Trial Outcomes & Findings for A Study of Invirase (Saquinavir)/Ritonavir in HIV-Infected Infants and Children. (NCT NCT00623597)

Last Updated: 2016-03-07

Results Overview

Plasma trough concentration is the average steady state concentration prior to morning and evening dose. Ctrough of Saquinavir was normalized to a dose of 50 mg/kg.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

18 participants

Primary outcome timeframe

Pre-dose at Weeks 8, 12, 24.

Results posted on

2016-03-07

Participant Flow

A total of 18 participants were recruited from 8 centers in Argentina (3 centers), Spain (1 center) and Thailand (4 centers). This study was conducted between May 20, 2008 and March 11, 2010.

Participants were human immunodeficiency virus (HIV) infected infants and young children who met the eligibility criteria were stratified into 2 groups - low age (\>= 4 months to \<2 years) and high age group (\>= 2 years to \<6 years). Participants commenced treatment with saquinavir and ritonavir along with background antiretroviral (ARV) regimen.

Participant milestones

Participant milestones
Measure	Group A Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Overall Study STARTED	5	13
Overall Study COMPLETED	4	13
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Group A Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Overall Study Failed to return	1	0

Baseline Characteristics

A Study of Invirase (Saquinavir)/Ritonavir in HIV-Infected Infants and Children.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 Participants Total of all reporting groups
Age, Continuous	0.8 years STANDARD_DEVIATION 0.45 • n=5 Participants	4.0 years STANDARD_DEVIATION 1.08 • n=7 Participants	3.1 years STANDARD_DEVIATION 1.75 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose at Weeks 8, 12, 24.

Population: The pharmacokinetics Analysis Population (PKP) comprised all the participants from whom blood samples for pharmacokinetic analysis were collected. Participants could be excluded from the PKP if no reliable PK parameters could be determined or if justified by circumstances (e.g. vomiting after drug administration) and in agreement with the sponsor.

Plasma trough concentration is the average steady state concentration prior to morning and evening dose. Ctrough of Saquinavir was normalized to a dose of 50 mg/kg.

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Plasma Trough Concentrations (Ctrough) for Saquinavir	645 ng/mL Standard Deviation 536	1860 ng/mL Standard Deviation 1060	—

PRIMARY outcome

Timeframe: Pre-dose and 3, 4, 8, 12 hours (post-dose) on Day 14 (± 2 days), or Day 28(+ 2 days) for patients switching from an Non-nucleoside reverse transcriptase inhibitor [NNRTI] containing regimen).

The area under the plasma concentration-time curve from time zero to twelve hours (AUC0-12h) is area under the plasma concentration-time curve from time zero through actual tlast. The area under the plasma concentration-time curve from time zero to twelve hours of saquinavir was normalized to a dose of 50 mg/kg.

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to Twelve Hours (AUC0-12h) for Saquinavir	18.7 h*ug/mL Standard Deviation 20.0	38 h*ug/mL Standard Deviation 18.1	—

PRIMARY outcome

Timeframe: From Baseline (Day 1) till Week 48 and Follow-up (Week 52)

Population: The Safety Analysis Population (SAP) comprised all participants who received at least one dose of study medication. The SAP was used for all efficacy and safety analyses.

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 Participants Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Incidence of Adverse Events (AE) and Serious Adverse Events (SAE) Any serious adverse events	1 participants	2 participants	3 participants
Incidence of Adverse Events (AE) and Serious Adverse Events (SAE) Any non-serious adverse events	5 participants	9 participants	14 participants

PRIMARY outcome

Timeframe: Baseline (Day 1), Week 24 and Week 48

Population: The Safety Analysis Population comprised all patients who received at least one dose of study medication. The SAP was used for all efficacy and safety analyses.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 Participants Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Change In Hematocrit From Baseline Change from Baseline at Week 24 (n= 4, 13, 17)	0.01 fraction Standard Deviation 0.011	-0 fraction Standard Deviation 0.03	-0 fraction Standard Deviation 0.027
Change In Hematocrit From Baseline Change from Baseline at Week 48 (n= 4, 13, 17)	0.03 fraction Standard Deviation 0.037	-0.01 fraction Standard Deviation 0.044	0 fraction Standard Deviation 0.044

