Trial of Maraviroc (UK-427,857) in Combination With Optimized Background Therapy Versus Optimized Background Therapy Alone for the Treatment of Antiretroviral-Experienced NonCCR5-Tropic HIV-1 Infected Subjects

This study has been completed.

Sponsor:

Collaborator:

Pfizer

Information provided by:

ViiV Healthcare

ClinicalTrials.gov Identifier:

NCT00098748

First received: December 7, 2004

Last updated: November 19, 2010

Last verified: November 2010

History of Changes

Results First Received: March 25, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Condition:	HIV Infections
Interventions:	Drug: Optimized Background Therapy (OBT) Drug: maraviroc (UK-427,857)

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID	Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo	Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Participant Flow for 3 periods

Period 1: Assigned to Study Treatment

	Maraviroc QD	Maraviroc BID	Placebo
STARTED	63	63	64
COMPLETED	63	61	62
NOT COMPLETED	0	2	2
Randomized, but not treated	0	2	2

Period 2: Received Study Treatment

	Maraviroc QD	Maraviroc BID	Placebo
STARTED	63	61 ^[1]	62 ^[2]
Dual-tropic Subjects by Phenotype Assay	57 ^[3]	52	58
COMPLETED	15	25	18
NOT COMPLETED	48	36	44
Death	2	1	2
Adverse Event	1	2	5
Lack of Efficacy	40	27	27
Unspecified	2	2	6
Subject defaulted	3	4	4

[1]	Due to 1 placebo subject switched to maraviroc BID, BID = 62 subjects in Adverse event tables.
[2]	Due to 1 placebo subject switched to maraviroc BID, Placebo = 61 subjects in Adverse event tables.
[3]	Dual-tropic: Virus capable of using both CCR5 and CXCR4 coreceptors for cell entry.

Period 3: Continued on Open-Label Treatment

	Maraviroc QD	Maraviroc BID	Placebo
STARTED	15	25	0 ^[1]
COMPLETED	7	10	0
NOT COMPLETED	8	15	0
Adverse Event	0	1	0
Lack of Efficacy	1	2	0
Other reason includes protocol violation	6	7	0
Lost to Follow-up	1	1	0
Withdrawal by Subject	0	4	0

[1]	Placebo group not offered open-label maraviroc due to study not reaching primary endpoint at Week 24

Baseline Characteristics

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Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID	Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo	Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Total	Total of all reporting groups

Baseline Measures

	Maraviroc QD	Maraviroc BID	Placebo	Total
Number of Participants [units: participants]	63	61	62	186
Age, Customized [units: participants]
<18 years	2	2	0	4
Between 18 and 24 years	1	1	1	3
Between 25 and 34 years	2	3	2	7
Between 35 and 44 years	30	31	31	92
Between 45 and 54 years	25	21	20	66
Between 55 and 64 years	3	3	7	13
≥65 years	0	0	1	1
Age [units: years] Mean ( Full Range )	42.7 ( 16 to 59 )	42.5 ( 16 to 62 )	44.6 ( 23 to 65 )	43.3 ( 16 to 65 )
Gender [units: participants]
Female	10	6	9	25
Male	53	55	53	161

Outcome Measures

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1. Primary:

Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA]) [ Time Frame: Baseline to Week 24 and Week 48 ]

Measure Type	Primary
Measure Title	Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA])
Measure Description	Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log 10 copies per milliliter [log10 copies/mL]). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time Frame	Baseline to Week 24 and Week 48
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set (FAS)-as treated: all randomized subjects classified as dual-tropic by phenotype assay; received at least 1 dose of study treatment. Missing values: discontinuations (DC) imputed as baseline value (change from baseline=0); missing data imputed as Last Observation Carried Forward (LOCF).

Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID	Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo	Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Measured Values

	Maraviroc QD	Maraviroc BID	Placebo
Number of Participants Analyzed [units: participants]	57	52	58
Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA]) [units: log10 copies/mL] Mean ± Standard Error
Week 24	-0.890 ± 0.1706	-1.194 ± 0.2060	-0.953 ± 0.1795
Week 48	-0.604 ± 0.1596	-1.105 ± 0.2071	0.839 ± 0.1851

Statistical Analysis 1 for Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA])

Groups ^[1]	Maraviroc QD vs. Placebo
Non-Inferiority/Equivalence Test ^[2]	Yes
Least squares mean ^[3]	0.055
Standard Error of the mean	± 0.2575
97.5% Confidence Interval	( -0.528 to 0.638 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Maraviroc (MVC) QD versus placebo (PBO) treatment (TX) difference at Week 24. If upper bound of 97.5% confidence interval is <0, it is concluded that dose is superior to PBO. If upper bound is <0.25, it is concluded that MVC is non-inferior to PBO. Assumption: 79% of subjects are dual-tropic; total N=192 needed to be randomized to get N=150 dual-tropic. Standard deviation=0.8 with 2-sided p-value=0.025: 80% power for TX difference of 0.5 for change from baseline in log10-transformed viral load.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	For hypothesis of superiority, if upper bound of 97.5% confidence interval (CI) of TX difference was <0 log10 copies/mL, it was concluded that MVC regimen was superior to PBO meaning that MVC added to Optimized Background Therapy (OBT) provides an additional reduction in plasma HIV-1 RNA compared to OBT alone. If superiority could not be concluded, then a hypothesis of noninferiority was tested. If upper bound of CI is <0.25 log10 copies/mL, noninferiority of MVC regimen to placebo was claimed.
[3]	Other relevant estimation information:
	Negative values for change from baseline=benefit of TX; negative values for MVC versus (vs) PBO=advantage of MVC.

Statistical Analysis 2 for Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA])

Groups ^[1]	Maraviroc BID vs. Placebo
Least squares mean ^[2]	-0.232
Standard Error of the mean	± 0.2637
97.5% Confidence Interval	( -0.829 to 0.364 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO treatment difference at Week 24.
[2]	Other relevant estimation information:
	Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.

Statistical Analysis 3 for Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA])

Groups ^[1]	Maraviroc QD vs. Placebo
Least squares mean ^[2]	0.229
Standard Error of the mean	± 0.2567
97.5% Confidence Interval	( -0.351 to 0.810 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO treatment difference at Week 48.
[2]	Other relevant estimation information:
	Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.

Statistical Analysis 4 for Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA])

Groups ^[1]	Maraviroc BID vs. Placebo
Least squares mean ^[2]	-0.261
Standard Error of the mean	± 0.2628
97.5% Confidence Interval	( -0.856 to 0.333 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO treatment difference at Week 48.
[2]	Other relevant estimation information:
	Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.

2. Secondary:

Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL [ Time Frame: Week 24, Week 48 ]

Measure Type	Secondary
Measure Title	Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL
Measure Description	No text entered.
Time Frame	Week 24, Week 48
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS - as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion).

Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID	Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo	Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Measured Values

	Maraviroc QD	Maraviroc BID	Placebo
Number of Participants Analyzed [units: participants]	57	52	58
Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL [units: participants]
Week 24	14	16	14
Week 48	13	16	13

Statistical Analysis 1 for Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL

Groups ^[1]	Maraviroc QD vs. Placebo
difference in proportions ^[2]	0.03
95% Confidence Interval	( -0.12 to 0.18 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO treatment difference in proportions at Week 24.
[2]	Other relevant estimation information:
	The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.

Statistical Analysis 2 for Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL

Groups ^[1]	Maraviroc BID vs. Placebo
difference in proportions ^[2]	0.07
95% Confidence Interval	( -0.08 to 0.23 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO treatment difference in proportions at Week 24.
[2]	Other relevant estimation information:
	The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.

Statistical Analysis 3 for Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL

Groups ^[1]	Maraviroc QD vs. Placebo
difference in proportions ^[2]	0.02
95% Confidence Interval	( -0.12 to 0.17 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO treatment difference in proportions at Week 48.
[2]	Other relevant estimation information:
	The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.

Statistical Analysis 4 for Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL

Groups ^[1]	Maraviroc BID vs. Placebo
difference in proportions ^[2]	0.09
95% Confidence Interval	( -0.07 to 0.25 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO treatment difference in proportions at Week 48.
[2]	Other relevant estimation information:
	The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.

