Trial Outcomes & Findings for Evaluating the Safety and Pharmacokinetics of Maraviroc in HIV-1-Exposed Infants at Risk of Acquiring HIV-1 Infection (NCT NCT02778204)

Last Updated: 2022-01-04

Results Overview

Percentage (%) of failure and Clopper-Pearson 95% Confidence Interval (CI). Failure is defined as having: Any life threatening adverse event (AE), including death, assessed as at least possibly related to the study drug, AEs 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 AE, judged by Core Protocol Team to be at least possibly related to study drug

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

47 participants

Primary outcome timeframe

Cohort 1: Measured from first dose of maraviroc to 7 Day Post Dose Visit (up to 25 days). Cohort 2: Measured from first dose of maraviroc to Week 6 Visit (up to 42 days).

Results posted on

2022-01-04

Participant Flow

Accrual occurred between June 2017 and July 2019 in Kenya, Thailand, South Africa, and the United States at 9 different medical clinic sites. Pregnant mothers were screened and subsequently enrolled for 1 day at the same day their newborn infants were enrolled (within 3 days of life).

The sample size of the study (47) represents the infants enrolled. As multiple births are disallowed in the study, this also represents the total mother-infant pairs.

Participant milestones

Participant milestones
Measure	Cohort 1 Stratum 1A Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz.	Cohort 1 Stratum 1B Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz.	Cohort 2 Stratum 2A Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz.	Cohort 2 Stratum 2B Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Overall Study STARTED	8	7	16	16
Overall Study COMPLETED	6	7	12	12
Overall Study NOT COMPLETED	2	0	4	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 Stratum 1A Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz.	Cohort 2 Stratum 2A Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz.	Cohort 2 Stratum 2B Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Overall Study Adverse Event	1	0	0
Overall Study Withdrawal by Subject	0	1	2
Overall Study Lost to Follow-up	1	2	1
Overall Study Protocol Violation	0	1	0
Overall Study Eligibility Violation	0	0	1

Baseline Characteristics

Evaluating the Safety and Pharmacokinetics of Maraviroc in HIV-1-Exposed Infants at Risk of Acquiring HIV-1 Infection

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 Stratum 1A n=8 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz.	Cohort 1 Stratum 1B n=7 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz.	Cohort 2 Stratum 2A n=16 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz.	Cohort 2 Stratum 2B n=16 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz	Total n=47 Participants Total of all reporting groups
Age, Continuous Mean (Standard Deviation)	1.5 days n=5 Participants	0 days n=7 Participants	1 days n=5 Participants	2 days n=4 Participants	2 days n=21 Participants
Age, Continuous	29.5 years n=5 Participants	26 years n=7 Participants	32 years n=5 Participants	32 years n=4 Participants	31 years n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants	7 Participants n=4 Participants	23 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants	9 Participants n=4 Participants	24 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	5 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants	16 Participants n=4 Participants	42 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants	16 Participants n=4 Participants	38 Participants n=21 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	6 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	7 participants n=5 Participants	0 participants n=7 Participants	13 participants n=5 Participants	0 participants n=4 Participants	20 participants n=21 Participants
Region of Enrollment South Africa	1 participants n=5 Participants	7 participants n=7 Participants	0 participants n=5 Participants	14 participants n=4 Participants	22 participants n=21 Participants
Region of Enrollment Thailand	0 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants	0 participants n=4 Participants	3 participants n=21 Participants
Region of Enrollment Kenya	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants	2 participants n=21 Participants
Birth Weight	3.2 kilograms n=5 Participants	3.4 kilograms n=7 Participants	3.0 kilograms n=5 Participants	3.0 kilograms n=4 Participants	3.05 kilograms n=21 Participants
Birth Length	50.0 centimeters n=5 Participants	50.0 centimeters n=7 Participants	49.0 centimeters n=5 Participants	48.5 centimeters n=4 Participants	49.0 centimeters n=21 Participants
Gestational Age	38.5 weeks n=5 Participants	39.0 weeks n=7 Participants	39.0 weeks n=5 Participants	40.0 weeks n=4 Participants	39.0 weeks n=21 Participants
APGAR at 1 minute	9.0 units on a scale n=5 Participants	8.0 units on a scale n=7 Participants	8.5 units on a scale n=5 Participants	9.0 units on a scale n=4 Participants	9.0 units on a scale n=21 Participants
Alanine Aminotransferase (ALT)	0.2 ukat/L n=5 Participants	0.2 ukat/L n=7 Participants	0.2 ukat/L n=5 Participants	0.2 ukat/L n=4 Participants	0.2 ukat/L n=21 Participants
Aspartate Aminotransferase (AST)	0.7 ukat/L n=5 Participants	1.1 ukat/L n=7 Participants	0.9 ukat/L n=5 Participants	1.0 ukat/L n=4 Participants	0.9 ukat/L n=21 Participants
Total Bilirubin	39.3 umol/L n=5 Participants	44.0 umol/L n=7 Participants	76.1 umol/L n=5 Participants	75.3 umol/L n=4 Participants	50.7 umol/L n=21 Participants
Creatinine	70.7 umol/L n=5 Participants	62.0 umol/L n=7 Participants	61.9 umol/L n=5 Participants	69.0 umol/L n=4 Participants	66 umol/L n=21 Participants
Platelets	274.0 10^9 platelets/L n=5 Participants	297.0 10^9 platelets/L n=7 Participants	252.5 10^9 platelets/L n=5 Participants	311.0 10^9 platelets/L n=4 Participants	289.0 10^9 platelets/L n=21 Participants
Hemoglobin	163.0 g/L n=5 Participants	178.0 g/L n=7 Participants	166.5 g/L n=5 Participants	179.0 g/L n=4 Participants	170.0 g/L n=21 Participants
White Blood Cell Count (WBC)	14.6 10^9 cells/L n=5 Participants	17.3 10^9 cells/L n=7 Participants	15.5 10^9 cells/L n=5 Participants	12.6 10^9 cells/L n=4 Participants	14.6 10^9 cells/L n=21 Participants

