HIV-1 Infection Study of Once a Day Versus Twice a Day Protease Inhibitor in Antiretroviral Treatment Naive Adults

• Sponsor: ViiV Healthcare (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00450580
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 212
• Locations: 69
• Arms: 2
• Duration (Months): 17.1
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a Phase IIIB, 48 Week, multicentre, randomized, open-label, parallel group study comparing the safety and efficacy of fosamprenavir plus ritonavir 1400mg/100mg once-daily to fosamprenavir plus ritonavir 700mg/100mg twice-daily, both administered with abacavir/lamivudine 600mg/300mg once-daily in antiretroviral-naive HIV-1 infected adults. This study utilizes a group-sequential design with two stages: 1) an interim 24 week cohort analysis of approximately 200 subjects and 2) if study continuation criteria are met at this interim analysis, further enrolment of an additional 528 subjects, followed over a minimum of 48 weeks. The objectives of the study are to demonstrate 1) non-inferior antiviral activity of fosamprenavir/ritonavir 1400mg/100mg QD compared to fosamprenavir/ritonavir 700mg/100mg BID and 2) a superior fasting non-HDL lipid profile in subjects receiving fosamprenavir/ritonavir 1400mg/100mg QD.

Condition or Disease	Intervention/Treatment	Phase
Infection, Human Immunodeficiency Virus I; HIV-1 Infection	Drug: fosamprenavir/ritonavir	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 212 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Study of Once-Daily Versus Twice-Daily Fosamprenavir Plus Ritonavir, Administered With Abacavir/Lamivudine Once-Daily in Antiretroviral-Naive HIV-1 Infected Adult Subjects.
• Study Start Date: Mar 1, 2007
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A Fosamprenavir/ritonavir 1400mg/100mg QD + ABC/3TC FDC 600/300mg QD	Drug: fosamprenavir/ritonavir; Fosamprenavir (FPV, TELZIR) is currently licensed in Europe for twice daily (BID) dosing in combination with ritonavir (RTV, Norvir) as a boosting agent
Active Comparator: Arm B Fosamprenavir/ritonavir 700mg/100mg BID + ABC/3TC FDC 600/300mg QD	Drug: fosamprenavir/ritonavir; Fosamprenavir (FPV, TELZIR) is currently licensed in Europe for twice daily (BID) dosing in combination with ritonavir (RTV, Norvir) as a boosting agent

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With HIV-1 RNA <400 and >=400 Copies/mL Over 48 Weeks [Week 48]

   A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at week 48. The percentage of participants with HIV-1 RNA <400 copies/mL at Week 48 was determined by the Time to Loss Of Virologic Response (TLOVR) algorithm.

Secondary Outcome Measures

1. Percentage of Participants With HIV-1 RNA <50 and >=50 Copies/mL by Visit Over 48 Weeks [Week 48]

   A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at week 48. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 48 was determined by the TLOVR algorithm

2. Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline Viral Load, TLOVR Analysis [Week 48]

   The number of participants with HIV-1 RNA <400 copies/mL at Week 48 was determined (by analysis of blood draw) and categorised by baseline viral load (BVL).

3. Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline CD4+ Count, TLOVR Analysis [Week 48]

   The number of participants with HIV-1 RNA <400 copies/mL at week 48 was determined (by analysis of blood draw) and categorised by baseline CD4+ count.

4. Change From Baseline in Non-HDL Cholesterol at Week 48 [Week 48]

   Blood samples were drawn to determine the non-HDL cholesterol levels at Week 48. The mean absolute change in non-HDL cholesterol was defined as the Week 48 levels minus levels at baseline.

5. Number of Protocol-defined Virological Failures With Genotypic and Phenotypic Resistance Changes [Time to virologic failure; Week 4 up to Week 48]

   A blood sample was drawn at the time of confirmation of virological failure, and mutations present in the virus were identified and compared to those found in the blood sample at baseline. New mutations were tabulated by drug class. RT, reverse transcriptase. Virological failure could occur anytime from Week 4 to Week 48.

6. Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24 [Weeks 4, 12, and 24]

   Blood samples were drawn at Weeks 4, 12, and 24 to determine plasma concentrations (Ctau) of APV and RTV

7. Study Endpoints for a Subset of Subjects Receiving Study Drug Beyond 48 Weeks [Up to 60 weeks]

   Adaptive two-stage design study up to 48 weeks. N=200, expanding to 728 if continuation criteria were achieved based on a 24-week interim analysis. The initial 200 participants would continue until the last subject of the expanded cohort reached 48 weeks and would constitute the subset. As continuation criteria were not achieved, the study did not proceed to the second stage, and full analysis was performed on the initial 200 participants only.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject is ≥18 years of age.

• Subject is antiretroviral-naïve (defined as having ≤14 days of prior therapy with any antiretroviral agent).

• Subject has plasma HIV-1 RNA ≥1,000 copies/mL at screening.

• Subject is willing and able to understand and provide written informed consent prior to participation in this study.

• A female is eligible to enter and participate in the study if she is of:

1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or,

2. Child-bearing potential, has a negative pregnancy test (serum b-HCG) at screen and agrees to one of the following methods of contraception (any contraception method must be used consistently and correctly, i.e., in accordance with both the approved product label and the instructions of a physician):

• Complete abstinence from intercourse from 2 weeks prior to administration of the investigational products, throughout the study, and for at least 2 weeks after discontinuation of all study medications

• Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide). Hormonal contraception will not be permitted in this study

• Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year.

• Sterilization (female subject or male partner of female subject). All subjects participating in the study should be counselled on the practice of safer sex.

• Prior to randomization, subjects entering Stage 2 must have been screened and be negative for the HLA-B*5701 allele. Test may be performed by local laboratory and results must be available for source document verification according to local practices.

Exclusion Criteria:

• Subject is in the initial acute phase of a CDC Clinical Category C infection at Baseline. Subjects may be enrolled provided they are receiving treatment for such infections and are clinically improving at the Baseline visit.

• Subject is enrolled in one or more investigational drug protocols, which may impact HIV RNA suppression.

• Subject is, in the opinion of the Investigator, unable to complete the study dosing period and protocol evaluations and assessments.

• Subject is either pregnant or breastfeeding.

• Subject suffers from any serious medical condition (such as pancreatitis, diabetes, congestive heart failure, cardiomyopathy or other cardiac dysfunction) which in the opinion of the Investigator would compromise the safety of the subject.

• Subject has a pre-existing mental, physical, or substance abuse disorder which, in the opinion of the Investigator, may interfere with the subject's ability to comply with the dosing schedule and protocol evaluations and assessments.

• Subject has a history of inflammatory bowel disease or intestinal malignancy, intestinal ischemia, malabsorption, or other gastrointestinal dysfunction, which, in the opinion of the Investigator, may interfere with drug absorption or render the subject unable to take oral medication.

• Subject has any acute laboratory abnormality at screening, which, in the opinion of the Investigator, would 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 45-day screening window. Any verified Grade 4 laboratory abnormality would exclude a subject from study participation.

• Subject has an estimated creatinine clearance < 50 mL/min via the Cockcroft-Gault method [Cockcroft, 1976]. This test may be repeated once within the 45-day screening window.

NOTE: Creatinine clearance should be estimated using the following formula:

For serum creatinine concentration in mg/dL:

For serum creatinine concentration in µmol/L:

• Alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN) or hepatic impairment as determined by Child-Pugh Score ≥ 5.

• Subject is receiving, or has received within 90 days prior to screen, any lipid lowering agent, including drugs from the following classes: HMG-CoA reductase inhibitors (statins), niacin, fibrates, bile acid sequestrants, and/or fish oil supplements. Subjects anticipated to require initiation of therapy with these agents within 12 weeks of Baseline are not eligible to participate.

• Subject has received treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days prior to Screening, or has an anticipated need for these agents within the study period.

