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Trial of Maraviroc (UK-427,857) in Combination With Zidovudine/Lamivudine Versus Efavirenz in Combination With Zidovudine/Lamivudine (MERIT)

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ClinicalTrials.gov Identifier: NCT00098293
Recruitment Status : Completed
First Posted : December 7, 2004
Results First Posted : October 5, 2012
Last Update Posted : October 9, 2013
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
ViiV Healthcare

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition HIV-1
Interventions Drug: Maraviroc + Zidovudine/Lamivudine
Drug: Efavirenz + Zidovudine/Lamivudine
Drug: Maraviroc (UK-427,857) + Zidovudine/Lamivudine
Enrollment 916

Recruitment Details  
Pre-assignment Details Data Safety Monitoring Board (DSMB) recommended termination of maraviroc once daily treatment after interim analysis at nominal week 16, 130 participants of 177 randomized were switched to open-label (OL) maraviroc twice daily.
Arm/Group Title Maraviroc Once Daily + CBV (DB) Maraviroc Twice Daily + CBV (DB and OL) Efavirenz Once Daily + CBV (DB and OL) Maraviroc Twice Daily + CBV (OL) Maraviroc Twice Daily + CBV (SP)
Hide Arm/Group Description Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the double-blind (DB) phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. DB phase nominally ended at last participant’s Week 96 visit. Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase. DB phase nominally ended at last participant’s Week 96 visit. Maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the open-label (OL) phase. OL phase continued for at least 3 years after DB phase. Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase. DB phase nominally ended at last participant’s Week 96 visit. Efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the OL phase. OL phase continued for at least 3 years after DB phase. Participants who received maraviroc 300 mg tablet orally once daily treatment during the DB phase and who were eligible based on safety criteria and virologic response, switched to OL maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, following the DSMB recommendation to terminate the maraviroc once daily treatment arm after planned interim analysis. OL phase continued for at least 3 years after DB phase. Participants who remained on mararviroc until their open-label phase End-of-Study visit and for whom maraviroc was commercially or otherwise unavailable entered an additional supplemental phase (SP) (initially planned for 6 months and subsequently extended for another 6 months) which consisted of study visits at 3-month intervals and received maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily until maraviroc was commercially or otherwise available.
Period Title: Double-blind (DB) Phase
Started 177 368 372 0 0
Treated 174 360 361 0 0
Completed 0 202 202 0 0
Not Completed 177 166 170 0 0
Reason Not Completed
Adverse Event             14             27             60             0             0
Pregnancy             0             7             9             0             0
Participant Defaulted             11             40             36             0             0
Lack of Efficacy             11             64             30             0             0
Death             1             2             2             0             0
Randomized, Not Treated             3             8             11             0             0
Protocol Violation             2             18             22             0             0
Terminated by sponsor             135             0             0             0             0
Period Title: Between DB and OL Phase
Started 0 202 202 0 0
Completed 0 202 199 0 0
Not Completed 0 0 3 0 0
Reason Not Completed
Did Not Enter Open-label Phase             0             0             3             0             0
Period Title: Open-label (OL) Phase
Started 0 202 199 130 0
Completed 0 177 158 65 0
Not Completed 0 25 41 65 0
Reason Not Completed
Adverse Event             0             3             7             6             0
Lack of Efficacy             0             7             2             20             0
Pregnancy             0             1             0             3             0
Protocol Violation             0             6             13             16             0
Participant Defaulted             0             6             16             20             0
Death             0             2             3             0             0
Period Title: Supplemental Phase (SP)
Started 0 0 0 0 127
Completed 0 0 0 0 94
Not Completed 0 0 0 0 33
Reason Not Completed
Death             0             0             0             0             1
Lost to Follow-up             0             0             0             0             2
Withdrawal by Subject             0             0             0             0             8
Other             0             0             0             0             22
Arm/Group Title Maraviroc Once Daily + CBV (DB) Maraviroc Twice Daily + CBV (DB and OL) Efavirenz Once Daily + CBV (DB and OL) Total
