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Trial of Maraviroc (UK-427,857) in Combination With Optimized Background Therapy Versus Optimized Background Therapy Alone for the Treatment of HIV-1 Infected Subjects (MOTIVATE 2)

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00098722
First received: December 7, 2004
Last updated: April 16, 2012
Last verified: April 2012
Results First Received: April 16, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: Maraviroc (UK-427,857)
Drug: optimized background therapy

  Participant Flow
  Hide Participant Flow

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, Double Blind Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID, Double Blind Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo, Double Blind Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Maraviroc BID, Open Label Participants from maraviroc QD, maraviroc BID and Placebo (double blind phase) who received maraviroc 150 or 300 mg BID in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during open label phase.
In Study-off Drug (ISOD), Open Label Participants from maraviroc QD, maraviroc BID and Placebo (double blind phase) who received no study treatment along with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during open label phase.
Maraviroc BID, Observation Phase Participants continuing from open label phase, who received maraviroc 150 or 300 mg BID in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during observational phase.
In Study-off Drug (ISOD), Observation Phase Participants continuing from open label phase, who received no study treatment along with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during observational phase.

Participant Flow for 3 periods

Period 1:   Double Blind Phase
    Maraviroc QD, Double Blind   Maraviroc BID, Double Blind   Placebo, Double Blind   Maraviroc BID, Open Label   In Study-off Drug (ISOD), Open Label   Maraviroc BID, Observation Phase   In Study-off Drug (ISOD), Observation Phase
STARTED   186   194   94   0   0   0   0 
Treated   182   191   91   0   0   0   0 
COMPLETED   0   0   0   0   0   0   0 
NOT COMPLETED   186   194   94   0   0   0   0 
Adverse Event                7                7                3                0                0                0                0 
Death                2                5                0                0                0                0                0 
Lack of Efficacy                21                23                15                0                0                0                0 
Participant defaulted                16                11                9                0                0                0                0 
Pregnancy                1                0                0                0                0                0                0 
Randomized, not treated                4                3                3                0                0                0                0 
Ongoing at cut-off date                128                137                57                0                0                0                0 
Unspecified                7                8                7                0                0                0                0 

Period 2:   Open Label Phase
    Maraviroc QD, Double Blind   Maraviroc BID, Double Blind   Placebo, Double Blind   Maraviroc BID, Open Label   In Study-off Drug (ISOD), Open Label   Maraviroc BID, Observation Phase   In Study-off Drug (ISOD), Observation Phase
STARTED   0   0   0   272   50   0   0 
COMPLETED   0   0   0   0   0   0   0 
NOT COMPLETED   0   0   0   272   50   0   0 
Adverse Event                0                0                0                5                0                0                0 
Death                0                0                0                2                0                0                0 
Lack of Efficacy                0                0                0                8                0                0                0 
Pregnancy                0                0                0                1                0                0                0 
Participant defaulted                0                0                0                18                0                0                0 
Ongoing at cut-off date                0                0                0                220                50                0                0 
Unspecified                0                0                0                18                0                0                0 

Period 3:   Observation Phase
    Maraviroc QD, Double Blind   Maraviroc BID, Double Blind   Placebo, Double Blind   Maraviroc BID, Open Label   In Study-off Drug (ISOD), Open Label   Maraviroc BID, Observation Phase   In Study-off Drug (ISOD), Observation Phase
STARTED   0   0   0   0   0   205   65 
COMPLETED   0   0   0   0   0   160   48 
NOT COMPLETED   0   0   0   0   0   45   17 
Death                0                0                0                0                0                5                3 
Lack of Efficacy                0                0                0                0                0                2                0 
Participant defaulted                0                0                0                0                0                17                4 
Unspecified                0                0                0                0                0                21                10 



  Baseline Characteristics
  Hide Baseline Characteristics

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.
No text entered.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Total Total of all reporting groups

Baseline Measures
   Maraviroc QD   Maraviroc BID   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 182   191   91   464 
Age, Customized [1] 
[Units: Participants]
       
Less than 18 years   1   0   0   1 
18 to 24 years   1   1   0   2 
25 to 34 years   8   9   6   23 
35 to 44 years   85   71   40   196 
45 to 54 years   63   70   32   165 
55 to 64 years   19   37   11   67 
Greater than or equal to 65 years   5   3   2   10 
[1] Out of a total of 474 participants, data for baseline measure (age) was available for 464 participants who were treated.
Gender [1] 
[Units: Participants]
       
Female   29   21   12   62 
Male   153   170   79   402 
[1] Out of a total of 474 participants, data for baseline measure (gender) was available for 464 participants who were treated.