• Subject has received treatment with an HIV-1 immunotherapeutic vaccine or any agents with documented activity against HIV-1 in vitro within 28 days prior Screening, or an anticipated need during the study.

• Subjects who require treatment with any of the following medications within 28 days of commencement of investigational product, or an anticipated need during the study:

• Amiodarone, astemizole, bepridil, cisapride, dihydroergotamine, ergonovine, ergotamine, flecainide, halofantrine, lidocaine, lovastatin, methylergonovine, midazolam, pimozide, propafenone, quinidine, simvastatin, terfenadine, triazolam.

• Carbamazepine, dexamethasone, phenobarbital, phenytoin, primidone, rifampin, St Johns Wort (Hypericum perforatum), troglitazone.

• Systemic interleukins or interferons.

• Subject has a history of allergy to any of the investigational products or any excipients therein.

• Subject has evidence of genotypic (as defined by the current ANRS AC-11 algorithm) resistance at screening or prior documented evidence of genotypic and/or phenotypic (above threshold for reduced susceptibility) resistance to amprenavir/ritonavir, abacavir or lamivudine.

• Subjects recruited at sites in France will be excluded if:

• The subject is not affiliated with or a beneficiary of a social security.

• The subject has previously participated in an experimental drug and/or vaccine trial(s) within 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine - whichever is longer, prior to screening for the study.

• The subject will participate simultaneously in another clinical study. Notwithstanding these minimum inclusion and exclusion criteria, investigators are urged to follow country specific guidelines where they exist when making decisions about subjects who are eligible for study participation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Antwerpen		Belgium	2000
2	GSK Investigational Site	Brussel		Belgium	1090
3	GSK Investigational Site	Gent		Belgium	9000
4	GSK Investigational Site	Besançon		France	25030
5	GSK Investigational Site	Bordeaux		France	33000
6	GSK Investigational Site	Clamart		France	92140
7	GSK Investigational Site	La Roche Sur Yon cedex 9		France	85025
8	GSK Investigational Site	Levallois-Perret		France	92300
9	GSK Investigational Site	Lyon Cedex 03		France	69437
10	GSK Investigational Site	Nantes		France	44093
11	GSK Investigational Site	Nice		France	06202
12	GSK Investigational Site	Orléans		France	45100
13	GSK Investigational Site	Paris Cedex 10		France	75475
14	GSK Investigational Site	Paris Cedex 13		France	75651
15	GSK Investigational Site	Paris		France	75010
16	GSK Investigational Site	Paris		France	75018
17	GSK Investigational Site	Saint Denis Cedex 01		France	93205
18	GSK Investigational Site	Strasbourg		France	67000
19	GSK Investigational Site	Suresnes Cedex		France	92151
20	GSK Investigational Site	Tourcoing		France	59208
21	GSK Investigational Site	Freiburg	Baden-Wuerttemberg	Germany	79098
22	GSK Investigational Site	Freiburg	Baden-Wuerttemberg	Germany	79106
23	GSK Investigational Site	Stuttgart	Baden-Wuerttemberg	Germany	70197
24	GSK Investigational Site	Fuerth	Bayern	Germany	90762
25	GSK Investigational Site	Muenchen	Bayern	Germany	80801
26	GSK Investigational Site	Frankfurt	Hessen	Germany	60311
27	GSK Investigational Site	Frankfurt	Hessen	Germany	60590
28	GSK Investigational Site	Frankfurt	Hessen	Germany	60596
29	GSK Investigational Site	Hannover	Niedersachsen	Germany	30159
30	GSK Investigational Site	Hannover	Niedersachsen	Germany	30625
31	GSK Investigational Site	Osnabrueck	Niedersachsen	Germany	49090
32	GSK Investigational Site	Dortmund	Nordrhein-Westfalen	Germany	44137
33	GSK Investigational Site	Koeln	Nordrhein-Westfalen	Germany	50937
34	GSK Investigational Site	Hamburg		Germany	20146
35	GSK Investigational Site	Hamburg		Germany	20246
36	GSK Investigational Site	Catanzaro	Calabria	Italy	88100
37	GSK Investigational Site	Roma	Lazio	Italy	00161
38	GSK Investigational Site	Roma	Lazio	Italy	00185
39	GSK Investigational Site	Brescia	Lombardia	Italy	25125
40	GSK Investigational Site	Busto Arsizio (VA)	Lombardia	Italy	21052
41	GSK Investigational Site	Milano	Lombardia	Italy	20127
42	GSK Investigational Site	Milano	Lombardia	Italy	20142
43	GSK Investigational Site	Grosseto	Toscana	Italy	58100
44	GSK Investigational Site	Bucharest		Romania	021105
45	GSK Investigational Site	Bucharest		Romania	030303
46	GSK Investigational Site	Constanta		Romania	900709
47	GSK Investigational Site	Iasi		Romania	700116
48	GSK Investigational Site	St. Petersburg		Russian Federation	196645
49	GSK Investigational Site	Volgograd		Russian Federation	400040
50	GSK Investigational Site	Barcelona		Spain	08025
51	GSK Investigational Site	Barcelona		Spain	08036
52	GSK Investigational Site	Barcelona		Spain	08907
53	GSK Investigational Site	Barcelona		Spain	8400
54	GSK Investigational Site	Elche (Alicante)		Spain	03202
55	GSK Investigational Site	La Coruña		Spain	15006
56	GSK Investigational Site	Madrid		Spain	28029
57	GSK Investigational Site	Madrid		Spain	28040
58	GSK Investigational Site	Madrid		Spain	28041
59	GSK Investigational Site	Madrid		Spain	28046
60	GSK Investigational Site	Malaga		Spain	29010
61	GSK Investigational Site	Marid		Spain	28040
62	GSK Investigational Site	Mataro		Spain	08034
63	GSK Investigational Site	Santiago de Compostela		Spain	15706
64	GSK Investigational Site	Sevilla		Spain	41013
65	GSK Investigational Site	Valencia		Spain	46015
66	GSK Investigational Site	St Gallen		Switzerland	9007
67	GSK Investigational Site	London		United Kingdom	NW3 2QG
68	GSK Investigational Site	London		United Kingdom	SE1 7EH
69	GSK Investigational Site	London		United Kingdom	SW10 9TH