Hide Arm/Group Description Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the double-blind (DB) phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. DB phase nominally ended at last participant’s Week 96 visit. Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase. DB phase nominally ended at last participant’s Week 96 visit. Maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the open-label (OL) phase. OL phase continued for at least 3 years after DB phase. Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, up to week 96 in DB phase. Efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily from Week 97 up to Week 240 in open-label (OL) phase. Total of all reporting groups
Overall Number of Baseline Participants 174 360 361 895
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 174 participants 360 participants 361 participants 895 participants
Less than 18 years 0 0 0 0
18 to 24 years 17 24 25 66
25 to 34 years 47 147 120 314
35 to 44 years 73 117 141 331
45 to 54 years 29 56 55 140
55 to 64 years 7 14 15 36
Greater than or equal to 65 years 1 2 5 8
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 174 participants 360 participants 361 participants 895 participants
Female
44
  25.3%
104
  28.9%
102
  28.3%
250
  27.9%
Male
130
  74.7%
256
  71.1%
259
  71.7%
645
  72.1%
1.Primary Outcome
Title Percentage of Participants With Viral Load of Less Than 400 Copies/Milliliter [Copies/mL] and Less Than 50 Copies/mL of Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) at Week 48 for Full Analysis Set (FAS) Population
Hide Description [Not Specified]
Time Frame Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population included all the randomized participants who had taken at least 1 dose of the study medication. Missing data (MD) imputed as failure (F); that is, participants with missing data classified as not achieving the viral load criterion (MD=F).
Arm/Group Title Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL) Maraviroc Twice Daily + CBV (DB) Efavirenz Once Daily + CBV (DB)
Hide Arm/Group Description:
Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.
Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Overall Number of Participants Analyzed 174 360 361
Measure Type: Number
Unit of Measure: Percentage of participants
Less than 400 copies/mL 61.5 70.6 73.1
Less than 50 copies/mL 55.8 65.3 69.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Less than 400 copies/mL: Treatment difference in percentages stratified by randomization strata (screening viral load and geographic region) was presented along with the lower bound of the 1-sided 97.5% confidence interval (CI) based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Step down procedure used to control for multiple comparisons.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was to be concluded if the lower bound of the 1-sided 97.5% CI was greater than (>) -10%.
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value -3.0
Confidence Interval (1-Sided) 97.5%
-9.5
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Less than 50 copies/mL: Treatment difference in percentages stratified by randomization strata (screening viral load and geographic region) was presented along with the lower bound of the 1-sided 97.5% CI based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Step down procedure used to control for multiple comparisons.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was to be concluded if the lower bound of the 1-sided 97.5% CI was > -10%.
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value -4.2
Confidence Interval (1-Sided) 97.5%
-10.9
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants With Viral Load of Less Than 400 Copies/mL and Less Than 50 Copies/mL of HIV-1 RNA at Week 48 for Per Protocol (PP) Population
Hide Description Percentage of participants with viral load of less than 400 copies/mL and less than 50 copies/mL of HIV-1 RNA were not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.
Time Frame Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Per protocol (PP) population included all randomized participants who had taken at least 1 dose of study medication, were treated for at least 14 days or discontinued before this time due to treatment failure, were >80% compliant with randomized treatment and had no violation of any inclusion or exclusion criteria, which affected efficacy. MD=F.
Arm/Group Title Maraviroc Twice Daily + CBV (DB) Efavirenz Once Daily + CBV (DB)
Hide Arm/Group Description:
Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Overall Number of Participants Analyzed 360 361
Measure Type: Number
Unit of Measure: Percentage of participants
Less than 400 copies/mL 75.00 78.27
Less than 50 copies/mL 70.00 74.44
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Less than 400 copies/mL: Treatment difference in percentage stratified by randomization strata (screening viral load and geographic region) was presented along with the lower bound of the 1-sided 97.5% CI based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Step down procedure used to control for multiple comparisons.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was to be concluded if the lower bound of the 1-sided 97.5% CI was > -10%.
