KENYA MEDICAL RESEARCH INSTITUTE US ARMY MEDICAL RESEARCH DIRECTORATE - KENYA Mbagathi Road Nairobi, Kenya P.O. Box 606, 00621 Villages Mkt. Tel: 2729303, 2719694 Fax: 2714592 E-mail: info@usamru-k.org Date: 24 November, 2017 To: The Registrar, Pharmacy and Poisons Board, Expert Committee on Clinical Trial P.O. Box 27663- 00506 NAIROBI. KENYA. From: Isaac Tsikhutsu, MBChB, MMED, FPCCM. Principal Investigator ECCT 17/08/05 (KEMRI/SERU/CCR/0056/3411) KEMRI/WRP HIV Program P.O. Box 1357- 20200 Kericho. Tel; 052 5220 30686 Email: isaac.tsikhutsu@usamru-k.org RE: Amendment submission to ECCT17/08/05 for protocol titled: Phase I Safety and Pharmacokinetic Study of Maraviroc in HIV-1-Exposed Infants at Risk of Acquiring HIV-1 Infection” (SERU 3411/P2007). The purpose of this memo is to request PPB ECCT to review and approve the revised protocol documents for ECCT17/08/05. Initial approval for the above mentioned study was granted by ECCT via letter dated 11 October 2017 and SERU via SERU letter dated April 19, 2017. Since then revision has been made to the study Site Specific Addendum and ICFs to incoporate WRAIR IRB comments ( attached) and the purpose of this memo is to submit the following listed revised documents to ECCT for review and approval. Please find below summary of changes. Summary of changes 1. Site Specific Addendum(SSA): The SSA has been revised from version 1.2 dated 20 Feb 2017 to version 1.3 dated 14 June 2017 as below. i. Section 10: Removed other study sites from this section because they were already mentioned elsewhere in the protocol ii. Section 10.2.1: Specified that the legal age to provide consent is 18 years and older iii. Section 10.4.1: Added that Kericho Site will establish Standard Operating Procedures for eligibility determination. Added that for mothers who deliver elsewhere, arrangements will be made by the Kericho site to transport the mother and the baby to the Unilever Tea Central Hospital iv. Section 10.4.3: Addded that apart from maraviroc , the infant will also receive nevirapine and zidovudine as part of the standard of care for Prevention of Mother to Child Transmission of HIV. These drugs will be provided by the Kericho CRC. Added that instructions and adherence counseling will also be given to the mother on nevirapine and zidovudine. v. Section 10.4.4.17: Added that at each visit, the mother will receive counseling on the importance of adherence to the ART medications. This will be done by the pharmacy staff. Also added that only specimens where the subject’s mother give their consent for future use will be sent to the repository at the biomedical research institute, Rockville, Maryland. vi. Section 10.4.4.7: Specified the PMTCT regimens as nevirapine and zidovudine. vii. Section 13.1: Added that mothers are consenting for both their own participation and their babies participation in the study. viii. Section 13.3: Added a section on Communicable Disease reporting. ix. Section 13.15: Added KEMRI SERU, WRAIR IRB, Ministry o Health, Kenya Pharmacy and Poisons Board as organizations that information may be released to without written permission of the participant. 2. Informed Consent Forms (ICFs) a). Cohort 1 and Cohort 2 ICFs Both English and Kiswahili consents for cohort 1 and Cohort 2 got revised from version 1.2 dated 20 Feb 2017 to version 1.3 dated 14 June 2017 then to version 1.4 dated 24 July 2017 as shown below. Changes made on both English and Kiswahili ICF cohort 1 and cohort 2 from version 1.2 dated 20 Feb 2017 to version 1.3 dated 14 June 2017 1. Title section changes; • The funding agency was included. 2. Introduction section changes • The P.I credentials were added. • “You can search this Web site at any time” has been added. 3. Page 2 why is this study being done section • This is the first study in newborns to study safety and amount of maraviroc in blood of newborns. There have been no other Maraviroc studies done in newborns has been added. 4. Who can join this study • The age ranges for the pregnant women to be included in the study(18 years and over) has been added. It was noted that some of the language in this section is too technical and does not meet the requirements for an appropriate reading level thus The revisions have been made and the language has been simplified. 5. Who cannot take part in this study? • The changes made on this section was basically to make the language simpler. 