PRIMARY outcome

Timeframe: Baseline (Day 1), Week 24 and Week 48

Population: The Safety Analysis Population comprised all patients who received at least one dose of study medication. The SAP was used for all efficacy and safety analyses.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 Participants Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Change In Hemoglobin, Total Protein And Total Albumin From Baseline Hemoglobin, Change from BL at Wk 24 (n= 4, 13, 17)	-0 g/L Standard Deviation 3.3	1 g/L Standard Deviation 12.1	1 g/L Standard Deviation 10.6
Change In Hemoglobin, Total Protein And Total Albumin From Baseline Hemoglobin, Change from BL at Wk 48 (n= 4, 13, 17)	6 g/L Standard Deviation 11.8	0 g/L Standard Deviation 14.4	2 g/L Standard Deviation 13.7
Change In Hemoglobin, Total Protein And Total Albumin From Baseline Total Protein, Change from BL at Wk 24 (n=4,13,17)	-4 g/L Standard Deviation 6.0	2 g/L Standard Deviation 12.6	0 g/L Standard Deviation 11.5
Change In Hemoglobin, Total Protein And Total Albumin From Baseline Total Protein, Change from BL at Wk 48 (n=4,13,17)	-5 g/L Standard Deviation 5.7	-0 g/L Standard Deviation 14.3	-1 g/L Standard Deviation 12.8
Change In Hemoglobin, Total Protein And Total Albumin From Baseline Total Albumin, Change from BL at Wk 24 (n=4,13,17)	0.5 g/L Standard Deviation 5.41	5 g/L Standard Deviation 7.68	4 g/L Standard Deviation 7.32
Change In Hemoglobin, Total Protein And Total Albumin From Baseline Total Albumin, Change from BL at Wk 48 (n=4,13,17)	1.3 g/L Standard Deviation 2.29	4 g/L Standard Deviation 8.7	3.4 g/L Standard Deviation 7.7

PRIMARY outcome

Timeframe: Baseline (Day 1), Week 24 and Week 48

Population: The Safety Analysis Population comprised all patients who received at least one dose of study medication. The SAP was used for all efficacy and safety analyses.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 Participants Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline WBC, Change from BL at Wk 24 (n= 4,13,17)	-3 10*9/L Standard Deviation 2.31	-1 10*9/L Standard Deviation 4.35	-1.5 10*9/L Standard Deviation 4.0
Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline WBC, Change from BL at Wk 48 (n= 4,13,17)	-2.1 10*9/L Standard Deviation 1.72	-0.9 10*9/L Standard Deviation 4.38	-1.2 10*9/L Standard Deviation 3.9
Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline Platelet, Change from BL at Wk 24 (n= 4,13,17)	-119 10*9/L Standard Deviation 93.4	24 10*9/L Standard Deviation 148.9	-9 10*9/L Standard Deviation 148.9
Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline Platelet, Change from BL at Wk 48 (n= 4,13,17)	-50 10*9/L Standard Deviation 130.4	-2 10*9/L Standard Deviation 118.9	-13 10*9/L Standard Deviation 119.3
Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline Basophil, Change from BL at Wk 24 (n=4 ,13,17)	-0.02 10*9/L Standard Deviation 0.028	0 10*9/L Standard Deviation 0.031	-0.01 10*9/L Standard Deviation 0.031
Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline Basophil, Change from BL at Wk 48 (n=4 ,13,17)	-0 10*9/L Standard Deviation 0.03	-0.01 10*9/L Standard Deviation 0.029	-0.01 10*9/L Standard Deviation 0.028
Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline Lymphocyte, Change from BL at Wk 24 (n=2, 2, 4)	-0.9 10*9/L Standard Deviation 0.3	-1.1 10*9/L Standard Deviation 1.20	-1 10*9/L Standard Deviation 0.72
Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline Lymphocyte, Change from BL at Wk 48 (n= 2, 2, 4)	-1.5 10*9/L Standard Deviation 0.29	-0.7 10*9/L Standard Deviation 1.05	-1.1 10*9/L Standard Deviation 0.76
Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline Monocyte, Change from BL at Wk 24 (n= ,13,17)	-0.41 10*9/L Standard Deviation 0.295	-0.01 10*9/L Standard Deviation 0.361	-0.11 10*9/L Standard Deviation 0.379
Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline Monocyte, Change from BL at Wk 48 (n= ,13,17)	-0.21 10*9/L Standard Deviation 0.179	-0.05 10*9/L Standard Deviation 0.384	-0.09 10*9/L Standard Deviation 0.348
Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline Neutrophil, Change from BL at Wk 24 (n=2, 2, 4)	-1.4 10*9/L Standard Deviation 0.33	-2.8 10*9/L Standard Deviation 1.87	-2.1 10*9/L Standard Deviation 1.36
Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline Neutrophil, Change from BL at Wk 48 (n= 2, 2, 4)	-1.7 10*9/L Standard Deviation 1.15	-1.6 10*9/L Standard Deviation 2.55	-1.6 10*9/L Standard Deviation 1.62
Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline Eosinophil, Change from BL at Wk 24 (n=2, 2, 4)	-0 10*9/L Standard Deviation 0.2	-0 10*9/L Standard Deviation 0.1	-0 10*9/L Standard Deviation 0.1
Change In White Blood Cell (WBC), Platelet, Basophil, Lymphocyte, Monocyte, Neutrophil And Eosinophil Cell Counts From Baseline Eosinophil, Change from BL at Wk 48 (n= 2, 2, 4)	-0 10*9/L Standard Deviation 0.2	0 10*9/L Standard Deviation 1.1	0 10*9/L Standard Deviation 0.7

