Study Of An Investigational Regimen Including FDA Approved HIV Drugs In HIV-Infected Pediatric Subjects

• Sponsor: ViiV Healthcare (Industry)
• Overall Status: Unknown status
• CT.gov ID: NCT00071760
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 75
• Locations: 15
• Arms: 2
• Duration (Months): 212
• Patients Per Site: 5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a 48-week study to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of an investigational regimen including FDA approved HIV drugs in HIV-infected pediatric subjects, ages 4 weeks to < 2 years old.

Condition or Disease	Intervention/Treatment	Phase
Infection, Human Immunodeficiency Virus	Drug: GW433908; Drug: ritonavir	Phase 2

Detailed Description

A 48 week, Phase II, open-label, 2-cohort, multicenter study to evaluate the pharmacokinetics, safety, tolerability and antiviral activity of GW433908 and GW433908/RTV when administered to HIV-1 infected protease inhibitor (PI) naive and PI-experienced pediatric subjects aged 4 weeks to <2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 75 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 48 Week, Phase II, Open-label, 2-cohort, Multicenter Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Antiviral Activity of GW433908 and GW433908/RTV When Administered to HIV-1 Infected Protease Inhibitor (PI) Naive and PI-experienced Pediatric Subjects Aged 4 Weeks to <2 Years.
• Study Start Date: Oct 1, 2003
• Actual Primary Completion Date: Jul 1, 2011
• Anticipated Study Completion Date: Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A - 4weeks - less than 2 years old (FPV/RTV bid) Cohort 2A - 4weeks - less than 6 months old. Fosamprenavir (FPV) 50 mg/mL oral suspension/ritonavir (RTV) 80 mg/mL oral solution twice daily (BID) Cohort 1A - 6 months - less than 2yrs old. Fosamprenavir (FPV) 50 mg/mL oral suspension/ritonavir (RTV) 80 mg/mL oral solution twice daily (BID)	Drug: GW433908; Fosamprenavir suspension bid; Drug: ritonavir; Ritonavir solution bid; Other Names: GW433908
Experimental: Arm B- 4weeks - less than 2 years old (FPV bid) Cohort 2B - 4weeks - less than 6 months old. Fosamprenavir (FPV) 50 mg/mL oral suspension twice daily (BID) Cohort 1B - 6 months - less than 2yrs old. Fosamprenavir (FPV) 50 mg/mL oral suspension twice daily (BID)	Drug: GW433908; Fosamprenavir suspension bid

Outcome Measures

Primary Outcome Measures

1. Plasma Amprenavir (APV) AUC (0-tau[τ]) [Week 48]

   Plasma samples were assayed for APV concentrations using a validated assay. The GlaxoSmithKline (GSK) Department of Clinical Pharmacology Modeling and Simulation conducted pharmacokinetic (PK) analysis of the plasma APV concentration-time data using a model-independent approach. As a measure of total drug exposure, the area under the plasma-concentration-versus-time curve over the dosing interval at steady-state (AUC[0-τ]), where "τ" is the length of the dosing interval, was calculated by the linear up/log down trapezoidal method. hours, hr.

2. Plasma APV Cmax [Week 48]

   The maximum concentration at steady state (Cmax) was measured.

3. Plasma APV Cτ [Week 48]

   The plasma concentration at the end of the dosing interval at steady state (Cτ) was measured.

4. Plasma APV CL/F Following Dosing Expressed in mL/Min/kg [Week 48]

   Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated using the formulation: APV Dose in mg/kg units divided by AUC(0-τ). For FPV, doses were expressed in APV molar equivalents (50 mg of FPV = 43.2 mg of APV). Normalizing CL/F for bodyweight allows for comparison of CL/F across populations.

5. Plasma APV CL/F Following Dosing Expressed in mL/Min [Week 48]

   Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated as dose/AUC(0-τ). For FPV, doses were expressed in APV molar equivalents (50 mg of FPV = 43.2 mg of APV).

6. Plasma Unbound APV Cτ [Week 48]

   Participants who are <2 years old may have reduced protein binding; therefore, plasma unbound APV concentrations were measured to determine dosing recommendations at acceptable dosing volumes. Unbound or "free" APV is the fraction of drug that is not bound to protein. Cτ is the plasma concentration at the end of the dosing interval at steady state.

7. Plasma Unbound APV Percent Protein Binding (%Cτ) [Week 48]

   Participants who are <2 years old may have reduced protein binding; therefore, plasma unbound APV concentrations were measured to determine dosing recommendations at acceptable dosing volumes. APV %Cτ unbound is the percentage of the total APV Cτ that is unbound.

8. Median Change From Baseline in Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST) at Weeks 4, 12, 24, 36, and 48 [Baseline (Day 1) and Weeks 4, 12, 24, 36, and 48]

   Blood samples of the participants were collected for the evaluation of ALT and AST. Clinical chemistry analyses were carried out using the observed analysis strategy. Change from Baseline in ALT and AST was calculated as the value at the indicated time point minus the value at Baseline.

9. Median Change From Baseline in Cholesterol, Glucose, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Triglyceride (TG), Potassium, and Sodium at Weeks 4, 12, 24, 36, and 48 [Baseline (Day 1) and Weeks 4, 12, 24, 36, and 48]

   Blood samples of all participants were generally collected under non-fasting conditions (given the age of participants) for the evaluation of cholesterol, serum glucose, HDL cholesterol, LDL cholesterol, triglyceride, potassium, and sodium. Clinical chemistry analyses were carried out using the observed analysis strategy. Change from Baseline in cholesterol, serum glucose, HDL cholesterol, LDL cholesterol, triglyceride, potassium, and sodium was calculated as the value at the indicated time point minus the value at Baseline.

10. Median Change From Baseline in Serum Lipase at Weeks 4, 12, 24, and 48 [Baseline (Day 1) and Weeks 4, 12, 24, and 48]

    Blood samples of all participants were collected for the evaluation of serum lipase. Clinical chemistry analyses were carried out using the observed analysis strategy. Change from Baseline in serum lipase was calculated as the value at the indicated time point minus the value at Baseline.

11. Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Laboratory Abnormalities [Baseline (Day 1) until Week 48]

    TE toxicities were presented for each laboratory parameter. A toxicity was considered TE if it was greater than the Baseline grade, and if it was observed on/after the date of the first dose of study drug (SD), and on/before the date of the last dose of SD. Neutropenia is a decrease (d) in the number of Ns, d/increase (I) in glucose is hypo (Hp)/hyper (Hy)glycemia, in potassium is Hp/Hykalemia, and in sodium is Hp/Hynatremia. Per the Division of AIDS Table for Grading the Severity of Adult and Pediatric AEs, Grade 3=severe; Grade 4=potentially life-threatening.

12. Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Adverse Events (AE) [Baseline (Day 1) until Week 48]

    An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE is considered TE if it has an onset date on or after the date of the first dose of study drug, and on or before the date of the final dose of study drug. As per the Division of AIDS Table for Grading the Severity of Adult and Pediatric AEs, Grade 3=severe; Grade 4=potentially life-threatening.

13. Number of Participants Who Permanently Discontinued the Treatment Due to an AE [Baseline (Day 1) until Week 48]

    An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Secondary Outcome Measures

1. Number of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) <400 Copies Per Milliliter at Baseline and Weeks 4, 12, 24, 36, and 48 (MSD=F) [Baseline and Weeks 4, 12, 24, 36, and 48]

   Blood samples of participants were collected to measure plasma HIV-1 RNA concentrations. Viral load, measured in RNA copies per milliliter of plasma, is an efficacy measure for antiretroviral drugs. In the Missing, Switch, or Discontinuation=Failure (MSD=F) analysis, participants who had missing data at or had discontinued the study prior to a certain time point or had changed their background antiretroviral regimen are classified as non-responders.

2. Median Plasma HIV-1 RNA (log10 Copies/mL) at Baseline and Weeks 4, 12, 24, 36, and 48 (Observed Analysis) [Baseline and Weeks 4, 12, 24, 36, and 48]

   Blood samples of participants were collected to assess the decrease in the number of HIV-1 RNA copies.

3. Median Change From Baseline in Plasma HIV-1 RNA (log10 Copies/mL) at Weeks 4, 12, 24, 36, and 48 (Observed Analysis) [Baseline and Weeks 4, 12, 24, 36, and 48]

   Blood samples of participants were collected to assess the decrease in the number of HIV-1 RNA copies. Change from Baseline in plasma HIV-1 RNA was calculated as the value at the indicated time point minus the value at Baseline.

4. Number of Participants With at Least a 1.0 log10 HIV-1 RNA Decrease From Baseline at Weeks 4, 12, 24, 36, and 48 (MSD=F Analysis) [Baseline and Weeks 4, 12, 24, 36, and 48]

   Blood samples of participants were collected to assess the decrease in the number of HIV-1 RNA copies. In the MSD=F analysis, participants who had missing data at or had discontinued the study prior to a certain time point or had changed their background antiretroviral regimen are classified as non-responders.