6. Can my baby and i participate in other studies section • You and your baby may take part in this study, if you are also participating in another study known as P 1081. We will ensure that the amount of blood drawn will not exceed the safe limits for you and your baby, was added. 7. What do my baby and i have to do as part of this study • Abbreviations for CRC was written in full. • The logistics for transporting mothers and their babies who could have not delivered at Unilever hospital was added. 8. Why is this study being done? • This is the first study in newborns to study safety and amount of maraviroc in blood of newborns. There have been no other Maraviroc studies done in newborns. This has been added. 9. Who can join this study? • The legal age has been clarified to be 18 years and older. • The language was simplified to be understood by the participant. 10. Who cannot take part in this study? • The language was simplified to be understood by the participant. 11. Can my baby and I participate in other studies? • You and your baby may take part in this study, if you are also participating in another study known as P 1081. We will ensure that the amount of blood drawn will not exceed the safe limits for you and your baby. This was added. 12. What do my baby and I have to do as part of this study • . In case you will not deliver at the Unilever hospital please inform us immediately so that we provide transport for you from the hospital where you delivered to the Unilever hospital. This was added. • Your baby will also continue receiving two other drugs which are important to prevent you from passing the virus to the baby. Maraviroc does not substitute these drugs. This was added. • We will also continue counseling you on the importance of continuing taking your antiretroviral medications regardless of your baby's HIV status. This was added. • We will also draw blood for resistance and to check the amount of maraviroc in your baby’s blood here in the clinic. This was added. • We will try to give you the results of these tests when they have been tested during the study or after the study is over. This was added. • The results regarding the amounts of Maraviroc in the baby's blood will not be provided to you, as this is for research purposes only. This was added. 13. What are the risks of the study? • Maraviroc has been used extensively in adults and also has been tested and been shown to be safe in children from age 2 to 18 years, but has not been tested in children under 2 years of age. Therefore, the rates of some known side effects may differ and there maybe unknown side effects. This was added. • The drug is not currently approved for use in the age group being studied in the protocol. This was added. • The risks were split into common and uncommon side effects. • The heart problem and stroke were explained in a simpler language. 14. What about confidentiality • The groups that oversee the study , some institutions were listed twice, this was corrected. • The 4th paragraph was removed because it was a repetition. 15. What happens if I am injured/my baby is injured? • The NIH or the U.S. Federal Government will not provide long-term medical care or financial compensation for research-related injuries. This was added. • If the limit is exceeded, non-covered costs may be transferred to you and/or your health insurance provider. This was added. 16. Signature page • Spaces for thumbprint were added. • 1st and 2nd parent or guardian spaces for signing were added. Change made on both English and Kiswahili ICF cohort 1 and cohort 2 from version 1.3 dated 14 June 2017 to version 1.4 dated 24 July 2017. What are the risks of the study? • On the common side effects these were added; May get cancer, Kidney failure ( may occur in individuals who already have pre-existing kidney disease),Itchiness of the body, Fatigue(The baby may look tired),Joint pains, Red and discharging eyes, constipation, vomiting, Low amounts of red blood cell counts(anaemia). • The list above is not a complete list of all side effects for maraviroc. As a reminder, if your baby joins the study, we will tell you about the side effects of maraviroc your baby will take. This paragraph was deleted. b).Changes made on Consent Form for specimen storage and future use ICF for specimen storage and future use was revised from version 1.2 dated 20 Feb 2017 to version 1.3 dated 20 March 2017 on the Signature page as shown below; • Spaces for thumbprint were added. • 1st and 2nd parent or guardian spaces for signing were added Revisions made to the Cohort 1 and Cohort 2 consent forms (Version 1.4/Date 24 July 2017). 