PRIMARY outcome

Timeframe: Baseline (Day 1), Week 24 and Week 48

Population: The Safety Analysis Population comprised all patients who received at least one dose of study medication. The SAP was used for all efficacy and safety analyses.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 Participants Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Change In Red Blood Cell (RBC) Counts From Baseline RBC,Change from Baseline at Week 24 (n= 4, 13, 17)	-0.18 10*12/L Standard Deviation 0.227	-0.07 10*12/L Standard Deviation 0.673	-0.1 10*12/L Standard Deviation 0.593
Change In Red Blood Cell (RBC) Counts From Baseline RBC,Change from Baseline at Week 48 (n= 4, 13, 17)	0.02 10*12/L Standard Deviation 0.125	-0.16 10*12/L Standard Deviation 0.74	-0.12 10*12/L Standard Deviation 0.648

PRIMARY outcome

Timeframe: Baseline (Day 1), Week 24 and Week 48

Population: The Safety Analysis Population comprised all patients who received at least one dose of study medication. The SAP was used for all efficacy and safety analyses.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 Participants Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Change In Creatine Kinase (CK), Serum Glutamic Oxaloacetic Transaminase (SGOT), Alkaline Phosphatase (ALP), Serum Glutamic-Pyruvic Transaminase (SGPT), Gamma-Glutamyl Transferase (GGT) Counts From Baseline CK, Change from Baseline at Week 24 (n= 3, 3, 16)	112 U/L Standard Deviation 112.0	-12 U/L Standard Deviation 115.9	11 U/L Standard Deviation 122.2
Change In Creatine Kinase (CK), Serum Glutamic Oxaloacetic Transaminase (SGOT), Alkaline Phosphatase (ALP), Serum Glutamic-Pyruvic Transaminase (SGPT), Gamma-Glutamyl Transferase (GGT) Counts From Baseline CK, Change from Baseline at Week 48 (n= 3, 3, 16)	257 U/L Standard Deviation 244.8	-7 U/L Standard Deviation 84	43 U/L Standard Deviation 158
Change In Creatine Kinase (CK), Serum Glutamic Oxaloacetic Transaminase (SGOT), Alkaline Phosphatase (ALP), Serum Glutamic-Pyruvic Transaminase (SGPT), Gamma-Glutamyl Transferase (GGT) Counts From Baseline SGOT, Change from Baseline at Week 24 (n= 4,13,17)	-0 U/L Standard Deviation 1.5	-0 U/L Standard Deviation 8.2	-0 U/L Standard Deviation 7.1
Change In Creatine Kinase (CK), Serum Glutamic Oxaloacetic Transaminase (SGOT), Alkaline Phosphatase (ALP), Serum Glutamic-Pyruvic Transaminase (SGPT), Gamma-Glutamyl Transferase (GGT) Counts From Baseline SGOT, Change from Baseline at Week 48 (n= 4,13,17)	-1 U/L Standard Deviation 7.8	-0 U/L Standard Deviation 6.9	-0 U/L Standard Deviation 6.8
Change In Creatine Kinase (CK), Serum Glutamic Oxaloacetic Transaminase (SGOT), Alkaline Phosphatase (ALP), Serum Glutamic-Pyruvic Transaminase (SGPT), Gamma-Glutamyl Transferase (GGT) Counts From Baseline ALP, Change from Baseline at Week 24 (n=4, 12, 16)	10 U/L Standard Deviation 29.8	26 U/L Standard Deviation 23.2	22 U/L Standard Deviation 24.9
Change In Creatine Kinase (CK), Serum Glutamic Oxaloacetic Transaminase (SGOT), Alkaline Phosphatase (ALP), Serum Glutamic-Pyruvic Transaminase (SGPT), Gamma-Glutamyl Transferase (GGT) Counts From Baseline ALP, Change from Baseline at Week 48 (n=4, 12, 16)	47 U/L Standard Deviation 87.6	36 U/L Standard Deviation 26.5	39 U/L Standard Deviation 45.6
Change In Creatine Kinase (CK), Serum Glutamic Oxaloacetic Transaminase (SGOT), Alkaline Phosphatase (ALP), Serum Glutamic-Pyruvic Transaminase (SGPT), Gamma-Glutamyl Transferase (GGT) Counts From Baseline SGPT, Change from Baseline at Week 24 (n=4,13,17)	-9 U/L Standard Deviation 15.3	-2 U/L Standard Deviation 13.6	-4 U/L Standard Deviation 13.8
Change In Creatine Kinase (CK), Serum Glutamic Oxaloacetic Transaminase (SGOT), Alkaline Phosphatase (ALP), Serum Glutamic-Pyruvic Transaminase (SGPT), Gamma-Glutamyl Transferase (GGT) Counts From Baseline SGPT, Change from Baseline at Week 48 (n=4,13,17)	-2 U/L Standard Deviation 13.4	-3 U/L Standard Deviation 12.1	-3 U/L Standard Deviation 12
Change In Creatine Kinase (CK), Serum Glutamic Oxaloacetic Transaminase (SGOT), Alkaline Phosphatase (ALP), Serum Glutamic-Pyruvic Transaminase (SGPT), Gamma-Glutamyl Transferase (GGT) Counts From Baseline GGT, Change from Baseline at Week 24 (n=4, 13, 17)	5 U/L Standard Deviation 4.7	-7 U/L Standard Deviation 18.7	-4 U/L Standard Deviation 17.1
Change In Creatine Kinase (CK), Serum Glutamic Oxaloacetic Transaminase (SGOT), Alkaline Phosphatase (ALP), Serum Glutamic-Pyruvic Transaminase (SGPT), Gamma-Glutamyl Transferase (GGT) Counts From Baseline GGT, Change from Baseline at Week 48 (n=4, 13, 17)	5 U/L Standard Deviation 2.1	-5 U/L Standard Deviation 18.5	-2 U/L Standard Deviation 16.7

