Safety of and Immune Response to Dolutegravir in HIV-1 Infected Infants, Children, and Adolescents

• ClinicalTrials.gov Identifier: NCT01302847
• Recruitment Status: Active, not recruiting
• First Posted: February 24, 2011
• Results First Posted: March 22, 2022
• Last Update Posted: March 22, 2022
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV Infections
• Interventions: Drug: DTG film-coated tablets; Drug: DTG granules for suspension; Drug: DTG dispersible tablets
• Enrollment: 181

Participant Flow

Recruitment Details	Participants were enrolled from April 20, 2011 to February 19, 2020. Participants were recruited from 9 countries in North America, South America, Africa, and Asia.
Pre-assignment Details	There was no study randomization. A participant was enrolled to a cohort based on their age at study entry.

Arm/Group Title	Cohort I	Cohort IIA	Cohort III	Cohort IIB	Cohort IV	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description	Adolescents 12 to younger than 18 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~0.8 mg/kg with a maximum dose of 30 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.	Infants 4 weeks to younger than 6 months of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.
Period Title: Overall Study
Started	23	23	17	15	7	36	35	25
Completed [1]	10	16	15	14	5	6	9	3
Not Completed	13	7	2	1	2	30	26	22
Reason Not Completed
Ongoing	0	0	0	0	0	27	22	17
Death	0	1	0	0	0	1	1	0
Pregnancy	2	0	0	0	0	0	0	0
Virologic failure	0	2	2	0	1	1	0	2
Severe debilitation, unable to continue	0	0	0	0	0	1	1	0
Not able to get to clinic	1	1	0	0	0	0	0	0
Site closing	2	2	0	0	0	0	0	0
Withdrawal by Subject	1	0	0	0	1	0	0	1
Not willing to adhere to requirements	5	0	0	1	0	0	0	2
Site unable to contact participant	2	1	0	0	0	0	2	0
[1] Study is ongoing. Some participants are still in follow-up. Participant Flow Overview will be updated upon study completion. Summary tables are based on data through database freeze date (March 24, 2021) for this primary results submission.

Baseline Characteristics

Arm/Group Title		Cohort I	Cohort IIA	Cohort IIB	Cohort III	Cohort IV	Cohort III-DT	Cohort IV-DT	Cohort V-DT	Total
Arm/Group Description		Adolescents 12 to younger than 18 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG granules for suspension. DDTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~0.8 mg/kg with a maximum dose of 30 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.	Infants 4 weeks to younger than 6 months of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.	Total of all reporting groups
Overall Number of Baseline Participants		23	23	15	17	7	36	35	25	181
Baseline Analysis Population Description		Participants who received at least one dose of DTG.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
		14.26 (1.79)	8.96 (1.99)	7.73 (1.79)	3.59 (1.00)	1.14 (0.41)	3.25 (1.18)	1.13 (0.44)	0.03 (0.01)	4.84 (4.78)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
	Female	18 78.3%	7 30.4%	3 20.0%	8 47.1%	5 71.4%	13 36.1%	20 57.1%	12 48.0%	86 47.5%
	Male	5 21.7%	16 69.6%	12 80.0%	9 52.9%	2 28.6%	23 63.9%	15 42.9%	13 52.0%	95 52.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
	Hispanic or Latino	6 26.1%	6 26.1%	4 26.7%	8 47.1%	1 14.3%	6 16.7%	4 11.4%	2 8.0%	37 20.4%
	Not Hispanic or Latino	16 69.6%	13 56.5%	6 40.0%	6 35.3%	6 85.7%	28 77.8%	31 88.6%	23 92.0%	129 71.3%
	Unknown or Not Reported	1 4.3%	4 17.4%	5 33.3%	3 17.6%	0 0.0%	2 5.6%	0 0.0%	0 0.0%	15 8.3%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	3 13.0%	3 13.0%	3 20.0%	2 11.8%	3 42.9%	7 19.4%	1 2.9%	3 12.0%	25 13.8%
	Native Hawaiian or Other Pacific Islander	0 0.0%	1 4.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 0.6%
	Black or African American	12 52.2%	12 52.2%	10 66.7%	11 64.7%	3 42.9%	25 69.4%	30 85.7%	20 80.0%	123 68.0%
	White	7 30.4%	3 13.0%	0 0.0%	2 11.8%	0 0.0%	1 2.8%	2 5.7%	0 0.0%	15 8.3%
	More than one race	0 0.0%	1 4.3%	0 0.0%	1 5.9%	0 0.0%	3 8.3%	2 5.7%	2 8.0%	9 5.0%
	Unknown or Not Reported	1 4.3%	3 13.0%	2 13.3%	1 5.9%	1 14.3%	0 0.0%	0 0.0%	0 0.0%	8 4.4%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
		20 87.0%	16 69.6%	5 33.3%	5 29.4%	0 0.0%	3 8.3%	2 5.7%	0 0.0%	51 28.2%
Botswana	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 14.3%	1 2.8%	1 2.9%	2 8.0%	5 2.8%
Tanzania	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
		0 0.0%	0 0.0%	0 0.0%	1 5.9%	0 0.0%	3 8.3%	3 8.6%	3 12.0%	10 5.5%
Brazil	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
		0 0.0%	0 0.0%	2 13.3%	5 29.4%	1 14.3%	6 16.7%	2 5.7%	3 12.0%	19 10.5%
South Africa	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
		0 0.0%	4 17.4%	6 40.0%	4 23.5%	2 28.6%	6 16.7%	4 11.4%	2 8.0%	28 15.5%
Uganda	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	2 5.7%	1 4.0%	3 1.7%
Zimbabwe	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	3 8.3%	15 42.9%	10 40.0%	28 15.5%
Kenya	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
		0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	8 22.2%	5 14.3%	1 4.0%	14 7.7%
Thailand	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
		3 13.0%	3 13.0%	2 13.3%	2 11.8%	3 42.9%	6 16.7%	1 2.9%	3 12.0%	23 12.7%
Weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
		55.1 (15.6)	30.1 (10.4)	23.0 (4.6)	14.4 (2.9)	8.4 (2.0)	13.7 (2.6)	8.5 (1.8)	5.7 (1.1)	19.6 (17.0)
Height; Mean (Standard Deviation); Unit of measure: Cm
	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
		155.4 (8.9)	131.1 (14.0)	121.2 (9.6)	95.9 (8.7)	71.0 (6.0)	93.4 (8.9)	71.9 (5.7)	59.2 (3.7)	98.9 (32.4)
CD4 Cell Count [1]; Median (Inter-Quartile Range); Unit of measure: Cells/mm^3
	Number Analyzed	23 participants	23 participants	15 participants	17 participants	6 participants	36 participants	35 participants	25 participants	180 participants
		466.0; (297 to 771)	645.0; (466 to 732)	749.0; (306 to 1041)	900.0; (565 to 1399)	1482.5; (1190 to 1827)	1049.5; (559.5 to 1883)	2121.0; (1422 to 2384)	1916.0; (1357 to 2680)	1053.0; (618 to 1914.5)
		[1] Measure Analysis Population Description: Participants who had non-missing values were summarized. One participant in Cohort IV had missing value.
CD4 Percent [1]; Median (Inter-Quartile Range); Unit of measure: Percentage of total lymphocytes
	Number Analyzed	23 participants	23 participants	15 participants	17 participants	6 participants	36 participants	35 participants	25 participants	180 participants
		22.0; (18.4 to 29.2)	24.0; (14.3 to 28.7)	25.3; (20 to 33)	25.0; (20 to 31)	20.7; (14.6 to 31.1)	24.0; (17.2 to 31.1)	24.2; (19.8 to 32.2)	22.7; (20.6 to 30.4)	24.0; (18.3 to 31)
		[1] Measure Analysis Population Description: Participants who had non-missing values were summarized. One participant in Cohort IV had missing value.
CD8 Cell Count [1]; Median (Inter-Quartile Range); Unit of measure: Cells/mm^3
	Number Analyzed	23 participants	23 participants	15 participants	17 participants	6 participants	36 participants	35 participants	25 participants	180 participants
		1009.0; (788 to 1303)	1089.0; (955 to 1774)	1103.0; (948 to 1757)	1730.0; (1148 to 1991)	1888.5; (1441 to 2796)	1725.0; (1258 to 2561.5)	2922.0; (2050 to 4546)	2435.0; (1468 to 3789)	1679.0; (1074.5 to 2725)
		[1] Measure Analysis Population Description: Participants who had non-missing values were summarized. One participant in Cohort IV had missing value.
CD8 Percent [1]; Median (Inter-Quartile Range); Unit of measure: Percentage of total lymphocytes
	Number Analyzed	23 participants	23 participants	15 participants	17 participants	6 participants	36 participants	35 participants	25 participants	180 participants
		49.5; (43.8 to 59)	53.0; (43 to 58.6)	48.0; (44 to 51)	39.7; (35.1 to 49.3)	28.5; (18.2 to 34.4)	42.2; (29.5 to 50.2)	39.4; (31.3 to 47.2)	31.6; (24 to 41.8)	43.0; (32 to 50.8)
		[1] Measure Analysis Population Description: Participants who had non-missing values were summarized. One participant in Cohort IV had missing value.
Baseline Plasma HIV-1 RNA (copies/mL); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
	<400	0 0.0%	0 0.0%	1 6.7%	0 0.0%	1 14.3%	2 5.6%	1 2.9%	1 4.0%	6 3.3%
	400 - <1,000	0 0.0%	1 4.3%	0 0.0%	0 0.0%	1 14.3%	3 8.3%	1 2.9%	0 0.0%	6 3.3%
	1,000 - <5,000	2 8.7%	3 13.0%	1 6.7%	2 11.8%	0 0.0%	5 13.9%	7 20.0%	7 28.0%	27 14.9%
	5,000 - <10,000	4 17.4%	1 4.3%	1 6.7%	1 5.9%	0 0.0%	1 2.8%	4 11.4%	3 12.0%	15 8.3%
	10,000 - <25,000	8 34.8%	0 0.0%	3 20.0%	0 0.0%	0 0.0%	4 11.1%	4 11.4%	2 8.0%	21 11.6%
	25,000 - <50,000	5 21.7%	4 17.4%	1 6.7%	2 11.8%	1 14.3%	5 13.9%	3 8.6%	1 4.0%	22 12.2%
	50,000 - <100,000	2 8.7%	3 13.0%	6 40.0%	5 29.4%	1 14.3%	4 11.1%	1 2.9%	0 0.0%	22 12.2%
	>=100,000	2 8.7%	11 47.8%	2 13.3%	7 41.2%	3 42.9%	12 33.3%	14 40.0%	11 44.0%	62 34.3%
HIV-1 log10 RNA; Mean (Standard Deviation); Unit of measure: Log10 copies/mL
	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
		4.3 (0.5)	4.9 (1.0)	4.4 (0.8)	4.9 (0.9)	4.5 (1.4)	4.5 (1.2)	4.6 (1.1)	4.6 (1.4)	4.6 (1.1)
Class of Prior Antiretroviral Therapy (ART) [1]; Measure Type: Count of Participants; Unit of measure: Participants
Nucleoside reverse transcriptase inhibitor (NRTI)	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
		23 100.0%	23 100.0%	14 93.3%	17 100.0%	6 85.7%	30 83.3%	29 82.9%	23 92.0%	165 91.2%
Non-nucleoside reverse transcriptase inhibitor (NNRTI)	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
		12 52.2%	13 56.5%	10 66.7%	5 29.4%	5 71.4%	14 38.9%	18 51.4%	15 60.0%	92 50.8%
Protease inhibitor (PI)	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
		18 78.3%	17 73.9%	10 66.7%	15 88.2%	5 71.4%	25 69.4%	28 80.0%	20 80.0%	138 76.2%
Fusion inhibitor (FI)	Number Analyzed	23 participants	23 participants	15 participants	17 participants	7 participants	36 participants	35 participants	25 participants	181 participants
		2 8.7%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	2 1.1%
		[1] Measure Description: Note: These categories are not mutually exclusive since some participants would have received multiple ARTs.