PRIMARY outcome

Timeframe: Cohort 1: Measured from first dose of maraviroc to 7 Day Post Dose Visit (up to 25 days). Cohort 2: Measured from first dose of maraviroc to Week 6 Visit (up to 42 days).

Population: Safety-evaluable population are those who were taking maraviroc for the expected time-frame (Cohort 1: through 7 day post-dose visit, Cohort 2: Through week 6)

Outcome measures

Outcome measures
Measure	Cohort 1 Stratum 1A n=6 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz.	Cohort 1 Stratum 1B n=7 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz.	Cohort 2 Stratum 2A n=12 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz.	Cohort 2 Stratum 2B n=12 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Dose-Finding	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 41.0	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 26.5

PRIMARY outcome

Timeframe: Measured from first dose of maraviroc to Week 6 Visit (up to 42 days)

Population: Analysis Endpoint includes all treated participants

Percentage (%) of failure and Clopper-Pearson 95% CI. Failure is defined as: Any life threatening AE, including death, assessed as at least possibly related to the study drug, AEs 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 AE, judged by Core Protocol Team to be at least possibly related to study drug

Outcome measures

Outcome measures
Measure	Cohort 1 Stratum 1A n=8 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz.	Cohort 1 Stratum 1B n=7 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz.	Cohort 2 Stratum 2A n=16 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz.	Cohort 2 Stratum 2B n=16 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Analysis	0 percentage of participants Interval 0.0 to 36.9	0 percentage of participants Interval 0.0 to 41.0	0 percentage of participants Interval 0.0 to 20.6	0 percentage of participants Interval 0.0 to 20.6

PRIMARY outcome

Timeframe: Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).

Population: Analysis population included dose-finding evaluable participants with intensive pharmacokinetic (PK) results. In Cohort 1 Stratum 1A and 1B at the week 1 visit (Second Visit), only 3 PK sample were drawn (pre-dose, 1-2 hours post-dose, and 22-26 hours post-dose). Maraviroc was only measurable (above assay limit) at 1 time point (1-2 hours post-dose). Therefore, AUC (hence Cavg) could not be estimated with non-compartmental methods from only 1 concentration and thus the number analyzed was 0.

Number of failures. The pharmacokinetic (PK) target is Average Concentration (Cavg) greater than or equal to 75 ng/mL (based on a dose interval of every 12 hours). Failure is defined as Cavg \<75 ng/mL at each intensive PK visit. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

Outcome measures

Outcome measures
Measure	Cohort 1 Stratum 1A n=6 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz.	Cohort 1 Stratum 1B n=7 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz.	Cohort 2 Stratum 2A n=13 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz.	Cohort 2 Stratum 2B n=12 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Number of Participants Failing to Meet PK Target First Visit	0 participants	0 participants	3 participants	4 participants
Number of Participants Failing to Meet PK Target Second Visit	—	—	4 participants	5 participants

PRIMARY outcome

Timeframe: Cohort 1: Measured at Entry and Week 1 Visit. Cohort 2: Measured at Week 1 and Week 4 Visit

Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix 64, WinNonlin, Pharsight Corp., Mountain View, CA). Cavg was determined as the area-under-the-curve (AUC) divided by the dose interval, tau (τ) of every 12 hours. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