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value -4.1
Confidence Interval (1-Sided) 97.5%
-10.5
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Less than 50 copies/mL: Treatment difference in percentage stratified by randomization strata (screening viral load and geographic region) was presented along with the lower bound of the 1-sided 97.5% CI based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Step down procedure used to control for multiple comparisons.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was to be concluded if the lower bound of the 1-sided 97.5% CI was > -10%.
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value -4.4
Confidence Interval (1-Sided) 97.5%
-11.2
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 48 Analyzed Using Logistic Regression
Hide Description [Not Specified]
Time Frame Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population included all the randomized participants who had taken at least 1 dose of the study medication. Missing data (MD) imputed as failure (F); that is, participants with missing data classified as not achieving the viral load criterion (MD=F).
Arm/Group Title Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL) Maraviroc Twice Daily + CBV (DB) Efavirenz Once Daily + CBV (DB)
Hide Arm/Group Description:
Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.
Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Overall Number of Participants Analyzed 174 360 361
Measure Type: Number
Unit of Measure: Percentage of participants
Less than 400 copies/mL 61.5 70.6 73.1
Less than 50 copies/mL 55.8 65.3 69.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Less than 400 copies/mL: Two-sided 95% CI was presented for the odds ratio between treatment groups. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), geographic region (Northern or Southern Hemisphere) as covariates was used. Odds ratio > 1 would favor maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4485
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.64 to 1.22
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Less than 50 copies/mL: Two-sided 95% CI was presented for the odds ratio between treatment groups. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), geographic region (Northern or Southern Hemisphere) as covariates were used. Odds ratio > 1 would favor maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2724
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.61 to 1.15
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 96 Analyzed Using Logistic Regression
Hide Description [Not Specified]
Time Frame Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population included all the randomized participants who had taken at least 1 dose of the study medication. Missing data (MD) imputed as failure (F); that is, participants with missing data classified as not achieving the viral load criterion (MD=F).
Arm/Group Title Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL) Maraviroc Twice Daily + CBV (DB) Efavirenz Once Daily + CBV (DB)
Hide Arm/Group Description:
Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.
Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Overall Number of Participants Analyzed 174 360 361
Measure Type: Number
Unit of Measure: Percentage of participants
Less than 400 copies/mL 52.9 61.4 64.5
Less than 50 copies/mL 48.3 56.9 62.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Less than 400 copies/mL: Two-sided 95% CI was presented for the odds ratio between treatment groups. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), geographic region (Northern or Southern Hemisphere) as covariates were used. Odds ratio > 1 would favor maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3943
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.65 to 1.19
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Less than 50 copies/mL: Two-sided 95% CI was presented for the odds ratio between treatment groups. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), geographic region (Northern or Southern Hemisphere) as covariates were used. Odds ratio > 1 would favor maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1289
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.59 to 1.07
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Log 10-transformed Plasma Viral Load (HIV-1 RNA) Levels at Week 48 and 96
Hide 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, Week 48, Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population. Missing values for viral load at week 48 and 96 were imputed as baseline value for participants who discontinued and as last observation carried forward (LOCF) for participants who did not discontinue for maraviroc twice daily and efavirenz once daily arm and as LOCF for participants randomized to maraviroc once daily arm.
Arm/Group Title Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL) Maraviroc Twice Daily + CBV (DB) Efavirenz Once Daily + CBV (DB)
Hide Arm/Group Description:
Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.
Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Overall Number of Participants Analyzed 174 360 361
Mean (Standard Deviation)
Unit of Measure: log10 copies/mL
Baseline 4.899  (0.6273) 4.851  (0.6511) 4.857  (0.6156)
Change at Week 48 -2.665  (0.9454) -2.240  (1.484) -2.347  (1.455)
Change at Week 96 -2.565  (0.9731) -1.961  (1.575) -2.053  (1.564)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Change at week 48: P-value was calculated using Analysis of Covariance (ANCOVA) with the model including treatment arm and, as covariates, the randomization strata (screening viral load and geographic region). The difference between the treatment least squares means (LS means) adjusted for the covariates was presented in addition to 2-sided 95% CI. Negative value would favor maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2741
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.118
Confidence Interval (2-Sided) 95%
-0.094 to 0.329
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1077
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Change at week 96: P-value was calculated using ANCOVA with the model including treatment arm and, as covariates, the randomization strata (screening viral load and geographic region). The difference between the treatment LS means adjusted for the covariates was presented in addition to 2-sided 95% CI. Negative value would favor maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3899
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.100
Confidence Interval (2-Sided) 95%
-0.128 to 0.328
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1162
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Time-Averaged Difference (TAD) in log10-transformed HIV-1 RNA Levels
Hide Description TAD from baseline was calculated as area under the curve (AUC) 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 average of pre-dose measurements collected at screening, randomization, and immediately pre-dose. Data not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.
Time Frame Baseline up to Week 48 and Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population included all the randomized participants who had taken at least 1 dose of the study medication. TAD imputed as 0 for participants who discontinued. TAD calculated using the last non-missing value prior to the analysis time point for participants with a missing value at the analysis time point but who had not discontinued.
Arm/Group Title Maraviroc Twice Daily + CBV (DB) Efavirenz Once Daily + CBV (DB)
Hide Arm/Group Description:
Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Overall Number of Participants Analyzed 360 361
Least Squares Mean (Standard Error)
Unit of Measure: log10 copies/mL
Week 48 -2.152  (0.0713) -2.262  (0.0714)
Week 96 -1.945  (0.0798) -2.034  (0.0800)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Week 48: P-value was calculated using ANCOVA with the model including treatment arm and, as covariates, the randomization strata (screening viral load and geographic region). The difference between the treatment LS means adjusted for the covariates was presented in addition to 2-sided 95% CI. Negative value would favor maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2693
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.111
Confidence Interval (2-Sided) 95%
-0.086 to 0.307
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1002
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Week 96: P-value was calculated using ANCOVA with the model including treatment arm and, as covariates, the randomization strata (screening viral load and geographic region). The difference between the treatment LS means adjusted for the covariates was presented in addition to 2-sided 95% CI. Negative value would favor maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4270
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.089
Confidence Interval (2-Sided) 95%
-0.131 to 0.309
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1121
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Lymphocyte Cluster of Differentiation 4 (CD4) Count at Week 48 and 96
Hide Description Baseline value calculated as the average of pre-dose measurements collected at screening and immediately pre-dose.
Time Frame Baseline, Week 48, Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population included all the randomized participants who had taken at least 1 dose of the study medication. 'N' (number of participants analyzed) signifies participants evaluable for this measure. Missing values were imputed using LOCF.
Arm/Group Title Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL) Maraviroc Twice Daily + CBV (DB) Efavirenz Once Daily + CBV (DB)
Hide Arm/Group Description:
Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.
Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Overall Number of Participants Analyzed 174 360 360
Mean (Standard Deviation)
Unit of Measure: cells per microliter (cells/µL)
Baseline 274.1  (175.45) 264.70  (153.508) 271.87  (133.491)
Change at Week 48 172.50  (205.561) 169.53  (134.409) 143.52  (124.931)
Change at Week 96 183.75  (166.454) 206.31  (152.682) 171.50  (149.163)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Change at Week 48: P-value was calculated using ANCOVA with the model including treatment arm and, as covariates, baseline CD4 count and the randomization strata (screening viral load and geographic region). The difference between the treatment LS means adjusted for the covariates was presented in addition to 2-sided 95% CI. Positive value would favor maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0075
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 26.34
Confidence Interval (2-Sided) 95%
7.04 to 45.63
Parameter Dispersion
Type: Standard Error of the mean
Value: 9.827
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Change at Week 96: P-value was calculated using ANCOVA with the model including treatment arm and, as covariates, baseline CD4 count and the randomization strata (screening viral load and geographic region). The difference between the treatment LS means adjusted for the covariates was presented in addition to 2-sided 95% CI. Positive value would favor maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0020
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 35.44
Confidence Interval (2-Sided) 95%
13.02 to 57.86
Parameter Dispersion
Type: Standard Error of the mean
Value: 11.419
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Lymphocyte Cluster of Differentiation 8 (CD8) Count at Week 48 and 96
Hide Description Baseline value calculated as the average of pre-dose measurements collected at screening and immediately pre-dose. Change from baseline in lymphocyte CD8 count at Week 48 and 96 was not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.