Sponsors and Collaborators

• ViiV Healthcare
• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, ViiV Healthcare

Study Documents (Full-Text)

None provided.

More Information

Publications

• Carosi G, Lazzarin A, Stellbrink H, et al. Efficacy and Safety of Fosamprenavir + Ritonavir (FPV/RTV) 700mg/100mg Twice Daily (BID) Versus FPV/RTV 1400mg/100mg Once Daily (QD) with ABC/3TC QD over 24 Weeks. Abstract H-1244, 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 2008.
• Ross LL, Robinson MD, Carosi G, et al. Impact of HIV subtype on response and resistance in antiretroviral-naïve adults comparing treatment with once daily versus twice daily Ritonavir boosted Fosamprenavir in combination with Abacavir/Lamivudine. [Drugs Ther Stud]. 2012;2(e1):

• Responsible Party: ViiV Healthcare
• ClinicalTrials.gov Identifier: NCT00450580
• Other Study ID Numbers: APV109141
• First Posted: Mar 22, 2007
• Last Update Posted: Jun 7, 2012
• Last Verified: Apr 1, 2012

• Keywords provided by ViiV Healthcare: protease inhibitor,; HIV-1,; Fosamprenavir,; non-HDL cholesterol; ritonavir,; naive,
• Additional relevant MeSH terms: Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome; HIV Infections; Ritonavir; Fosamprenavir

Study Results

Participant Flow

Arm/Group Title	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q	FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Arm/Group Description	Fosamprenavir (FPV)/ritonavir (RTV) 1400 mg/100 mg once daily administered with abacavir/lamivudine fixed dose combination (ABC/3TC FDC) 600/300 mg once daily	FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Period Title: Overall Study
STARTED	106	106
COMPLETED	90	90
NOT COMPLETED	16	16