  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Log 10-transformed Human Immunodeficiency Virus Ribonucleic Acid (HIV-1 RNA) Levels at Baseline   [ Time Frame: Baseline ]

Measure Type Primary
Measure Title Log 10-transformed Human Immunodeficiency Virus Ribonucleic Acid (HIV-1 RNA) Levels at Baseline
Measure Description Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.
Time Frame Baseline  

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) included all the randomized participants who had taken at least one dose of the study medication.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
   Maraviroc QD   Maraviroc BID   Placebo 
Participants Analyzed 
[Units: Participants]
 182   191   91 
Log 10-transformed Human Immunodeficiency Virus Ribonucleic Acid (HIV-1 RNA) Levels at Baseline 
[Units: Log10 copies/milliliter(log10 copies/mL)]
Mean (Standard Deviation)
 4.873  (0.6641)   4.840  (0.6205)   4.886  (0.6957) 

No statistical analysis provided for Log 10-transformed Human Immunodeficiency Virus Ribonucleic Acid (HIV-1 RNA) Levels at Baseline



2.  Primary:   Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 24   [ Time Frame: Baseline and Week 24 ]

Measure Type Primary
Measure Title Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 24
Measure Description Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.
Time Frame Baseline and Week 24  

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 included all the randomized participants who had taken at least one dose of the study medication. Missing values have been imputed as baseline value for the participants who discontinued and as Last observation carried forward (LOCF) for participants who did not discontinue.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
   Maraviroc QD   Maraviroc BID   Placebo 
Participants Analyzed 
[Units: Participants]
 182   191   91 
Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 24 
[Units: Log10 copies/mL]
Least Squares Mean (Standard Error)
 -1.950  (0.1054)   -1.971  (0.1026)   -0.929  (0.1473) 


Statistical Analysis 1 for Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 24
Groups [1] Maraviroc QD vs. Placebo
Statistical Test Type [2] Superiority or Other
LS mean difference [3] -1.021
97.5% Confidence Interval -1.426 to -0.616
Standard Error of the mean (0.1802)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The difference between the treatment least square means (LS means) adjusted for randomization strata was presented in addition to 2-sided 97.5% confidence interval (CI) as an adjustment for multiplicity using a Bonferroni correction. Negative value favors maraviroc over placebo.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 24
Groups [1] Maraviroc BID vs. Placebo
Statistical Test Type [2] Superiority or Other
LS mean difference [3] -1.042
97.5% Confidence Interval -1.444 to -0.640
Standard Error of the mean (0.1786)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The difference between the treatment LS means adjusted for randomization strata was presented in addition to 2-sided 97.5% CI as an adjustment for multiplicity using a Bonferroni correction. Negative value favors maraviroc over placebo.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



3.  Primary:   Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 48   [ Time Frame: Baseline and Week 48 ]

Measure Type Primary
Measure Title Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 48
Measure Description Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.
Time Frame Baseline and Week 48  

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 included all the randomized participants who had taken at least one dose of the study medication. Missing values have been imputed as baseline value for the participants who discontinued and as LOCF for participants who did not discontinue.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
   Maraviroc QD   Maraviroc BID   Placebo 
Participants Analyzed 
[Units: Participants]
 182   191   91 
Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 48 
[Units: Log10 copies/mL]
Least Squares Mean (Standard Error)
 -1.718  (0.1086)   -1.865  (0.1057)   -0.757  (0.1518) 


Statistical Analysis 1 for Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 48
Groups [1] Maraviroc QD vs. Placebo
Statistical Test Type [2] Superiority or Other
LS mean difference [3] -0.961
97.5% Confidence Interval -1.379 to -0.544
Standard Error of the mean (0.1856)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The difference between the treatment LS means adjusted for randomization strata was presented in addition to 2-sided 97.5% CI as an adjustment for multiplicity using a Bonferroni correction. Negative value favors maraviroc over placebo.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 48
Groups [1] Maraviroc BID vs. Placebo
Statistical Test Type [2] Superiority or Other
LS mean difference [3] -1.109
97.5% Confidence Interval -1.523 to -0.695
Standard Error of the mean (0.1840)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The difference between the treatment LS means adjusted for randomization strata was presented in addition to 2-sided 97.5% CI as an adjustment for multiplicity using a Bonferroni correction. Negative value favors maraviroc over placebo.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



4.  Secondary:   Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL   [ Time Frame: Week 24 and 48 ]

Measure Type Secondary
Measure Title Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL
Measure Description No text entered.
Time Frame Week 24 and 48  

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 included all the randomized participants who had taken at least one dose of the study medication. Missing data was imputed as "failure" which was defined as not meeting the criteria of less than 400 copies/mL of HIV-1 RNA levels.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
   Maraviroc QD   Maraviroc BID   Placebo 
Participants Analyzed 
[Units: Participants]
 182   191   91 
Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL 
[Units: Percentage of participants]
     
Week 24   55.49   61.26   23.08 
Week 48   52.75   54.97   23.08 


Statistical Analysis 1 for Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL
Groups [1] Maraviroc QD vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Regression, Logistic
P Value [4] <0.0001
Odds Ratio (OR) [5] 4.59
95% Confidence Interval 2.56 to 8.23
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (less than [<] 100,000 or greater than or equal to [>=] 100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio greater than (>) 1 favors maraviroc.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL
Groups [1] Maraviroc BID vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Regression, Logistic
P Value [4] <0.0001
Odds Ratio (OR) [5] 6.01
95% Confidence Interval 3.35 to 10.78
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL
Groups [1] Maraviroc QD vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Regression, Logistic
P Value [4] <0.0001
Odds Ratio (OR) [5] 4.03
95% Confidence Interval 2.25 to 7.20
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL
Groups [1] Maraviroc BID vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Regression, Logistic
P Value [4] <0.0001
Odds Ratio (OR) [5] 4.41
95% Confidence Interval 2.47 to 7.85
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.