3. Secondary:

Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels [ Time Frame: Baseline, Week 24, Week 48 ]

Measure Type	Secondary
Measure Title	Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels
Measure Description	Number of subjects with HIV-1 RNA levels < 400 copies/mL or at least 0.5 log 10-transformed decrease from baseline in HIV-1 RNA levels. Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time Frame	Baseline, Week 24, Week 48
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS-as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion).

Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID	Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo	Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Measured Values

	Maraviroc QD	Maraviroc BID	Placebo
Number of Participants Analyzed [units: participants]	57	52	58
Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels [units: participants]
Week 24	24	25	23
Week 48	14	22	18

Statistical Analysis 1 for Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels

Groups ^[1]	Maraviroc QD vs. Placebo
difference in proportions ^[2]	0.03
95% Confidence Interval	( -0.15 to 0.20 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO treatment difference in proportions at Week 24.
[2]	Other relevant estimation information:
	The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.

Statistical Analysis 2 for Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels

Groups ^[1]	Maraviroc BID vs. Placebo
difference in proportions ^[2]	0.08
95% Confidence Interval	( -0.10 to 0.26 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO treatment difference in proportions at Week 24.
[2]	Other relevant estimation information:
	The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.

Statistical Analysis 3 for Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels

Groups ^[1]	Maraviroc QD vs. Placebo
difference in proportions ^[2]	-0.06
95% Confidence Interval	( -0.22 to 0.10 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO treatment difference in proportions at Week 48.
[2]	Other relevant estimation information:
	The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.

Statistical Analysis 4 for Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels

Groups ^[1]	Maraviroc BID vs. Placebo
difference in proportions ^[2]	0.11
95% Confidence Interval	( -0.07 to 0.28 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO treatment difference in proportions at Week 48.
[2]	Other relevant estimation information:
	The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.

4. Secondary:

Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels [ Time Frame: Baseline, Week 24, Week 48 ]

Measure Type	Secondary
Measure Title	Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels
Measure Description	Number of subjects with HIV-1 RNA levels < 400 copies/mL or at least 1.0 log 10-transformed decrease from baseline in HIV-1 RNA levels. Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time Frame	Baseline, Week 24, Week 48
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS-as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion).

Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID	Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo	Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Measured Values

	Maraviroc QD	Maraviroc BID	Placebo
Number of Participants Analyzed [units: participants]	57	52	58
Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels [units: participants]
Week 24	18	23	21
Week 48	13	20	15

Statistical Analysis 1 for Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels

Groups ^[1]	Maraviroc QD vs. Placebo
difference in proportions ^[2]	-0.05
95% Confidence Interval	( -0.21 to 0.12 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO treatment difference in proportions at Week 24.
[2]	Other relevant estimation information:
	The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.

Statistical Analysis 2 for Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels

Groups ^[1]	Maraviroc BID vs. Placebo
difference in proportions ^[2]	0.08
95% Confidence Interval	( -0.10 to 0.26 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO treatment difference in proportions at Week 24.
[2]	Other relevant estimation information:
	The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.

Statistical Analysis 3 for Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels

Groups ^[1]	Maraviroc QD vs. Placebo
difference in proportions ^[2]	-0.02
95% Confidence Interval	( -0.18 to 0.13 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO treatment difference in proportions at Week 48.
[2]	Other relevant estimation information:
	The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.

Statistical Analysis 4 for Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels

Groups ^[1]	Maraviroc BID vs. Placebo
difference in proportions ^[2]	0.12
95% Confidence Interval	( -0.04 to 0.29 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO treatment difference in proportions at Week 48.
[2]	Other relevant estimation information:
	The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.

5. Secondary:

Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL [ Time Frame: Baseline, Week 24, Week 48 ]

Measure Type	Secondary
Measure Title	Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL
Measure Description	No text entered.
Time Frame	Baseline, Week 24, Week 48
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS - as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion).

Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID	Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo	Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Measured Values

	Maraviroc QD	Maraviroc BID	Placebo
Number of Participants Analyzed [units: participants]	57	52	58
Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL [units: participants]
Week 24	12	14	9
Week 48	10	14	13

Statistical Analysis 1 for Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL

Groups ^[1]	Maraviroc QD vs. Placebo
difference in proportions ^[2]	0.07
95% Confidence Interval	( -0.07 to 0.20 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO treatment difference in proportions at Week 24.
[2]	Other relevant estimation information:
	The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.

