1. No category

Supplementary appendix
This appendix formed part of the original submission and has been peer reviewed.
We post it as supplied by the authors.
Supplement to: Homsy J, Dorsey G, Arinaitwe E. et al. Protective efficacy of
prolonged co-trimoxazole prophylaxis in HIV-exposed children up to age 4 years
for the prevention of malaria in Uganda: a randomised controlled open-label trial.
Lancet Glob Health 2014; 2: e727–36.
Appendix Homsy et al. - Protective efficacy of prolonged cotrimoxazole prophylaxis against malaria in Ugandan children up to age 4 years
Table A. Incidence of complicated malaria among HIV-exposed, -unexposed and -infected children according to cotrimoxazole (CTX) randomisations and age ranges
Episodes
PY
Incidence
PPY
On CTX
2
105.5
0.019
HIV-exposed
HIV-exposed
Randomised to stop CTX
Randomised to continue CTX
6
3
86.9
104.1
0.069
0.029
HIV-unexposed 
Not on CTX
5
145.7
0.034
HIV-infected 
On CTX
0
73.5
0
HIV status
CTX prophylaxis status
IRR (95% CI) 
p-value
Enrolment – end of BF
HIV-exposed
N/A
Before age 2 years†
Reference group
0.46 (0.09-2.33)
0.35
Between age 2 years and 4 years
HIV-exposed
HIV-exposed
CTX stopped after cessation of BF
CTX stopped at 2 years of age
10
14
151.2
89.9
0.066
0.156
Reference group
2.68 (0.70-10.2)
0.15
HIV-exposed
Randomised to continue CTX
8
83.4
0.096
1.56 (0.37-6.57)
0.55
HIV-unexposed 
Not on CTX
7
164.8
0.042
0.87 (0.23-3.24)
0.83
HIV-infected 
On CTX
1
62.4
0.016
0.29 (0.41-3.99)
0.30
Reference group
N/A
-
Between age 4 years and 5 years
HIV-exposed
HIV-exposed
CTX stopped after cessation of BF
CTX stopped at 2 years of age
2
0
69.7
42.4
0.029
0
HIV-exposed
CTX stopped at 4 years of age
0
36.2
0
HIV-unexposed 
Not on CTX
1
76.8
0.013
HIV-infected 
On CTX
0
22.8
0
45
14
863.6
451.7
0.052
0.031
N/A
0.59 (0.02-15.9)
0.75
N/A
Enrolment - age 5 years
All groups
Not on CTX
On CTX
Reference group
0.45 (0.41-0.50)
<0.0001
PY= person-years of follow-up. PPY=Per person-year of follow-up. IRR= incidence rate ratio. CTX=cotrimoxazole. BF=breastfeeding.

Malaria incidence rate ratio with 95% confidence interval, controlling for place of residence and antimalarial treatment arm
† For randomised groups, incidence is from cessation of breastfeeding to 2 years of age. For observational cohorts, incidence is from enrolment (6 weeks-12 months of age) to 2 years of age.
 Observational cohorts, not randomised.
1
Appendix Homsy et al. - Protective efficacy of prolonged cotrimoxazole prophylaxis against malaria in Ugandan children up to age 4 years
Table B. Incidence of all-cause hospitalizations among HIV-exposed, -unexposed and -infected children according to cotrimoxazole (CTX) randomisations and age ranges
Episodes
PY
Incidence
PPY
On CTX
13
105.5
0.123
N/A
HIV-exposed
HIV-exposed
Randomised to stop CTX
Randomised to continue CTX
8
15
86.9
104.1
0.092
0.144
Reference group
1.86 (0.65-5.33)
0.25
HIV-unexposed 
HIV-infected 
Not on CTX
On CTX
11
9
145.7
73.5
0.075
0.122
HIV status
CTX prophylaxis status
IRR (95% CI) 
p-value
Enrolment – end of BF
HIV-exposed
Before age 2 years†
Between age 2 years and 4 years
HIV-exposed
HIV-exposed
CTX stopped after cessation of BF
CTX stopped at 2 years of age
13
17
151.2
89.9
0.086
0.189
Reference group
2.68 (0.76-9.43)
0.13
HIV-exposed
Randomised to continue CTX
15
83.4
0.180
2.59 (0.72-9.25)
0.14
HIV-unexposed 
Not on CTX
8
164.8
0.049
0.71 (0.21-2.40)
0.58
HIV-infected 
On CTX
4
62.4
0.064
0.84 (0.18-3.88)
0.83
Reference group
N/A
-
Between age 4 years and 5 years
HIV-exposed
HIV-exposed
CTX stopped after cessation of BF
CTX stopped at 2 years of age
2
0
69.7
42.4
0.029
0
HIV-exposed
CTX stopped at 4 years of age
0
36.2
0
HIV-unexposed 
HIV-infected 
Not on CTX
On CTX
1
0
76.8
22.8
0.013
0
0.59 (0.02-15.9)
N/A
0.75
38
43
328.0
293.0
0.116
0.147
Reference group
1.27 (0.80- .2.01)
0.29
N/A
Enrolment - age 4 years
HIV-exposed
Not on CTX
On CTX
PY= person-years of follow-up. PPY=Per person-year of follow-up. IRR= incidence rate ratio. CTX=cotrimoxazole. BF=breastfeeding.