Time Frame Baseline, Week 48, Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population included all the randomized participants who had taken at least 1 dose of the study medication. 'N' (number of participants analyzed) signifies participants evaluable for this measure. Missing values were imputed using LOCF.
Arm/Group Title Maraviroc Twice Daily + CBV (DB) Efavirenz Once Daily + CBV (DB)
Hide Arm/Group Description:
Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Overall Number of Participants Analyzed 360 360
Mean (Standard Deviation)
Unit of Measure: cells/µL
Baseline 938.80  (503.392) 935.78  (476.607)
Change at Week 48 38.34  (397.503) -126.83  (374.494)
Change at Week 96 20.74  (412.081) -150.27  (389.996)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Change at Week 48: P-value was calculated using ANCOVA with the model including treatment arm and, as covariates, baseline CD8 count and the randomization strata (screening viral load and geographic region). The difference between the treatment LS means adjusted for the covariates was presented in addition to 2-sided 95% CI. Positive value would favor maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 166.29
Confidence Interval (2-Sided) 95%
117.13 to 215.46
Parameter Dispersion
Type: Standard Error of the mean
Value: 25.040
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Change at Week 96: P-value was calculated using ANCOVA with the model including treatment arm and, as covariates, baseline CD8 count and the randomization strata (screening viral load and geographic region). The difference between the treatment LS means adjusted for the covariates was presented in addition to 2-sided 95% CI. Positive value would favor maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 172.22
Confidence Interval (2-Sided) 95%
122.21 to 222.23
Parameter Dispersion
Type: Standard Error of the mean
Value: 25.471
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Time to Virologic Failure
Hide 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, Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population; Data not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.
Arm/Group Title Maraviroc Twice Daily + CBV (DB) Efavirenz Once Daily + CBV (DB)
Hide Arm/Group Description:
Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Overall Number of Participants Analyzed 360 361
Median (95% Confidence Interval)
Unit of Measure: days
Week 48
NA [1] 
(354 to NA)
NA [1] 
(364 to NA)
Week 96
NA [2] 
(NA to NA)
NA [1] 
(691 to NA)
[1]
Median was not estimable because less than 50% of the participants experienced virological failure; upper confidence limit not estimable because the empirical distribution of the data rendered the algorithmic formula non-calculable.
[2]
Median was not estimable because less than 50% of the participants experienced virological failure; confidence limits not estimable because the empirical distribution of the data rendered the algorithmic formula non-calculable.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Week 48: P-value was calculated using Log rank test controlling for the effect of the randomization strata. Hazard ratio was calculated by fitting a Cox proportional hazards model including treatment group and the two randomization strata, HIV-1 RNA at screening and geographic region. Hazard ratio < 1 would favor maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5874
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.83 to 1.45
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Week 96: P-value was calculated using Log rank test controlling for the effect of the randomization strata. Hazard ratio was calculated by fitting a Cox proportional hazards model including treatment group and the two randomization strata, HIV-1 RNA at screening and geographic region. Hazard ratio < 1 would favor maraviroc.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4811
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.86 to 1.40
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 48
Hide 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 48 visit. Treatment failure: discontinuation due to insufficient clinical response. Tropism result was censored for participants with viral load <500 copies/mL at time of treatment failure categorized as below lower limit of quantification (BLQ). The assessment for time of treatment failure was defined as last on treatment assessment.