Statistical Analysis 2 for Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL

Groups ^[1]	Maraviroc BID vs. Placebo
difference in proportions ^[2]	0.11
95% Confidence Interval	( -0.03 to 0.26 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO difference in proportions at Week 24.
[2]	Other relevant estimation information:
	The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.

Statistical Analysis 3 for Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL

Groups ^[1]	Maraviroc QD vs. Placebo
difference in proportions ^[2]	-0.04
95% Confidence Interval	( -0.18 to 0.10 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO treatment difference in proportions at Week 48.
[2]	Other relevant estimation information:
	The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.

Statistical Analysis 4 for Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL

Groups ^[1]	Maraviroc BID vs. Placebo
difference in proportions ^[2]	0.06
95% Confidence Interval	( -0.10 to 0.21 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO treatment difference in proportions at Week 48.
[2]	Other relevant estimation information:
	The TX difference is weighted (by inverse of the variance) difference in proportions adjusted for randomization strata. Positive values for TX difference favor MVC. CI estimated using the normal approximation to the binomial distribution.

6. Secondary:

Change From Baseline in CD4 Cell Count [ Time Frame: Baseline to Week 24 and Week 48 ]

Measure Type	Secondary
Measure Title	Change From Baseline in CD4 Cell Count
Measure Description	Change from baseline in CD4 cell count (measured as cells per microliter [cells/µL]). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time Frame	Baseline to Week 24 and Week 48
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS - as treated dual-tropic subjects. Placebo N: 4 subjects did not have on-treatment information. Missing data imputed using LOCF.

Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID	Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo	Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Measured Values

	Maraviroc QD	Maraviroc BID	Placebo
Number of Participants Analyzed [units: participants]	57	52	54
Change From Baseline in CD4 Cell Count [units: cells/µL] Mean ± Standard Error
Week 24	59.237 ± 8.9661	62.651 ± 10.0234	36.367 ± 8.4477
Week 48	65.86 ± 10.822	78.87 ± 11.566	51.29 ± 12.523

Statistical Analysis 1 for Change From Baseline in CD4 Cell Count

Groups ^[1]	Maraviroc QD vs. Placebo
Least squares mean ^[2]	23.927
Standard Error of the mean	± 12.8025
95% Confidence Interval	( -1.359 to 49.213 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO treatment difference at Week 24.
[2]	Other relevant estimation information:
	Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.

Statistical Analysis 2 for Change From Baseline in CD4 Cell Count

Groups ^[1]	Maraviroc BID vs. Placebo
Least squares mean ^[2]	26.679
Standard Error of the mean	± 13.0678
95% Confidence Interval	( 0.869 to 52.490 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO treatment difference at Week 24.
[2]	Other relevant estimation information:
	Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.

Statistical Analysis 3 for Change From Baseline in CD4 Cell Count

Groups ^[1]	Maraviroc QD vs. Placebo
Least squares mean ^[2]	14.61
Standard Error of the mean	± 16.412
95% Confidence Interval	( -17.80 to 47.03 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO treatment difference at Week 48.
[2]	Other relevant estimation information:
	Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.

Statistical Analysis 4 for Change From Baseline in CD4 Cell Count

Groups ^[1]	Maraviroc BID vs. Placebo
Least squares mean ^[2]	27.71
Standard Error of the mean	± 16.754
95% Confidence Interval	( -5.38 to 60.80 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO treatment difference at Week 48.
[2]	Other relevant estimation information:
	Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.

7. Secondary:

Change From Baseline in CD8 Cell Count [ Time Frame: Baseline to Week 24 and Week 48 ]

Measure Type	Secondary
Measure Title	Change From Baseline in CD8 Cell Count
Measure Description	Change from baseline in CD8 cell count (measured as cells/µL). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time Frame	Baseline to Week 24 and Week 48
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS - as treated dual-tropic subjects. Placebo N: 4 subjects did not have on-treatment information. Missing data imputed using LOCF.

Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID	Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo	Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Measured Values

	Maraviroc QD	Maraviroc BID	Placebo
Number of Participants Analyzed [units: participants]	57	52	54
Change From Baseline in CD8 Cell Count [units: cells/µL] Mean ± Standard Error
Week 24	391.061 ± 57.0135	322.683 ± 68.3315	154.293 ± 46.8100
Week 48	351.23 ± 54.653	342.87 ± 72.222	192.30 ± 62.578

Statistical Analysis 1 for Change From Baseline in CD8 Cell Count

Groups ^[1]	Maraviroc QD vs. Placebo
Least squares mean ^[2]	234.499
Standard Error of the mean	± 80.7990
95% Confidence Interval	( 74.913 to 394.084 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO treatment difference at Week 24.
[2]	Other relevant estimation information:
	Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.

Statistical Analysis 2 for Change From Baseline in CD8 Cell Count

Groups ^[1]	Maraviroc BID vs. Placebo
Least squares mean ^[2]	188.817
Standard Error of the mean	± 83.4484
95% Confidence Interval	( 23.999 to 353.635 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO treatment difference at Week 24.
[2]	Other relevant estimation information:
	Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.

Statistical Analysis 3 for Change From Baseline in CD8 Cell Count

Groups ^[1]	Maraviroc QD vs. Placebo
Least squares mean ^[2]	155.94
Standard Error of the mean	± 87.304
95% Confidence Interval	( -16.49 to 328.37 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO treatment difference at Week 48.
[2]	Other relevant estimation information:
	Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.

Statistical Analysis 4 for Change From Baseline in CD8 Cell Count

Groups ^[1]	Maraviroc BID vs. Placebo
Least squares mean ^[2]	182.91
Standard Error of the mean	± 90.174
95% Confidence Interval	( 4.81 to 361.02 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO treatment difference at Week 48.
[2]	Other relevant estimation information:
	Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.

8. Secondary:

Time (50% Quartile Point Estimate) to Virologic Failure [ Time Frame: Day 1 through Week 24 and through Week 48 ]

Measure Type	Secondary
Measure Title	Time (50% Quartile Point Estimate) to Virologic Failure
Measure Description	Time to virologic failure based on observed HIV-1 RNA levels and failure events (death; permanent discontinuation of test drug [perm DC]; lost to follow-up [LTFU]; new anti-retroviral drug added (except background drug change to drug of same class); or on open label for early non-response or rebound). Failure: at Time 0 if level not <400 copies/mL (2 consecutive visits) before event(s) or last available visit; at time of earliest event if level <400 copies/mL (on 2 consecutive visits); failure if level ≥400 copies/mL (2 consecutive visits) or 1 visit ≥400 copies/mL followed by perm DC or LTFU.
Time Frame	Day 1 through Week 24 and through Week 48
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS - as treated dual-tropic subjects; (n)=number of subjects with virologic failure at observation for maraviroc QD, maraviroc BID, and placebo, respectively; Week 48 result values (0.00)=virologic failure at Day 0.

Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID	Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo	Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Measured Values

	Maraviroc QD	Maraviroc BID	Placebo
Number of Participants Analyzed [units: participants]	57	52	58
Time (50% Quartile Point Estimate) to Virologic Failure [units: days] Median ( 95% Confidence Interval )
Week 24 (n=35, 23, 29)	88.00 ( 59.00 to NA ) ^[1]	189.00 ( 113.00 to 189.00 )	100.00 ( 60.00 to NA ) ^[1]
Week 48 (n=45, 37, 44)	0.00 ( NA to NA ) ^[2]	0.00 ( 0.00 to 142.00 )	0.00 ( 0.00 to 29.00 )

[1]	Parameter was not calculable.
[2]	Parameters were not calculable.