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Grade 3 or Higher Adverse Events (AEs)
Description	All grade 3 or higher signs/symptoms, diagnoses, and laboratory AEs were included. AE grading was based on DAIDS AE Grading Table, Version 1.0, December 2004 (Clarification, August 2009). A 2-sided 95% Confidence Interval (CI) was calculated for the percentage using the binominal exact method.
Time Frame	From treatment initiation through Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of DTG and were deemed safety evaluable by the protocol team.

Arm/Group Title	Cohort I	Cohort IIA	Cohort IIB	Cohort III	Cohort IV	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description:	Adolescents 12 to younger than 18 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG granules for suspension DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG granules for suspension DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~0.8 mg/kg with a maximum dose of 30 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.	Infants 4 weeks to younger than 6 months of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.
Overall Number of Participants Analyzed	23	23	15	17	7	36	35	25
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Through Week 24	4.3; (0.1 to 22.0)	8.7; (1.1 to 28.0)	6.7; (0.2 to 32.0)	29.4; (10.3 to 56.0)	57.1; (18.4 to 90.1)	38.9; (23.1 to 56.5)	42.9; (26.3 to 60.7)	60; (38.7 to 78.9)
Through Week 48	8.7; (1.1 to 28.0)	17.4; (5.0 to 38.8)	13.3; (1.7 to 40.5)	35.3; (14.2 to 61.7)	57.1; (18.4 to 90.1)	41.7; (25.5 to 59.2)	51.4; (34.0 to 68.6)	64; (42.5 to 82.0)

2. Primary Outcome

Title	Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug
Description	All grade 3 or higher signs/symptoms, diagnoses, and laboratory AEs were included. AE grading was based on DAIDS AE Grading Table, Version 1.0, December 2004 (Clarification, August 2009). A 2-sided 95% Confidence Interval (CI) was calculated for the percentage using the binominal exact method.
Time Frame	From treatment initiation through Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of DTG and were deemed safety evaluable by the protocol team.

Arm/Group Title	Cohort I	Cohort IIA	Cohort IIB	Cohort III	Cohort IV	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description:	Adolescents 12 to younger than 18 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG granules for suspension DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~0.8 mg/kg with a maximum dose of 30 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.	Infants 4 weeks to younger than 6 months of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.
Overall Number of Participants Analyzed	23	23	15	17	7	36	35	25
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Through Week 24	0; (0.0 to 14.8)	0; (0.0 to 14.8)	0; (0.0 to 21.8)	0; (0.0 to 19.5)	14.3; (0.4 to 57.9)	0; (0.0 to 9.7)	0; (0.0 to 10.0)	0; (0.0 to 13.7)
Through Week 48	0; (0.0 to 14.8)	0; (0.0 to 14.8)	0; (0.0 to 21.8)	0; (0.0 to 19.5)	14.3; (0.4 to 57.9)	0; (0.0 to 9.7)	0; (0.0 to 10.0)	0; (0.0 to 13.7)

3. Primary Outcome

Title	Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug
Description	Number of participants with permanent discontinuation of study drug due to AEs assessed by the site investigator as related to the study drug.
Time Frame	From treatment initiation through Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of DTG and were deemed safety evaluable by the protocol team.

Arm/Group Title	Cohort I	Cohort IIA	Cohort IIB	Cohort III	Cohort IV	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description:	Adolescents 12 to younger than 18 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG granules for suspension DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~0.8 mg/kg with a maximum dose of 30 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.	Infants 4 weeks to younger than 6 months of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.
Overall Number of Participants Analyzed	23	23	15	17	7	36	35	25
Measure Type: Count of Participants; Unit of Measure: Participants
Through Week 24	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Through Week 48	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

4. Primary Outcome

Title	Number of Participants Who Died
Description	Number of participants who died were summarized
Time Frame	From treatment initiation through Weeks 24 and 48

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of DTG and were deemed safety evaluable by the protocol team.

Arm/Group Title	Cohort I	Cohort IIA	Cohort IIB	Cohort III	Cohort IV	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description:	Adolescents 12 to younger than 18 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~0.8 mg/kg with a maximum dose of 30 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.	Infants 4 weeks to younger than 6 months of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.
Overall Number of Participants Analyzed	23	23	15	17	7	36	35	25
Measure Type: Count of Participants; Unit of Measure: Participants
Through Week 24	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 2.8%	1 2.9%	0 0.0%
Through Week 48	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 2.8%	1 2.9%	0 0.0%

5. Primary Outcome

Title	PK Parameter: Area-under-the-curve From 0 to 24 Hours (AUC0-24)
Description	Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). AUC0-24 was determined using linear up-log down estimation in WinNonlin.
Time Frame	One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing

Outcome Measure Data

Analysis Population Description

Participants with intensive pharmacokinetic (PK) data at the proposed dose for Cohorts I, IIA, III-DT, IV-DT, and V-DT.

