Pharmacokinetic Properties of Antiretroviral and Related Drugs During Pregnancy and Postpartum
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Letter of Amendment #1 to  
Page 1 of 5 
14 December 2016 
IMPAACT P1026s, Protocol Version 10.0 
Letter of Amendment #1 for:  
 
IMPAACT P1026s  
Pharmacokinetic Properties of Antiretroviral and Related Drugs During Pregnancy and 
Postpartum 
 
IND # 64,535  
DAIDS ES # 10040  
 
Letter of Amendment Date: 14 December 2016 
 
 
Information/Instructions to Study Sites from the Division of AIDS 
 
The information contained in this Letter of Amendment (LoA) affects the IMPAACT P1026s study 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 other site regulatory entities 
if applicable per the policies and procedures of the regulatory entities. All IRB/EC and regulatory entity 
requirements must be followed.  
 
Upon obtaining IRB/EC approval and any other applicable regulatory entity approvals, this LoA is to be 
implemented immediately.  Study sites must submit an LoA registration packet to the DAIDS Protocol 
Registration Office (DAIDS PRO) at the Regulatory Support Center (RSC). 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. A LoA registration notification from the DAIDS PRO is 
not required prior to implementing the LoA. Please file this LoA, all associated IRB/EC and regulatory 
entity correspondence, and all correspondence with the DAIDS PRO in your essential documents files for 
IMPAACT P1026s. 
 
If the IMPAACT P1026s protocol is amended in the future, the contents of this LoA will be incorporated 
into the next version of the protocol. 
 
 
Summary of Modifications and Rationale 
 
The following modifications are included in this LoA: 
 
• 
One of the three tenofovir alafenamide fumarate (TAF) antepartum arms for HIV-infected pregnant 
women not on tuberculosis treatment has been corrected for consistency with the formulations of this 
drug that are currently approved by the United States Food and Drug Administration (FDA).  These 
formulations are as follows:   
⎯ Genvoya® – TAF 10 mg co-formulated with elvitegravir and emtricitabine 
⎯ Odefsy – TAF 25 mg co-formulated with rilpivirine and emtricitabine 
⎯ Descovy ®– TAF 25 mg co-formulated with emtricitabine (may be taken with or without 
cobicistat or ritonavir boosting) 
 
• 
Instructions for collection of vaginal secretions have been updated.  
• 
Disallowed medicines for the newly added TAF arms have been updated.  
• 
Other minor updates, clarifications, and corrections have been incorporated.  

Letter of Amendment #1 to  
Page 2 of 5 
14 December 2016 
IMPAACT P1026s, Protocol Version 10.0 
 
Implementation 
 
Detailed modifications of the protocol text are shown 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. Protocol Team Roster: 
 
Protocol Data Manager 
Adriane Hernandez  
Benjamin Johnston 
Phone: 716-834-0900 x7404 
E-mail: johnston@fstrf.org 
 
Elise Tjaden, MPH 
Phone: 716-834-0900 x7272 
Email: tjaden@fstrf.org 
  
Laboratory Data Manager 
Amy Gonzalez, BS 
Katelyn Hergott, MPH, MSW 
Phone: 716-834-0900 x7212 
Email: hergott@fstrf.org 
Investigators  
Nantasak Chotivanich, MD 
 
Jullapong Achalapong, MD. 
Site Principle Investigator 
Obstetrics &Gynecology Department 
Chiangrai Prachanukroh Hospital 
1039 Sathanpayaban Rd., Muang  
Chiang Rai  57000 Thailand 
Tel: +66 (0) 53 711 300 Fax: +66 0 53 713 
044 Mobile: +66 0 81 950 0707 
Email: jullapongachalapong@gmail.com
2. Schema: 
Study Arms, Antiretrovirals (ARVs) without tuberculosis (TB) Treatment (10 Arms): HIV-infected 
pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment receiving one or more of the 
following ARV drugs/drug combinations (sixth bullet point): 
 
- darunavir/ritonavir twice daily 600/100 mg b.i.d. or 800/100 mg b.i.d. until 30 weeks gestation; 
then 800/100 mg b.i.d. until postpartum hospital discharge; then 600/100 mg b.i.d. after 
postpartum hospital discharge until 2 week postpartum PK samples are drawn 
- darunavir/ritonavir twice daily 600/100 mg b.i.d. or 900/100 mg b.i.d. until 30 weeks gestation; 
then 900/100 mg b.i.d. until postpartum hospital discharge; then 600/100 mg b.i.d. after 
postpartum hospital discharge until 2 week postpartum PK samples are drawn 
- dolutegravir 50 mg q.d. 
- tenofovir alafenamide fumarate (TAF) 25 mg q.d. without cobicistat or ritonavir boosting 
- tenofovir alafenamide fumarate (TAF) 10 mg q.d. with cobicistat 
- tenofovir alafenamide fumarate (TAF) 10 25 mg q.d. with cobicistat or ritonavir boosting 
- elvitegravir/cobicistat 150/150 mg q.d. 
- darunavir/cobicistat 800/150 mg q.d. 
- atazanavir/cobicistat 300/150 mg q.d. 
- Participants outside of Thailand only:  efavirenz 600 mg q.d.   
 