Baseline Characteristics

Arm/Group Title	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q	FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD	Total
Arm/Group Description	Fosamprenavir (FPV)/ritonavir (RTV) 1400 mg/100 mg once daily administered with abacavir/lamivudine fixed dose combination (ABC/3TC FDC) 600/300 mg once daily	FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily	Total of all reporting groups
Overall Participants	106	106	212
Age, Customized (years) [Mean (Full Range) ]
Mean (Full Range) [years]	37	38	38
Sex: Female, Male (Count of Participants)
Female	27 25.5%	29 27.4%	56 26.4%
Male	79 74.5%	77 72.6%	156 73.6%
Race/Ethnicity, Customized (participants) [Number]
African American/African heritage	23 21.7%	22 20.8%	45 21.2%
American Indian/Alaskan native	3 2.8%	3 2.8%	6 2.8%
Asian - South East Asian	2 1.9%	2 1.9%	4 1.9%
White - Arabic/North African	1 0.9%	1 0.9%	2 0.9%
White - White/Caucasian/European	75 70.8%	78 73.6%	153 72.2%
Mixed race	2 1.9%	0 0%	2 0.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With HIV-1 RNA <400 and >=400 Copies/mL Over 48 Weeks
Description	A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at week 48. The percentage of participants with HIV-1 RNA <400 copies/mL at Week 48 was determined by the Time to Loss Of Virologic Response (TLOVR) algorithm.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Intent-to-Treat-Exposed (ITT-E) Population: All randomised participants who received at least one dose of study medication

Arm/Group Title	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q	FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Arm/Group Description	Fosamprenavir (FPV)/ritonavir (RTV) 1400 mg/100 mg once daily administered with abacavir/lamivudine fixed dose combination (ABC/3TC FDC) 600/300 mg once daily	FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Measure Participants	106	106
HIV-1 RNA <400 copies/mL	81 76.4%	82 77.4%
HIV-1 RNA >=400 copies/mL	19 17.9%	18 17%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q, FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority can be concluded if the lower bound of a two-sided 95% confidence interval for the difference in response rates between the two treatment arms is greater than -12%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.9
	Confidence Interval	() 95%; -11.4 to 9.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With HIV-1 RNA <50 and >=50 Copies/mL by Visit Over 48 Weeks
Description	A blood sample was drawn to determine the amount of HIV-1 RNA virus in copies/mL at week 48. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 48 was determined by the TLOVR algorithm
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT-E Population

Arm/Group Title	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q	FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Arm/Group Description	Fosamprenavir (FPV)/ritonavir (RTV) 1400 mg/100 mg once daily administered with abacavir/lamivudine fixed dose combination (ABC/3TC FDC) 600/300 mg once daily	FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Measure Participants	106	106
HIV-1 RNA <50 copies/mL	76 71.7%	77 72.6%
HIV-1 RNA >=50 copies/mL	24 22.6%	23 21.7%

3. Secondary Outcome

Title	Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline Viral Load, TLOVR Analysis
Description	The number of participants with HIV-1 RNA <400 copies/mL at Week 48 was determined (by analysis of blood draw) and categorised by baseline viral load (BVL).
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT-E Population

Arm/Group Title	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q	FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Arm/Group Description	Fosamprenavir (FPV)/ritonavir (RTV) 1400 mg/100 mg once daily administered with abacavir/lamivudine fixed dose combination (ABC/3TC FDC) 600/300 mg once daily	FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Measure Participants	106	106
<50000 cp/mL (n=35, 40)	26 24.5%	37 34.9%
>=50000 to <100000 cp/mL (n=21, 19)	18 17%	15 14.2%
>=100000 to <200000 cp/mL (n=25, 17)	21 19.8%	11 10.4%
>=200000 cp/mL (n=25, 30)	21 19.8%	24 22.6%