5.  Secondary:   Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 0.5 log10 Decrease From Baseline   [ Time Frame: Week 24 and 48 ]

Measure Type Secondary
Measure Title Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 0.5 log10 Decrease From Baseline
Measure Description No text entered.
Time Frame Week 24 and 48  

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 included all the randomized participants who had taken at least one dose of the study medication. Missing data was imputed as "failure" which was defined as not meeting the criteria of less than 400 copies/mL or with at least 0.5 log10 decrease from baseline of HIV-1 RNA levels.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
   Maraviroc QD   Maraviroc BID   Placebo 
Participants Analyzed 
[Units: Participants]
 182   191   91 
Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 0.5 log10 Decrease From Baseline 
[Units: Percentage of participants]
     
Week 24   69.78   72.25   37.36 
Week 48   60.99   65.97   31.87 


Statistical Analysis 1 for Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 0.5 log10 Decrease From Baseline
Groups [1] Maraviroc QD vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Regression, Logistic
P Value [4] <0.0001
Odds Ratio (OR) [5] 4.69
95% Confidence Interval 2.72 to 8.10
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 0.5 log10 Decrease From Baseline
Groups [1] Maraviroc BID vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Regression, Logistic
P Value [4] <0.0001
Odds Ratio (OR) [5] 5.01
95% Confidence Interval 2.91 to 8.62
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 0.5 log10 Decrease From Baseline
Groups [1] Maraviroc QD vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Regression, Logistic
P Value [4] <0.0001
Odds Ratio (OR) [5] 3.67
95% Confidence Interval 2.13 to 6.32
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 0.5 log10 Decrease From Baseline
Groups [1] Maraviroc BID vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Regression, Logistic
P Value [4] <0.0001
Odds Ratio (OR) [5] 4.64
95% Confidence Interval 2.69 to 8.02
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.



6.  Secondary:   Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 1.0 log10 Decrease From Baseline   [ Time Frame: Week 24 and 48 ]

Measure Type Secondary
Measure Title Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 1.0 log10 Decrease From Baseline
Measure Description No text entered.
Time Frame Week 24 and 48  

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 included all the randomized participants who had taken at least one dose of the study medication. Missing data was imputed as "failure" which was defined as not meeting the criteria of less than 400 copies/mL or with at least 1.0 log10 decrease from baseline of HIV-1 RNA levels.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
   Maraviroc QD   Maraviroc BID   Placebo 
Participants Analyzed 
[Units: Participants]
 182   191   91 
Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 1.0 log10 Decrease From Baseline 
[Units: Percentage of participants]
     
Week 24   66.48   69.63   30.77 
Week 48   58.79   63.35   27.47 


Statistical Analysis 1 for Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 1.0 log10 Decrease From Baseline
Groups [1] Maraviroc QD vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Regression, Logistic
P Value [4] <0.0001
Odds Ratio (OR) [5] 4.58
95% Confidence Interval 2.64 to 7.92
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 1.0 log10 Decrease From Baseline
Groups [1] Maraviroc BID vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Regression, Logistic
P Value [4] <0.0001
Odds Ratio (OR) [5] 5.42
95% Confidence Interval 3.13 to 9.39
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 1.0 log10 Decrease From Baseline
Groups [1] Maraviroc QD vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Regression, Logistic
P Value [4] <0.0001
Odds Ratio (OR) [5] 4.01
95% Confidence Interval 2.29 to 7.00
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 1.0 log10 Decrease From Baseline
Groups [1] Maraviroc BID vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Regression, Logistic
P Value [4] <0.0001
Odds Ratio (OR) [5] 5.08
95% Confidence Interval 2.91 to 8.89
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.



7.  Secondary:   Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL   [ Time Frame: Week 24 and 48 ]

Measure Type Secondary
Measure Title Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL
Measure Description No text entered.
Time Frame Week 24 and 48  

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 included all the randomized participants who had taken at least one dose of the study medication. Missing data was imputed as "failure" which was defined as not meeting the criteria of less than 50 copies/mL of HIV-1 RNA levels.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
   Maraviroc QD   Maraviroc BID   Placebo 
Participants Analyzed 
[Units: Participants]
 182   191   91 
Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL 
[Units: Percentage of participants]
     