Arm/Group Title	Cohort I	Cohort IIA	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description:	Adolescents 12 to younger than 18 years of age who received 50 mg DTG film-coated tablets orally once daily for those weighing ≥ 35kg.	Children 6 to younger than 12 years of age who received 50 mg DTG film-coated tablets orally once daily for those weighing ≥ 35kg.	Children 2 to younger than 6 years of age who received weight band dosing at ~1 mg/kg of DTG dispersible tablet orally once daily.	Children 6 months to younger than 2 years of age who received weight band dosing at ~1 mg/kg of DTG dispersible tablet orally once daily.	Infants 4 weeks to younger than 6 months of age who received weight band doing at ~1 mg/kg of DTG dispersible tablet orally once daily.
Overall Number of Participants Analyzed	9	5	17	13	13
Mean (Standard Deviation); Unit of Measure: hr*mg/L
	52.98 (23.11)	68.33 (43.33)	63.16 (37.77)	82.67 (47.05)	71.45 (28.21)

6. Secondary Outcome

Title	Percentage of Participants With Grade 3 or Higher Adverse Events (AEs)
Description	Percentage and exact 95% Confidence Interval (CI) of participants with Grade 3 or higher AEs. AEs were graded based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004, Clarification August 2009 (see References). All grade 3 or higher signs, symptoms, and laboratory toxicities were included. The study is ongoing. Results for extended long term safety will be posted upon study completion.
Time Frame	From treatment initiation through Week 192

Outcome Measure Data Not Reported

7. Secondary Outcome

Title	Percentage of Participants With Grade 3 or Higher Adverse Events (AEs) Assessed as Related to Study Drug
Description	Percentage and exact 95% Confidence Interval (CI) of participants with Grade 3 or higher AEs assessed by the site investigator as related to the study drug. The study is ongoing. Results for extended long term safety will be posted upon study completion.
Time Frame	From treatment initiation through Week 192

Outcome Measure Data Not Reported

8. Secondary Outcome

Title	Number of Participants With Permanent Discontinuation of Study Drug Due to Adverse Events (AEs) Assessed as Related to Study Drug
Description	Number of participants with permanent discontinuation of study drug due to AEs assessed by the site investigator as related to the study drug. The study is ongoing. Results for extended long term safety will be posted upon study completion.
Time Frame	From treatment initiation through Week 192

Outcome Measure Data Not Reported

9. Secondary Outcome

Title	Number of Participants Who Died
Description	Number of participants who died were summarized. The study is ongoing. Results for extended long term safety will be posted upon study completion.
Time Frame	From treatment initiation through Week 192

Outcome Measure Data Not Reported

10. Secondary Outcome

Title	Percentage of Participants With Plasma HIV-1 RNA Less Than 400 Copies/ml
Description	Virologic responses were assessed at weeks 24 and 48 as percentages of participants and exact 95% Confidence Interval (CI). The virologic response or virologic failure was defined and calculated according to FDA's Snapshot algorithm.
Time Frame	Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of DTG.

Arm/Group Title	Cohort I	Cohort IIA	Cohort IIB	Cohort III	Cohort IV	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description:	Adolescents 12 to younger than 18 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~0.8 mg/kg with a maximum dose of 30 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.	Infants 4 weeks to younger than 6 months of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.
Overall Number of Participants Analyzed	23	23	15	17	7	36	35	25
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Week 24	82.6; (61.2 to 95)	78.3; (56.3 to 92.5)	100; (78.2 to 100)	88.2; (63.6 to 98.5)	71.4; (29 to 96.3)	86.1; (70.5 to 95.3)	88.6; (73.3 to 96.8)	68; (46.5 to 85.1)
Week 48	73.9; (51.6 to 89.8)	78.3; (56.3 to 92.5)	93.3; (68.1 to 99.8)	94.1; (71.3 to 99.9)	71.4; (29 to 96.3)	86.1; (70.5 to 95.3)	85.7; (69.7 to 95.2)	72; (50.6 to 87.9)

11. Secondary Outcome

Title	Percentage of Participants With Plasma HIV-1 RNA Less Than 50 Copies/ml
Description	Virologic responses were assessed at weeks 24 and 48 as percentages of participants and exact 95% Confidence Interval (CI), The virologic response or virologic failure was defined and calculated according to FDA's Snapshot algorithm.
Time Frame	Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of DTG.

Arm/Group Title	Cohort I	Cohort IIA	Cohort IIB	Cohort III	Cohort IV	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description:	Adolescents 12 to younger than 18 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~0.8 mg/kg with a maximum dose of 30 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.	Infants 4 weeks to younger than 6 months of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.
Overall Number of Participants Analyzed	23	23	15	17	7	36	35	25
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Week 24	69.6; (47.1 to 86.8)	60.9; (38.5 to 80.3)	93.3; (68.1 to 99.8)	58.8; (32.9 to 81.6)	42.9; (9.9 to 81.6)	61.1; (43.5 to 76.9)	51.4; (34 to 68.6)	32; (14.9 to 53.5)
Week 48	60.9; (38.5 to 80.3)	69.6; (47.1 to 86.8)	93.3; (68.1 to 99.8)	64.7; (38.3 to 85.8)	42.9; (9.9 to 81.6)	69.4; (51.9 to 83.7)	65.7; (47.8 to 80.9)	36; (18 to 57.5)

12. Secondary Outcome

Title	PK Parameter: Plasma Concentration Observed at End of 24 Hour Dosing Interval (C24h)
Description	Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). C24h was taken directly from the observed concentration-time data or estimated using the elimination rate constant.
Time Frame	One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing

Outcome Measure Data

Analysis Population Description

Participants with intensive pharmacokinetic (PK) data at the proposed dose for Cohorts I, IIA, III-DT, IV-DT, and V-DT.

Arm/Group Title	Cohort I	Cohort IIA	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description:	Adolescents 12 to younger than 18 years of age who received 50 mg DTG film-coated tablets orally once daily for those weighing ≥ 35kg.	Children 6 to younger than 12 years of age who received 50 mg DTG film-coated tablets orally once daily for those weighing ≥ 35kg.	Children 2 to younger than 6 years of age who received weight band dosing at ~1 mg/kg of DTG dispersible tablet orally once daily.	Children 6 months to younger than 2 years of age who received weight band dosing at ~1 mg/kg of DTG dispersible tablet orally once daily.	Infants 4 weeks to younger than 6 months of age who received weight band doing at ~1 mg/kg of DTG dispersible tablet orally once daily.
Overall Number of Participants Analyzed	9	5	17	13	13
Mean (Standard Deviation); Unit of Measure: ng/mL
	1145.36 (659.65)	1475.46 (1139.52)	1065.12 (1112.46)	1488.24 (1175.44)	1765.19 (929.97)

13. Secondary Outcome

Title	PK Parameter: Plasma Concentration Observed Immediately to Dosing of 24 Hour Dosing Interval (C0h)
Description	Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). C0h was taken directly from the observed concentration-time data.
Time Frame	One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing

Outcome Measure Data

Analysis Population Description

Participants with intensive pharmacokinetic (PK) data at the proposed dose for Cohorts I, IIA, III-DT, IV-DT, and V-DT.