PRIMARY outcome

Timeframe: Baseline (Day 1), Week 24 and Week 48

Population: The Safety Analysis Population comprised all patients who received at least one dose of study medication. The SAP was used for all efficacy and safety analyses.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 Participants Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Change In Total Bilirubin, Creatinine, Uric Acid From Baseline Total Bilirubin-Change from BL at Wk 24(n=4,12,16)	2 umol/L Standard Deviation 2.8	2 umol/L Standard Deviation 5.5	2 umol/L Standard Deviation 4.9
Change In Total Bilirubin, Creatinine, Uric Acid From Baseline Total Bilirubin-Change from BL at Wk 48(n=4,12,16)	1 umol/L Standard Deviation 1.1	2 umol/L Standard Deviation 6.9	1 umol/L Standard Deviation 5.9
Change In Total Bilirubin, Creatinine, Uric Acid From Baseline Cretainine- Change from BL at Wk 24 (n=4, 13,17)	-2 umol/L Standard Deviation 6.7	3 umol/L Standard Deviation 10	2 umol/L Standard Deviation 9.5
Change In Total Bilirubin, Creatinine, Uric Acid From Baseline Cretainine- Change from BL at Wk 48 (n=4, 13,17)	3 umol/L Standard Deviation 10.7	5 umol/L Standard Deviation 9.2	5 umol/L Standard Deviation 9.3
Change In Total Bilirubin, Creatinine, Uric Acid From Baseline Uric acid- Change from BL at Wk 24 (n=4, 13,17)	-27 umol/L Standard Deviation 54.3	68 umol/L Standard Deviation 55.1	46 umol/L Standard Deviation 67.6
Change In Total Bilirubin, Creatinine, Uric Acid From Baseline Uric acid- Change from BL at Wk 48 (n=3,13,16)	-42 umol/L Standard Deviation 108.4	61 umol/L Standard Deviation 63.5	41 umol/L Standard Deviation 80.6