5. Median Percent Cluster of Differentiation Antigen 4 (CD4+) Cell Count at Baseline and at Weeks 4, 12, 24, 36, and 48 [Baseline and Weeks 4, 12, 24, 36, and 48]

   Blood samples of participants were collected for the measurement of the percentage of total lymphocytes that are CD4+ cells. Observed analysis was used for the summary of proportion endpoints using viral load data. CD4+ cells are white blood cells that are important in fighting infection. HIV infects CD4+ cells, replicates in them, and destroys them. A CD4+ cell count provides a measure of the status of the immune system and to what extent it is affected by HIV.

6. Median Percent Change From Baseline in CD4+ Cell Count at Weeks 4, 12, 24, 36, and 48 [Baseline and Weeks 4, 12, 24, 36, and 48]

   Blood samples of participants were collected for the measurement of the percentage of total lymphocytes that are CD4+ cells. Observed analysis was used for the summary of proportion endpoints using viral load data. Change from Baseline in percentage was calculated as the value at indicated time points minus the value at Baseline.

7. Number of Participants With the Indicated Virological Outcome at Week 48 [Week 48]

   Blood samples of participants were collected to measure plasma HIV-1 RNA concentrations. PI-exp = PI-experienced. Virologic success was defined as plasma HIV-1 RNA <400 copies/mL. Virologic failure: (1) HIV-1 RNA >=400 copies/mL, (2) change of background antiretroviral treatment (ART), (3) discontinued study due to lack of efficacy, (4) discontinued study with last HIV-1 >=400 copies/mL. No virologic data at Week 48 window: (a) discontinued study due to an adverse event or death, (b) discontinued study due to other reasons (withdrew consent, loss to follow-up, moved, etc.).

8. Plasma Ritonavir (RTV) AUC (0-τ) [Week 48]

   Plasma samples were assayed for RTV concentrations using a validated assay. The GSK Department of Clinical Pharmacology Modeling and Simulation conducted PK analysis of the plasma RTV concentration-time data using a model-independent approach. As a measure of total drug exposure, the area under the plasma-concentration-versus-time curve over the dosing interval at steady-state (AUC[0-τ]), where τ is the length of the dosing interval, was calculated by the linear up/log down trapezoidal method.

9. Plasma RTV Cmax [Week 48]

   The maximum concentration at steady state (Cmax) was measured.

10. Plasma RTV Cτ [Week 48]

    The plasma concentration at the end of the dosing interval at steady state (Cτ) was measured.

11. Plasma RTV CL/F Expressed in mL/Min/kg [Week 48]

    Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated as dose in mg/kg units divided by AUC(0-τ). Normalizing CL/F for bodyweight allows for comparison of CL/F across populations.

12. Plasma RTV CL/F Expressed in mL/Min [Week 48]

    Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated as dose in mg/kg units divided by AUC(0-τ).

13. Number of Confirmed Virologic Failure Participants (Par.) With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease [Baseline through Week 48]

    A blood sample was drawn for par. failing to respond to therapy, and the mutations present in the virus were identified. For each par., the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New International AIDS Society-USA defined resistance mutations that developed at the time of failure were tabulated by drug class. VF, virologic failure; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor. Par. are grouped by study arm and prior therapy experience.

14. Number of Confirmed Virologic Failure Participants (Par.) With Treatment-emergent Reductions in Drug Susceptibility (DS) [Baseline through Week 48]

    A blood sample was drawn for par. failing to respond to therapy, and changes in DS for HIV isolated from the par. for each drug used in the study were assessed. The changes in DS detected by phenotypic assay in virus from the sample collected at the time of failure was compared with DS in the virus from the blood sample at baseline. Par. are grouped by study arm and prior therapy experience. DS is the state of HIV being susceptible to the antiretroviral agent (the virus can be inhibited by the drug). Reduced DS (i.e., HIV is resistant to the antiretroviral agent) can lead to treatment failure.

15. Number of Participants Reporting Perfect Adherence Over the 3 Days and Last Weekend Prior to the Study Visits at Weeks 2, 12, 24, and 48 as Assessed by the Study Coordinator Using the Adherence Questionnaire [Weeks 2, 12, 24, and 48]

    A separate questionnaire were administered for FPV and RTV. Items 1-4 of the Adherence Questionnaire measured a participant's adherence with FPV or RTV during the last 3 days and the weekend prior to the indicated study visits. Question 5 queried about the number of doses of FPV or RTV missed since the participant's last study visit. Perfect adherence was defined as not missing any doses of FPV or RTV since the last study visit.

16. Number of Participants With the Indicated Response Scores for the Parent/Guardian (P/G) Perception of FPV Oral Suspension Questionnaire: Items 1 to 4 [Weeks 2, 24, and 48/premature study discontinuation]

    P/G perceptions of FPV/RTV BID were assessed using a P/G Perception of Study Medication questionnaire administered during Weeks 2, 24, and 48/premature study discontinuation. Questions 1 to 4 ask directly about the P/G's assessment of 1=color, 2=texture/consistency, 3=odor, and 4=general satisfaction. Questions 5 to 10 ask about the P/G's perception of the child's assessment of the oral suspension. Data are reported as the number of participants with the indicated response by question, response category (1-3=dislike, 4=neutral, 5-7=like), and timing of visit.

17. Number of Participants With the Indicated Response Scores for the Parent/Guardian Perception of the Child's Assessment of FPV Oral Suspension Questionnaire: Items (I) 5 to 10 [Weeks (W) 2, 24, and 48/premature study discontinuation]

    Parent/guardian perceptions of FPV/RTV BID was assessed using a Parent/Guardian Perception of Study Medication questionnaire. Questions 1 to 4 ask directly about the parent/guardian's assessment of the color, texture/consistency, odor, and general satisfaction. Questions 5 to 10 ask about the parent/guardian's perception of the child's assessment of the oral suspension (Items: 5=reaction to new medicine [med.]; 6=taste; 7=acceptance; 8=swallowing; 9=willingness compared to other med.; 10=overall liking. Data for items 6/10 are reported in response categories: 1-3=dislike; 4=neutral; 5-7=like.

18. Correlation Between Steady-state Plasma APV PK Parameters to Changes in Plasma HIV-1 RNA Concentrations, CD4+ Percentages, and/or the Occurrence of Adverse Events [Week 48]

    No formal analysis has been performed or is planned to correlate plasma APV PK with efficacy and safety outcomes.

19. Plasma FPV AUC (0-τ) [Week 48]

    The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.

20. Plasma FPV Cmax and Cτ [Week 48]

    The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.

21. Plasma FPV CL/F Expressed in mL/Min/kg [Week 48]

    The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.

22. Plasma FPV CL/F Expressed in mL/Min [Week 48]

    The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Weeks to 2 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female 4 weeks to <2 years of age. Cohort 1 (6 months - <2 years): Subjects must be <2 years of age at the Week 2 visit therefore the maximum age at screening is 22 months.

Cohort 2 (4 weeks - <6 months): Subjects must be <6 months of age at the Week 2 visit, therefore the maximum age at screening is 4 months for entry into this cohort.

• Parent or legal guardian is willing and able to provide written informed consent for the subject to participate in the trial.

• Screening plasma HIV-1 RNA level >=400copies/mL.

• Subjects who, in the investigator's opinion, and following viral resistance testing if conducted, are able to construct an active Nucleoside Reverse Transcriptase Inhibitor (NRTI) backbone regimen consisting of 2 NRTIs.

• Subjects must meet one of the following criteria:

Therapy-naïve or PI-naïve subjects (defined as having received less than one week of any PI).

PI-experienced subjects defined as having prior experience with no more than three PIs. Prior RTV-boosted PI therapy will be considered as only one PI as long as the RTV dose was lower than that recommended for use of RTV as an antiretroviral agent.

Exclusion Criteria:

• Prior history of having received APV.

• Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) therapy within 14 days prior to study drug administration (single or multiple dose) or anticipated need for concurrent NNRTI therapy during the study period.

• PI therapy within 5 days prior to study drug administration (applicable only for subjects undergoing single dose visits)

• Subjects and/or parents/legal guardians who, in the investigator's opinion, are not able to comply with the requirements of the study.

• Subject is in the initial acute phase of a Centers for Disease Control and Prevention (CDC) Clinical Category C event or infection (per 1994 classification) at Baseline. Subject may be enrolled provided they are receiving treatment for the infections, such treatment not being contraindicated with FPV, and subjects are clinically improving at the Baseline visit.

• Presence of a malabsorption syndrome or other gastrointestinal dysfunction which might interfere with drug absorption or render the subject unable to take oral medication.

• Presence of any serious medical condition (e.g., hemoglobinopathy, chronic anemia, diabetes, cardiac dysfunction, hepatitis, or clinically relevant pancreatitis) which, in the opinion of the investigator, might compromise the safety of the subject.

• Any acute laboratory abnormality at screen which, in the opinion of the investigator, should preclude the subject's participation in the study of an investigational compound. If subjects are found to have an acute Grade 4 laboratory abnormality at screening, this test may be repeated once within the screening window. Any verified Grade 4 laboratory abnormality would exclude a subject from study participation.