1. On pg. 2 of the consent forms, Section "Who Can Join This Study", item 7 references the exclusion criteria of the baby being born alone, then states in parentheses "not after multiple births." This may be confusing to subjects as it could be interpreted as the baby must be the first-born to the infected mother. Recommend that the consent form be revised to state that the baby is born alone, not as part of a multiple birth (where more than 1 baby is born at a time such as twins or triplets, etc.). The consent section “Who can join This study “has been revised to state the baby is born alone, not as part of multiple part as guided. 2. Additionally, on pg. 3, there are some formatting issues under the Section "Who Cannot Take Part in This Study", where items 1 and 2 appear to be combined in the same section. It is recommended that the study team review this section and separate the exclusion criteria pertaining to the baby testing as HIV positive. Items 1 and 2 have been separated under the Section "Who Cannot Take Part in This Study" as guided. 3. Consider naming the US locations/labs where study specimens will be analyzed (pg. 6). The following language identifying the location of the labs has been added on pg 6 under the header “Tests for how much Maraviroc is in your baby’s blood will be done at different laboratories”…The other tests will be done at the Pharmacology Speciality Laboratory at University of California San Diego (UCSD), California, USA. If you give permission for future use of your blood or baby’s blood , then it will be send to the Biomedical Research Institute in Rockville, Maryland, USA. Thank you for your time and review. Attachments: 1. SERU Amendment Approval letter dated October 18, 2017. 2. SSA version 1.3 dated 14 Jun 2017. 3. HRPO comment dated September 11, 2017. 4. English main ICF cohort 1 version 1.5 dated 10 Oct 2017(Cl and Rl). 5. Kiswahili main ICF cohort 1 version 1.5 dated 10 Oct 2017 (Cl and Rl). 6. English main ICF cohort 2 version 1.5 dated 10 Oct 2017 (Cl and Rl) 7. Kiswahili main ICF cohort 2 version 1.5 dated 10 Oct 2017 (Cl and Rl).

Letter of Amendment #2 for: IMPAACT 2007 Phase I Safety and Pharmacokinetic Study of Maraviroc in HIV-1-Exposed Infants at Risk of Acquiring HIV-1 Infection Ve rs ion 1.0, date d 13 April 2016 DAIDS Docume nt ID #20734 IND # 130,613 Le tte r of Ame ndme nt Date : 21 May 2018 Inform ation/Instructions to Study Sites from the Division of AIDS The information contained in this Letter of Amendment (LoA) impacts the IMPAACT 2007 study, including the study informed consent forms (ICFs), and must be submitted to site Institutional Review Boards (IRBs) and/or Ethics Committees (ECs) as soon as possible for their review and approval. Approval must also be obtained from site regulatory entities if applicable per the policies and procedures of the regulatory entities. All IRB/EC and regulatory entity requirements must be follow ed. Upon obtaining IRB/EC approval and any other applicable regulatory entity approvals, each site should immediately begin implementing this LoA. After all required approvals are obtained, all previously enrolled participants must re-consent to ongoing study participation using the updated site-specific ICFs. Re-consenting should take place at each enrolled participant’s next study visit after all required approvals are obtained. The updated ICFs should be used for all new participants. In addition, participants should not be enrolled into Cohort 2 (Stratum 2A and 2B) until after all required approvals for this LoA and the updated site-specific ICFs have been obtained. Sites are required to submit an LoA registration packet to the DAIDS Protocol Registration Office (DAIDS PRO) at the Regulatory Support Center (RSC). Sites w ill 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 aw ait this notification before implementing this LoA. Please file this LoA, all associated IRB/EC and regulatory entity correspondence, and all correspondence w ith the DAIDS PRO in your essential documents files for IMPAACT 2007. If the IMPAACT 2007 protocol is amended in the future, the contents of this LoA w ill be incorporated into the next version of the protocol. IMPAACT 2007 Phas e I Safe ty and Pharmacokine tic Study of Maraviroc in HIV-1-Expos e d Infants at Ris k of Acquiring HIV-1 Infe ction Ve rs