Arm/Group Title	Cohort I	Cohort IIA	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description:	Adolescents 12 to younger than 18 years of age who received 50 mg DTG film-coated tablets orally once daily for those weighing ≥ 35kg.	Children 6 to younger than 12 years of age who received 50 mg DTG film-coated tablets orally once daily for those weighing ≥ 35kg.	Children 2 to younger than 6 years of age who received weight band dosing at ~1 mg/kg of DTG dispersible tablet orally once daily.	Children 6 months to younger than 2 years of age who received weight band dosing at ~1 mg/kg of DTG dispersible tablet orally once daily.	Infants 4 weeks to younger than 6 months of age who received weight band doing at ~1 mg/kg of DTG dispersible tablet orally once daily.
Overall Number of Participants Analyzed	9	5	17	13	13
Mean (Standard Deviation); Unit of Measure: ng/mL
	1429.09 (738.69)	1508.44 (1271.93)	944.22 (549.36)	1584.29 (1388.27)	1376.15 (1132.28)

14. Secondary Outcome

Title	PK Parameter: Minimum Plasma Concentration (Cmin)
Description	Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ) and were performed in real-time. Cmin was taken directly from the observed concentration-time data.
Time Frame	One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing

Outcome Measure Data

Analysis Population Description

Participants with intensive pharmacokinetic (PK) data at the proposed dose for Cohorts I, IIA, III-DT, IV-DT, and V-DT.

Arm/Group Title	Cohort I	Cohort IIA	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description:	Adolescents 12 to younger than 18 years of age who received 50 mg DTG film-coated tablets orally once daily for those weighing ≥ 35kg.	Children 6 to younger than 12 years of age who received 50 mg DTG film-coated tablets orally once daily for those weighing ≥ 35kg.	Children 2 to younger than 6 years of age who received weight band dosing at ~1 mg/kg of DTG dispersible tablet orally once daily.	Children 6 months to younger than 2 years of age who received weight band dosing at ~1 mg/kg of DTG dispersible tablet orally once daily.	Infants 4 weeks to younger than 6 months of age who received weight band doing at ~1 mg/kg of DTG dispersible tablet orally once daily.
Overall Number of Participants Analyzed	9	5	17	13	13
Mean (Standard Deviation); Unit of Measure: ng/mL
	1193.94 (668.76)	1155.52 (1152.98)	757.92 (439.83)	1343.74 (1370.79)	1213.68 (886.21)

15. Secondary Outcome

Title	PK Parameter: Maximum Plasma Concentration (Cmax)
Description	Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). Cmax was taken directly from the observed concentration-time data.
Time Frame	One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing

Outcome Measure Data

Analysis Population Description

Participants with intensive pharmacokinetic (PK) data at the proposed dose for Cohorts I, IIA, III-DT, IV-DT, and V-DT.

Arm/Group Title	Cohort I	Cohort IIA	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description:	Adolescents 12 to younger than 18 years of age who received 50 mg DTG film-coated tablets orally once daily for those weighing ≥ 35kg.	Children 6 to younger than 12 years of age who received 50 mg DTG film-coated tablets orally once daily for those weighing ≥ 35kg.	Children 2 to younger than 6 years of age who received weight band dosing at ~1 mg/kg of DTG dispersible tablet orally once daily.	Children 6 months to younger than 2 years of age who received weight band dosing at ~1 mg/kg of DTG dispersible tablet orally once daily.	Infants 4 weeks to younger than 6 months of age who received weight band doing at ~1 mg/kg of DTG dispersible tablet orally once daily.
Overall Number of Participants Analyzed	9	5	17	13	13
Mean (Standard Deviation); Unit of Measure: ng/mL
	3945.97 (1499.34)	5111.10 (2459.92)	5530.16 (2466.62)	6256.67 (2508.57)	4832.58 (1679.69)

16. Secondary Outcome

Title	PK Parameter: Apparent Clearance (CL/F)
Description	Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). CL/F was calculated as Dose/AUC.
Time Frame	One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing

Outcome Measure Data

Analysis Population Description

Participants with intensive pharmacokinetic (PK) data at the proposed dose for Cohorts I, IIA, III-DT, IV-DT, and V-DT.

Arm/Group Title	Cohort I	Cohort IIA	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description:	Adolescents 12 to younger than 18 years of age who received 50 mg DTG film-coated tablets orally once daily for those weighing ≥ 35kg.	Children 6 to younger than 12 years of age who received 50 mg DTG film-coated tablets orally once daily for those weighing ≥ 35kg.	Children 2 to younger than 6 years of age who received weight band dosing at ~1 mg/kg of DTG dispersible tablet orally once daily.	Children 6 months to younger than 2 years of age who received weight band dosing at ~1 mg/kg of DTG dispersible tablet orally once daily.	Infants 4 weeks to younger than 6 months of age who received weight band doing at ~1 mg/kg of DTG dispersible tablet orally once daily.
Overall Number of Participants Analyzed	9	5	17	13	13
Mean (Standard Deviation); Unit of Measure: L/h
	1.29 (1.03)	1.11 (0.92)	0.49 (0.31)	0.23 (0.11)	0.11 (0.05)

17. Secondary Outcome

Title	PK Parameter: Apparent Volume of Distribution (Vz/F)
Description	Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). Vz/F was calculated as Dose/(ke x AUC).
Time Frame	One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing

Outcome Measure Data

Analysis Population Description

Participants with intensive pharmacokinetic (PK) data at the proposed dose for Cohorts I, IIA, III-DT, IV-DT, and V-DT.

Arm/Group Title	Cohort I	Cohort IIA	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description:	Adolescents 12 to younger than 18 years of age who received 50 mg DTG film-coated tablets orally once daily for those weighing ≥ 35kg.	Children 6 to younger than 12 years of age who received 50 mg DTG film-coated tablets orally once daily for those weighing ≥ 35kg.	Children 2 to younger than 6 years of age who received weight band dosing at ~1 mg/kg of DTG dispersible tablet orally once daily.	Children 6 months to younger than 2 years of age who received weight band dosing at ~1 mg/kg of DTG dispersible tablet orally once daily.	Infants 4 weeks to younger than 6 months of age who received weight band doing at ~1 mg/kg of DTG dispersible tablet orally once daily.
Overall Number of Participants Analyzed	9	5	17	13	13
Mean (Standard Deviation); Unit of Measure: L
	21.95 (13.71)	19.11 (16.51)	5.75 (3.66)	3.19 (1.50)	2.37 (1.04)

18. Secondary Outcome

Title	PK Parameter: Terminal Half-life (t1/2)
Description	Determined from plasma concentration-time profiles using non-compartmental methods (Phoenix WinNonlin 8.0 or current, Certara, Princeton, NJ). t1/2 was calculated as ln(2)/ke.
Time Frame	One intensive PK visit between 5 and 10 days of DTG initiation. At intensive PK visit, blood samples were drawn pre-dose and at 1, 2, 3, 4, 6, 8 and 24 hours post dosing

Outcome Measure Data

Analysis Population Description

Participants with intensive pharmacokinetic (PK) data at the proposed dose for Cohorts I, IIA, III-DT, IV-DT, and V-DT.

Arm/Group Title	Cohort I	Cohort IIA	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description:	Adolescents 12 to younger than 18 years of age who received 50 mg DTG film-coated tablets orally once daily for those weighing ≥ 35kg.	Children 6 to younger than 12 years of age who received 50 mg DTG film-coated tablets orally once daily for those weighing ≥ 35kg.	Children 2 to younger than 6 years of age who received weight band dosing at ~1 mg/kg of DTG dispersible tablet orally once daily.	Children 6 months to younger than 2 years of age who received weight band dosing at ~1 mg/kg of DTG dispersible tablet orally once daily.	Infants 4 weeks to younger than 6 months of age who received weight band doing at ~1 mg/kg of DTG dispersible tablet orally once daily.
Overall Number of Participants Analyzed	9	5	17	13	13
Mean (Standard Deviation); Unit of Measure: h
	13.21 (5.51)	12.22 (2.63)	9.10 (3.40)	9.93 (2.58)	16.85 (8.22)

19. Secondary Outcome

Title	Summary of Changes in CD4 Count From Baseline
Description	The median differences between CD4 count at Week 24 and 48 minus at the Day 0 (baseline), and Interquartile Ranges (IQRs) are presented.
Time Frame	Measured at Day 0, Week 24, and Week 48

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of DTG. Study participants who had non-missing values were summarized.