• Grade 3 or higher (>10x ULN) serum aminotransferase levels (alanine aminotransferase, ALT and/or aspartate aminotransferase, AST) within 28 days prior to study drug administration and / or clinically relevant hepatitis within the previous 6 months.

• Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days of study drug administration or an anticipated need for such treatment within the study period.

• Treatment with immunomodulating agents (e.g., systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (e.g., hydroxyurea or foscarnet) within 28 days of study drug administration.

• Treatment with any of the following medications within 28 days prior to receiving study medication or the anticipated need during the study:

Amiodarone, astemizole, bepridil, bupropion, cisapride, clorazepate, clozapine, diazepam, dihydroergotamine, encainide, ergonovine, ergotamine, estazolam, flecainide, flurazepam, lovastatin, meperidine, methylergonovine, midazolam, pimozide, piroxicam, propafenone, propoxyphene, quinidine, simvastatin, terfenadine, and triazolam (these drugs have been excluded for safety reasons).

Carbamazepine, dexamethasone, phenobarbital, primidone, rifampin, St Johns Wort, (these drugs have been excluded because they have the potential to decrease plasma protease inhibitor concentrations).

• Treatment with other investigational drugs/therapies within 28 days prior to receiving study medication (note: treatments available through a Treatment IND or other expanded-access mechanism will be evaluated on a case-by-case basis in consultation with the sponsor).

• History of drug or other allergy which, in the opinion of the investigator, contraindicates participation in the trial or known hypersensitivity to any study medications (e.g. documented hypersensitivity to a nucleoside analogue).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Jacksonville	Florida	United States	32209
2	GSK Investigational Site	Durham	North Carolina	United States	27705
3	GSK Investigational Site	Buenos Aires		Argentina	1405
4	GSK Investigational Site	Mexico, D.F.		Mexico	06720
5	GSK Investigational Site	Mexico		Mexico	6720
6	GSK Investigational Site	Almada		Portugal	2805-267
7	GSK Investigational Site	Amadora		Portugal	2700
8	GSK Investigational Site	Lisboa		Portugal	1649-035
9	GSK Investigational Site	San Juan		Puerto Rico	00935
10	GSK Investigational Site	Moscow		Russian Federation	105275
11	GSK Investigational Site	Moscow		Russian Federation	129110
12	GSK Investigational Site	St. Petersburg		Russian Federation	196645
13	GSK Investigational Site	Durban	KwaZulu- Natal	South Africa	4013
14	GSK Investigational Site	Parow Valley	Western Province	South Africa	7505
15	GSK Investigational Site	Soweto		South Africa	2013

Sponsors and Collaborators

• ViiV Healthcare
• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, ViiV Healthcare

Study Documents (Full-Text)

None provided.

More Information

Publications

• Cotton M, Cassim H, Pavía-Ruz N, Garges HP, Perger T, Ford SL, Wire MB, Givens N, Ross LL, Lou Y, Sievers J, Cheng K. Pharmacokinetics, safety and antiviral activity of fosamprenavir/ritonavir-containing regimens in HIV-infected children aged 4 weeks to 2 years-48-week study data. Pediatr Infect Dis J. 2014 Jan;33(1):57-62. doi: 10.1097/INF.0b013e3182a1123a.

• Responsible Party: ViiV Healthcare
• ClinicalTrials.gov Identifier: NCT00071760
• Other Study ID Numbers: APV20002
• First Posted: Oct 31, 2003
• Last Update Posted: Jan 13, 2017
• Last Verified: Nov 1, 2016

• Keywords provided by ViiV Healthcare: pediatrics; ritonavir; amprenavir; AGENERASE; HIV; Lexiva; protease inhibitors; HIV Infection; fosamprenavir
• Additional relevant MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Ritonavir; Fosamprenavir

Study Results

Participant Flow

Recruitment Details	59 unique participants (par.) received >=1 investigational product (IP) dose; however, 1 par. was not given a randomization number and therefore was not enrolled into the study. Thus, the number of par. enrolled in the protocol record=58. 5/59 par. receiving only single doses of IP are not included in the Intent-to-Treat Exposed Population (N=54).
Pre-assignment Detail	Per protocol, the initial intention was to enroll par. to receive fosamprenavir; however, ultimately, no par. were enrolled into cohorts to receive repeat dosing of fosamprenavir without ritonavir boosting. The 59 par. who received >=1 IP dose were included in the Safety Population.

Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
Period Title: Overall Study
STARTED	54
Ongoing	25
COMPLETED	0
NOT COMPLETED	54

Baseline Characteristics

Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
Overall Participants	54
Age (Months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Months]	8.6 (6.43)
Gender (Count of Participants)
Female	31 57.4%
Male	23 42.6%
Race/Ethnicity, Customized (participants) [Number]
Black	44 81.5%
White/Caucasian	2 3.7%
American Indian	8 14.8%

Outcome Measures

1. Primary Outcome

Title	Plasma Amprenavir (APV) AUC (0-tau[τ])
Description	Plasma samples were assayed for APV concentrations using a validated assay. The GlaxoSmithKline (GSK) Department of Clinical Pharmacology Modeling and Simulation conducted pharmacokinetic (PK) analysis of the plasma APV concentration-time data using a model-independent approach. As a measure of total drug exposure, the area under the plasma-concentration-versus-time curve over the dosing interval at steady-state (AUC[0-τ]), where "τ" is the length of the dosing interval, was calculated by the linear up/log down trapezoidal method. hours, hr.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Population: all participants for whom serial plasma PK samples were analyzed. Only those participants contributing data were analyzed.

Arm/Group Title	FPV/RTV BID: 4 Weeks to <6 Months	FPV/RTV BID: 6 Months to <2 Years
Arm/Group Description	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout.
Measure Participants	9	10
45/10 mg/kg BID; n=9, 1	26.6	64.51
60/10 mg/kg BID; n=2, 2	54.2	26.22
45/7 mg/kg BID; n=2, 10	35.08	27.5
60/7 mg/kg BID; n=0, 8	NA	48.4

2. Primary Outcome

Title	Plasma APV Cmax
Description	The maximum concentration at steady state (Cmax) was measured.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants contributing data were analyzed.

Arm/Group Title	FPV/RTV BID: 4 Weeks to <6 Months	FPV/RTV BID: 6 Months to <2 Years
Arm/Group Description	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout.
Measure Participants	9	10
45/10 mg/kg BID; n=9, 1	6.25	21.82
60/10 mg/kg BID; n=2, 2	10.44	7.47
45/7 mg/kg BID; n=2, 10	8.20	5.84
60/7 mg/kg BID; n=0, 9	NA	10.4

3. Primary Outcome

Title	Plasma APV Cτ
Description	The plasma concentration at the end of the dosing interval at steady state (Cτ) was measured.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants contributing data were analyzed.

Arm/Group Title	FPV/RTV BID: 4 Weeks to <6 Months	FPV/RTV BID: 6 Months to <2 Years
Arm/Group Description	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout.
Measure Participants	11	29
45/10 mg/kg BID; n=11, 15	0.86	1.92
60/10 mg/kg BID; n=3, 5	0.60	2.58
45/7 mg/kg BID; n=3, 29	0.44	2.17
60/7 mg/kg BID; n=0, 12	NA	2.81

4. Primary Outcome

Title	Plasma APV CL/F Following Dosing Expressed in mL/Min/kg
Description	Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated using the formulation: APV Dose in mg/kg units divided by AUC(0-τ). For FPV, doses were expressed in APV molar equivalents (50 mg of FPV = 43.2 mg of APV). Normalizing CL/F for bodyweight allows for comparison of CL/F across populations.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants contributing data were analyzed.

Arm/Group Title	FPV/RTV BID: 4 Weeks to <6 Months	FPV/RTV BID: 6 Months to <2 Years
Arm/Group Description	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout.
Measure Participants	9	10
45/10 mg/kg BID; n=9, 1	22.9	10.42
60/10 mg/kg BID; n=2, 2	15.3	31.92
45/7 mg/kg BID; n=2, 10	17.50	22.8
60/7 mg/kg BID; n=0, 8	NA	17.8

5. Primary Outcome

Title	Plasma APV CL/F Following Dosing Expressed in mL/Min
Description	Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated as dose/AUC(0-τ). For FPV, doses were expressed in APV molar equivalents (50 mg of FPV = 43.2 mg of APV).
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants contributing data were analyzed.

Arm/Group Title	FPV/RTV BID: 4 Weeks to <6 Months	FPV/RTV BID: 6 Months to <2 Years
Arm/Group Description	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout.
Measure Participants	9	10
45/10 mg/kg BID; n=9, 1	135	62.5
60/10 mg/kg BID; n=2, 2	86.4	234.3
45/7 mg/kg BID; n=2, 10	106.7	190
60/7 mg/kg BID; n=0, 8	NA	172

6. Primary Outcome

Title	Plasma Unbound APV Cτ
Description	Participants who are <2 years old may have reduced protein binding; therefore, plasma unbound APV concentrations were measured to determine dosing recommendations at acceptable dosing volumes. Unbound or "free" APV is the fraction of drug that is not bound to protein. Cτ is the plasma concentration at the end of the dosing interval at steady state.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants contributing data were analyzed.