ion 1.0, date d 13 April 2016 DAIDS Docume nt ID #20734 Le tte r of Ame ndme nt #2, date d 21 May 2018 Letter of Amendment Signature Page I w ill conduct this study in accordance w ith the provisions of this protocol and all applicable protocol- related documents. I agree to conduct this study in compliance w ith 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 law s 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) Sum m ary of Modifications and Rationale The follow ing modifications are included in this LoA: • To specify that participants enrolled in Cohort 2, Stratum 2A and Stratum 2B, in IMPAACT 2007 w ill be administered maraviroc oral solution at 8 mg/kg dose given tw ice daily. Table D in Appendix II, Maraviroc Weight Based Dosing Table for Solution, and the infant’s current w eight at the visit should be used to determine the dose. • Sections 9.2 and 10.3.2 are updated to clarify the dose-finding algorithm and PK guidelines for dose adjustment for Cohort 1 and Cohort 2. • Section 7.3.3, Grading Severity of Adverse Events, is updated to specify the use of the Corrected Version 2.1, dated July 2017 of the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events for grading severity of adverse events in IMPAACT 2007 and modifications made via Clarification Memorandum #1, dated 17 May 2017, are incorporated in this LoA. • Section 8.2.2 is updated for consistency with modifications in Section 7.1.1 in LoA #1 regarding Core Protocol Team consultation required for confirmed Grade 1 ALT. • The primary and secondary endpoints in Sections 9.3.1 and 9.3.3, respectively, are updated for consistency w ith modifications in Section 9.6.2.1 per LoA #1 and the study objectives. Section 9.7 has also been updated for consistency w ith the modifications in Sections 9.3.1 and 9.3.3. • Per ICH GCP E6 4.8.10(n) and DAIDS requirements, it is mandatory that all DAIDS -sponsored and/or supported trials include language that informs participants that other US, local, and international regulatory entities may also review study records. Protocol Section 11.2 and the sample ICFs have been updated accordingly. • The sample informed consent for Cohort 1 and Cohort 2 is updated to reflect the current DAIDS Drug Risk List for maraviroc . • The blood volume for HIV confirmatory testing is modified for consistency w ith testing requirements. • The Protocol Team roster has been updated to reflect current membership. • Minor clarifications are also incorporated. Im plem entation Based on evaluation of the Cohort 1, Stratum 1A and Stratum 1B safety and PK data, the initial daily dose of maraviroc oral solution to be administered in Cohort 2, Stratum 2A and Stratum 2B, participants in IMPAACT 2007 w ill be 8 mg/kg dose given tw ice daily. Participants enrolled in Stratum 2A and Stratum 2B should follow the intensive PK procedures w ith tw ice daily dosing at the Week 1 and Week 4 visits specified in Sections 6.5.3 and 6.7.2, respectively, and Section 10.2.3 per protocol Version 1.0, dated 13 April 2016, w ith Letter of Amendment #1, dated 12 August 2016. Detailed modifications of the protocol text are show n below in general order of appearance in the protocol. Deletions in the protocol text are indicated by strikethrough, and additions are indicated in bold. 1. Section 7.3.3, Grading Severity of Events, f irst paragraph: Adverse events identified in this study w ill be graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated Marc h July 2017, w hich is available on the RSC w ebsite: http://rsc.tech- res.com/clinical-research-sites/safety-reporting/daids-grading-tables. 2. Section 8.2.2, Grade 1 ALT: Grade 1 – For Grade 1 ALT, repeat test as soon as possible (w ithin three business days) and c onsult the Core Protoc ol Team. iIf the repeat test result is Grade 1, notify the Core Protocol Team, and continue maraviroc w ith close monitoring as determined by the site investigator and w ork-up to exclude other causes. 