PRIMARY outcome

Timeframe: Baseline (Day 1), Week 24 and Week 48

Population: The Safety Analysis Population comprised all patients who received at least one dose of study medication. The SAP was used for all efficacy and safety analyses.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 Participants Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline BUN,Change from Baseline at Week 24 (n= 3, 13, 16)	-1.5 mmol/L Standard Deviation 2.78	1 mmol/L Standard Deviation 2.2	0.5 mmol/L Standard Deviation 2.43
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline BUN,Change from Baseline at Week 48 (n= 3, 13, 16)	0.4 mmol/L Standard Deviation 0.66	1.1 mmol/L Standard Deviation 2.0	0.9 mmol/L Standard Deviation 1.82
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline LDL,Change from Baseline at Week 24 (n= 3, 13, 16)	0.21 mmol/L Standard Deviation 0.237	0.21 mmol/L Standard Deviation 1.389	0.21 mmol/L Standard Deviation 1.245
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline LDL,Change from Baseline at Week 48 (n= 3, 13, 16)	0.23 mmol/L Standard Deviation 0.596	-0.11 mmol/L Standard Deviation 1.038	-0.04 mmol/L Standard Deviation 0.963
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline HDL,Change from Baseline at Week 24 (n= 3, 13, 16)	0.21 mmol/L Standard Deviation 0.202	0.13 mmol/L Standard Deviation 0.369	0.15 mmol/L Standard Deviation 0.34
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline HDL,Change from Baseline at Week 48 (n= 3, 13, 16)	0.41 mmol/L Standard Deviation 0.233	0.17 mmol/L Standard Deviation 0.387	0.21 mmol/L Standard Deviation 0.37
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline Triglyceride,Change from BL at Wk 24 (n=4,13, 17)	-0.28 mmol/L Standard Deviation 0.597	-0.19 mmol/L Standard Deviation 1.376	-0.21 mmol/L Standard Deviation 1.22
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline Triglyceride,Change from BL at Wk 48 (n=4,13, 17)	-0.19 mmol/L Standard Deviation 0.496	-0.15 mmol/L Standard Deviation 1.558	-0.16 mmol/L Standard Deviation 1.366
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline Calcium,Change from BL at Wk 24 (n=2, 12, 14)	-0.15 mmol/L Standard Deviation 0.04	0.15 mmol/L Standard Deviation 0.17	0.11 mmol/L Standard Deviation 0.19
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline Calcium,Change from BL at Wk 48 (n=2, 12, 14)	-0.16 mmol/L Standard Deviation 0.09	0.09 mmol/L Standard Deviation 0.17	0.06 mmol/L Standard Deviation 0.18
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline Potassium,Change from BL at Wk 24 (n=4,13, 17)	-0.1 mmol/L Standard Deviation 0.16	-0.3 mmol/L Standard Deviation 0.63	-0.2 mmol/L Standard Deviation 0.56
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline Potassium,Change from BL at Wk 48 (n=4,13, 17)	0.2 mmol/L Standard Deviation 0.59	-0.2 mmol/L Standard Deviation 0.54	-0.1 mmol/L Standard Deviation 0.57
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline Sodium,Change from BL at Wk 24 (n=4,13, 17)	2 mmol/L Standard Deviation 1.3	-1 mmol/L Standard Deviation 2.3	-0 mmol/L Standard Deviation 2.3
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline Sodium,Change from BL at Wk 48 (n=4,13, 17)	1 mmol/L Standard Deviation 2.2	-1 mmol/L Standard Deviation 3.8	-0 mmol/L Standard Deviation 3.5
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline Chloride,Change from BL at Wk 24 (n=4,13, 17)	-1 mmol/L Standard Deviation 2.8	-2 mmol/L Standard Deviation 4.2	-2 mmol/L Standard Deviation 3.9
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline Chloride,Change from BL at Wk 48 (n=4,13, 17)	1 mmol/L Standard Deviation 1.3	-2 mmol/L Standard Deviation 3.6	-1 mmol/L Standard Deviation 3.3
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline Phosphate,Change from BL at Wk 24 (n=2, 12, 14)	-0.02 mmol/L Standard Deviation 0.114	0.17 mmol/L Standard Deviation 0.188	0.14 mmol/L Standard Deviation 0.188
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline Phosphate,Change from BL at Wk 48 (n=2, 13, 15)	-0.26 mmol/L Standard Deviation 0.0	0.12 mmol/L Standard Deviation 0.212	0.07 mmol/L Standard Deviation 0.237
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline Fasting Glucose,Change from BL at Wk 24(n=4,13,17)	-0.26 mmol/L Standard Deviation 0.963	0.02 mmol/L Standard Deviation 1.253	-0.05 mmol/L Standard Deviation 1.169
Change In Blood Urea Nitrogen (BUN), Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL Cholesterol), Triglycerides, Calcium, Potassium, Sodium, Chloride, Phosphate, Fasting Glucose From Baseline Fasting Glucose,Change from BL at Wk 48(n=4,13,17)	-0.07 mmol/L Standard Deviation 0.857	0.14 mmol/L Standard Deviation 1.537	0.09 mmol/L Standard Deviation 1.385

PRIMARY outcome

Timeframe: Baseline (Day 1), Week 24 and Week 48

Population: The Safety Analysis Population comprised all patients who received at least one dose of study medication. The SAP was used for all efficacy and safety analyses.

Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 Participants Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Change In Hematuria, Glycosuria And Proteinuria From Baseline Hematuria-Change from BL at Wk 24 (n= 1, 2, 3)	0 [0 to 4+] Standard Deviation 0	0 [0 to 4+] Standard Deviation 0	0 [0 to 4+] Standard Deviation 0
Change In Hematuria, Glycosuria And Proteinuria From Baseline Hematuria-Change from BL at Wk 48 (n= 1, 2, 3)	0 [0 to 4+] Standard Deviation 0	0 [0 to 4+] Standard Deviation 0	0 [0 to 4+] Standard Deviation 0
Change In Hematuria, Glycosuria And Proteinuria From Baseline Glycosuria-Change from BL at Wk 24 (n= 1, 2, 3)	0 [0 to 4+] Standard Deviation 0	0 [0 to 4+] Standard Deviation 0	0 [0 to 4+] Standard Deviation 0
Change In Hematuria, Glycosuria And Proteinuria From Baseline Glycosuria-Change from BL at Wk 48 (n= 1, 2, 3)	0 [0 to 4+] Standard Deviation 0	0 [0 to 4+] Standard Deviation 0	0 [0 to 4+] Standard Deviation 0
Change In Hematuria, Glycosuria And Proteinuria From Baseline Proteinuria-Change from BL at Wk 24 (n= 1, 2, 3)	0 [0 to 4+] Standard Deviation 0	0 [0 to 4+] Standard Deviation 0	0 [0 to 4+] Standard Deviation 0
Change In Hematuria, Glycosuria And Proteinuria From Baseline Proteinuria-Change from BL at Wk 48 (n= 1, 2, 3)	0 [0 to 4+] Standard Deviation 0	0 [0 to 4+] Standard Deviation 0	0 [0 to 4+] Standard Deviation 0

SECONDARY outcome

Timeframe: Pre-dose at Weeks 8, 12, 24

Population: The PKP population comprised all the participants from whom blood samples for pharmacokinetic analysis were collected. Participants could be excluded from the PKP if no reliable PK parameters could be determined or if justified by circumstances (e.g. vomiting after drug administration) and in agreement with the sponsor.

Plasma trough concentration is the average steady state concentration prior to morning and evening dose. Ctrough of Ritonavir was normalized to a dose of 100 mg/kg.

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Plasma Trough Concentrations (Ctrough) for Ritonavir	577 ng/mL Standard Deviation 366	995 ng/mL Standard Deviation 548	—

SECONDARY outcome

Timeframe: Pre-dose and 3, 4, 8, 12 hours (post-dose) on Day 14 (± 2 days), or Day 28(+ 2 days) for patients switching from an NNRTI containing regimen and at Week 24

The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration. Cmax was normalized to a dose of 50 mg/kg for Saquinavir and100 mg/kg for Ritonavir.

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Maximum Observed Concentration (Cmax) for Saquinavir and Ritonavir Saquinavir	2910 ng/mL Standard Deviation 3110	5570 ng/mL Standard Deviation 2780	—
Maximum Observed Concentration (Cmax) for Saquinavir and Ritonavir Ritonavir	2050 ng/mL Standard Deviation 1270	3370 ng/mL Standard Deviation 2020	—

SECONDARY outcome

Timeframe: Pre-dose and 3, 4, 8, 12 hours (post-dose) on Day 14 (± 2 days), or Day 28(+ 2 days) for patients switching from an NNRTI containing regimen).

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to Twelve Hours (AUC0-12h) for Ritonavir	13.6 h*ug/mL Standard Deviation 8.18	21.8 h*ug/mL Standard Deviation 11.6	—

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 (or upon premature discontinuation); a baseline collection was made if there was not already a value available taken within the previous 4 weeks.

Population: The Safety Analysis Population (SAP) comprised all patients who received at least one dose of study medication. The SAP was used for all efficacy and safety analyses.

Change from baseline in plasma HIV-1 RNA was derived as Change from baseline = Log10 (HIV-1 RNA at week x) - Log10 (HIV-1 RNA at baseline)

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 Participants Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Change From Baseline in Mean Human Immunodeficiency Virus Viral Load Change from Baseline at Week 24 (n= 3, 13, 16)	-0.75 log10 copies/mL Standard Deviation 1.48	-1.81 log10 copies/mL Standard Deviation 1.57	-1.61 log10 copies/mL Standard Deviation 1.57
Change From Baseline in Mean Human Immunodeficiency Virus Viral Load Change from Baseline at Week 48 (n= 3, 13, 16)	-1.27 log10 copies/mL Standard Deviation 1.01	-1.39 log10 copies/mL Standard Deviation 1.53	-1.36 log10 copies/mL Standard Deviation 1.42

SECONDARY outcome

Population: The Safety Analysis Population comprised all patients who received at least one dose of study medication. The SAP was used for all efficacy and safety analyses.