Arm/Group Title	FPV/RTV BID: 4 Weeks to <6 Months	FPV/RTV BID: 6 Months to <2 Years
Arm/Group Description	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout.
Measure Participants	7	16
45/10 mg/kg BID; n=7, 16	0.091 (0.083)	0.087 (0.076)
60/10 mg/kg BID; n=1, 7	0.003 (NA)	0.069 (0.052)
45/7 mg/kg BID; n=1, 16	0.027 (NA)	0.150 (0.086)
60/7 mg/kg BID; n=0, 12	NA (NA)	0.290 (0.310)

7. Primary Outcome

Title	Plasma Unbound APV Percent Protein Binding (%Cτ)
Description	Participants who are <2 years old may have reduced protein binding; therefore, plasma unbound APV concentrations were measured to determine dosing recommendations at acceptable dosing volumes. APV %Cτ unbound is the percentage of the total APV Cτ that is unbound.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants contributing data were analyzed.

Arm/Group Title	FPV/RTV BID: 4 Weeks to <6 Months	FPV/RTV BID: 6 Months to <2 Years
Arm/Group Description	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout.
Measure Participants	7	16
45/10 mg/kg BID; n=7, 15	5.79 (2.05)	6.56 (2.27)
60/10 mg/kg BID; n=1, 7	5.32 (NA)	5.81 (1.68)
45/7 mg/kg BID; n=1, 16	7.55 (NA)	8.23 (8.67)
60/7 mg/kg BID; n=0, 9	NA (NA)	9.20 (5.39)

8. Primary Outcome

Title	Median Change From Baseline in Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST) at Weeks 4, 12, 24, 36, and 48
Description	Blood samples of the participants were collected for the evaluation of ALT and AST. Clinical chemistry analyses were carried out using the observed analysis strategy. Change from Baseline in ALT and AST was calculated as the value at the indicated time point minus the value at Baseline.
Time Frame	Baseline (Day 1) and Weeks 4, 12, 24, 36, and 48

Outcome Measure Data

Analysis Population Description

Safety Population: all participants with documented evidence of having received at least one dose of investigational treatment. Only those participants contributing data were analyzed.

Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
Measure Participants	49
ALT, Week 4; n=49	-7.0
ALT, Week 12; n=47	-4.0
ALT, Week 24; n=46	-7.5
ALT, Week 36; n=43	-5.0
ALT, Week 48; n=40	-4.0
AST, Week 4; n=49	-8.0
AST, Week 12; n=47	-9.0
AST, Week 24; n=46	-10.5
AST, Week 36; n=42	-11.5
AST, Week 48; n=39	-9.0

9. Primary Outcome

Title	Median Change From Baseline in Cholesterol, Glucose, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Triglyceride (TG), Potassium, and Sodium at Weeks 4, 12, 24, 36, and 48
Description	Blood samples of all participants were generally collected under non-fasting conditions (given the age of participants) for the evaluation of cholesterol, serum glucose, HDL cholesterol, LDL cholesterol, triglyceride, potassium, and sodium. Clinical chemistry analyses were carried out using the observed analysis strategy. Change from Baseline in cholesterol, serum glucose, HDL cholesterol, LDL cholesterol, triglyceride, potassium, and sodium was calculated as the value at the indicated time point minus the value at Baseline.
Time Frame	Baseline (Day 1) and Weeks 4, 12, 24, 36, and 48

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants contributing data were analyzed.

Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
Measure Participants	49
Cholesterol, Week 4; n=1	1.300
Cholesterol, Week 12; n=2	1.125
Cholesterol, Week 24; n=41	1.220
Cholesterol, Week 36; n=5	-0.140
Cholesterol, Week 48; n=35	1.460
Glucose, Week 4; n=49	-0.10
Glucose, Week 12; n=47	-0.10
Glucose, Week 24; n=46	-0.35
Glucose, Week 36; n=43	-0.20
Glucose, Week 48; n=40	-0.10
HDL, Week 4; n=1	0.400
HDL, Week 12; n=2	0.275
HDL, Week 24; n=41	0.250
HDL, Week 36; n=5	0.120
HDL, Week 48; n=35	0.270
LDL, Week 4; n=1	2.00
LDL, Week 12; n=2	0.82
LDL, Week 24; n=40	1.08
LDL, Week 36; n=5	0.65
LDL, Week 48; n=34	1.50
TG, Week 4; n=1	-2.360
TG, Week 12; n=2	0.070
TG, Week 24; n=41	-0.120
TG, Week 36; n=5	0.010
TG, Week 48; n=35	-0.340
Potassium, Week 4; n=49	-0.10
Potassium, Week 12; n=47	-0.20
Potassium, Week 24; n=46	-0.10
Potassium, Week 36; n=43	0
Potassium, Week 48; n=40	-0.25
Sodium, Week 4; n=49	0
Sodium, Week 12; n=47	0
Sodium, Week 24; n=46	0
Sodium, Week 36; n=43	-1.0
Sodium, Week 48; n=40	0

10. Primary Outcome

Title	Median Change From Baseline in Serum Lipase at Weeks 4, 12, 24, and 48
Description	Blood samples of all participants were collected for the evaluation of serum lipase. Clinical chemistry analyses were carried out using the observed analysis strategy. Change from Baseline in serum lipase was calculated as the value at the indicated time point minus the value at Baseline.
Time Frame	Baseline (Day 1) and Weeks 4, 12, 24, and 48

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants contributing data were analyzed.

Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
Measure Participants	8
Week 4; n=1	-6.0
Week 12; n=1	5.0
Week 24; n=8	-4.0
Week 48; n=8	-3.0

11. Primary Outcome

Title	Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Laboratory Abnormalities
Description	TE toxicities were presented for each laboratory parameter. A toxicity was considered TE if it was greater than the Baseline grade, and if it was observed on/after the date of the first dose of study drug (SD), and on/before the date of the last dose of SD. Neutropenia is a decrease (d) in the number of Ns, d/increase (I) in glucose is hypo (Hp)/hyper (Hy)glycemia, in potassium is Hp/Hykalemia, and in sodium is Hp/Hynatremia. Per the Division of AIDS Table for Grading the Severity of Adult and Pediatric AEs, Grade 3=severe; Grade 4=potentially life-threatening.
Time Frame	Baseline (Day 1) until Week 48

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants contributing data were analyzed.

Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
Measure Participants	51
ALT >5.0x upper limit of normal (ULN); n=51	3 5.6%
AST >5.0x ULN; n=51	0 0%
Cholesterol >7.77 millimoles/liter (mmol/L); n=49	0 0%
Lipase increased >3.0x ULN; n=10	0 0%
Hypoglycemia <2.22 mmol/L; n=51	0 0%
Hyperglycemia >13.88 mmol/L; n=51	0 0%
Hemoglobin <1.16 mmol/L; n=51	1 1.9%
Platelet count <50.000x10^9/L; n=51	0 0%
Albumin <20 grams (g)/L; n=51	0 0%
Alkaline Phosphatase >5.0x ULN; n=51	4 7.4%
Creatine Kinase >=10x ULN; n=51	3 5.6%
Hyperkalemia >6.5 mmol/L; n=51	0 0%
Hypokalemia <2.5 mmol/L; n=51	0 0%
Hypernatremia >=155 mmol/L; n=51	0 0%
Hyponatremia <125 mmol/L; n=51	0 0%
Total Neutrophils (Ns) <0.750x10^9/L; n=51	5 9.3%

12. Primary Outcome

Title	Number of Participants With the Indicated Treatment-emergent (TE) Grade 3/4 Adverse Events (AE)
Description	An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE is considered TE if it has an onset date on or after the date of the first dose of study drug, and on or before the date of the final dose of study drug. As per the Division of AIDS Table for Grading the Severity of Adult and Pediatric AEs, Grade 3=severe; Grade 4=potentially life-threatening.
Time Frame	Baseline (Day 1) until Week 48

Outcome Measure Data

Analysis Population Description

Safety Population. In addition to the 54 participants starting FPV/RTV BID treatment, the FPV/RTV BID treatment group includes 5 participants who only received investigational product at the single dose visits in APV20002.

Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
Measure Participants	59
Bronchopneumonia	4 7.4%
Gastroenteritis	4 7.4%
Neutropenia	2 3.7%
Pneumonia	2 3.7%
Urinary tract infection	2 3.7%
Blood creatinine phosphokinase increased	2 3.7%
Hypertension	2 3.7%
Bronchiolitis	1 1.9%
Bronchitis	1 1.9%
Lower respiratory tract infection	1 1.9%
Meningitis	1 1.9%
Meningitis bacterial	1 1.9%
Pneumonia viral	1 1.9%
ALT increased	1 1.9%
Transaminase increased	1 1.9%
Thrombocytopenia	1 1.9%
Greenstick fracture	1 1.9%
Herbal toxicity	1 1.9%
Pneumonitis chemical	1 1.9%
Hypernatremia	1 1.9%
Kwashiorkor	1 1.9%
Inflammation	1 1.9%
Anogenital warts	1 1.9%
Febrile convulsion	1 1.9%

13. Primary Outcome

Title	Number of Participants Who Permanently Discontinued the Treatment Due to an AE
Description	An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame	Baseline (Day 1) until Week 48

Outcome Measure Data

Analysis Population Description

Safety Population. In addition to the 54 participants starting FPV/RTV BID treatment, the FPV/RTV BID treatment group includes 5 participants who only received investigational product at the single dose visits in APV20002.

Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
Measure Participants	59
Number [participants]	1 1.9%

14. Secondary Outcome

Title	Number of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) <400 Copies Per Milliliter at Baseline and Weeks 4, 12, 24, 36, and 48 (MSD=F)
Description	Blood samples of participants were collected to measure plasma HIV-1 RNA concentrations. Viral load, measured in RNA copies per milliliter of plasma, is an efficacy measure for antiretroviral drugs. In the Missing, Switch, or Discontinuation=Failure (MSD=F) analysis, participants who had missing data at or had discontinued the study prior to a certain time point or had changed their background antiretroviral regimen are classified as non-responders.
Time Frame	Baseline and Weeks 4, 12, 24, 36, and 48

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Exposed (ITT-E) Population: participants who received chronic therapy with FPV or FPV/RTV at any dose. Only those participants contributing data at the indicated time points were analyzed.

Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
Measure Participants	54
Baseline	1 1.9%
Week 4	11 20.4%
Week 12	31 57.4%
Week 24	40 74.1%
Week 36	39 72.2%
Week 48	35 64.8%

15. Secondary Outcome

Title	Median Plasma HIV-1 RNA (log10 Copies/mL) at Baseline and Weeks 4, 12, 24, 36, and 48 (Observed Analysis)
Description	Blood samples of participants were collected to assess the decrease in the number of HIV-1 RNA copies.
Time Frame	Baseline and Weeks 4, 12, 24, 36, and 48

Outcome Measure Data

Analysis Population Description

ITT-E Population. In the observed analysis, data are presented for the number of participants still enrolled in the study at a certain time point.

Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
Measure Participants	54
Baseline, n=54	5.60
Week 4, n=49	3.11
Week 12, n=49	2.16
Week 24, n=47	1.69
Week 36, n=46	1.69
Week 48, n=42	1.69

16. Secondary Outcome

Title	Median Change From Baseline in Plasma HIV-1 RNA (log10 Copies/mL) at Weeks 4, 12, 24, 36, and 48 (Observed Analysis)
Description	Blood samples of participants were collected to assess the decrease in the number of HIV-1 RNA copies. Change from Baseline in plasma HIV-1 RNA was calculated as the value at the indicated time point minus the value at Baseline.
Time Frame	Baseline and Weeks 4, 12, 24, 36, and 48

Outcome Measure Data

Analysis Population Description

ITT-E Population. In the observed analysis, data are presented for the number of participants still enrolled in the study at a certain time point.

Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
Measure Participants	49
Week 4, n=49	-2.34
Week 12, n=49	-3.13
Week 24, n=47	-3.62
Week 36, n=46	-3.55
Week 48, n=42	-3.66

17. Secondary Outcome

Title	Number of Participants With at Least a 1.0 log10 HIV-1 RNA Decrease From Baseline at Weeks 4, 12, 24, 36, and 48 (MSD=F Analysis)
Description	Blood samples of participants were collected to assess the decrease in the number of HIV-1 RNA copies. In the MSD=F analysis, participants who had missing data at or had discontinued the study prior to a certain time point or had changed their background antiretroviral regimen are classified as non-responders.
Time Frame	Baseline and Weeks 4, 12, 24, 36, and 48

Outcome Measure Data

Analysis Population Description

ITT-E Population. Only those participants contributing data at the indicated time points were analyzed.

Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
Measure Participants	54
Week 4	44 81.5%
Week 12	46 85.2%
Week 24	44 81.5%
Week 36	41 75.9%
Week 48	37 68.5%

18. Secondary Outcome

Title	Median Percent Cluster of Differentiation Antigen 4 (CD4+) Cell Count at Baseline and at Weeks 4, 12, 24, 36, and 48
Description	Blood samples of participants were collected for the measurement of the percentage of total lymphocytes that are CD4+ cells. Observed analysis was used for the summary of proportion endpoints using viral load data. CD4+ cells are white blood cells that are important in fighting infection. HIV infects CD4+ cells, replicates in them, and destroys them. A CD4+ cell count provides a measure of the status of the immune system and to what extent it is affected by HIV.
Time Frame	Baseline and Weeks 4, 12, 24, 36, and 48

Outcome Measure Data

Analysis Population Description

ITT-E Population. Only those participants contributing data at the indicated time points were analyzed.

Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
Measure Participants	51
Baseline, n=51	26
Week 4, n=51	28
Week 12, n=49	32
Week 24, n=48	32
Week 36, n=46	31
Week 48, n=42	29

19. Secondary Outcome

Title	Median Percent Change From Baseline in CD4+ Cell Count at Weeks 4, 12, 24, 36, and 48
Description	Blood samples of participants were collected for the measurement of the percentage of total lymphocytes that are CD4+ cells. Observed analysis was used for the summary of proportion endpoints using viral load data. Change from Baseline in percentage was calculated as the value at indicated time points minus the value at Baseline.
Time Frame	Baseline and Weeks 4, 12, 24, 36, and 48

Outcome Measure Data

Analysis Population Description

ITT-E Population. Only those participants contributing data at the indicated time points were analyzed. Not all participants had values at both baseline and the indicated time points; thus, change from baseline could not be calculated for all participants.

Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
Measure Participants	48
Week 4, n=48	3.4
Week 12, n=46	4.5
Week 24, n=45	6.0
Week 36, n=43	6.1
Week 48, n=39	5.0

20. Secondary Outcome

Title	Number of Participants With the Indicated Virological Outcome at Week 48
Description	Blood samples of participants were collected to measure plasma HIV-1 RNA concentrations. PI-exp = PI-experienced. Virologic success was defined as plasma HIV-1 RNA <400 copies/mL. Virologic failure: (1) HIV-1 RNA >=400 copies/mL, (2) change of background antiretroviral treatment (ART), (3) discontinued study due to lack of efficacy, (4) discontinued study with last HIV-1 >=400 copies/mL. No virologic data at Week 48 window: (a) discontinued study due to an adverse event or death, (b) discontinued study due to other reasons (withdrew consent, loss to follow-up, moved, etc.).
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT-E Population. Only those participants contributing data were analyzed.

Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
Measure Participants	54
Virological (V) success	35 64.8%
V failure (1)	5 9.3%
V failure (2)	2 3.7%
V failure (3)	2 3.7%
V failure (4)	3 5.6%
No V data at Week 48 (a)	2 3.7%
No V data at Week 48 (b)	5 9.3%

21. Secondary Outcome

Title	Plasma Ritonavir (RTV) AUC (0-τ)
Description	Plasma samples were assayed for RTV concentrations using a validated assay. The GSK Department of Clinical Pharmacology Modeling and Simulation conducted PK analysis of the plasma RTV concentration-time data using a model-independent approach. As a measure of total drug exposure, the area under the plasma-concentration-versus-time curve over the dosing interval at steady-state (AUC[0-τ]), where τ is the length of the dosing interval, was calculated by the linear up/log down trapezoidal method.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants contributing data were analyzed.

Arm/Group Title	FPV/RTV BID: 4 Weeks to <6 Months	FPV/RTV BID: 6 Months to <2 Years
Arm/Group Description	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout.
Measure Participants	11	22
7 mg/kg BID; n=2, 22	1.921	7.363
10 mg/kg BID; n=11, 2	12.952	18.750

22. Secondary Outcome

Title	Plasma RTV Cmax
Description	The maximum concentration at steady state (Cmax) was measured.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants contributing data were analyzed.

Arm/Group Title	FPV/RTV BID: 4 Weeks to <6 Months	FPV/RTV BID: 6 Months to <2 Years
Arm/Group Description	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout.
Measure Participants	12	23
7 mg/kg BID, n=2, 23	0.404	1.576
10 mg/kg BID, n=12, 2	2.388	3.823

23. Secondary Outcome

Title	Plasma RTV Cτ
Description	The plasma concentration at the end of the dosing interval at steady state (Cτ) was measured.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants contributing data were analyzed.