3. Section 9.2: a. Cohort 1, the second paragraph has been replaced with the f ollowing: The study will implement a dose -finding algorithm applied to each stratum based on evaluation of single -dose PK data and safety data through the 7 Day Post Dose Safety Visit from an initial group of six infants from Stratum 1A and Stratum 1B. If these six infants meet both safety and PK guidelines (specified in Sections 9.6.2 and 10.3.2, respectively), then the starting dose for the corresponding Cohort 2 stratum will be established, and that stratum wi ll begin to accrue. If the initial group of six infants receiving the initial Cohort 1 dose for the stratum do not meet either the safety or the PK guidelines, then the Core Protocol Team will use PK modeling and safety data to evaluate whether to: • Continue with additional enrollments in the Cohort 1 stratum at the initial dose or an adjusted dose, OR • Begin enrollment into the corresponding stratum in Cohort 2 with the initial dose or an adjusted dose, as recommended based on Cohort 1 data, OR • Stop the study. Individual dose adjustments will not be made. The PK guidelines for dose adjustment are described in Section 10.3.2. Note that if additional Cohort 1 infants are enrolled at an adjusted dose, additional infants will be enrolled in groups of six, and the same algorithm above will apply. b. Cohort 2, the second paragraph has been replaced with the f ollowing: Each stratum in Cohort 2 (2A and 2B) will start with an initial group of six infants per stratum and the dose -finding algorithm will be applied independently to each stratum based on PK and safety data through the Week 6 Visit. If a stratum meets both the safety and PK guidelines at a given dose (see Sections 9.6.2 and 10.3.2, respectively), then an additional six infants will be enrolled and administered this dose to complete a full stratum of n=12 infants. Safety and PK will then be assessed on the full stratum. If safety and PK guidelines are met in the full stratum, then the dose is established for the stratum. If safety and PK guidelines are not met in a stratum, the dose may be adjusted and a new group of six infants will be enrolled at the adjusted dose . The evaluation procedures described above will be repeated. This will proceed until a full stratum of 12 infants administered a given dose has met both safety and PK guidelines . 4. Section 9.3.1, Primary Endpoints (from the initial maraviroc dose through week 6 of life): Safety • For dose finding purposes: Any life threatening adverse event, including death, assessed as at least possibly related to the study drug, A adverse events of Grade 3 or higher judged by the Core Protocol team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an adverse event, judged by the Core Protocol Team, to be at least possibly related to study drug. (Cohort 1: through 7 Day Post Dose Visit; Cohort 2: through Week 6 Visit). • For analysis purposes: All adverse events of grade 3 or higher, or that result in permanent disc ontinuation of study drug. Any life threatening adverse event, including death, assessed as at least possibly related to the study drug, adverse events of Grade 3 or higher judged by the Core Protocol team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an adverse event, judged by the Core Protocol Team, to be at least possibly related to study drug. (Cohort 1 and Cohort 2: through Week 6 Visit). 5. Section 9.3.3, Secondary Endpoints (from the initial maraviroc dose through week 16 of lif e): Safety • For dose finding purposes: Adverse events of Grade 3 or higher judged by the Core Protoc ol team to be probably or definitely related to the study drug, or that result in permanent disc ontinuation of study drug due to an adverse event, judged by the Core Protoc ol Team to be at least possibly related to the study drug. • For analysis purposes: All adverse events of Grade 3 or higher or that result in permanent disc ontinuation of study drug due to toxic ity. Any life threatening adverse event, including death, assessed as at least possibly related to the study drug, adverse events of Grade 3 or higher judged by the Core Protocol team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an adverse event, judged by the Core Protocol Team to be at least possibly related to the study drug. 6. Section 9.7, Analyses, Analysis of Data Representing Exposure to the Doses Selected f or Each Stratum within a Cohort, second and third paragraph, and Table 2: Each participant’s safety data w ill be summarized as: the w orst grade of adverse event experienced at these time points and the w orst grade of adverse event assessed as at least possibly probably related to study drug. Frequency distributions of these safety outcomes will be presented. Also, Llistings of all Grade 3 or higher events w ill be provided., including the Core Protocol Team’s attribution to the study drug, and adverse events deemed to be at least possibly related that result in