Week 24   45.60   40.84   20.88 
Week 48   45.05   44.50   17.58 


Statistical Analysis 1 for Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL
Groups [1] Maraviroc QD vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Regression, Logistic
P Value [4] <0.0001
Odds Ratio (OR) [5] 3.55
95% Confidence Interval 1.95 to 6.48
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL
Groups [1] Maraviroc BID vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Regression, Logistic
P Value [4] 0.0005
Odds Ratio (OR) [5] 2.88
95% Confidence Interval 1.59 to 5.23
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odd ratio >1 favors maraviroc.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL
Groups [1] Maraviroc QD vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Regression, Logistic
P Value [4] <0.0001
Odds Ratio (OR) [5] 4.23
95% Confidence Interval 2.26 to 7.92
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL
Groups [1] Maraviroc BID vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Regression, Logistic
P Value [4] <0.0001
Odds Ratio (OR) [5] 4.10
95% Confidence Interval 2.20 to 7.64
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.



8.  Secondary:   Cluster of Differentiation 4 (CD4) and Cluster of Differentiation 8 (CD8) Cell Count at Baseline   [ Time Frame: Baseline ]

Measure Type Secondary
Measure Title Cluster of Differentiation 4 (CD4) and Cluster of Differentiation 8 (CD8) Cell Count at Baseline
Measure Description Baseline value calculated as average of pre-dose measurements collected at screening and immediately pre-dose.
Time Frame Baseline  

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 included all the randomized participants who had taken at least one dose of the study medication. 'N' (number of participants analyzed) signifies participants evaluable for this measure.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
   Maraviroc QD   Maraviroc BID   Placebo 
Participants Analyzed 
[Units: Participants]
 182   191   90 
Cluster of Differentiation 4 (CD4) and Cluster of Differentiation 8 (CD8) Cell Count at Baseline 
[Units: Cells per microliter (cells/μL)]
Mean (Standard Deviation)
     
CD4   206.0  (171.99)   204.9  (149.21)   198.5  (140.39) 
CD8   994.6  (658.03)   996.9  (576.97)   952.3  (598.19) 

No statistical analysis provided for Cluster of Differentiation 4 (CD4) and Cluster of Differentiation 8 (CD8) Cell Count at Baseline



9.  Secondary:   Change From Baseline in CD4 Cell Count at Week 24 and 48   [ Time Frame: Week 24 and 48 ]

Measure Type Secondary
Measure Title Change From Baseline in CD4 Cell Count at Week 24 and 48
Measure Description Change from baseline in CD4 cell count measured as cells/µL. Baseline value calculated as average of pre-dose measurements collected at screening and immediately pre-dose.
Time Frame Week 24 and 48  

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 included all the randomized participants who had taken at least one dose of the study medication. 'N' (number of participants analyzed) signifies participants evaluable for this measure. Missing values were imputed using LOCF.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
   Maraviroc QD   Maraviroc BID   Placebo 
Participants Analyzed 
[Units: Participants]
 180   185   90 
Change From Baseline in CD4 Cell Count at Week 24 and 48 
[Units: cells/μL]
Least Squares Mean (Standard Error)
     
Week 24   111.72  (7.821)   101.89  (7.684)   63.78  (10.929) 
Week 48   121.49  (8.651)   127.80  (8.499)   69.34  (12.088) 


Statistical Analysis 1 for Change From Baseline in CD4 Cell Count at Week 24 and 48
Groups [1] Maraviroc QD vs. Placebo
Statistical Test Type [2] Superiority or Other
LS mean difference [3] 47.94
95% Confidence Interval 21.64 to 74.25
Standard Error of the mean (13.383)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 24: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Baseline in CD4 Cell Count at Week 24 and 48
Groups [1] Maraviroc BID vs. Placebo
Statistical Test Type [2] Superiority or Other
LS mean difference [3] 38.12
95% Confidence Interval 11.96 to 64.28
Standard Error of the mean (13.313)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 24: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Change From Baseline in CD4 Cell Count at Week 24 and 48
Groups [1] Maraviroc QD vs. Placebo
Statistical Test Type [2] Superiority or Other
LS mean difference [3] 52.15
95% Confidence Interval 23.06 to 81.25
Standard Error of the mean (14.803)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 48: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Change From Baseline in CD4 Cell Count at Week 24 and 48
Groups [1] Maraviroc BID vs. Placebo
Statistical Test Type [2] Superiority or Other
LS mean difference [3] 58.46
95% Confidence Interval 29.53 to 87.40
Standard Error of the mean (14.725)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 48: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



10.  Secondary:   Change From Baseline in CD8 Cell Count at Week 24 and 48   [ Time Frame: Week 24 and 48 ]

Measure Type Secondary
Measure Title Change From Baseline in CD8 Cell Count at Week 24 and 48
Measure Description Change from baseline in CD8 cell count measured as cells/µL. Baseline value calculated as average of pre-dose measurements collected at screening and immediately pre-dose.
Time Frame Week 24 and 48  