Outcome measures

Outcome measures
Measure	Cohort 1 Stratum 1A n=6 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz.	Cohort 1 Stratum 1B n=7 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz.	Cohort 2 Stratum 2A n=13 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz.	Cohort 2 Stratum 2B n=12 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Pharmacokinetic (PK) Parameter: Average Concentration (Cavg) First Visit	190.47 ng/mL Interval 93.54 to 1278.62	375.47 ng/mL Interval 110.4 to 684.84	152.24 ng/mL Interval 19.75 to 565.68	124.67 ng/mL Interval 17.07 to 550.86
Pharmacokinetic (PK) Parameter: Average Concentration (Cavg) Second Visit	—	—	93.58 ng/mL Interval 32.92 to 488.21	101.39 ng/mL Interval 42.65 to 351.19

PRIMARY outcome

Timeframe: Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).

Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix 64, WinNonlin, Pharsight Corp., Mountain View, CA). For Cohort 1 (single doses), area-under-the-curve (AUC) was determined from time zero to infinity. For Cohort 2 (at steady-state), area-under-the-curve (AUC) was determined from time pre-dose to tau (12 hours). For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

Outcome measures

Outcome measures
Measure	Cohort 1 Stratum 1A n=6 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz.	Cohort 1 Stratum 1B n=7 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz.	Cohort 2 Stratum 2A n=13 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz.	Cohort 2 Stratum 2B n=12 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Pharmacokinetic (PK) Parameter: Area-under-the-curve (AUC) First Visit	2285.68 ng*hr/mL Interval 1122.53 to 15343.42	4506.17 ng*hr/mL Interval 1325.02 to 8218.03	1826.87 ng*hr/mL Interval 236.96 to 6788.18	1496.05 ng*hr/mL Interval 204.89 to 6610.35
Pharmacokinetic (PK) Parameter: Area-under-the-curve (AUC) Second Visit	—	—	1122.99 ng*hr/mL Interval 395.01 to 5858.51	1216.62 ng*hr/mL Interval 511.85 to 4214.34

PRIMARY outcome

Timeframe: Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).

Population: Analysis population included dose-finding evaluable participants with intensive pharmacokinetic (PK) results.

Pharmacokinetic parameters were determined from plasma concentration-time profiles. Cmax was the observed highest concentration. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

Outcome measures

Outcome measures
Measure	Cohort 1 Stratum 1A n=6 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz.	Cohort 1 Stratum 1B n=7 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz.	Cohort 2 Stratum 2A n=13 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz.	Cohort 2 Stratum 2B n=12 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Pharmacokinetic (PK) Parameter: Maximum Concentration (Cmax) First Visit	227.3 ng/mL Interval 29.9 to 1618.4	550.5 ng/mL Interval 203.8 to 1153.0	256.9 ng/mL Interval 51.5 to 1468.4	308.8 ng/mL Interval 34.4 to 1273.5
Pharmacokinetic (PK) Parameter: Maximum Concentration (Cmax) Second Visit	128.9 ng/mL Interval 22.8 to 296.2	163.4 ng/mL Interval 8.7 to 609.4	416.5 ng/mL Interval 125.1 to 793.4	221.8 ng/mL Interval 76.5 to 738.7

PRIMARY outcome

Timeframe: Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).

Population: Analysis population included dose-finding evaluable participants with intensive pharmacokinetic (PK) results.

Pharmacokinetic parameters were determined from plasma concentration-time profiles. Tmax was the time at which Cmax, the observed highest concentration, occurred. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

Outcome measures

Outcome measures
Measure	Cohort 1 Stratum 1A n=6 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz.	Cohort 1 Stratum 1B n=7 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz.	Cohort 2 Stratum 2A n=13 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz.	Cohort 2 Stratum 2B n=12 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Pharmacokinetic (PK) Parameter: Time of Maximum Concentration (Tmax) First Visit	4.68 hours Interval 1.05 to 12.75	1.52 hours Interval 1.25 to 4.42	1.50 hours Interval 0.83 to 4.0	3.00 hours Interval 1.0 to 6.18
Pharmacokinetic (PK) Parameter: Time of Maximum Concentration (Tmax) Second Visit	1.18 hours Interval 1.05 to 1.25	1.08 hours Interval 1.07 to 1.33	1.50 hours Interval 1.0 to 4.0	2.19 hours Interval 0.0 to 11.43

PRIMARY outcome

Timeframe: Measured at Week 1 and Week 4 Visit

Population: Analysis population included Cohort 2 dose-finding evaluable participants with intensive pharmacokinetic (PK) results.

Pharmacokinetic parameters were determined from plasma concentration-time profiles. Ctau was the observed concentration at the trough time of 12 hours post-dose with steady-state dosing. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.