3. Section 3.11, Enrollment Procedures, Maternal Antepartum Enrollment (during pregnancy): 
 
Pregnant women who meet the eligibility criteria, as specified, in Section 4.1 will enroll in P1026s 
prior to or at the time of pharmacokinetic sampling. The initial PK sampling visit must should occur 
within 5 days of participant enrollment. If the PK visit cannot be done within 5 days contact the 
protocol team for permission to perform the sampling visit after 5 days. See Appendix I-A 
through I-C for a complete description of the procedures to be performed for each study arm, and 
Section 10 Data Collection Requirements, for a description of data to be collected. 

Letter of Amendment #1 to  
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14 December 2016 
IMPAACT P1026s, Protocol Version 10.0 
4. Section 3.21, Genital Tract Viral Load and Drug Concentrations, last sentence (added):  
 
HIV-infected pregnant women not on TB drugs will have vaginal samples for ARV concentrations 
obtained at the second and third trimester and the 6-12 postpartum PK sampling visits. Samples will 
be obtained pre-dose and at 1, 2, and 4 hours after dosing. Samples for drug concentrations will be 
obtained with the soft plastic aspirator without speculum placement or by another appropriate 
technique and can be collected by the participant or by a clinician. Samples will be stored and batch 
shipped for testing. Since target drug concentrations for vaginal samples have not been determined, 
real time testing and reporting of vaginal specimen results to the sites will not be done. A single 
vaginal swab will also be obtained without speculum placement for viral load testing once during 
each PK visit. No vaginal specimens will be collected if contraindicated by a pregnancy complication 
such as placenta previa or premature rupture of membranes. Also, no specimens should be collected 
from women who are menstruating or have vaginal bleeding.   
 
5.  Section 3.4, Intrapartum Pharmacokinetic Sampling, 2nd sentence: 
 
A single maternal specimen will be drawn at the time the cord is clamped, unless it is medically 
contraindicated, in which case it can be obtained as soon as possible. 
 
6. Section 4.1, Maternal Inclusion Criteria: 
 
4.111 HIV-infected pregnant women ≥ 20 weeks gestation NOT on tuberculosis treatment receiving 
one or more of the following ARV drugs/drug combinations (sixth bullet point): 
 
- darunavir/ritonavir twice daily 600/100 mg b.i.d. or 800/100 mg b.i.d. until 30 weeks gestation; 
then 800/100 mg b.i.d. until postpartum hospital discharge; then 600/100 mg b.i.d. after 
postpartum hospital discharge until 2 week postpartum PK samples are drawn 
- darunavir/ritonavir twice daily 600/100 mg b.i.d. or 900/100 mg b.i.d. until 30 weeks gestation; 
then 900/100 mg b.i.d. until postpartum hospital discharge; then 600/100 mg b.i.d. after 
postpartum hospital discharge until 2 week postpartum PK samples are drawn 
- dolutegravir 50 mg q.d. 
- tenofovir alafenamide fumarate (TAF) 25 mg q.d. without cobicistat or ritonavir boosting 
- tenofovir alafenamide fumarate (TAF) 10 mg q.d. with cobicistat 
- tenofovir alafenamide fumarate (TAF) 10 25 mg q.d. with cobicistat or ritonavir boosting 
- elvitegravir/cobicistat 150/150 mg q.d. 
- darunavir/cobicistat 800/150 mg q.d. 
- atazanavir/cobicistat 300/150 mg q.d. 
- Participants outside of Thailand only:  efavirenz 600 mg q.d.   
 