Arm/Group Title	FPV/RTV BID: 4 Weeks to <6 Months	FPV/RTV BID: 6 Months to <2 Years
Arm/Group Description	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout.
Measure Participants	15	33
7 mg/kg BID, n=4, 33	0.0795	0.2468
10 mg/kg BID, n=15, 19	0.1855	0.4200

24. Secondary Outcome

Title	Plasma RTV CL/F Expressed in mL/Min/kg
Description	Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated as dose in mg/kg units divided by AUC(0-τ). Normalizing CL/F for bodyweight allows for comparison of CL/F across populations.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants contributing data were analyzed.

Arm/Group Title	FPV/RTV BID: 4 Weeks to <6 Months	FPV/RTV BID: 6 Months to <2 Years
Arm/Group Description	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout.
Measure Participants	11	22
7 mg/kg BID, n=2, 22	58.668	14.960
10 mg/kg BID, n=11, 2	12.118	8.938

25. Secondary Outcome

Title	Plasma RTV CL/F Expressed in mL/Min
Description	Apparent clearance of drug from plasma following extravascular administration (CL/F) was calculated as dose in mg/kg units divided by AUC(0-τ).
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

PK Population. Only those participants contributing data were analyzed.

Arm/Group Title	FPV/RTV BID: 4 Weeks to <6 Months	FPV/RTV BID: 6 Months to <2 Years
Arm/Group Description	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout.
Measure Participants	11	22
7 mg/kg BID, n=2, 22	335.2	134.1
10 mg/kg BID, n=11, 2	72.1	57.9

26. Secondary Outcome

Title	Number of Confirmed Virologic Failure Participants (Par.) With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease
Description	A blood sample was drawn for par. failing to respond to therapy, and the mutations present in the virus were identified. For each par., the mutations found at the time of failure were compared with any mutations found in the blood sample at baseline. New International AIDS Society-USA defined resistance mutations that developed at the time of failure were tabulated by drug class. VF, virologic failure; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor. Par. are grouped by study arm and prior therapy experience.
Time Frame	Baseline through Week 48

Outcome Measure Data

Analysis Population Description

VF: par. with failure to achieve plasma HIV-RNA <400 copies/mL by Week 24; or confirmed HIV-RNA rebound to >=400 copies/mL any time after achieving plasma HIV-RNA <400 copies/mL and had evaluable viral isolate genotypic and/or phenotypic data. Only par. contributing viral genotype at both baseline and the indicated time of VF points were evaluable.

Arm/Group Title	ART-naïve FPV/RTV Treatment Group	PI-naïve, ART-experienced FPV/RTV Treatment Group	PI-experienced, ART-experienced FPV/RTV Treatment Group
Arm/Group Description	ART-naïve Human immunodeficiency virus (HIV)-1-infected pediatric participants (received no antiretroviral agents prior to study enrollment) were enrolled in one of two cohorts based on their age: 6 months to <2 years (Cohort 1); 4 weeks to <6 months (Cohort 2). Participants initially underwent single dose visits (SDV). Cohort 1: SDV 1: 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, followed by SDV 2: 30/6 mg/kg FPV/ritonavir (RTV) oral solution. Cohort 2: SDV 1: 45/7 mg/kg FPV/RTV. The chronic dosing regimen for Cohort 1 was 45/7 mg/kg twice a day (BID) FPV/RTV, and for Cohort 2 was 30/7 mg/kg BID to 60/10 mg/kg BID. Per the preliminary data at Week 2 in Cohort 1, additional enrolled participants received 60/7 mg/kg FPV/RTV BID; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID with no dose increase at Week 2. In Cohort 2, additional enrolled participants received 45/10 mg/kg FPV/RTV BID.	PI-naïve, ART experienced, HIV-1-infected pediatric participants (received ART previously, but received <1 week's treatment with a PI) were enrolled in one of two cohorts based on their age: 6 months to <2 years (Cohort 1); 4 weeks to <6 months (Cohort 2). Participants initially underwent single dose visits (SDV). Cohort 1: SDV 1: 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, followed by SDV 2: 30/6 mg/kg FPV/ritonavir (RTV) oral solution. Cohort 2: SDV 1: 45/7 mg/kg FPV/RTV. The chronic dosing regimen for Cohort 1 was 45/7 mg/kg twice a day (BID) FPV/RTV, and for Cohort 2 was 30/7 mg/kg BID to 60/10 mg/kg BID. Per the preliminary data at Week 2 in Cohort 1, additional enrolled participants received 60/7 mg/kg FPV/RTV BID; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID with no dose increase at Week 2. In Cohort 2, additional enrolled participants received 45/10 mg/kg FPV/RTV BID.	PI- experienced, ART-experienced, HIV-1-infected pediatric participants (received ART previously, and >1 week prior PI therapy [no more than 3 PIs before study enrollment]) were enrolled in one of two cohorts based on their age: 6 months to <2 years (Cohort 1); 4 weeks to <6 months (Cohort 2). Participants initially underwent SDVs. Cohort 1: SDV 1: 30 mg/kg fosamprenavir (FPV) oral suspension, followed by SDV 2: 30/6 mg/kg FPV/ritonavir (RTV) oral solution. Cohort 2: SDV 1: 45/7 mg/kg FPV/RTV. The chronic dosing regimen for Cohort 1 was 45/7 mg/kg twice a day (BID) FPV/RTV, and for Cohort 2 was 30/7 mg/kg BID to 60/10 mg/kg BID. Per the preliminary data at Week 2 in Cohort 1, additional enrolled participants received 60/7 mg/kg FPV/RTV BID; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID with no dose increase at Week 2. In Cohort 2, additional enrolled participants received 45/10 mg/kg FPV/RTV BID.
Measure Participants	2	3	2
Any HIV NRTI Mutation	1 1.9%	0 NaN	0 NaN
HIV NRTI mutation M184V	1 1.9%	0 NaN	0 NaN
Any HIV NNRTI Mutation	0 0%	0 NaN	1 NaN
HIV NNRTI Mutation K101K/E	0 0%	0 NaN	1 NaN
Any HIV Major PI Mutations	0 0%	0 NaN	0 NaN
Any Minor HIV PI Mutations	2 3.7%	0 NaN	1 NaN
Minor HIV PI Mutation L10F	0 0%	0 NaN	1 NaN
Minor HIV PI Mutation L10I	1 1.9%	0 NaN	0 NaN
Minor HIV PI Mutation L33L/F	1 1.9%	0 NaN	0 NaN
Minor HIV PI Mutation L33F	0 0%	0 NaN	1 NaN

27. Secondary Outcome

Title	Number of Confirmed Virologic Failure Participants (Par.) With Treatment-emergent Reductions in Drug Susceptibility (DS)
Description	A blood sample was drawn for par. failing to respond to therapy, and changes in DS for HIV isolated from the par. for each drug used in the study were assessed. The changes in DS detected by phenotypic assay in virus from the sample collected at the time of failure was compared with DS in the virus from the blood sample at baseline. Par. are grouped by study arm and prior therapy experience. DS is the state of HIV being susceptible to the antiretroviral agent (the virus can be inhibited by the drug). Reduced DS (i.e., HIV is resistant to the antiretroviral agent) can lead to treatment failure.
Time Frame	Baseline through Week 48

Outcome Measure Data

Analysis Population Description

VF: par. with failure to achieve plasma HIV-RNA <400 copies/mL by Week 24; or confirmed HIV-RNA rebound to >=400 copies/mL any time after achieving plasma HIV-RNA <400 copies/mL and had evaluable viral isolate genotypic and/or phenotypic data. Only par. contributing viral phenotype at both baseline and the indicated time of VF points were evaluable

