We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
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
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
Hide 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.
Arm/Group Title Cohort I Cohort IIA Cohort IIB Cohort III Cohort IV Cohort III-DT Cohort IV-DT Cohort V-DT Total
Hide 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
Hide 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.
1.Primary Outcome
Title Percentage of Participants With Grade 3 or Higher Adverse Events (AEs)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide Description Number of participants who died were summarized
Time Frame From treatment initiation through Weeks 24 and 48
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide 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
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Hide 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
Hide 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
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
Hide 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%) 
Hide 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
Hide 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