Arm/Group Title		Cohort I	Cohort IIA	Cohort IIB	Cohort III	Cohort IV	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description:		Adolescents 12 to younger than 18 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~0.8 mg/kg with a maximum dose of 30 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.	Infants 4 weeks to younger than 6 months of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~0.8 mg/kg with a maximum dose of 30 mg; orally once daily.
Overall Number of Participants Analyzed		23	23	15	17	7	36	35	25
Median (Inter-Quartile Range); Unit of Measure: cells/mm^3
From baseline to Week 24	Number Analyzed	23 participants	21 participants	15 participants	17 participants	6 participants	33 participants	33 participants	23 participants
		63; (-56 to 180)	209; (30 to 403)	268; (142 to 372)	199; (-59 to 644)	472; (-20 to 883)	249; (47 to 535)	110; (-284 to 434)	441; (-114 to 1023)
From baseline to Week 48	Number Analyzed	22 participants	21 participants	15 participants	16 participants	5 participants	33 participants	33 participants	22 participants
		84; (-81 to 238)	387; (49 to 575)	246; (160 to 466)	134.5; (-183.5 to 569.5)	577; (135 to 777)	191; (-202 to 541)	-1; (-449 to 577)	721; (-114 to 972)

20. Secondary Outcome

Title	Summary of Changes in CD4 Percent From Baseline
Description	The median differences between CD4 percent at Week 24 and 48 minus at the Day 0 (baseline), and Interquartile Ranges (IQRs) are presented.
Time Frame	Measured at Day 0, Week 24, and Week 48

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of DTG. Study participants who had non-missing values were summarized.

Arm/Group Title		Cohort I	Cohort IIA	Cohort IIB	Cohort III	Cohort IV	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description:		Adolescents 12 to younger than 18 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~0.8 mg/kg with a maximum dose of 30 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.	Infants 4 weeks to younger than 6 months of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.
Overall Number of Participants Analyzed		23	23	15	17	7	36	35	25
Median (Inter-Quartile Range); Unit of Measure: Percentage of total lymphocytes
From baseline to Week 24	Number Analyzed	23 participants	21 participants	15 participants	17 participants	6 participants	33 participants	33 participants	23 participants
		4.9; (1 to 8)	8; (5 to 11)	6; (3.3 to 9.1)	6; (4.5 to 9)	5.7; (3.9 to 8.1)	6.1; (3.4 to 10.9)	6; (2.5 to 12)	5.1; (1 to 10)
From baseline to Week 48	Number Analyzed	22 participants	21 participants	15 participants	16 participants	5 participants	33 participants	33 participants	22 participants
		4.7; (0 to 9.4)	9; (7 to 14)	9.2; (5 to 11.9)	5.6; (1.5 to 11)	9.9; (8.5 to 10)	9.1; (4.4 to 13.4)	8.8; (0.7 to 14)	9.7; (4.1 to 11)

21. Secondary Outcome

Title	Summary of Changes in CD8 Count From Baseline
Description	The median differences between CD8 count at Week 24 and 48 minus at the Day 0 (baseline), and Interquartile Ranges (IQRs) are presented.
Time Frame	Measured at Day 0, Week 24, and Week 48

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of DTG. Study participants who had non-missing values were summarized.

Arm/Group Title		Cohort I	Cohort IIA	Cohort IIB	Cohort III	Cohort IV	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description:		Adolescents 12 to younger than 18 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~0.8 mg/kg with a maximum dose of 30 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.	Infants 4 weeks to younger than 6 months of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.
Overall Number of Participants Analyzed		23	23	15	17	7	36	35	25
Median (Inter-Quartile Range); Unit of Measure: cells/mm^3
From baseline to Week 24	Number Analyzed	23 participants	21 participants	15 participants	17 participants	6 participants	33 participants	33 participants	23 participants
		-36; (-371 to 30)	-147; (-804 to 30)	-43; (-247 to 151)	-282; (-533 to 176)	223; (-592 to 668)	-395; (-732 to 69)	-813; (-2013 to -65)	-210; (-1206 to 910)
From baseline to Week 48	Number Analyzed	22 participants	21 participants	15 participants	16 participants	5 participants	33 participants	33 participants	22 participants
		-52.5; (-365 to 105)	-117; (-607 to 131)	-126; (-302 to 166)	-431.5; (-782 to -169.5)	-376; (-411 to 21)	-464; (-1013 to -94)	-1242; (-2433 to -280)	-442; (-1435 to 870)

22. Secondary Outcome

Title	Summary of Changes in CD8 Percent From Baseline
Description	The median differences between CD8 percent at Week 24 and 48 minus at the Day 0 (baseline), and Interquartile Ranges (IQRs) are presented.
Time Frame	Measured at Day 0, Week 24, and Week 48

Outcome Measure Data

Analysis Population Description

Participants who received at least one dose of DTG. Study participants who had non-missing values were summarized.

Arm/Group Title		Cohort I	Cohort IIA	Cohort IIB	Cohort III	Cohort IV	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description:		Adolescents 12 to younger than 18 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~0.8 mg/kg with a maximum dose of 30 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.	Infants 4 weeks to younger than 6 months of age who received DTG dispersible tablets. DTG dispersible tablets initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.
Overall Number of Participants Analyzed		23	23	15	17	7	36	35	25
Median (Inter-Quartile Range); Unit of Measure: Percentage of total lymphocytes
From baseline to Week 24	Number Analyzed	23 participants	21 participants	15 participants	17 participants	6 participants	33 participants	33 participants	23 participants
		-5; (-9.7 to -2.3)	-10; (-17.4 to -6)	-7; (-9.2 to -4)	-6.8; (-9.9 to 2.5)	-2; (-4.1 to 3.5)	-3; (-9 to 0.1)	-4.2; (-9.9 to -1.3)	-4; (-10.2 to 2)
From baseline to Week 48	Number Analyzed	22 participants	21 participants	15 participants	16 participants	5 participants	33 participants	33 participants	22 participants
		-6; (-12 to -2.4)	-11.4; (-22 to -7)	-8; (-15 to -5)	-6.5; (-14.5 to -3)	-1.8; (-4 to 0.3)	-6.5; (-10 to -1.9)	-9; (-15.2 to -4.9)	-3.5; (-11.5 to 1.7)

23. Secondary Outcome

Title	Genotypic and Phenotypic Measures of Resistance
Description	Genotypic and phenotypic measures of resistance. The study is ongoing. Results for extended long term safety will be posted upon study completion.
Time Frame	From baseline through Week 192

Outcome Measure Data Not Reported

24. Secondary Outcome

Title	Disease Progression as Measured by Change in Centers for Disease Control and Prevention (CDC) Category
Description	Disease progression as measured by change in Centers for Disease Control and Prevention (CDC) category. The study is ongoing. Results for extended long term safety will be posted upon study completion.
Time Frame	From baseline through Week 192

