network leadership and 
the study Sponsor, the IMPAACT 2010 Protocol Team will determine when, in the future, the 
specifications of this LoA are no longer applicable. When such a determination is made, study sites will 
be formally notified and instructed to inform IRBs/ECs and other applicable regulatory entities. 
 
  
Operational Guidance from Protocol CM #2, dated 31 March 2020 
 
This CM provides operational guidance to study sites from the IMPAACT 2010 Protocol Team. The 
Protocol Team acknowledges that the extent to which site operations may be disrupted by the COVID-19 
pandemic may vary across sites and over time. All sites should follow applicable government, health 
authority, and institutional policies with respect to conduct of study visits and procedures, with 
utmost importance placed on the health and well-being of study participants and study staff. Site 
investigators should continue to follow current protocol specifications for communication with the 
Protocol Team and/or Clinical Management Committee and should contact the Clinical Management 
Committee (impaact.2010cmc@fstrf.org) with any questions or concerns regarding this CM or 
management of study participants.  
 
Visit Scheduling 
 
Sites that anticipate operational disruptions or closures in the near future are advised to conduct study 
visits early in the allowable visit window. Visits conducted prior to opening of the allowable window 
would also be preferred to completely missing a visit at a later date. 
 
Sites that are currently experiencing operational disruptions or closures are advised to conduct study 
visits late in the allowable visit window. Visits conducted after closing of the allowable window 
would also be preferred to completely missed visits.  
 
Effective with the issuance of this CM, the allowable window for conducting maternal and infant 
Week 50 Visits is broadened to include up to 12 weeks before and up to 24 weeks after the visit target 
date.  
 
Prioritization of Study Visit Procedures 
 
Sites with full capacity to conduct study visits in-person at the study clinic should continue to do so in 
full compliance with the protocol. 
 
Sites may also conduct study visits — in full or in part — off-site if permitted by applicable 
government, health authority, and institutional policies. Where this option is permitted, site staff 
should communicate with maternal participants to determine in advance where and when such visits 
will take place, with adequate protections for safety, privacy, and confidentiality. Off-site visit 
procedures should be conducted by site staff who are adequately qualified and trained to conduct the 
procedures, as determined by the site Investigator of Record (IoR), with attention paid to occupational 
health, biohazard containment, and specimen and data chain of custody. These staff should also be 
adequately qualified and trained to immediately assess and/or manage any adverse events or social 

Letter of Amendment #3 
Page 4 of 5 
10 June 2020 
IMPAACT 2010 Protocol Version 2.0 
impacts that may occur during the visits. If adverse events requiring further evaluation or 
management are identified during an off-site visit, staff conducting the visit should arrange for 
appropriate clinical management, in consultation with the IoR or designee as needed.  
 
Sites with limited capacity to conduct in-person study visits should prioritize maternal HIV-1 RNA 
(viral load) testing and infant diagnostic HIV nucleic acid testing (NAT). If these tests cannot be 
performed consistent with a site’s Protocol Analyte List, the tests may be performed in alternate 
laboratories using alternate assays (alternate laboratories must adhere to local regulations for clinical 
laboratory testing).  
­ Maternal serum creatinine testing is the next highest priority (following maternal HIV-1 RNA 
testing and infant NAT), followed by other maternal chemistries and hematology. Specimen 
collection for storage is of lowest priority. 
­ Medical and medication histories may be obtained remotely (e.g., by telephone) 
­ Adherence assessment, counseling, and support may be provided remotely.  
­ Contraception counseling may be provided remotely. Sites should discuss options for ongoing 
access to contraception throughout the duration of study participation. 
­ Questionnaires may be administered remotely. 
­ DXA scans may be skipped/missed. 
 
Study Drug Supply 
 Prior to the Week 50 visit, sites are advised to dispense maternal study drug supplies in quantities 
sufficient for the remainder of the study follow-up period, i.e., through the end of the Week 50 visit 
window.  
 At the Week 50 visit, where feasible, sites are encouraged to provide a supply of non-study ARVs or 
to implement other post-study access plans to facilitate successful maternal transition to non-study 
ART and care. 
 Where feasible, sites are encouraged to implement study drug delivery options involving outdoor pick-
up or drop-off. Where outdoor pick-up or drop-off is not feasible, the Pharmacy Guidelines and 
Instructions for DAIDS Clinical Trials Networks permit shipment or courier of study drug from the site 
directly to participants. This method should only be used in the short-term and if permissible per local 
institutional and IRB/EC policies. Refer to the Guidelines for additional details on this method. 
 Sites are permitted to utilize rapid urine pregnancy test kits (either performed by study staff or given to 
and performed by mothers themselves) in the context of these study drug pick-up or drop-off options. 
If pregnancy testing cannot be performed for any reason, however, study drug supplies should still be 
provided. Dolutegravir will not be provided to any mother who reports that she is newly pregnant.  
 
Documentation 
 
Site-specific contingency plans, and the implementation thereof, should be documented in essential 
document files for IMPAACT 2010.  
 
Documentation should be entered in participant study charts in real-time should any of the following 
occur: 
­ Missed visits  
­ Out-of-window visits 
­ Off-site visits (document the location of the visit) 
­ Incomplete or partial visits (document which procedures were performed and which were not) 
­ Remote contacts performed in lieu of in-person visits (document method used to complete the 
contact and which procedures were performed) 
­ Any other participant contacts  
­ Use of alternate laboratories or alternate laboratory assays 
­ Alternate provision of study drug  

Letter of Amendment #3 
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10 June 2020 
IMPAACT 2010 Protocol Version 2.0 
 
In consultation with the Division of AIDS, the IMPAACT Network is developing comprehensive 
guidance for documenting and/or reporting protocol deviations that may occur due to limited site 
capacity to conduct study visits or procedures during the COVID-19 pandemic. Similar guidance will 
be provided for documentation of use of alternate laboratories or alternate laboratory assays. Once 
this Network-level guidance is available, it will be provided in a separate communication to all sites.