Arm/Group Title	ART-naïve FPV/RTV Treatment Group	ART-experienced, PI-naïve FPV/RTV Treatment Group	PI-experienced, ART-experienced FPV/RTV Treatment Group
Arm/Group Description	ART-naïve Human immunodeficiency virus (HIV)-1-infected pediatric participants (received no antiretroviral agents prior to study enrollment) were enrolled in one of two cohorts based on their age: 6 months to <2 years (Cohort 1); 4 weeks to <6 months (Cohort 2). Participants initially underwent single dose visits (SDV). Cohort 1: SDV 1: 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, followed by SDV 2: 30/6 mg/kg FPV/ritonavir (RTV) oral solution. Cohort 2: SDV 1: 45/7 mg/kg FPV/RTV. The chronic dosing regimen for Cohort 1 was 45/7 mg/kg twice a day (BID) FPV/RTV, and for Cohort 2 was 30/7 mg/kg BID to 60/10 mg/kg BID. Per the preliminary data at Week 2 in Cohort 1, additional enrolled participants received 60/7 mg/kg FPV/RTV BID; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID with no dose increase at Week 2. In Cohort 2, additional enrolled participants received 45/10 mg/kg FPV/RTV BID.	PI-naïve, ART experienced, HIV-1-infected pediatric participants (received ART previously, but received <1 week's treatment with a PI) were enrolled in one of two cohorts based on their age: 6 months to <2 years (Cohort 1); 4 weeks to <6 months (Cohort 2). Participants initially underwent single dose visits (SDV). Cohort 1: SDV 1: 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, followed by SDV 2: 30/6 mg/kg FPV/ritonavir (RTV) oral solution. Cohort 2: SDV 1: 45/7 mg/kg FPV/RTV. The chronic dosing regimen for Cohort 1 was 45/7 mg/kg twice a day (BID) FPV/RTV, and for Cohort 2 was 30/7 mg/kg BID to 60/10 mg/kg BID. Per the preliminary data at Week 2 in Cohort 1, additional enrolled participants received 60/7 mg/kg FPV/RTV BID; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID with no dose increase at Week 2. In Cohort 2, additional enrolled participants received 45/10 mg/kg FPV/RTV BID.	PI- experienced, ART-experienced, HIV-1-infected pediatric participants (received ART previously, and >1 week prior PI therapy [no more than 3 PIs before study enrollment]) were enrolled in one of two cohorts based on their age: 6 months to <2 years (Cohort 1); 4 weeks to <6 months (Cohort 2). Participants initially underwent SDVs. Cohort 1: SDV 1: 30 mg/kg fosamprenavir (FPV) oral suspension, followed by SDV 2: 30/6 mg/kg FPV/ritonavir (RTV) oral solution. Cohort 2: SDV 1: 45/7 mg/kg FPV/RTV. The chronic dosing regimen for Cohort 1 was 45/7 mg/kg twice a day (BID) FPV/RTV, and for Cohort 2 was 30/7 mg/kg BID to 60/10 mg/kg BID. Per the preliminary data at Week 2 in Cohort 1, additional enrolled participants received 60/7 mg/kg FPV/RTV BID; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID with no dose increase at Week 2. In Cohort 2, additional enrolled participants received 45/10 mg/kg FPV/RTV BID.
Measure Participants	2	3	2
Any NRTI	1 1.9%	0 NaN	0 NaN
Emtricitabine	1 1.9%	0 NaN	0 NaN
Lamivudine	1 1.9%	0 NaN	0 NaN
Any NNRTI	0 0%	0 NaN	0 NaN
Any PI	0 0%	0 NaN	1 NaN
Ritonavir-boosted Fosamprenavir	0 0%	0 NaN	1 NaN

28. Secondary Outcome

Title	Number of Participants Reporting Perfect Adherence Over the 3 Days and Last Weekend Prior to the Study Visits at Weeks 2, 12, 24, and 48 as Assessed by the Study Coordinator Using the Adherence Questionnaire
Description	A separate questionnaire were administered for FPV and RTV. Items 1-4 of the Adherence Questionnaire measured a participant's adherence with FPV or RTV during the last 3 days and the weekend prior to the indicated study visits. Question 5 queried about the number of doses of FPV or RTV missed since the participant's last study visit. Perfect adherence was defined as not missing any doses of FPV or RTV since the last study visit.
Time Frame	Weeks 2, 12, 24, and 48

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants contributing data at the indicated time points were analyzed.

Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
Measure Participants	49
Week 2, FPV=0 doses missed, n=49	45 83.3%
Week 12, FPV=0 doses missed, n=49	46 85.2%
Week 24, FPV=0 doses missed, n=46	42 77.8%
Week 48, FPV=0 doses missed, n=34	30 55.6%
Week 2, RTV=0 doses missed, n=49	45 83.3%
Week 12, RTV=0 doses missed, n=49	46 85.2%
Week 24, RTV=0 doses missed, n=46	42 77.8%
Week 48, RTV=0 doses missed, n=34	31 57.4%

29. Secondary Outcome

Title	Number of Participants With the Indicated Response Scores for the Parent/Guardian (P/G) Perception of FPV Oral Suspension Questionnaire: Items 1 to 4
Description	P/G perceptions of FPV/RTV BID were assessed using a P/G Perception of Study Medication questionnaire administered during Weeks 2, 24, and 48/premature study discontinuation. Questions 1 to 4 ask directly about the P/G's assessment of 1=color, 2=texture/consistency, 3=odor, and 4=general satisfaction. Questions 5 to 10 ask about the P/G's perception of the child's assessment of the oral suspension. Data are reported as the number of participants with the indicated response by question, response category (1-3=dislike, 4=neutral, 5-7=like), and timing of visit.
Time Frame	Weeks 2, 24, and 48/premature study discontinuation

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
Measure Participants	50
Week 2, color, dislike, n=50	8 14.8%
Week 2, color, neutral, n=50	20 37%
Week 2, color, like, n=50	22 40.7%
Week 24, color, dislike, n=44	8 14.8%
Week 24, color, neutral, n=44	12 22.2%
Week 24, color, like, n=44	24 44.4%
Week 48, color, dislike, n=35	12 22.2%
Week 48, color, neutral, n=35	8 14.8%
Week 48, color, like, n=35	15 27.8%
Week 2, texture, dislike, n=50	9 16.7%
Week 2, texture, neutral, n=50	17 31.5%
Week 2, texture, like, n=50	24 44.4%
Week 24, texture, dislike, n=44	10 18.5%
Week 24, texture, neutral, n=44	16 29.6%
Week 24, texture, like, n=44	18 33.3%
Week 48, texture, dislike, n=34	11 20.4%
Week 48, texture, neutral, n=34	8 14.8%
Week 48, texture, like, n=34	15 27.8%
Week 2, odor, dislike, n=50	8 14.8%
Week 2, odor, neutral, n=50	10 18.5%
Week 2, odor, like, n=50	32 59.3%
Week 24, odor, dislike, n=44	11 20.4%
Week 24, odor, neutral, n=44	10 18.5%
Week 24, odor, like, n=44	23 42.6%
Week 48, odor, dislike, n=35	10 18.5%
Week 48, odor, neutral, n=35	6 11.1%
Week 48, odor, like, n=35	19 35.2%
Week 2, general satisfaction, dislike, n=50	8 14.8%
Week 2, general satisfaction, neutral, n=50	11 20.4%
Week 2, general satisfaction, like, n=50	31 57.4%
Week 24, general satisfaction, dislike, n=44	10 18.5%
Week 24, general satisfaction, neutral, n=44	9 16.7%
Week 24, general satisfaction, like, n=44	25 46.3%
Week 48, general satisfaction, dislike, n=35	12 22.2%
Week 48, general satisfaction, neutral, n=35	5 9.3%
Week 48, general satisfaction, like, n=35	18 33.3%

30. Secondary Outcome

Title	Number of Participants With the Indicated Response Scores for the Parent/Guardian Perception of the Child's Assessment of FPV Oral Suspension Questionnaire: Items (I) 5 to 10
Description	Parent/guardian perceptions of FPV/RTV BID was assessed using a Parent/Guardian Perception of Study Medication questionnaire. Questions 1 to 4 ask directly about the parent/guardian's assessment of the color, texture/consistency, odor, and general satisfaction. Questions 5 to 10 ask about the parent/guardian's perception of the child's assessment of the oral suspension (Items: 5=reaction to new medicine [med.]; 6=taste; 7=acceptance; 8=swallowing; 9=willingness compared to other med.; 10=overall liking. Data for items 6/10 are reported in response categories: 1-3=dislike; 4=neutral; 5-7=like.
Time Frame	Weeks (W) 2, 24, and 48/premature study discontinuation