Outcome measures

Outcome measures
Measure	Cohort 1 Stratum 1A n=13 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz.	Cohort 1 Stratum 1B n=12 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz.	Cohort 2 Stratum 2A Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz.	Cohort 2 Stratum 2B Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Pharmacokinetic (PK) Parameter: Trough Concentration (Ctau) Week 1 Visit	27.9 ng/mL Interval 0.0 to 138.9	23.4 ng/mL Interval 0.0 to 824.9	—	—
Pharmacokinetic (PK) Parameter: Trough Concentration (Ctau) Week 4 Visit	34.4 ng/mL Interval 0.0 to 373.1	54.9 ng/mL Interval 8.2 to 233.9	—	—

SECONDARY outcome

Timeframe: Measured from first dose of maraviroc to Week 16 Visit (up to 140 days)

Population: Safety-evaluable population are those who were taking maraviroc for the expected time-frame (Cohort 1: through 7 day post-dose visit, Cohort 2: Through week 6)

Percentage (%) of failure and Clopper-Pearson 95% CI. Failure is defined as having: Any life threatening AE, including death, assessed as at least possibly related to the study drug, AEs 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 AE, judged by Core Protocol Team to be at least possibly related to study drug

Outcome measures

Outcome measures
Measure	Cohort 1 Stratum 1A n=6 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz.	Cohort 1 Stratum 1B n=7 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz.	Cohort 2 Stratum 2A n=12 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz.	Cohort 2 Stratum 2B n=12 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Dose-Finding	0 percentage of participants Interval 0.0 to 45.9	0 percentage of participants Interval 0.0 to 41.0	0 percentage of participants Interval 0.0 to 26.5	0 percentage of participants Interval 0.0 to 26.5

SECONDARY outcome

Timeframe: Measured from first dose of maraviroc to Week 16 Visit (up to 140 days)

Population: All treated participants

Outcome measures

Outcome measures
Measure	Cohort 1 Stratum 1A n=8 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz.	Cohort 1 Stratum 1B n=7 Participants Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz.	Cohort 2 Stratum 2A n=16 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz.	Cohort 2 Stratum 2B n=16 Participants Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Analysis	0 percentage of participants Interval 0.0 to 36.9	0 percentage of participants Interval 0.0 to 41.0	0 percentage of participants Interval 0.0 to 20.6	0 percentage of participants Interval 0.0 to 20.6

Adverse Events

Cohort 1 Stratum 1A

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Cohort 1 Stratum 1B

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Cohort 2 Stratum 2A

Serious events: 4 serious events

Other events: 15 other events

Deaths: 0 deaths

Cohort 2 Stratum 2B

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1 Stratum 1A n=8 participants at risk Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz.	Cohort 1 Stratum 1B n=7 participants at risk Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz.	Cohort 2 Stratum 2A n=16 participants at risk Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz.	Cohort 2 Stratum 2B n=16 participants at risk Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz
Blood and lymphatic system disorders Haemolytic anaemia	0.00% 0/8 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/7 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	6.2% 1/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017
Cardiac disorders Cyanosis	12.5% 1/8 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/7 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017
Congenital, familial and genetic disorders Hypospadias	0.00% 0/8 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	14.3% 1/7 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017
Hepatobiliary disorders Jaundice	0.00% 0/8 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/7 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	6.2% 1/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017
Infections and infestations Escherichia urinary tract infection	0.00% 0/8 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/7 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	6.2% 1/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017
Infections and infestations Pneumonia bacterial	0.00% 0/8 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/7 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	6.2% 1/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017
Infections and infestations Sepsis neonatal	0.00% 0/8 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/7 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	6.2% 1/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017
Infections and infestations Staphylococcal sepsis	12.5% 1/8 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/7 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017
Investigations Haemoglobin decreased	0.00% 0/8 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/7 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	6.2% 1/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017
Investigations Neutrophil count decreased	0.00% 0/8 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/7 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	6.2% 1/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017
Investigations Weight decreased	0.00% 0/8 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/7 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	6.2% 1/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017
Metabolism and nutrition disorders Failure to thrive	0.00% 0/8 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/7 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	6.2% 1/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	6.2% 1/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017
Nervous system disorders Slow response to stimuli	12.5% 1/8 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/7 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017
Nervous system disorders Tremor	12.5% 1/8 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/7 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017	0.00% 0/16 • From study entry to study completion at Week 16 or premature study discontinuation All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017

Other adverse events

Additional Information

Melissa Allen, Director, IMPAACT Operations Center

Family Health International (FHI 360)

Phone: (919) 405-1429

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights
Publication restrictions are in place

Restriction type: OTHER