Outcome Measure Data Not Reported

Adverse Events

Time Frame	From study entry to completion of follow-up at Week 48 and Week 192, for participants on short-term and long-term follow-up, respectively. The study is ongoing and some participants are still on study follow-up. AE summaries include available data as of database freeze date (March 24, 2021) and will be updated upon study completion.
Adverse Event Reporting Description	AEs were summarized for participants who received at least one dose of of Dolutegravir (DTG). AEs were restricted to those onset dates less than or equal to the database freeze date (March 24, 2021). AE severity grading was based on the DAIDS AE Grading Table, Version 1.0. SAEs were reported according to DAIDS EAE Manual V2.0.
Arm/Group Title	Cohort I	Cohort IIA	Cohort IIB	Cohort III	Cohort IV	Cohort III-DT	Cohort IV-DT	Cohort V-DT
Arm/Group Description	Adolescents 12 to younger than 18 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG film-coated tablets. DTG film-coated tablets initial starting dose at ~1 mg/kg with a maximum dose of 50 mg; orally once daily.	Children 6 to younger than 12 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG granules for suspension. DTG granules for suspension initial starting dose at ~0.64 mg/kg with a maximum dose of 32 mg; orally once daily.	Children 2 to younger than 6 years of age who received DTG dispersible tablets. DTG dispersible tables initial starting dose of ~0.8 mg/kg with a maximum dose of 30 mg; orally once daily.	Children 6 months to younger than 2 years of age who received DTG dispersible tablets. DTG dispersible tables initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.	Infants 4 weeks to younger than 6 months of age who received DTG dispersible tablets. DTG dispersible tables initial starting dose of ~1.25 mg/kg with a maximum dose of 30 mg; orally once daily.
All-Cause Mortality
	Cohort I	Cohort IIA	Cohort IIB	Cohort III	Cohort IV	Cohort III-DT	Cohort IV-DT	Cohort V-DT
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	1/35 (2.86%)	0/25 (0.00%)
Serious Adverse Events
	Cohort I	Cohort IIA	Cohort IIB	Cohort III	Cohort IV	Cohort III-DT	Cohort IV-DT	Cohort V-DT
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	8/23 (34.78%)	5/23 (21.74%)	1/15 (6.67%)	8/17 (47.06%)	2/7 (28.57%)	10/36 (27.78%)	8/35 (22.86%)	2/25 (8.00%)
Congenital, familial and genetic disorders
Hydrocele † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Eye disorders
Cataract † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Gastrointestinal disorders
Diarrhoea † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Gastritis † 1	1/23 (4.35%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
General disorders
Death † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Drowning † 1	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Pyrexia † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Infections and infestations
Abscess limb † 1	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Atypical mycobacterial lymphadenitis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Bacterial sepsis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	1/35 (2.86%)	0/25 (0.00%)
Bronchitis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Bronchitis viral † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Cellulitis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	2/17 (11.76%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Disseminated mycobacterium avium complex infection † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Gastritis viral † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Gastroenteritis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	0/36 (0.00%)	2/35 (5.71%)	1/25 (4.00%)
Gastroenteritis bacterial † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Hepatitis viral † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Herpes zoster † 1	1/23 (4.35%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	1/35 (2.86%)	0/25 (0.00%)
Influenza † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Ophthalmic herpes simplex † 1	1/23 (4.35%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Oral herpes † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Pelvic inflammatory disease † 1	2/23 (8.70%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Plasmodium falciparum infection † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	1/35 (2.86%)	0/25 (0.00%)
Pneumonia † 1	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	1/36 (2.78%)	1/35 (2.86%)	1/25 (4.00%)
Pneumonia adenoviral † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	2/36 (5.56%)	0/35 (0.00%)	0/25 (0.00%)
Pneumonia bacterial † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	2/17 (11.76%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Pneumonia respiratory syncytial viral † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Pneumonia viral † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Sepsis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Sinusitis bacterial † 1	1/23 (4.35%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Tinea versicolour † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Viral rash † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Injury, poisoning and procedural complications
Concussion † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Contusion † 1	1/23 (4.35%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Investigations
Alanine aminotransferase increased † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	0/36 (0.00%)	1/35 (2.86%)	0/25 (0.00%)
Blood alkaline phosphatase increased † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Blood glucose decreased † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Lipase increased † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	1/35 (2.86%)	0/25 (0.00%)
Neutrophil count decreased † 1	1/23 (4.35%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	1/35 (2.86%)	0/25 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma † 1	1/23 (4.35%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Retinoblastoma † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Nervous system disorders
Febrile convulsion † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Hemiparesis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	1/35 (2.86%)	0/25 (0.00%)
Pregnancy, puerperium and perinatal conditions
Pregnancy † 1	3/23 (13.04%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Psychiatric disorders
Abnormal behaviour † 1	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Suicidal ideation † 1	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Suicide attempt † 1	1/23 (4.35%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Respiratory, thoracic and mediastinal disorders
Respiratory disorder † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Respiratory distress † 1	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Skin and subcutaneous tissue disorders
Angioedema † 1	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Urticaria † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Surgical and medical procedures
Abortion induced † 1	1/23 (4.35%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Vascular disorders
Deep vein thrombosis † 1	2/23 (8.70%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
1 Term from vocabulary, MedDRA 24.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Cohort I	Cohort IIA	Cohort IIB	Cohort III	Cohort IV	Cohort III-DT	Cohort IV-DT	Cohort V-DT
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	23/23 (100.00%)	23/23 (100.00%)	15/15 (100.00%)	17/17 (100.00%)	7/7 (100.00%)	36/36 (100.00%)	35/35 (100.00%)	25/25 (100.00%)
Blood and lymphatic system disorders
Iron deficiency anaemia † 1	0/23 (0.00%)	2/23 (8.70%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	2/36 (5.56%)	2/35 (5.71%)	3/25 (12.00%)
Lymphadenitis † 1	0/23 (0.00%)	1/23 (4.35%)	1/15 (6.67%)	0/17 (0.00%)	1/7 (14.29%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Lymphadenopathy † 1	7/23 (30.43%)	7/23 (30.43%)	3/15 (20.00%)	2/17 (11.76%)	2/7 (28.57%)	6/36 (16.67%)	1/35 (2.86%)	2/25 (8.00%)
Splenomegaly † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	2/7 (28.57%)	2/36 (5.56%)	0/35 (0.00%)	0/25 (0.00%)
Cardiac disorders
Bradycardia † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Tachycardia † 1	1/23 (4.35%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	2/35 (5.71%)	0/25 (0.00%)
Congenital, familial and genetic disorders
Craniosynostosis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Phimosis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Ear and labyrinth disorders
Ear pain † 1	2/23 (8.70%)	3/23 (13.04%)	2/15 (13.33%)	4/17 (23.53%)	1/7 (14.29%)	4/36 (11.11%)	0/35 (0.00%)	0/25 (0.00%)