Incidence rate ratio with 95% confidence interval, controlling for place of residence and antimalarial treatment arm
† For randomised groups, incidence is from cessation of breastfeeding to 2 years of age. For observational cohorts, incidence is from enrolment (6 weeks-12 months of age) to 2 years of age.
 Observational cohorts, not randomised.
2
Appendix Homsy et al. - Protective efficacy of prolonged cotrimoxazole prophylaxis against malaria in Ugandan children up to age 4 years
Table C1. Incidence of diarrheal episodes among HIV-exposed children according to cotrimoxazole (CTX) randomisations and
age ranges
Incidence
HIV status
CTX prophylaxis status
Episodes
PY
IRR (95% CI) 
p-value
PPY
Enrolment – end of BF
HIV exposed
On CTX
359
105.5
3.40
128
158
86.9
104.1
1.47
1.52
Reference group
1.05 (0.78-1.40)
0.75
Before age 2 years†
HIV exposed
HIV exposed
Randomised to stop CTX
Randomised to continue CTX
Between age 2 years and 4 years
HIV exposed
CTX stopped after cessation of BF
89
151.2
0.59
Reference group
-
HIV exposed
CTX stopped at 2 years of age
36
89.9
0.40
0.71 (0.41-1.24)
0.22
HIV exposed
Randomised to continue CTX
40
83.4
0.48
0.84 (0.49-1.46)
0.54
Between age 4 years and 5 years
HIV exposed
HIV exposed
CTX stopped after cessation of BF
CTX stopped at 2 years of age
28
14
69.7
42.4
0.40
0.33
Reference group
0.83 (0.35-1.98)
0.67
HIV exposed
CTX stopped at 4 years of age
18
36.2
0.50
1.12 (0.48-2.63)
0.79
PY= person-years of follow-up. PPY=Per person-year of follow-up. IRR= incidence rate ratio. CTX=cotrimoxazole. BF=breastfeeding.

Incidence rate ratio with 95% confidence interval (CI), controlling for place of residence and antimalarial treatment arm
† For randomised groups, incidence is from cessation of breastfeeding to 2 years of age. For observational cohorts, incidence is from
enrolment (6 weeks-12 months of age) to 2 years of age.
3
Appendix Homsy et al. - Protective efficacy of prolonged cotrimoxazole prophylaxis against malaria in Ugandan children up to age 4 years
Table C2. Incidence of pneumonia among HIV-exposed children according to cotrimoxazole (CTX) randomisations and age ranges
Incidence
HIV status
CTX prophylaxis status
Episodes
PY*
IRR (95% CI)
p-value
PPY**
Enrolment – end of BF
HIV exposed
On CTX
14
105.5
0.133
9
23
86.9
104.1
0.104
0.221
Reference group
2.14 (0.97-4.71)
Before age 2 years†
HIV exposed
HIV exposed
Randomised to stop CTX
Randomised to continue CTX
0.06
Between age 2 years and 4 years
HIV exposed
HIV exposed
CTX stopped after cessation of BFβ
CTX stopped at 2 years of age
13
6
151.2
89.9
0.086
0.067
Reference group
0.78 (0.27-2.21)
0.64
HIV exposed
Randomised to continue CTX
14
83.4
0.168
1.96 (0.83-4.66)
0.13
Between age 4 years and 5 years
HIV exposed
HIV exposed
CTX stopped after cessation of BFβ
CTX stopped at 2 years of age
5
6
69.7
42.4
0.072
0.142
Reference group
1.98 (0.53-7.47)
0.31
HIV exposed
CTX stopped at 4 years of age
1
36.2
0.028
0.40 (0.04-3.75)
0.42
PY= person-years of follow-up. PPY=Per person-year of follow-up. IRR= incidence rate ratio. CTX=cotrimoxazole. BF=breastfeeding.

Incidence rate ratio with 95% confidence interval (CI), controlling for place of residence and antimalarial treatment arm
† For randomised groups, incidence is from cessation of breastfeeding to 2 years of age. For observational cohorts, incidence is from
enrolment (6 weeks-12 months of age) to 2 years of age.
4