The number of participants with HIV-1 RNA results \<400 copies/mL were reported

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 Participants Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Number of Participants With Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA) <400 Copies/mL Baseline (n= 5, 13, 18)	1 participants	5 participants	6 participants
Number of Participants With Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA) <400 Copies/mL Week 24 (n= 3, 13, 16)	2 participants	13 participants	15 participants
Number of Participants With Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA) <400 Copies/mL Week 48 (n= 3, 13, 16)	2 participants	11 participants	13 participants

SECONDARY outcome

Population: The Safety Analysis Population comprised all patients who received at least one dose of study medication. The SAP was used for all efficacy and safety analyses.

The number of participants with HIV-1 RNA results \<50 copies/mL were reported.

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 Participants Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Number of Participants With Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA) <50 Copies/mL Baseline (n= 5, 13, 18)	0 participants	4 participants	4 participants
Number of Participants With Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA) <50 Copies/mL Week 24 (n= 3, 13, 16)	2 participants	11 participants	13 participants
Number of Participants With Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA) <50 Copies/mL Week 48 (n= 3, 13, 16)	2 participants	9 participants	11 participants

SECONDARY outcome

Timeframe: From Week 8 till Week 48

Population: The Safety Analysis Population comprised all patients who received at least one dose of study medication. The SAP was used for all efficacy and safety analyses.

The number of participants experiencing a greater than 1 log drop from baseline (day 1) (log 10 transformed) were reported

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 Participants Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Number of Participants With >1 Log Decrease From Baseline in Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA ) Week 8 (n= 4, 12, 16)	1 participants	7 participants	8 participants
Number of Participants With >1 Log Decrease From Baseline in Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA ) Week 24 (n= 3, 13, 16)	1 participants	8 participants	9 participants
Number of Participants With >1 Log Decrease From Baseline in Human Immunodeficiency Virus (HIV) -Ribonucleic Acid (RNA ) Week 48 (n= 3, 13, 16)	1 participants	7 participants	8 participants

SECONDARY outcome

Timeframe: From Week 12 till Week 48

Population: The Safety Analysis Population comprised all patients who received at least one dose of study medication. The SAP was used for all efficacy and safety analyses.

Virological failure was defined as: viral load \>= 400 copies/mL on two consecutive occasions (missing visits was assumed to be above 400 copies/mL). The number of participants classified as virological failure by Age Group and viral load (≤ 10,000 copies, \>10,000 copies) were presented.

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 Participants Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Number of Participants With Virological Failure VF at Week 12 (n= 5, 13, 18)	2 participants	1 participants	3 participants
Number of Participants With Virological Failure VF at Week 24 (n= 5, 13, 18)	2 participants	0 participants	2 participants
Number of Participants With Virological Failure VF at Week 48 (n= 5, 13, 18)	3 participants	1 participants	4 participants
Number of Participants With Virological Failure HIV-RNA <= 10,000 copies/mL at Wk 12 (n= 3, 6, 9)	1 participants	0 participants	1 participants
Number of Participants With Virological Failure HIV-RNA <= 10,000 copies/mL at Wk 24 (n= 3, 6, 9)	1 participants	0 participants	1 participants
Number of Participants With Virological Failure HIV-RNA <= 10,000 copies/mL at Wk 48 (n= 3, 6, 9)	2 participants	0 participants	2 participants
Number of Participants With Virological Failure HIV-RNA >10,000 copies/mL at Week 12 (n= 2, 7, 9)	1 participants	1 participants	2 participants
Number of Participants With Virological Failure HIV-RNA >10,000 copies/mL at Week 24 (n= 2, 7, 9)	1 participants	0 participants	1 participants
Number of Participants With Virological Failure HIV-RNA >10,000 copies/mL at Week 48 (n= 2, 7, 9)	1 participants	1 participants	2 participants

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 or upon premature discontinuation

Population: The Safety Analysis Population comprised all patients who received at least one dose of study medication. The SAP was used for all efficacy and safety analyses.

Change from Baseline in CD4+ lymphocyte count at 24 weeks and 48 weeks were presented by age group. Change from baseline in CD4+ lymphocyte count was derived as follows: Change from baseline = (CD4+ count at week 24/48) - (CD4+ count at baseline). A baseline collection was made if there was not already a value available taken within the previous 4 weeks. Baseline was on Day 1.

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 Participants Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Change From Baseline in Cluster Differentiation Antigen 4 (CD4) Lymphocyte Count Change from Baseline at Week 24 (n= 3, 12, 15)	94.90 count/uL Standard Deviation 643.28	-34.53 count/uL Standard Deviation 821.31	-8.65 count/uL Standard Deviation 769.41
Change From Baseline in Cluster Differentiation Antigen 4 (CD4) Lymphocyte Count Change from Baseline at Week 48 (n= 3, 12, 15)	-50.07 count/uL Standard Deviation 1013.23	126.11 count/uL Standard Deviation 528.49	90.87 count/uL Standard Deviation 609.46

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 8, 12, 24, 36, and 48 or upon premature discontinuation

Population: The Safety Analysis Population comprised all patients who received at least one dose of study medication. The SAP was used for all efficacy and safety analyses.