4. Secondary Outcome

Title	Number of Participants With HIV-1 RNA <400 Copies/mL (Primary Endpoint) at Week 48 Categorised by Baseline CD4+ Count, TLOVR Analysis
Description	The number of participants with HIV-1 RNA <400 copies/mL at week 48 was determined (by analysis of blood draw) and categorised by baseline CD4+ count.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

ITT-E Population

Arm/Group Title	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q	FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Arm/Group Description	Fosamprenavir (FPV)/ritonavir (RTV) 1400 mg/100 mg once daily administered with abacavir/lamivudine fixed dose combination (ABC/3TC FDC) 600/300 mg once daily	FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Measure Participants	106	106
<150 cells/mm3 (n=24, 23)	18 17%	16 15.1%
>=150 to <250 cells/mm3 (n=29, 31)	24 22.6%	26 24.5%
>=250 to <350 cell/mm3 (n=29, 31)	23 21.7%	26 24.5%
>=350 cell/mm3 (n=24, 21)	21 19.8%	19 17.9%

5. Secondary Outcome

Title	Change From Baseline in Non-HDL Cholesterol at Week 48
Description	Blood samples were drawn to determine the non-HDL cholesterol levels at Week 48. The mean absolute change in non-HDL cholesterol was defined as the Week 48 levels minus levels at baseline.
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least one dose of study medication

Arm/Group Title	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q	FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Arm/Group Description	Fosamprenavir (FPV)/ritonavir (RTV) 1400 mg/100 mg once daily administered with abacavir/lamivudine fixed dose combination (ABC/3TC FDC) 600/300 mg once daily	FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Measure Participants	77	80
Mean (Standard Deviation) [mmol/L (millimoles/Liter)]	1.10 (0.81)	1.26 (0.90)

6. Secondary Outcome

Title	Number of Protocol-defined Virological Failures With Genotypic and Phenotypic Resistance Changes
Description	A blood sample was drawn at the time of confirmation of virological failure, and mutations present in the virus were identified and compared to those found in the blood sample at baseline. New mutations were tabulated by drug class. RT, reverse transcriptase. Virological failure could occur anytime from Week 4 to Week 48.
Time Frame	Time to virologic failure; Week 4 up to Week 48

Outcome Measure Data

Analysis Population Description

Participants in the ITT-E Population who met the definition of virological failure

Arm/Group Title	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q	FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Arm/Group Description	Fosamprenavir (FPV)/ritonavir (RTV) 1400 mg/100 mg once daily administered with abacavir/lamivudine fixed dose combination (ABC/3TC FDC) 600/300 mg once daily	FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Measure Participants	2	1
Treatment-Emergent Major HIV RT Mutations (M184V)	1 0.9%	0 0%
Treatment-Emergent Major HIV Protease Mutations	0 0%	0 0%

7. Secondary Outcome

Title	Steady-state Levels of Amprenavir (APV) and Ritonavir (RTV) Ctau at Weeks 4, 12, and 24
Description	Blood samples were drawn at Weeks 4, 12, and 24 to determine plasma concentrations (Ctau) of APV and RTV
Time Frame	Weeks 4, 12, and 24

Outcome Measure Data

Analysis Population Description

PK parameter (Ctau) Population - Participants in the ITT-E population who underwent PK sampling and had evaluable APV Ctau or RTV Ctau data

Arm/Group Title	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q	FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Arm/Group Description	Fosamprenavir (FPV)/ritonavir (RTV) 1400 mg/100 mg once daily administered with abacavir/lamivudine fixed dose combination (ABC/3TC FDC) 600/300 mg once daily	FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
Measure Participants	79	97
Week 4 APV Ctau	1.11	1.99
Week 12 APV Ctau	0.913	1.87
Week 24 APV Ctau	1.08	2.00
Week 4 RTV Ctau	0.0369	0.166
Week 12 RTV Ctau	0.0285	0.175
Week 24 RTV Ctau	0.0363	0.170