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 included all the randomized participants who had taken at least one dose of the study medication. 'N' (number of participants analyzed) signifies participants evaluable for this measure. Missing values were imputed using LOCF.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
   Maraviroc QD   Maraviroc BID   Placebo 
Participants Analyzed 
[Units: Participants]
 180   185   90 
Change From Baseline in CD8 Cell Count at Week 24 and 48 
[Units: cells/μL]
Least Squares Mean (Standard Error)
     
Week 24   340.74  (41.601)   255.40  (40.873)   122.18  (58.150) 
Week 48   241.43  (33.789)   244.75  (33.198)   104.51  (47.231) 


Statistical Analysis 1 for Change From Baseline in CD8 Cell Count at Week 24 and 48
Groups [1] Maraviroc QD vs. Placebo
Statistical Test Type [2] Superiority or Other
LS mean difference [3] 218.57
95% Confidence Interval 78.59 to 358.54
Standard Error of the mean (71.225)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 24: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Baseline in CD8 Cell Count at Week 24 and 48
Groups [1] Maraviroc BID vs. Placebo
Statistical Test Type [2] Superiority or Other
LS mean difference [3] 133.22
95% Confidence Interval -6.03 to 272.47
Standard Error of the mean (70.855)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 24: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Change From Baseline in CD8 Cell Count at Week 24 and 48
Groups [1] Maraviroc QD vs. Placebo
Statistical Test Type [2] Superiority or Other
LS mean difference [3] 136.93
95% Confidence Interval 23.24 to 250.62
Standard Error of the mean (57.850)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 48: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Change From Baseline in CD8 Cell Count at Week 24 and 48
Groups [1] Maraviroc BID vs. Placebo
Statistical Test Type [2] Superiority or Other
LS mean difference [3] 140.25
95% Confidence Interval 27.15 to 253.35
Standard Error of the mean (57.550)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 48: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



11.  Secondary:   Time to Virological Failure   [ Time Frame: Week 48 ]

Measure Type Secondary
Measure Title Time to Virological Failure
Measure Description Time to virologic failure based on observed HIV-1 RNA levels and failure events (death;permanent discontinuation of drug;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 events or last available visit;at time of earliest event if level <400 copies/mL (2 consecutive visits);failure if level >=400 copies/mL (2 consecutive visits) or 1 visit >=400 copies/mL followed by permanent discontinuation of drug or LTFU.
Time Frame Week 48  

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 included all the randomized participants who had taken at least one dose of the study medication.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
   Maraviroc QD   Maraviroc BID   Placebo 
Participants Analyzed 
[Units: Participants]
 182   191   91 
Time to Virological Failure 
[Units: Days]
Median (95% Confidence Interval)
 345.00 [1] 
 (197.00 to N/A) 
 361.00 [1] 
 (361.00 to N/A) 
 0.00 [2] 
[1] Upper limit of CI was not estimable because the empirical distribution rendered the algorithmic formula non-calculable.
[2] Data was not estimable because the empirical distribution of the data rendered the algorithmic formula non-calculable.


Statistical Analysis 1 for Time to Virological Failure
Groups [1] Maraviroc QD vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Log Rank
P Value [4] <0.0001
Hazard Ratio (HR) [5] 0.40
95% Confidence Interval 0.29 to 0.56
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  P-value was calculated using Log rank test controlling for the effect of the randomization strata. Hazard ratio calculated by fitting a Cox proportional hazards model including treatment group and randomization strata. Hazard ratio <1 favors maraviroc.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Time to Virological Failure
Groups [1] Maraviroc BID vs. Placebo
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Log Rank
P Value [4] <0.0001
Hazard Ratio (HR) [5] 0.33
95% Confidence Interval 0.23 to 0.46
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  P-value was calculated using Log rank test controlling for the effect of the randomization strata. Hazard ratio calculated by fitting a Cox proportional hazards model including treatment group and randomization strata. Hazard ratio <1 favors maraviroc.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.



12.  Secondary:   Time-Averaged Difference (TAD) From Baseline in log10 Transformed HIV-1 RNA Levels   [ Time Frame: Baseline to Week 24 and Week 48 ]

Measure Type Secondary
Measure Title Time-Averaged Difference (TAD) From Baseline in log10 Transformed HIV-1 RNA Levels
Measure Description TAD from baseline was calculated as area under the curve of HIV-1 RNA load (log10 copies/mL) divided by time period minus baseline HIV-1 RNA load (log10 copies/mL). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.
Time Frame Baseline to Week 24 and Week 48  

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 included all the randomized participants who had taken at least one dose of the study medication. Missing data imputed as 0 for participants who discontinued and through last available observation for participants who did not discontinue.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
   Maraviroc QD   Maraviroc BID   Placebo 
Participants Analyzed 
[Units: Participants]
 182   191   91 
Time-Averaged Difference (TAD) From Baseline in log10 Transformed HIV-1 RNA Levels 
[Units: Log10 copies/mL]
Least Squares Mean (Standard Error)
     
Week 24   -1.748  (0.0897)   -1.755  (0.0873)   -0.872  (0.1254) 
Week 48   -1.603  (0.0994)   -1.781  (0.0968)   -0.748  (0.1390) 