Statistical Analysis 1 for Time (50% Quartile Point Estimate) to Virologic Failure

Groups ^[1]	Maraviroc QD vs. Placebo
Method ^[2]	Log Rank
P Value ^[3]	0.7524

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO at Week 24. Kaplan-Meier survival estimates. TX difference evaluated by log-rank test.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 2 for Time (50% Quartile Point Estimate) to Virologic Failure

Groups ^[1]	Maraviroc BID vs. Placebo
Method ^[2]	Log Rank
P Value ^[3]	0.2540

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO at Week 24. Kaplan-Meier survival estimates. TX difference evaluated by log-rank test.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 3 for Time (50% Quartile Point Estimate) to Virologic Failure

Groups ^[1]	Maraviroc QD vs. Placebo
Method ^[2]	Log Rank
P Value ^[3]	0.8243

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO at Week 48. Kaplan-Meier survival estimates. TX difference evaluated by log-rank test.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 4 for Time (50% Quartile Point Estimate) to Virologic Failure

Groups ^[1]	Maraviroc BID vs. Placebo
Method ^[2]	Log Rank
P Value ^[3]	0.6657

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO at Week 48. Kaplan-Meier survival estimates. TX difference evaluated by log-rank test.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

9. Secondary:

Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA [ Time Frame: Baseline to Week 24 and Week 48 ]

Measure Type	Secondary
Measure Title	Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA
Measure Description	Change from baseline of TAD in log10 HIV-1 RNA viral load calculated as [AUC of HIV-1 RNA viral load (log10 copies/mL) / time period] - Baseline HIV-1 RNA viral load (log10 copies/mL). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time Frame	Baseline to Week 24 and Week 48
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS - as treated dual-tropic subjects. Discontinuations prior to time point of analysis imputed as 0.

Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID	Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo	Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Measured Values

	Maraviroc QD	Maraviroc BID	Placebo
Number of Participants Analyzed [units: participants]	57	52	58
Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA [units: log10 copies/mL] Mean ± Standard Error
Week 24	-0.850 ± 0.1510	-1.151 ± 0.1895	-0.926 ± 0.1679
Week 48	-0.561 ± 0.1475	-1.066 ± 0.1962	-0.776 ± 0.1700

Statistical Analysis 1 for Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA

Groups ^[1]	Maraviroc QD vs. Placebo
Least squares mean ^[2]	0.069
Standard Error of the mean	± 0.2356
95% Confidence Interval	( -0.396 to 0.535 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO treatment difference at Week 24.
[2]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA

Groups ^[1]	Maraviroc BID vs. Placebo
Least squares mean ^[2]	-0.218
Standard Error of the mean	± 0.2413
95% Confidence Interval	( -0.694 to 0.258 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO treatment difference at Week 24.
[2]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA

Groups ^[1]	Maraviroc QD vs. Placebo
Least squares mean ^[2]	0.209
Standard Error of the mean	± 0.2388
95% Confidence Interval	( -0.262 to 0.681 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO treatment difference at Week 48.
[2]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA

Groups ^[1]	Maraviroc BID vs. Placebo
Least squares mean ^[2]	-0.284
Standard Error of the mean	± 0.2445
95% Confidence Interval	( -0.767 to 0.199 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO treatment difference at Week 48.
[2]	Other relevant estimation information:
	No text entered.

10. Secondary:

Number of Subjects Per Genotype and Phenotype at Baseline and at Time of Failure [ Time Frame: Baseline through Week 48 ]

Measure Type	Secondary
Measure Title	Number of Subjects Per Genotype and Phenotype at Baseline and at Time of Failure
Measure Description	Number of subjects per genotype and phenotype (tests for presence of non CCR5-tropic HIV-1 and for resistance to reverse transcriptase, protease, and fusion inhibitors) at baseline and at time of failure through Week 48 visit. Sensitivity to drug categorized as 0-1, 2-4, >4; scores defined as 0=resistance, 1=sensitive or susceptible with higher number indicating greater sensitivity or susceptibility.
Time Frame	Baseline through Week 48
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS-as treated dual-tropic subjects. Genotype and phenotype at screening and at time of failure were not summarized as planned.

Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID	Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo	Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Measured Values

	Maraviroc QD	Maraviroc BID	Placebo
Number of Participants Analyzed [units: participants]	0	0	0
Number of Subjects Per Genotype and Phenotype at Baseline and at Time of Failure [units: participants]

No statistical analysis provided for Number of Subjects Per Genotype and Phenotype at Baseline and at Time of Failure

11. Secondary:

Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) [ Time Frame: Screening through Week 24 ]

Measure Type	Secondary
Measure Title	Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24)
Measure Description	Number of subjects per Tropism status (CCR5 [R5], CXCR4 [X4], Dual Mixed [DM], or Non-reportable/Non-phenotypable [NR/NP]) at Screening (Scr) and at time of treatment failure (Tx fail). Treatment failure defined as insufficient clinical response. HIV-1 RNA viral load <500 copies/ml categorized as below lower limit of quantification (BLQ). Tropism may have been assessed at either the Screening or Baseline visit. The assessment for time of treatment failure is defined as the last on-treatment assessment.
Time Frame	Screening through Week 24
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS-as treated; N=subjects with TX failure due to insufficient clinical response and who had a tropism assessment at Screening. Subjects with DC prior to timepoint not included; LOCF if no result (viral load too low for analysis).

Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID	Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo	Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Measured Values

	Maraviroc QD	Maraviroc BID	Placebo
Number of Participants Analyzed [units: participants]	35	24	24
Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) [units: participants]
Scr: X4, Tx fail: X4	1	1	1
Scr: X4, Tx fail: DM	1	1	0
Scr: DM, Tx fail: R5	1	0	4
Scr: DM, Tx fail: X4	12	12	2
Scr: DM, Tx fail: DM	19	9	16
Scr DM, Tx fail: NR/NP	0	0	1
Scr DM, Tx fail: BLQ	1	0	0
Scr NR/NP, Tx fail: NR/NP	0	1	0

No statistical analysis provided for Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24)

12. Secondary:

Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) [ Time Frame: Screening through Week 48 ]

Measure Type	Secondary
Measure Title	Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48)
Measure Description	Number of subjects per Tropism status (CCR5 [R5], CXCR4 [X4], Dual Mixed [DM], or Non-reportable/Non-phenotypable [NR/NP]) at Screening (Scr) and at time of treatment failure (Tx fail). Treatment failure defined as insufficient clinical response. HIV-1 RNA viral load <500 copies/ml categorized as below lower limit of quantification (BLQ). Tropism may have been assessed at either the Screening or Baseline visit. The assessment for time of treatment failure is defined as the last on-treatment assessment.
Time Frame	Screening through Week 48
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS-as treated; N=subjects with TX failure due to insufficient clinical response and who had a tropism assessment at Screening. Subjects with DC prior to timepoint not included; LOCF if no result (viral load too low for analysis).

Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID	Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo	Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Measured Values

	Maraviroc QD	Maraviroc BID	Placebo
Number of Participants Analyzed [units: participants]	40	27	27
Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) [units: participants]
Scr: X4, Tx fail: X4	1	1	1
Scr: X4, Tx fail: DM	1	1	0
Scr: DM, Tx fail: R5	1	1	5
Scr: DM, Tx fail: X4	12	12	2
Scr: DM, Tx fail: DM	24	10	18
Scr: DM, Tx fail: NR/NP	0	1	1
Scr: DM, Tx fail: BLQ	1	0	0
Scr: NR/NP, Tx fail: NR/NP	0	1	0

No statistical analysis provided for Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48)

13. Secondary:

Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening [ Time Frame: Screening, Week 24 ]

Measure Type	Secondary
Measure Title	Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening
Measure Description	Number of subjects for association between screening resistance and virologic response as determined by treatment failure and OSS at screening. OSS categorized as 0-1, 2-4, >4 (maximum value of 6) and calculated as the sum of the net assessment of in vitro phenotypic and genotypic susceptibility using a binary scoring system (0= reduced susceptibility, 1=susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility.
Time Frame	Screening, Week 24
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS - as treated dual-tropic subjects. Missing values imputed as LOCF.

Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID	Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo	Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Measured Values

	Maraviroc QD	Maraviroc BID	Placebo
Number of Participants Analyzed [units: participants]	57	52	58
Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening [units: participants]
Scr score: 0-1	21	12	17
Scr score: 2-4	35	35	40
Scr score: missing	1	1	1

No statistical analysis provided for Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening

14. Secondary:

Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening [ Time Frame: Screening, Week48 ]

Measure Type	Secondary
Measure Title	Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening
Measure Description	Number of subjects for association between screening resistance and virologic response as determined by treatment failure and OSS at screening. OSS categorized as 0, 1, 2, or ≥3 (maximum value of 6) and calculated as the sum of the net assessment of in vitro phenotypic and genotypic susceptibility using a binary scoring system (0= reduced susceptibility, 1=susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility.
Time Frame	Screening, Week48
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS - as treated dual-tropic subjects. Missing values imputed as LOCF.

Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID	Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo	Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Measured Values

	Maraviroc QD	Maraviroc BID	Placebo
Number of Participants Analyzed [units: participants]	57	52	58
Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening [units: particpants]
Scr score: 0	1	2	2
Scr score: 1	19	11	15
Scr score: 2	21	14	13
Scr score: ≥3	15	24	27
Scr score: missing	1	1	1

No statistical analysis provided for Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening

15. Secondary:

Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) [ Time Frame: Baseline through Week 24 ]

Measure Type	Secondary
Measure Title	Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24)
Measure Description	Number of subjects with AIDS-defining opportunistic illnesses based on investigator classification guided by a predefined list of clinical Category C Adverse Events per Center for Disease Control (CDC) HIV Classification System. Includes events occurring up to 7 days after last dose of study drug.
Time Frame	Baseline through Week 24
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS - as randomized; N=number of subjects with Category C Adverse Events for maraviroc QD, maraviroc BID, and placebo, respectively. Week 48 results reflect subsequent updates to data originally reported at Week 24.

Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID	Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo	Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Measured Values

	Maraviroc QD	Maraviroc BID	Placebo
Number of Participants Analyzed [units: participants]	63	61	62
Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) [units: participants]
Candidiasis	0	0	1
Cytomegalovirus chorioretinitis	1	0	0
Herpes simplex	1	0	0
Histoplasmosis	1	0	0
Mycobacterium avium complex infection	1	0	0
Oesophageal candidiasis	0	2	0
Pneumocystis jiroveci pneumonia	3	1	0
Pneumonia	0	0	1
Encephalitis	0	0	1

No statistical analysis provided for Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24)

16. Secondary:

Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) [ Time Frame: Baseline through Week 48 ]

Measure Type	Secondary
Measure Title	Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48)
Measure Description	Number of subjects with AIDS-defining opportunistic illnesses based on investigator classification guided by a predefined list of clinical Category C Adverse Events per CDC HIV Classification System. Includes events occurring up to 7 days after last dose of study drug.
Time Frame	Baseline through Week 48
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS - as randomized; N=number of subjects with Category C Adverse Events for maraviroc QD, maraviroc BID, and placebo, respectively. Week 48 results reflect subsequent updates to data originally reported at Week 24.

Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID	Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo	Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Measured Values

	Maraviroc QD	Maraviroc BID	Placebo
Number of Participants Analyzed [units: participants]	63	61	62
Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) [units: participants]
Candidiasis	0	1	1
Cytomegalovirus chorioretinitis	1	0	0
Histoplasmosis	1	0	0
Oesophageal candidiasis	0	2	0
Pneumococcal Sepsis	0	1	0
Pneumocystis jiroveci pneumonia	3	0	0
Pneumonia	0	1	0
Encephalitis	0	0	1

No statistical analysis provided for Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48)

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Pfizer has the right to review disclosures, requesting a delay of < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.govCallCenter@pfizer.com

No publications provided by ViiV Healthcare

Publications automatically indexed to this study:

Saag M, Goodrich J, Fätkenheuer G, Clotet B, Clumeck N, Sullivan J, Westby M, van der Ryst E, Mayer H; A4001029 Study Group. A double-blind, placebo-controlled trial of maraviroc in treatment-experienced patients infected with non-R5 HIV-1. J Infect Dis. 2009 Jun 1;199(11):1638-47.

Responsible Party:	Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier:	NCT00098748 History of Changes
Other Study ID Numbers:	A4001029
Study First Received:	December 7, 2004
Results First Received:	March 25, 2010
Last Updated:	November 19, 2010
Health Authority:	United States: Food and Drug Administration

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