Noninfective myringitis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Otorrhoea † 1	0/23 (0.00%)	3/23 (13.04%)	1/15 (6.67%)	2/17 (11.76%)	0/7 (0.00%)	2/36 (5.56%)	2/35 (5.71%)	1/25 (4.00%)
Tympanic membrane disorder † 1	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	2/17 (11.76%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Tympanic membrane hyperaemia † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	1/25 (4.00%)
Tympanic membrane perforation † 1	0/23 (0.00%)	3/23 (13.04%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Eye disorders
Blepharitis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Chalazion † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Conjunctival hyperaemia † 1	1/23 (4.35%)	0/23 (0.00%)	1/15 (6.67%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Conjunctival pallor † 1	2/23 (8.70%)	1/23 (4.35%)	0/15 (0.00%)	1/17 (5.88%)	2/7 (28.57%)	1/36 (2.78%)	2/35 (5.71%)	3/25 (12.00%)
Eye discharge † 1	1/23 (4.35%)	0/23 (0.00%)	1/15 (6.67%)	3/17 (17.65%)	1/7 (14.29%)	0/36 (0.00%)	4/35 (11.43%)	1/25 (4.00%)
Eye movement disorder † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Eye opacity † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Eye pain † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Eye pruritus † 1	1/23 (4.35%)	1/23 (4.35%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	1/25 (4.00%)
Ocular hyperaemia † 1	1/23 (4.35%)	1/23 (4.35%)	2/15 (13.33%)	0/17 (0.00%)	1/7 (14.29%)	1/36 (2.78%)	4/35 (11.43%)	1/25 (4.00%)
Pterygium † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Scleritis † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Gastrointestinal disorders
Abdominal discomfort † 1	2/23 (8.70%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Abdominal distension † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Abdominal hernia † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Abdominal pain † 1	7/23 (30.43%)	1/23 (4.35%)	2/15 (13.33%)	2/17 (11.76%)	1/7 (14.29%)	3/36 (8.33%)	0/35 (0.00%)	0/25 (0.00%)
Abdominal pain upper † 1	4/23 (17.39%)	3/23 (13.04%)	1/15 (6.67%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Abdominal tenderness † 1	1/23 (4.35%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Anal erythema † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Anal fissure † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Anal pruritus † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	1/7 (14.29%)	2/36 (5.56%)	0/35 (0.00%)	1/25 (4.00%)
Aphthous ulcer † 1	1/23 (4.35%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	1/7 (14.29%)	2/36 (5.56%)	0/35 (0.00%)	0/25 (0.00%)
Constipation † 1	2/23 (8.70%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	1/7 (14.29%)	1/36 (2.78%)	0/35 (0.00%)	1/25 (4.00%)
Dental caries † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Diarrhoea † 1	8/23 (34.78%)	6/23 (26.09%)	2/15 (13.33%)	9/17 (52.94%)	4/7 (57.14%)	7/36 (19.44%)	18/35 (51.43%)	5/25 (20.00%)
Dysphagia † 1	2/23 (8.70%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Gingival ulceration † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Haematochezia † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Infantile vomiting † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	4/35 (11.43%)	4/25 (16.00%)
Lip dry † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Lip pain † 1	1/23 (4.35%)	1/23 (4.35%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Lip ulceration † 1	1/23 (4.35%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	2/36 (5.56%)	0/35 (0.00%)	0/25 (0.00%)
Mouth ulceration † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	2/17 (11.76%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Nausea † 1	7/23 (30.43%)	1/23 (4.35%)	2/15 (13.33%)	1/17 (5.88%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Noninfective gingivitis † 1	2/23 (8.70%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Oral disorder † 1	1/23 (4.35%)	2/23 (8.70%)	1/15 (6.67%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	1/35 (2.86%)	0/25 (0.00%)
Oral mucosal erythema † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Oral pain † 1	2/23 (8.70%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Stomatitis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	1/36 (2.78%)	2/35 (5.71%)	1/25 (4.00%)
Toothache † 1	2/23 (8.70%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Vomiting † 1	6/23 (26.09%)	4/23 (17.39%)	6/15 (40.00%)	7/17 (41.18%)	3/7 (42.86%)	9/36 (25.00%)	12/35 (34.29%)	6/25 (24.00%)
General disorders
Chest discomfort † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Fatigue † 1	3/23 (13.04%)	2/23 (8.70%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Feeling hot † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	4/35 (11.43%)	0/25 (0.00%)
Influenza like illness † 1	2/23 (8.70%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Malaise † 1	1/23 (4.35%)	0/23 (0.00%)	2/15 (13.33%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Pain † 1	1/23 (4.35%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Peripheral swelling † 1	3/23 (13.04%)	2/23 (8.70%)	1/15 (6.67%)	2/17 (11.76%)	0/7 (0.00%)	0/36 (0.00%)	1/35 (2.86%)	0/25 (0.00%)
Pyrexia † 1	8/23 (34.78%)	7/23 (30.43%)	5/15 (33.33%)	9/17 (52.94%)	6/7 (85.71%)	16/36 (44.44%)	13/35 (37.14%)	7/25 (28.00%)
Hepatobiliary disorders
Hepatomegaly † 1	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	2/17 (11.76%)	1/7 (14.29%)	2/36 (5.56%)	0/35 (0.00%)	1/25 (4.00%)
Immune system disorders
Allergy to arthropod bite † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	1/7 (14.29%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Immune reconstitution inflammatory syndrome † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	1/36 (2.78%)	1/35 (2.86%)	1/25 (4.00%)
Infections and infestations
Acarodermatitis † 1	2/23 (8.70%)	0/23 (0.00%)	2/15 (13.33%)	2/17 (11.76%)	1/7 (14.29%)	2/36 (5.56%)	4/35 (11.43%)	1/25 (4.00%)
Adenoiditis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Anal candidiasis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	2/7 (28.57%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Ascariasis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Bacterial vaginosis † 1	2/23 (8.70%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Balanitis candida † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Body tinea † 1	1/23 (4.35%)	0/23 (0.00%)	1/15 (6.67%)	1/17 (5.88%)	1/7 (14.29%)	2/36 (5.56%)	3/35 (8.57%)	1/25 (4.00%)
Bronchiolitis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Bronchitis † 1	1/23 (4.35%)	2/23 (8.70%)	2/15 (13.33%)	1/17 (5.88%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Bronchitis viral † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Cellulitis † 1	1/23 (4.35%)	2/23 (8.70%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Conjunctivitis † 1	1/23 (4.35%)	0/23 (0.00%)	1/15 (6.67%)	1/17 (5.88%)	1/7 (14.29%)	0/36 (0.00%)	4/35 (11.43%)	0/25 (0.00%)
Enterobiasis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	1/7 (14.29%)	1/36 (2.78%)	0/35 (0.00%)	1/25 (4.00%)
Escherichia urinary tract infection † 1	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	2/17 (11.76%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Gastroenteritis † 1	1/23 (4.35%)	1/23 (4.35%)	1/15 (6.67%)	5/17 (29.41%)	1/7 (14.29%)	2/36 (5.56%)	7/35 (20.00%)	2/25 (8.00%)
Giardiasis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	1/25 (4.00%)
HIV-associated neurocognitive disorder † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Helminthic infection † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Herpangina † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	0/36 (0.00%)	1/35 (2.86%)	0/25 (0.00%)
Impetigo † 1	1/23 (4.35%)	3/23 (13.04%)	1/15 (6.67%)	4/17 (23.53%)	3/7 (42.86%)	4/36 (11.11%)	3/35 (8.57%)	1/25 (4.00%)
Influenza † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Lice infestation † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	2/17 (11.76%)	0/7 (0.00%)	0/36 (0.00%)	1/35 (2.86%)	0/25 (0.00%)
Lower respiratory tract infection † 1	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Measles † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Molluscum contagiosum † 1	1/23 (4.35%)	1/23 (4.35%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	1/35 (2.86%)	0/25 (0.00%)
Nasopharyngitis † 1	1/23 (4.35%)	1/23 (4.35%)	0/15 (0.00%)	2/17 (11.76%)	3/7 (42.86%)	2/36 (5.56%)	1/35 (2.86%)	0/25 (0.00%)
Oral candidiasis † 1	2/23 (8.70%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	1/7 (14.29%)	2/36 (5.56%)	4/35 (11.43%)	2/25 (8.00%)
Oral herpes † 1	1/23 (4.35%)	2/23 (8.70%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Otitis media † 1	2/23 (8.70%)	2/23 (8.70%)	0/15 (0.00%)	4/17 (23.53%)	0/7 (0.00%)	5/36 (13.89%)	4/35 (11.43%)	2/25 (8.00%)