permanent discontinuation of study drug. The proportions of partic ipants experienc ing grade 3 or higher adverse even ts, bounded by exac t 95% c onfidenc e intervals, w ill be presented. Similar analyses w ill present the proportions of partic ipants w ith Grade 3 or higher events assessed as at least possibly related to study drug, again bounded by exac t 95% c onfidenc e intervals. The proportion of participants experiencing any of the following primary safety endpoints will be presented and bounded by 95% exact confidence intervals: Any life threatening adverse event, including death, assessed as at least possibly related to th e study drug, adverse events of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in perm anent discontinuation of study drug due to an adverse event, judged by the Core Protocol Team to be at least possibly related to study drug. Table 2 presents the upper and low er limits of confidence intervals around potential results observed in the groups of n=6 and full cohorts of n=12 of the strata w ith and w ithout maternal EFV. Table 2: Percent of Participants Experiencing ≥ Grade 3 Adverse Events (or ≥ Grade 3 Adverse Events Attributed to the Study Medic ation) any of the primary safety endpoints in Section 9.3.1 w ith Exac t 95% Exact Confidence Intervals N* n (%) Participants who experienced any of the Primary Safety Endpoints listed in Section 9.3.1With ≥ Grade 3 Adverse Events 95% C.I. 6 0 (0%) 0% -- 46% 12 0 (0%) 0% -- 27% 6 1 (17%) .4% -- 64% 12 2 (17%) 2% -- 49% 6 2 (33%) 4% -- 78% 12 4 (33%) 10% -- 65% 7. Section 10.3.2, PK Guidelines f or Dose Adjustment, has been replaced with the f ollowing: The study will implement a dose -finding algorithm (see Section 9.2) based on the review of single -dose PK data and safety data from Stratum 1A and Stratum 1B separately. The maraviroc exposure target will be a Cavg of ≥ 75 ng/mL, which is the exposure associated with near-maximal efficacy in the treatment naïve adult study (MERIT) of maraviroc when dosed in combination with ZDV/3TC. [15] After enrollment of six infants in either Stratum 1A or Stratum 1B, the team will evaluate the safety and PK data for that stratum. If a stratum meets the safety guidelines (see section 9.6.2) and the maraviroc exposure target at the Entry visit and the Week 1 visits, then the corresponding Cohort 2 stratum (2A or 2B) will open with n=6 infants in the stratum receiving daily dosing, with a dose size and frequency (once or twice daily) to be determined based on the corresponding Stratum 1A or Stratum 1B PK data. If the maraviroc exposure target is not met in two or more of the six infants at the Entry visit and the Week 1 visits, the Core Protocol Team will evaluate the PK and safety data and decide whether to : • Continue with additional enrollments in the Cohort 1 stratum at the initial dose or an adjusted dose, OR • Begin enrollment into the corresponding stratum in Cohort 2 with the initial dose or an adjusted dose, as recommended based on Cohort 1 data, OR • Stop the study. If additional infants are enrolled in Cohort 1, they will be enrolled in groups of six, up to a maximum of 18 infants enrolled per stratum. Simulations derived from pharmacokinetic modeling of the Cohort 1 data will be used to evaluate potential daily doses and inform the dose selection for each Cohort 2 stratum. Cohort 2 daily dosing regimens that will optimize the potential to meet the maraviroc exposure target while minimizing the risk of over-exposure to maraviroc will be selected for each stratum. If PK modeling and simulations indicate that dosing should be changed during the treatment period (Entry through Week 6 visit) f or Cohort strata, then the appropriate changes will be com municated to sites via a protocol amendment. Strata 2A and 2B PK data from n=6 will be evaluated prior to the full accrual of n=12 for each stratum. Strata 2A and 2B will allow for further dose adjustment for PK or safety as needed (see Section 9.2 for the Dose Adjustment algorithm based on both safety and PK guidelines). The final enrollment target is 12 infants in both Stratum 2A and Stratum 2B with evaluable PK data for the final dose recommended. If three or more of the 12 infants in Strata 2A or 2B do not meet the maraviroc exposure target at both PK assessments (Weeks 1 and 4), the Core Protocol Team will evaluate the PK and safety data, and decide whether to continue with additional enrollments in the Cohort 2 stratum at the same dose, adjust the dose, or stop the study. Simulations derived from pharmacokinetic modeling of Cohort 1 and available Cohort 2 data will be used to evaluate daily doses and inform any dose adjustment decisions for each subsequent stratum in Cohort 2. Enrollment of additional groups of six infants receiving adjusted doses will be allowed, and the process above will be repeated. 