8. Secondary Outcome

Title	Study Endpoints for a Subset of Subjects Receiving Study Drug Beyond 48 Weeks
Description	Adaptive two-stage design study up to 48 weeks. N=200, expanding to 728 if continuation criteria were achieved based on a 24-week interim analysis. The initial 200 participants would continue until the last subject of the expanded cohort reached 48 weeks and would constitute the subset. As continuation criteria were not achieved, the study did not proceed to the second stage, and full analysis was performed on the initial 200 participants only.
Time Frame	Up to 60 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q		FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
Arm/Group Description	Fosamprenavir (FPV)/ritonavir (RTV) 1400 mg/100 mg once daily administered with abacavir/lamivudine fixed dose combination (ABC/3TC FDC) 600/300 mg once daily		FPV/RTV 700 mg/100 mg twice daily administered with ABC/3TC FDC 600/300 mg once daily
All Cause Mortality
	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q		FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q		FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/ (NaN)		18/ (NaN)
Blood and lymphatic system disorders
Lymphadenopathy	0/106 (0%)		1/106 (0.9%)
Cardiac disorders
Angina pectoris	1/106 (0.9%)		0/106 (0%)
Myocardial infarction	0/106 (0%)		1/106 (0.9%)
Gastrointestinal disorders
Pancreatitis	1/106 (0.9%)		0/106 (0%)
Hepatobiliary disorders
Hepatitis acute	0/106 (0%)		1/106 (0.9%)
Immune system disorders
Drug Hypersensitivity	15/106 (14.2%)		8/106 (7.5%)
Immune reconstitution syndrome	0/106 (0%)		1/106 (0.9%)
Infections and infestations
Pneumonia	2/106 (1.9%)		1/106 (0.9%)
Atypical mycobacterial infection	0/106 (0%)		1/106 (0.9%)
Cat scratch disease	0/106 (0%)		1/106 (0.9%)
Hepatitis C	0/106 (0%)		1/106 (0.9%)
Mycobacterium avium complex infection	0/106 (0%)		1/106 (0.9%)
Respiratory tract infection	0/106 (0%)		1/106 (0.9%)
Sepsis	1/106 (0.9%)		0/106 (0%)
Staphylococcal sepsis	0/106 (0%)		1/106 (0.9%)
Superinfection	0/106 (0%)		1/106 (0.9%)
Investigations
Alanine aminotransferase increased	0/106 (0%)		1/106 (0.9%)
Aspartate aminotransferase increased	1/106 (0.9%)		0/106 (0%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	1/106 (0.9%)		0/106 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Burkitt's lymphoma	1/106 (0.9%)		0/106 (0%)
Nervous system disorders
Facial paresis	1/106 (0.9%)		0/106 (0%)
Psychiatric disorders
Depression	0/106 (0%)		1/106 (0.9%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/106 (0.9%)		0/106 (0%)
Lung disorder	0/106 (0%)		1/106 (0.9%)
Other (Not Including Serious) Adverse Events
	FPV/RTV 1400/100 mg Once Daily (QD) + ABC/3TC FDC 600/300 mg Q		FPV/RTV 700/100 mg BID + ABC/3TC FDC 600/300 mg QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	79/ (NaN)		72/ (NaN)
Gastrointestinal disorders
Diarrhoea	45/106 (42.5%)		49/106 (46.2%)
Nausea	18/106 (17%)		9/106 (8.5%)
Vomiting	8/106 (7.5%)		5/106 (4.7%)
Dyspepsia	5/106 (4.7%)		2/106 (1.9%)
General disorders
Fatigue	7/106 (6.6%)		6/106 (5.7%)
Immune system disorders
Drug hypersensitivity	15/106 (14.2%)		8/106 (7.5%)
Infections and infestations
Nasopharyngitis	18/106 (17%)		7/106 (6.6%)
Metabolism and nutrition disorders
Hypercholesterolaemia	6/106 (5.7%)		8/106 (7.5%)
Hypertriglyceridaemia	2/106 (1.9%)		9/106 (8.5%)
Skin and subcutaneous tissue disorders
Rash	11/106 (10.4%)		13/106 (12.3%)

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.