Statistical Analysis 1 for Time-Averaged Difference (TAD) From Baseline in log10 Transformed HIV-1 RNA Levels
Groups [1] Maraviroc QD vs. Placebo
Statistical Test Type [2] Superiority or Other
LS mean difference [3] -0.876
95% Confidence Interval -1.177 to -0.575
Standard Error of the mean (0.1534)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 24: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Negative value favors maraviroc over placebo.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Time-Averaged Difference (TAD) From Baseline in log10 Transformed HIV-1 RNA Levels
Groups [1] Maraviroc BID vs. Placebo
Statistical Test Type [2] Superiority or Other
LS mean difference [3] -0.882
95% Confidence Interval -1.181 to -0.584
Standard Error of the mean (0.1521)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 24: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Negative value favors maraviroc over placebo.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Time-Averaged Difference (TAD) From Baseline in log10 Transformed HIV-1 RNA Levels
Groups [1] Maraviroc QD vs. Placebo
Statistical Test Type [2] Superiority or Other
LS mean difference [3] -0.855
95% Confidence Interval -1.189 to -0.521
Standard Error of the mean (0.1700)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 48: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Negative value favors maraviroc over placebo.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Time-Averaged Difference (TAD) From Baseline in log10 Transformed HIV-1 RNA Levels
Groups [1] Maraviroc BID vs. Placebo
Statistical Test Type [2] Superiority or Other
LS mean difference [3] -1.033
95% Confidence Interval -1.364 to -0.701
Standard Error of the mean (0.1685)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 48: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Negative value favors maraviroc over placebo.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant estimation information:
  No text entered.



13.  Secondary:   Number of Participants With Genotypic Susceptibility Score (GSS) and Phenotypic Susceptibility Score (PSS) at Screening   [ Time Frame: Screening ]

Measure Type Secondary
Measure Title Number of Participants With Genotypic Susceptibility Score (GSS) and Phenotypic Susceptibility Score (PSS) at Screening
Measure Description Number of participants with GSS and PSS were used as surrogates for genotype and phenotype. Genotypic and phenotypic resistance to protease inhibitors(PIs), nucleoside reverse transcriptase inhibitors(NRTIs) and non-nucleoside reverse transcriptase inhibitors(NNRTIs) were evaluated at screening (not at baseline), by Monogram Biosciences PhenoSense genotyping (GT) assay. Score was determined for each drug in OBT, giving 1:drug ‘sensitive'/'susceptible' and 0:'resistant'. GSS and PSS score range:0 to >3. Genotypic enfuvirtide value was used for PSS, no phenotypic enfuvirtide was recorded.
Time Frame Screening  

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 included all the randomized participants who had taken at least one dose of the study medication.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
   Maraviroc QD   Maraviroc BID   Placebo 
Participants Analyzed 
[Units: Participants]
 182   191   91 
Number of Participants With Genotypic Susceptibility Score (GSS) and Phenotypic Susceptibility Score (PSS) at Screening 
[Units: Participants]
     
GSS: 0   39   43   20 
GSS: 1   64   58   24 
GSS: 2   25   32   20 
GSS: greater than or equal to 3   52   57   25 
GSS: missing   2   1   2 
PSS: 0   20   26   12 
PSS: 1   46   42   20 
PSS: 2   42   38   23 
PSS: greater than or equal to 3   71   84   34 
PSS: missing   3   1   2 

No statistical analysis provided for Number of Participants With Genotypic Susceptibility Score (GSS) and Phenotypic Susceptibility Score (PSS) at Screening



14.  Secondary:   Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 24   [ Time Frame: Screening and time of failure through Week 24 ]

Measure Type Secondary
Measure Title Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 24
Measure Description Number of participants with GSS and PSS were used as surrogates for genotype and phenotype. Genotypic and phenotypic resistance to PIs, NRTIs, NNRTIs were evaluated at screening and time of treatment failure analyzed through Week 24 visit, by Monogram Biosciences PhenoSense GT assay. Score was determined for each drug in OBT, giving 1:drug ‘sensitive'/'susceptible' and 0:'resistant'. GSS and PSS score range:0 to >3. Genotypic enfuvirtide value was used for PSS, no phenotypic enfuvirtide was recorded.
Time Frame Screening and time of failure through Week 24  

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; 'N' (number of participants analyzed) is signifying those participants who experienced treatment failure defined as discontinuation due to insufficient response. 'n' is number of participants who were evaluable for the given change in GSS and PSS score for each arm group respectively.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
   Maraviroc QD   Maraviroc BID   Placebo 
Participants Analyzed 
[Units: Participants]
 27   31   44 
Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 24 
[Units: Participants]
     