Otitis media chronic † 1	0/23 (0.00%)	1/23 (4.35%)	2/15 (13.33%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	1/35 (2.86%)	0/25 (0.00%)
Parasitic gastroenteritis † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	1/7 (14.29%)	1/36 (2.78%)	1/35 (2.86%)	0/25 (0.00%)
Pharyngitis † 1	3/23 (13.04%)	2/23 (8.70%)	3/15 (20.00%)	4/17 (23.53%)	0/7 (0.00%)	5/36 (13.89%)	5/35 (14.29%)	2/25 (8.00%)
Pneumonia bacterial † 1	0/23 (0.00%)	3/23 (13.04%)	1/15 (6.67%)	1/17 (5.88%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	2/25 (8.00%)
Pustule † 1	2/23 (8.70%)	2/23 (8.70%)	1/15 (6.67%)	1/17 (5.88%)	1/7 (14.29%)	1/36 (2.78%)	1/35 (2.86%)	2/25 (8.00%)
Rhinitis † 1	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	5/35 (14.29%)	2/25 (8.00%)
Schistosomiasis † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Sinusitis † 1	0/23 (0.00%)	1/23 (4.35%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Sinusitis bacterial † 1	1/23 (4.35%)	1/23 (4.35%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	2/36 (5.56%)	0/35 (0.00%)	0/25 (0.00%)
Subcutaneous abscess † 1	1/23 (4.35%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Tinea capitis † 1	0/23 (0.00%)	4/23 (17.39%)	1/15 (6.67%)	0/17 (0.00%)	1/7 (14.29%)	3/36 (8.33%)	1/35 (2.86%)	2/25 (8.00%)
Tinea faciei † 1	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	1/17 (5.88%)	1/7 (14.29%)	1/36 (2.78%)	1/35 (2.86%)	0/25 (0.00%)
Tinea infection † 1	1/23 (4.35%)	1/23 (4.35%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Tinea versicolour † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	2/36 (5.56%)	0/35 (0.00%)	0/25 (0.00%)
Tonsillitis † 1	0/23 (0.00%)	1/23 (4.35%)	2/15 (13.33%)	3/17 (17.65%)	0/7 (0.00%)	1/36 (2.78%)	1/35 (2.86%)	0/25 (0.00%)
Upper respiratory tract infection † 1	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	1/17 (5.88%)	2/7 (28.57%)	5/36 (13.89%)	9/35 (25.71%)	3/25 (12.00%)
Upper respiratory tract infection bacterial † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Urinary tract infection † 1	1/23 (4.35%)	0/23 (0.00%)	1/15 (6.67%)	2/17 (11.76%)	0/7 (0.00%)	2/36 (5.56%)	4/35 (11.43%)	1/25 (4.00%)
Varicella † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	2/36 (5.56%)	1/35 (2.86%)	1/25 (4.00%)
Varicella zoster virus infection † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Viral infection † 1	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	1/35 (2.86%)	0/25 (0.00%)
Viral upper respiratory tract infection † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Vulvovaginal candidiasis † 1	1/23 (4.35%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Injury, poisoning and procedural complications
Adverse event following immunisation † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	2/25 (8.00%)
Arthropod bite † 1	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Limb injury † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Procedural pain † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Scar † 1	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	2/36 (5.56%)	0/35 (0.00%)	0/25 (0.00%)
Skin abrasion † 1	0/23 (0.00%)	2/23 (8.70%)	2/15 (13.33%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	1/25 (4.00%)
Skin laceration † 1	2/23 (8.70%)	1/23 (4.35%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Skin wound † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Stoma site pain † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Thermal burn † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Investigations
Alanine aminotransferase increased † 1	5/23 (21.74%)	8/23 (34.78%)	4/15 (26.67%)	5/17 (29.41%)	3/7 (42.86%)	7/36 (19.44%)	2/35 (5.71%)	4/25 (16.00%)
Aspartate aminotransferase increased † 1	5/23 (21.74%)	7/23 (30.43%)	3/15 (20.00%)	8/17 (47.06%)	3/7 (42.86%)	12/36 (33.33%)	9/35 (25.71%)	3/25 (12.00%)
Blood albumin decreased † 1	3/23 (13.04%)	4/23 (17.39%)	2/15 (13.33%)	2/17 (11.76%)	2/7 (28.57%)	6/36 (16.67%)	12/35 (34.29%)	11/25 (44.00%)
Blood alkaline phosphatase increased † 1	2/23 (8.70%)	5/23 (21.74%)	4/15 (26.67%)	3/17 (17.65%)	3/7 (42.86%)	11/36 (30.56%)	7/35 (20.00%)	6/25 (24.00%)
Blood bicarbonate decreased † 1	11/23 (47.83%)	10/23 (43.48%)	6/15 (40.00%)	13/17 (76.47%)	6/7 (85.71%)	33/36 (91.67%)	34/35 (97.14%)	23/25 (92.00%)
Blood bilirubin increased † 1	5/23 (21.74%)	6/23 (26.09%)	3/15 (20.00%)	1/17 (5.88%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Blood calcium decreased † 1	0/23 (0.00%)	1/23 (4.35%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Blood calcium increased † 1	0/23 (0.00%)	1/23 (4.35%)	0/15 (0.00%)	1/17 (5.88%)	1/7 (14.29%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Blood cholesterol increased † 1	2/23 (8.70%)	2/23 (8.70%)	1/15 (6.67%)	1/17 (5.88%)	1/7 (14.29%)	4/36 (11.11%)	0/35 (0.00%)	0/25 (0.00%)
Blood creatinine increased † 1	1/23 (4.35%)	1/23 (4.35%)	1/15 (6.67%)	1/17 (5.88%)	1/7 (14.29%)	1/36 (2.78%)	1/35 (2.86%)	2/25 (8.00%)
Blood glucose decreased † 1	8/23 (34.78%)	12/23 (52.17%)	7/15 (46.67%)	8/17 (47.06%)	3/7 (42.86%)	10/36 (27.78%)	10/35 (28.57%)	5/25 (20.00%)
Blood glucose increased † 1	2/23 (8.70%)	4/23 (17.39%)	2/15 (13.33%)	1/17 (5.88%)	3/7 (42.86%)	13/36 (36.11%)	12/35 (34.29%)	6/25 (24.00%)
Blood phosphorus decreased † 1	3/23 (13.04%)	2/23 (8.70%)	2/15 (13.33%)	0/17 (0.00%)	1/7 (14.29%)	3/36 (8.33%)	5/35 (14.29%)	5/25 (20.00%)
Blood potassium decreased † 1	4/23 (17.39%)	2/23 (8.70%)	1/15 (6.67%)	2/17 (11.76%)	1/7 (14.29%)	2/36 (5.56%)	4/35 (11.43%)	0/25 (0.00%)
Blood potassium increased † 1	0/23 (0.00%)	1/23 (4.35%)	1/15 (6.67%)	3/17 (17.65%)	1/7 (14.29%)	10/36 (27.78%)	11/35 (31.43%)	14/25 (56.00%)
Blood pressure diastolic increased † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	1/17 (5.88%)	0/7 (0.00%)	3/36 (8.33%)	0/35 (0.00%)	0/25 (0.00%)
Blood pressure increased † 1	2/23 (8.70%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Blood pressure systolic increased † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	1/17 (5.88%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Blood sodium decreased † 1	6/23 (26.09%)	8/23 (34.78%)	9/15 (60.00%)	8/17 (47.06%)	7/7 (100.00%)	23/36 (63.89%)	27/35 (77.14%)	14/25 (56.00%)
Blood sodium increased † 1	0/23 (0.00%)	2/23 (8.70%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	3/36 (8.33%)	0/35 (0.00%)	4/25 (16.00%)
Blood urine present † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Breath sounds abnormal † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	1/36 (2.78%)	1/35 (2.86%)	0/25 (0.00%)
Cardiac murmur † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	1/7 (14.29%)	1/36 (2.78%)	1/35 (2.86%)	0/25 (0.00%)
Haemoglobin decreased † 1	1/23 (4.35%)	6/23 (26.09%)	0/15 (0.00%)	5/17 (29.41%)	3/7 (42.86%)	14/36 (38.89%)	24/35 (68.57%)	20/25 (80.00%)
Lipase increased † 1	2/23 (8.70%)	2/23 (8.70%)	2/15 (13.33%)	3/17 (17.65%)	2/7 (28.57%)	6/36 (16.67%)	8/35 (22.86%)	3/25 (12.00%)
Low density lipoprotein increased † 1	1/23 (4.35%)	2/23 (8.70%)	1/15 (6.67%)	0/17 (0.00%)	0/7 (0.00%)	3/36 (8.33%)	0/35 (0.00%)	0/25 (0.00%)
Neutrophil count decreased † 1	4/23 (17.39%)	6/23 (26.09%)	7/15 (46.67%)	6/17 (35.29%)	3/7 (42.86%)	19/36 (52.78%)	20/35 (57.14%)	19/25 (76.00%)
Platelet count decreased † 1	2/23 (8.70%)	0/23 (0.00%)	2/15 (13.33%)	3/17 (17.65%)	0/7 (0.00%)	2/36 (5.56%)	1/35 (2.86%)	2/25 (8.00%)
Urine output decreased † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Weight decreased † 1	0/23 (0.00%)	2/23 (8.70%)	0/15 (0.00%)	3/17 (17.65%)	0/7 (0.00%)	2/36 (5.56%)	3/35 (8.57%)	0/25 (0.00%)
White blood cell count decreased † 1	2/23 (8.70%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	2/36 (5.56%)	0/35 (0.00%)	0/25 (0.00%)
Metabolism and nutrition disorders
Abnormal loss of weight † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	0/35 (0.00%)	0/25 (0.00%)
Decreased appetite † 1	7/23 (30.43%)	3/23 (13.04%)	3/15 (20.00%)	5/17 (29.41%)	5/7 (71.43%)	3/36 (8.33%)	10/35 (28.57%)	4/25 (16.00%)
Dehydration † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	1/7 (14.29%)	1/36 (2.78%)	2/35 (5.71%)	0/25 (0.00%)
Failure to thrive † 1	0/23 (0.00%)	2/23 (8.70%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Malnutrition † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	1/36 (2.78%)	2/35 (5.71%)	2/25 (8.00%)
Poor feeding infant † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	5/35 (14.29%)	0/25 (0.00%)
Underweight † 1	0/23 (0.00%)	0/23 (0.00%)	0/15 (0.00%)	0/17 (0.00%)	0/7 (0.00%)	0/36 (0.00%)	1/35 (2.86%)	2/25 (8.00%)
Vitamin D deficiency † 1	0/23 (0.00%)	3/23 (13.04%)	0/15 (0.00%)	1/17 (5.88%)	0/7 (0.00%)	1/36 (2.78%)	0/35 (0.00%)	0/25 (0.00%)
Weight gain poor † 1	0/23 (0.00%)	0/23 (0.00%)	1/15 (6.67%)	1/17 (5.88%)	0/7 (0.00%)	0/36 (0.00%)	1/35 (2.86%)	0/25 (0.00%)
Musculoskeletal and connective tissue disorders