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
Measure Participants	50
Week 2, Item 5, takes all/most med. easily, n=50	21 38.9%
Week 2, Item 5, problem taking a few med., n=50	20 37%
Week 2, Item 5, problem taking most med., n=50	8 14.8%
Week 2, Item 5, impossible to take med., n=50	1 1.9%
Week 24, Item 5, takes all/most med. easily, n=43	22 40.7%
Week 24, Item 5, problem taking a few med., n=43	15 27.8%
Week 24, Item 5, problem taking most med., n=43	5 9.3%
Week 24, Item 5, impossible to take med., n=43	1 1.9%
Week 48, Item 5, takes all/most med. easily, n=35	26 48.1%
Week 48, Item 5, problem taking a few med., n=35	9 16.7%
Week 48, Item 5, problem taking most med., n=35	0 0%
Week 48, Item 5, impossible to take med., n=35	0 0%
Week 2, Item 6, dislike, n=50	21 38.9%
Week 2, Item 6, neutral, n=50	14 25.9%
Week 2, Item 6, like, n=50	15 27.8%
Week 24, Item 6, dislike, n=43	23 42.6%
Week 24, Item 6, neutral, n=43	8 14.8%
Week 24, Item 6, like, n=43	12 22.2%
Week 48, Item 6, dislike, n=35	17 31.5%
Week 48, Item 6, neutral, n=35	7 13%
Week 48, Item 6, like, n=35	11 20.4%
Week 2, Item 7, no problem taking FPV, n=50	13 24.1%
Week 2, Item 7, few problems taking FPV, n=50	18 33.3%
Week 2, Item 7, problem taking most of time, n=50	15 27.8%
Week 2, Item 7, impossible to take, n=50	4 7.4%
Week 24, Item 7, no problem taking FPV, n=43	23 42.6%
Week 24, Item 7, few problems taking FPV, n=43	8 14.8%
Week 24, Item 7, problem taking most of time, n=43	12 22.2%
Week 24, Item 7, impossible to take, n=43	0 0%
Week 48, Item 7, no problem taking FPV, n=35	17 31.5%
Week 48, Item 7, few problems taking FPV, n=35	11 20.4%
Week 48, Item 7, problem taking most of time, n=35	4 7.4%
Week 48, Item 7, impossible to take, n=35	3 5.6%
Week 2, Item 8, swallows with no problem, n=50	19 35.2%
Week 2, Item 8, swallows with struggle, n=50	21 38.9%
Week 2, Item 8, spits out suspension, n=50	5 9.3%
Week 2, Item 8, vomits the suspension, n=50	5 9.3%
Week 24, Item 8, swallows with no problem, n=43	22 40.7%
Week 24, Item 8, swallows with struggle, n=43	16 29.6%
Week 24, Item 8, spits out suspension, n=43	5 9.3%
Week 24, Item 8, vomits the suspension, n=43	0 0%
Week 48, Item 8, swallows with no problem, n=35	22 40.7%
Week 48, Item 8, swallows with struggle, n=35	10 18.5%
Week 48, Item 8, spits out suspension, n=35	2 3.7%
Week 48, Item 8, vomits the suspension, n=35	1 1.9%
W2, I9, take more willingly than other med., n=50	6 11.1%
Week 2, Item 9, about the same, n=50	28 51.9%
W2, I9, not as willing to take as other med., n=50	16 29.6%
W24, I9, take more willingly than other med., n=42	4 7.4%
Week 24, Item 9, about the same, n=42	31 57.4%
W24, I9, not as willing to take as other med, n=42	7 13%
W48, I9, take more willingly than other med., n=35	10 18.5%
Week 48, Item 9, about the same, n=35	23 42.6%
W48, I9, not as willing to take as other med, n=35	2 3.7%
Week 2, Item 10, dislike, n=50	20 37%
Week 2, Item 10, neutral, n=50	14 25.9%
Week 2, Item 10, like, n=50	16 29.6%
Week 24, Item 10, dislike, n=44	20 37%
Week 24, Item 10, neutral, n=44	9 16.7%
Week 24, Item 10, like, n=44	15 27.8%
Week 48, Item 10, dislike, n=35	13 24.1%
Week 48, Item 10, neutral, n=35	11 20.4%
Week 48, Item 10, like, n=35	11 20.4%

31. Secondary Outcome

Title	Correlation Between Steady-state Plasma APV PK Parameters to Changes in Plasma HIV-1 RNA Concentrations, CD4+ Percentages, and/or the Occurrence of Adverse Events
Description	No formal analysis has been performed or is planned to correlate plasma APV PK with efficacy and safety outcomes.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	FPV/RTV BID: 4 Weeks to <6 Months	FPV/RTV BID: 6 Months to <2 Years
Arm/Group Description	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout.
Measure Participants	0	0

32. Secondary Outcome

Title	Plasma FPV AUC (0-τ)
Description	The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	FPV/RTV BID: 4 Weeks to <6 Months	FPV/RTV BID: 6 Months to <2 Years
Arm/Group Description	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout.
Measure Participants	0	0

33. Secondary Outcome

Title	Plasma FPV Cmax and Cτ
Description	The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	FPV/RTV BID: 4 Weeks to <6 Months	FPV/RTV BID: 6 Months to <2 Years
Arm/Group Description	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout.
Measure Participants	0	0

34. Secondary Outcome

Title	Plasma FPV CL/F Expressed in mL/Min/kg
Description	The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	FPV/RTV BID: 4 Weeks to <6 Months	FPV/RTV BID: 6 Months to <2 Years
Arm/Group Description	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout.
Measure Participants	0	0

35. Secondary Outcome

Title	Plasma FPV CL/F Expressed in mL/Min
Description	The majority of the FPV data were below the quantification limit. Therefore, plasma FPV PK parameters were not estimated.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	FPV/RTV BID: 4 Weeks to <6 Months	FPV/RTV BID: 6 Months to <2 Years
Arm/Group Description	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.	Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout.
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	The FPV/RTV BID treatment group includes 5 participants who only received treatment at the single dose visits in APV20002 (Safety Population, n=59).
Arm/Group Title	FPV/RTV BID
Arm/Group Description	Human immunodeficiency virus (HIV)-1-infected pediatric participants were enrolled based on age in Cohort 1 (6 months to <2 years) or Cohort 2 (4 weeks to <6 months). Participants initially underwent two single dose visits (SDV): 30 milligrams per kilogram (mg/kg) fosamprenavir (FPV) oral suspension, 30/6 mg/kg FPV/ritonavir (RTV) oral solution, followed by individualized dosing (30/7 mg/kg BID to 60/10 mg/kg FPV/RTV twice a day [BID]). Per preliminary data at Week 2, the chronic dosing regimen for Cohort 1 was 45/7 mg/kg FPV/RTV BID, then changed to 45/7 mg/kg FPV/RTV BID with an increase to 60/7 mg/kg FPV/RTV BID at Week 2; later, per another analysis, all additional participants enrolled remained on 45/7 mg/kg FPV/RTV BID throughout. Per data for Cohort 1, participants in Cohort 2 underwent one SDV (45/7 mg/kg FPV/RTV), followed by individualized dosing (30/7 mg/kg to 60/10 mg/kg FPV/RTV BID). Additional enrolled participants in Cohort 2 later received 45/10 mg/kg FPV/RTV BID.
All Cause Mortality
	FPV/RTV BID
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	FPV/RTV BID
	Affected / at Risk (%)	# Events
Total	22/59 (37.3%)
Blood and lymphatic system disorders
Neutropenia	1/59 (1.7%)
Gastrointestinal disorders
Gastroenteritis	5/59 (8.5%)
Abdominal symptom	1/59 (1.7%)
Diarrhea	1/59 (1.7%)
General disorders
Inflammation	1/59 (1.7%)
Infections and infestations
Pneumonia	5/59 (8.5%)
Bronchopneumonia	4/59 (6.8%)
Urinary tract infection	2/59 (3.4%)
Bronchiolitis	1/59 (1.7%)
Bronchitis	1/59 (1.7%)
Escherichia urinary tract infection	1/59 (1.7%)
Lower respiratory tract infection	1/59 (1.7%)
Mastoiditis	1/59 (1.7%)
Meningitis	1/59 (1.7%)
Meningitis bacterial	1/59 (1.7%)
Otitis media chronic	1/59 (1.7%)
Pneumonia viral	1/59 (1.7%)
Injury, poisoning and procedural complications
Greenstick fracture	1/59 (1.7%)
Herbal toxicity	1/59 (1.7%)
Pneumonitis chemical	1/59 (1.7%)
Investigations
Transaminases increased	1/59 (1.7%)
Metabolism and nutrition disorders
Hypernatremia	1/59 (1.7%)
Kwashiorkor	1/59 (1.7%)
Malnutrition	1/59 (1.7%)
Nervous system disorders
Convulsion	2/59 (3.4%)
Febrile convulsion	1/59 (1.7%)
Vascular disorders
Hypertension	2/59 (3.4%)
Other (Not Including Serious) Adverse Events
	FPV/RTV BID
	Affected / at Risk (%)	# Events
Total	50/59 (84.7%)
Ear and labyrinth disorders
Otorrhoea	5/59 (8.5%)
Eye disorders
Conjunctivitis	10/59 (16.9%)
Gastrointestinal disorders
Diarrhea	32/59 (54.2%)
Vomiting	13/59 (22%)
Aphthous stomatitis	3/59 (5.1%)
Dental caries	3/59 (5.1%)
General disorders
Pyrexia	4/59 (6.8%)
Infections and infestations
Upper respiratory tract infection	21/59 (35.6%)
Gastroenteritis	17/59 (28.8%)
Nasopharyngitis	17/59 (28.8%)
Pharyngitis	17/59 (28.8%)
Otitis media	16/59 (27.1%)
Rhinitis	15/59 (25.4%)
Tonsillitis	10/59 (16.9%)
Impetigo	7/59 (11.9%)
Otitis media acute	7/59 (11.9%)
Bronchitis	6/59 (10.2%)
Bronchiolitis	5/59 (8.5%)
Acarodermatitis	4/59 (6.8%)
Folliculitis	3/59 (5.1%)
Fungal skin infection	3/59 (5.1%)
Oral candidiasis	3/59 (5.1%)
Oral herpes	3/59 (5.1%)
Tinea infection	3/59 (5.1%)
Investigations
Blood cholesterol increased	11/59 (18.6%)
Blood triglycerides increased	5/59 (8.5%)
Metabolism and nutrition disorders
Failure to thrive	3/59 (5.1%)
Respiratory, thoracic and mediastinal disorders
Cough	10/59 (16.9%)
Nasal congestion	3/59 (5.1%)
Skin and subcutaneous tissue disorders
Dermatitis diaper	7/59 (11.9%)
Seborrhoeic dermatitis	7/59 (11.9%)
Eczema	6/59 (10.2%)
Rash	5/59 (8.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.