Change in GSS by less than -3 (n= 22, 25, 40)   0   1   0 
Change in GSS by -3 (n= 22, 25, 40)   0   0   0 
Change in GSS by -2 (n= 22, 25, 40)   0   0   1 
Change in GSS by -1 (n= 22, 25, 40)   9   6   15 
Change in GSS by 0 (n= 22, 25, 40)   13   15   22 
Change in GSS by 1 (n= 22, 25, 40)   0   3   1 
Change in GSS by 2 (n= 22, 25, 40)   0   0   1 
Change in GSS by 3 (n= 22, 25, 40)   0   0   0 
Change in GSS by greater than 3 (n= 22, 25, 40)   0   0   0 
Change in PSS by less than -3 (n= 22, 24, 40)   0   0   0 
Change in PSS by -3 (n= 22, 24, 40)   1   0   2 
Change in PSS by -2 (n= 22, 24, 40)   2   3   3 
Change in PSS by -1 (n= 22, 24, 40)   8   8   16 
Change in PSS by 0 (n= 22, 24, 40)   10   13   18 
Change in PSS by 1 (n= 22, 24, 40)   1   0   1 
Change in PSS by 2 (n= 22, 24, 40)   0   0   0 
Change in PSS by 3 (n= 22, 24, 40)   0   0   0 
Change in PSS by greater than 3 (n= 22, 24, 40)   0   0   0 

No statistical analysis provided for Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 24



15.  Secondary:   Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 48   [ Time Frame: Screening and time of failure through Week 48 ]

Measure Type Secondary
Measure Title Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 48
Measure Description Number of participants with GSS and PSS were used as surrogates for genotype and phenotype. Genotypic and phenotypic resistance to PIs, NRTIs, NNRTIs were evaluated at screening and time of treatment failure analyzed through Week 48 visit, by Monogram Biosciences PhenoSense GT assay. Score was determined for each drug in OBT, giving 1:drug ‘sensitive'/'susceptible' and 0:'resistant'. GSS and PSS score range:0 to >3. Genotypic enfuvirtide value was used for PSS, no phenotypic enfuvirtide was recorded.
Time Frame Screening and time of failure through Week 48  

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; 'N' (number of participants analyzed) is signifying those participants who experienced treatment failure defined as discontinuation due to insufficient response. 'n' is number of participants who were evaluable for the given change in GSS and PSS score for each arm group respectively.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
   Maraviroc QD   Maraviroc BID   Placebo 
Participants Analyzed 
[Units: Participants]
 41   38   49 
Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 48 
[Units: Participants]
     
Change in GSS by less than -3 (n= 35, 33, 46)   0   1   0 
Change in GSS by -3 (n= 35, 33, 46)   0   0   0 
Change in GSS by -2 (n= 35, 33, 46)   0   0   2 
Change in GSS by -1 (n= 35, 33, 46)   12   6   17 
Change in GSS by 0 (n= 35, 33, 46)   23   22   24 
Change in GSS by 1 (n= 35, 33, 46)   0   4   2 
Change in GSS by 2 (n= 35, 33, 46)   0   0   1 
Change in GSS by 3 (n= 35, 33, 46)   0   0   0 
Change in GSS by greater than 3 (n= 35, 33, 46)   0   0   0 
Change in PSS by less than -3 (n= 35, 32, 46)   0   0   0 
Change in PSS by -3 (n= 35, 32, 46)   1   0   3 
Change in PSS by -2 (n= 35, 32, 46)   3   3   4 
Change in PSS by -1 (n= 35, 32, 46)   13   9   18 
Change in PSS by 0 (n= 35, 32, 46)   16   19   19 
Change in PSS by 1 (n= 35, 32, 46)   2   0   2 
Change in PSS by 2 (n= 35, 32, 46)   0   1   0 
Change in PSS by 3 (n= 35, 32, 46)   0   0   0 
Change in PSS by greater than 3 (n= 35, 32, 46)   0   0   0 

No statistical analysis provided for Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 48



16.  Secondary:   Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 24   [ Time Frame: Baseline and time of failure through Week 24 ]

Measure Type Secondary
Measure Title Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 24
Measure Description Number of participants per tropism status (C-X-C chemokine receptor 5 {CCR5} [R5], C-X-C chemokine receptor type 4 {CXCR4} [X4], Dual/Mixed [DM], or Non-reportable/Non-phenotypable [NR/NP]) at baseline and time of treatment failure analyzed through week 24 visit. Treatment failure defined as discontinuation due to insufficient clinical response. HIV-1 RNA viral load <500 copies/ml categorized as below lower limit of quantification (BLQ). The assessment for time of treatment failure was defined as the last on treatment assessment.
Time Frame Baseline and time of failure through Week 24  

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; 'N' (number of participants analyzed) is signifying those participants who experienced treatment failure, defined as discontinuation due to insufficient response and had tropism assessment at baseline.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
   Maraviroc QD   Maraviroc BID   Placebo 
Participants Analyzed 
[Units: Participants]
 26   31   44 
Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 24 
[Units: Participants]
     