8. Section 11.2, Essential and Source Documents and Access to Source Data, f ourth paragraph, f irst sentence: All study records must be accessible for inspection, monitoring, and/or auditing during and after the conduct of the study by authorized representatives of the study sponsors and their contracted monitors, IMPAACT, the US Food and Drug Administration, site drug regulatory authorities, site IRBs/ECs, the US Office for Human Research Protections, and other US, local, and international applic able regulatory entities. 9. Appendix IB: Cohort 1 (Stratum 1A and 1B) – Infant Schedule of Evaluations and Appendix IC: Cohort 2 (Stratum 2A and 2B), row f or HIV Confirmatory Testing: HIV Confirmatory Tes ting If the initial HIV NAT is positive, confirm as soon as possible with a quantitative HIV RNA test on a second sample (2 mL) drawn on a different day and collect an additional 6 mL for tropism and resistance testing, per the LPC. See Section 6.11 for further instructions. Note: 6 8 mL does not appear in totals below since this will be a sample drawn on an unscheduled visit. 10. Appendix II: Maraviroc Weight Band Dosing Tables For Solution (Solution Concentration is 20 mg/mL) • First paragraph, second and third sentence: Sections 5.3.1 and 5.3.2 include the dosing regimen for Cohort 1 (Stratum 2A 1A or Stratum 2B 1B) and Cohort 2 (Stratum 2A or Stratum 2B), respectively. The selected table for any stratum dose adjustments for Cohort 1 and the dose and frequency for Cohort 2 (Stratum 1A 2A and Stratum 2B) w ill be communicated to study sites via a protocol Clarification Memorandum. • Table J – Dose of 20 mg/kg, row f or weight band: Weight Band (kg) 16 20 mg/kg Volume (mL) 11. Appendix III-A: Cohort 1 Sample Informed Consent Form f or Study Participation, and Appendix III- B: Cohort 2 Sample Inf ormed Consent Form f or Study Participation: a. Item 10, third paragraph, second sentence: Your baby w ill not receive maraviroc and your baby w ill have additional blood draw n ( 6 8 mL or a little more than 1.5 teaspoons) for another HIV test to see if your baby truly is infected and to test for resistance to the study medicine. b. Item 15, f ourth bullet: • Stroke c. Item 21: Groups that oversee the study include: • [insert name of site IRB/EC] • [insert name of other site drug entities that may review records] • [insert nam e of other site regulatory entities] • The United States National Institutes of Health and its study monitors • The United States Office for Human Research Protections • The US Food and Drug Administration • Other U.S., local, and international regulatory entities • The IMPAACT Netw ork that is coordinating the study • The companies that make maraviroc (PHIVCO) 12. Appendix IV: Sample Inf ormed Consent Form f or Specimen Storage and Future Use, item 7: These groups include: • The IMPAACT Netw ork • The ethics committees that review and approve the research • Government and other agencies that pay for the research • Government and other agencies that monitor the research • Other U.S., local, and international regulatory entities 13. Protocol Team Roster: The NICHD Medic al Offic er has been updated to: Jack Moye, Jr., MD Maternal and Pediatric Infectious Disease Branch Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health 6710B Rockledge Drive Bethesda, MD 20817 Phone: (301) 594-8624 Email: john.moye@nih.hhs.gov The Protoc ol Pharmac ist has been updated to: Lynette Purdue, PharmD PAB, DAIDS, NIAID, NIH 5601 Fishers Lane, Room 9D37 Rockville, MD 20852 Phone: (240) 627-3061 Email: lpurdue@niaid.nih.gov The Protoc ol Laboratory Data Manager has been updated to: Kyle Whitson, MA Frontier Science & Technology Research Foundation 4033 Maple Road Amherst, NY 14226 USA Phone: (716) 834-0900 x7273 Fax: (716) 834-8432 Email: w hitson@fstrf.org The follow ing Investigator has been added: Julia Rosebush, DO, FAAP Department of Pediatrics Section of Infectious Diseases The University of Chicago 5841 S. Maryland Ave., Rm. C-623B MC6054 Chicago, IL 60637 Phone: (773) 834-8518 Email: jrosebush@peds.bsd.uchicago.edu