Change from baseline in CD8+ lymphocyte count at 24 weeks and 48 weeks were presented by age group. Change from baseline in CD8+ lymphocyte count was derived as follows: Change from baseline = (CD8+ count at week 24/48) - (CD8+ count at baseline). A baseline collection was made if there was not already a value available taken within the previous 4 weeks. Baseline was on Day 1.

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 Participants Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 Participants Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Change From Baseline in Cluster Differentiation Antigen 8 (CD8) Lymphocyte Count Change from Baseline at Week 24 (n= 3, 12, 15)	-200.49 count/uL Standard Deviation 161.05	-3.50 count/uL Standard Deviation 790.86	-42.90 count/uL Standard Deviation 708.37
Change From Baseline in Cluster Differentiation Antigen 8 (CD8) Lymphocyte Count Change from Baseline at Week 48 (n= 3, 12, 15)	-92.07 count/uL Standard Deviation 455.23	40.52 count/uL Standard Deviation 641.27	14.00 count/uL Standard Deviation 596.43

Adverse Events

Group A

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Group B

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Total

Serious events: 3 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Group A n=5 participants at risk Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 participants at risk Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 participants at risk Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Infections and infestations Pneumonia	20.0% 1/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	11.1% 2/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Respiratory, thoracic and mediastinal disorders Bronchitis	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.

Other adverse events

Additional Information

Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 61 6878333

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Group A n=5 participants at risk Participants (infants \>= 4 months to \<2 years old) received saquinavir at a dose of 50 milligram per kilogram (mg/Kg) twice a day (BID) and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Group B n=13 participants at risk Participants (children \>= 2 years to \<6 years old) received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.	Total n=18 participants at risk Participants received saquinavir at a dose of 50 mg/Kg BID and ritonavir at a dose of 3 mg/kg BID for body weight from 5 to \< 15 kg, 2.5 mg/kg BID for body weight from 15 to 40 kg and 100 mg BID for body weight \> 40 kg plus \>= 2 background ARVs. After 14 days of treatment (or Day 28 for participants switching from an NNRTI containing regimen), saquinavir and ritonavir dose adjustments were made within the age group or for individual participants as deemed appropriate. The highest dose for saquinavir/ritonavir that was to be administered was not to exceed 1000 mg/100 mg BID. Participants received treatment for 48 weeks.
Infections and infestations Upper Respiratory Tract Infection	20.0% 1/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	11.1% 2/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Infections and infestations Bronchitis	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	15.4% 2/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	11.1% 2/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Infections and infestations Impetigo	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Infections and infestations Otitis Media	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Infections and infestations Cellulitis	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Infections and infestations Cystitis	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Infections and infestations Gastroenteritis	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Infections and infestations Giardiasis	20.0% 1/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	0.00% 0/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Infections and infestations Herpangina	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Infections and infestations Nasopharyngitis	20.0% 1/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	0.00% 0/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Infections and infestations Otitis Media Acute	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Infections and infestations Pharyngitis	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Infections and infestations Pneumonia	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Infections and infestations Pyoderma	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Infections and infestations Rhinitis	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Infections and infestations Toxocariasis	20.0% 1/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	0.00% 0/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Infections and infestations Urinary Tract Infection	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Gastrointestinal disorders Vomiting	20.0% 1/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	15.4% 2/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	16.7% 3/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Gastrointestinal disorders Diarrhoea	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	23.1% 3/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	16.7% 3/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Gastrointestinal disorders Dental Caries	20.0% 1/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	15.4% 2/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	16.7% 3/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Gastrointestinal disorders Abdominal Pain	20.0% 1/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	0.00% 0/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Gastrointestinal disorders Abdominal Pain Lower	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Gastrointestinal disorders Gingivitis	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Skin and subcutaneous tissue disorders Intertrigo	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
General disorders Gait Disturbance	20.0% 1/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	0.00% 0/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Investigations Weight Decreased	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Musculoskeletal and connective tissue disorders Synovitis	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Renal and urinary disorders Enuresis	0.00% 0/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	7.7% 1/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	5.6% 1/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.
Gastrointestinal disorders Constipation	40.0% 2/5 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	0.00% 0/13 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.	11.1% 2/18 • Up to 56 weeks Serious adverse events and non-serious adverse events are reported in Safety Population Set.