Baseline: R5; Treatment failure: R5   8   7   36 
Baseline: R5; Treatment failure: X4   2   2   0 
Baseline: R5; Treatment failure: DM   5   6   3 
Baseline: R5; Treatment failure: NR/NP   6   5   2 
Baseline: DM; Treatment failure: R5   1   0   2 
Baseline: DM; Treatment failure: X4   0   2   0 
Baseline: DM; Treatment failure: DM   3   7   0 
Baseline: DM; Treatment failure: NR/NP   0   1   0 

No statistical analysis provided for Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 24



17.  Secondary:   Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 48   [ Time Frame: Baseline and time of failure through Week 48 ]

Measure Type Secondary
Measure Title Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 48
Measure Description Number of participants per tropism status R5, X4, DM, or NR/NP at baseline and time of failure analyzed through week 48 visit. Treatment failure defined as discontinuation due to insufficient clinical response. HIV-1 RNA viral load <500 copies/ml categorized as BLQ. The assessment for time of treatment failure was defined as the last on treatment assessment.
Time Frame Baseline and time of failure through Week 48  

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; 'N' (number of participants analyzed) is signifying those participants who experienced treatment failure, defined as discontinuation due to insufficient response and had tropism assessment at baseline.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
   Maraviroc QD   Maraviroc BID   Placebo 
Participants Analyzed 
[Units: Participants]
 41   38   49 
Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 48 
[Units: Participants]
     
Baseline: R5; Treatment failure: R5   17   9   40 
Baseline: R5; Treatment failure: X4   2   2   0 
Baseline: R5; Treatment failure: DM   8   10   3 
Baseline: R5; Treatment failure: NR/NP   6   6   2 
Baseline: DM; Treatment failure: R5   1   0   3 
Baseline: DM; Treatment failure: X4   0   2   0 
Baseline: DM; Treatment failure: DM   3   7   0 
Baseline: DM; Treatment failure: NR/NP   0   1   0 

No statistical analysis provided for Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 48



18.  Secondary:   Change From Baseline in Viral Load at Week 24 and Week 48 by Overall Susceptibility Score (OSS) at Screening   [ Time Frame: Baseline, Week 24 and Week 48 ]

Measure Type Secondary
Measure Title Change From Baseline in Viral Load at Week 24 and Week 48 by Overall Susceptibility Score (OSS) at Screening
Measure Description Association between baseline resistance and virological response was assessed as change in viral load by OSS at screening. OSS categorized as 0, 1, 2, >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= resistant, 1= sensitive or susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility. Baseline value is the average of the values from screening, randomization and immediately pre-dose.
Time Frame Baseline, Week 24 and Week 48  

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; 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure. 'n' is number of participants with given OSS score at screening for each treatment arm measured at particular time-point. LOCF was used to impute missing values.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).

Measured Values
   Maraviroc QD   Maraviroc BID   Placebo 
Participants Analyzed 
[Units: Participants]
 180   185   91 
Change From Baseline in Viral Load at Week 24 and Week 48 by Overall Susceptibility Score (OSS) at Screening 
[Units: log10copies/mL]
Mean (Standard Deviation)
     
Week 24; Screening OSS 0 (n= 22, 29, 16)   -1.721  (1.0477)   -1.231  (1.2924)   -0.264  (0.8979) 
Week 24; Screening OSS 1 (n= 54, 48, 23)   -1.822  (1.0244)   -2.051  (1.1860)   -0.651  (0.9756) 
Week 24; Screening OSS 2 (n= 37, 39, 21)   -2.145  (1.4052)   -2.515  (0.8209)   -0.611  (0.9732) 
Week 24; Screening OSS >=3 (n= 64, 68, 29)   -2.655  (1.1364)   -2.530  (1.2694)   -2.109  (1.3495) 
Week 24; Screening OSS= Missing (n= 3, 1, 2)   -2.642  (0.9282)   -0.544 [1]   -1.169  (2.1350) 
Week 48; Screening OSS 0 (n= 22, 29, 16)   -1.745  (1.2354)   -1.290  (1.2978)   -0.249  (0.8727) 
Week 48; Screening OSS 1 (n= 54, 48, 23)   -1.678  (1.2115)   -1.899  (1.1966)   -0.594  (0.9454) 
Week 48; Screening OSS 2 (n= 38, 39, 21)   -2.207  (1.3866)   -2.565  (0.8734)   -0.591  (0.9309) 
Week 48; Screening OSS >=3 (n= 63, 68, 29)   -2.448  (1.2477)   -2.426  (1.2977)   -1.942  (1.4167) 
Week 48; Screening OSS= Missing (n= 3, 1, 2)   -2.795  (0.5079)   -0.833 [1]   -1.105  (2.0447) 
[1] Data was not estimable since only 1 participant was evaluable.

No statistical analysis provided for Change From Baseline in Viral Load at Week 24 and Week 48 by Overall Susceptibility Score (OSS) at Screening




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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
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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:
unchecked 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.
unchecked 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.


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


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT00098722     History of Changes
Other Study ID Numbers: A4001028
Study First Received: December 7, 2004
Results First Received: April 16, 2012
Last Updated: April 16, 2012