5. Section 7.0, Disallowed Medicines: 
 
7.1 NRTIs 
For tenofovir alafenamide fumarate, the following medicines are disallowed: no medicines are 
disallowed. 
• 
Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin 
• 
Antimycobacterials: rifabutin, rifampin, rifapentine 
• 
Herbal products: St. John’s wort (Hypericum perforatum) 
• 
Protease inhibitors: tipranavir/ritonavir 
 

Letter of Amendment #1 to  
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14 December 2016 
IMPAACT P1026s, Protocol Version 10.0 
 
7.3 PIs, 10th Bullet: 
• 
Neurleptic:  lurasidone, pimozide 
 
7.33 Ritonavir, 2nd Bullet: 
• 
Antifungal:  voriconazole 
 
7.4 Integrase Inhibitors, 15th Bullet: 
• 
Neuroleptic: lurasidone, pimozide 
 
7.6 Combined Oral Contraceptives (COCs) and Etonogestrel Implant, 1st and 6th Bullets: 
• 
Anticonvulsants: barbiturates, phenytoin, carbamazepine, felbamate, oxcarbazepine, 
topiramate  
• 
Psychostimulants:; modafinil 
 
6. Appendices IA, IB, I-AMR, IC, ID, II and III, Schedules of Evaluations: 
 
⎯ Appendix IA, footnotes 9 and 13 
9.  Entry may occur at the second or third trimester visit. The participant must be on the medicine 
of interest for at least 2 weeks prior to PK sampling. PK sampling visit should occur within 5 
days after enrollment using the Subject Enrollment System.  The PK sampling visit can be 
performed more than 5 days after enrollment with permission from the protocol team.  
 
13.  Draw at the time the cord is clamped, unless it is medically contraindicated, in which case 
draw can be obtained as soon as possible. 
 
⎯ Appendix IB, Schedule of Evaluations for Women on ARV Medicines with Tuberculosis 
Treatment, footnotes 8, 12 and 14: 
8. Entry may occur at the second or third trimester visit. The participant must be on the medicine 
of interest for at least 2 weeks prior to PK sampling. PK sampling visit should occur within 5 
days after enrollment using the Subject Enrollment System.  The PK sampling visit can be 
performed more than 5 days after enrollment with permission from the protocol team. 
 
12. Draw at time the cord is clamped, unless it is medically contraindicated, in which case, the 
draw can be obtained as soon as possible.  For this arm, collection of maternal delivery sample 
can be omitted if there are circumstances that prohibit collection (i.e. delivery at non-study 
facility, delivery during non-business hours). 
14. For participants treated with any injectable TB medication the audiology assessment can be 
from chart abstraction or otherwise can be performed at any time during follow-up; refer to the 
P1026s Protocol Specific Web Page at http://impaactnetwork.org/studies/P1026s.asp LPC 
for additional information. 
 
⎯ Appendix IC, Schedule of Evaluations for HIV-Uninfected Women with Tuberculosis Treatment, 
footnotes 6 and 10: 
6.  Entry may occur at the second or third trimester visit. The participant must be on the medicine 
of interest for at least 2 weeks prior to PK sampling. PK sampling visit should occur within 5 

Letter of Amendment #1 to  
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14 December 2016 
IMPAACT P1026s, Protocol Version 10.0 
days after enrollment using the Subject Enrollment System.  The PK sampling visit can be 
performed more than 5 days after enrollment with permission from the protocol team. 
 
10. For participants treated with any injectable TB medication the audiology assessment can be 
from chart abstraction or otherwise can be performed at any time during follow-up; refer to the 
P1026s Protocol Specific Web Page at http://impaactnetwork.org/studies/P1026s.asp LPC 
for additional information. 
 
⎯ Appendix I-D, footnote 12: 
12. The participant must be on the ARV of interest for at least 2 weeks prior to the initial PK 
sampling and not using any hormonal contraceptive method during that time. PK sampling visit 
should occur within 5 days after enrollment using the Subject Enrollment System.  The PK 
sampling visit can be performed more than 5 days after enrollment with permission from 
the protocol team. 
 
⎯ Appendix I-AMR, Title:  
ADDITIONAL MONITORING REQUIREMENTS FOR WOMEN ON DRV/r AND LPV 
 
⎯ Appendix II, Schedule of Evaluations for Infants, footnote 9:  
9. Only for infants of mothers treated with any injectable TB medication.  The audiology 
assessment can be from chart abstraction or otherwise can be performed at any time during 
follow-up; refer to the P1026s Protocol Specific Web Page at 
http://impaactnetwork.org/studies/P1026s.asp LPC for additional information. 
 
⎯ Appendix III, Maternal Intensive PK Sampling Schedule for ARV Medicines, Tuberculosis 
Treatment and Hormonal Contraceptives, row 8: 
tenofovir alafenamide fumarate 
10  25 mg q.d. with cobicistat or 
ritonavir boosting 
24 hour sampling during optional 2nd trimester, during 3rd 
trimester and 6-12 weeks postpartum