Time Frame Baseline, time of failure through Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population included all the randomized participants who had taken at least 1 dose of the study medication. ‘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.
Arm/Group Title Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL) Maraviroc Twice Daily + CBV (DB) Efavirenz Once Daily + CBV (DB)
Hide Arm/Group Description:
Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.
Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Overall Number of Participants Analyzed 20 42 15
Measure Type: Number
Unit of Measure: participants
Baseline: R5; Treatment failure: R5 5 11 6
Baseline: R5; Treatment failure: X4 0 0 0
Baseline: R5; Treatment failure: DM 3 10 0
Baseline: R5; Treatment failure: NR/NP 5 5 4
Baseline: DM; Treatment failure: R5 0 1 0
Baseline: DM; Treatment failure: X4 0 2 0
Baseline: DM; Treatment failure: DM 5 4 0
Baseline: DM; Treatment failure: NR/NP 0 0 0
11.Secondary Outcome
Title Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 96
Hide Description Number of participants per tropism status (R5, X4, DM, or NR/NP) at baseline and time of treatment failure analyzed through week 96 visit. Treatment failure defined as insufficient clinical response. Tropism result was censored for participants with viral load <500 copies/mL at time of treatment failure categorized as BLQ. The assessment for time of treatment failure was defined as last on treatment assessment.
Time Frame Baseline, time of failure through Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population included all the randomized participants who had taken at least 1 dose of the study medication. ‘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.
Arm/Group Title Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL) Maraviroc Twice Daily + CBV (DB) Efavirenz Once Daily + CBV (DB)
Hide Arm/Group Description:
Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.
Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Overall Number of Participants Analyzed 27 54 23
Measure Type: Number
Unit of Measure: participants
Baseline: R5; Treatment failure: R5 9 14 10
Baseline: R5; Treatment failure: X4 0 1 0
Baseline: R5; Treatment failure: DM 4 11 0
Baseline: R5; Treatment failure: NR/NP 6 7 5
Baseline: DM; Treatment failure: R5 0 1 1
Baseline: DM; Treatment failure: X4 0 2 0
Baseline: DM; Treatment failure: DM 5 4 0
Baseline: DM; Treatment failure: NR/NP 0 0 0
Baseline: NR/NP; Treatment failure: R5 0 1 0
Baseline: NR/NP; Treatment failure: X4 0 0 0
Baseline: NR/NP; Treatment failure: DM 0 0 0
Baseline: NR/NP; Treatment failure: NR/NP 0 1 0
12.Secondary Outcome
Title Number of Participants With Phenotypic Resistance at Time of Treatment Failure Through Week 48 and 96
Hide Description Phenotypic resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) assessed at screening by Monogram Bioscience PhenoSense genotype (MBPSGT) assay, repeated if viral load >500 copies/mL at treatment failure through week 48, 96. Phenotypic resistance to maraviroc was assumed in maraviroc treatment failures with X4-using virus and in R5 maraviroc treatment failures using Monogram Bioscience PhenoSense Entry Assay. Phenotypic resistance to zidovudine, lamivudine, efavirenz and maraviroc at time of failure was summarized.
Time Frame Screening, time of failure through Week 48, Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population included all the randomized participants who had taken at least 1 dose of the study medication. ‘n’ is signifying those participants who experienced treatment failure, defined as discontinuation due to insufficient response at specified time points for each arm group respectively.
Arm/Group Title Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL) Maraviroc Twice Daily + CBV (DB) Efavirenz Once Daily + CBV (DB)
Hide Arm/Group Description:
Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.
Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Overall Number of Participants Analyzed 174 360 361
Measure Type: Number
Unit of Measure: participants
Resistance to Zidovudine: Week 48 (n= 20, 43, 15) 0 0 0
Resistance to Lamivudine: Week 48 (n= 20, 43, 15) 14 27 3
Resistance to Efavirenz: Week 48 (n= 20, 43, 15) 0 0 7
Resistance to Maraviroc: Week 48 (n= 20, 43, 15) NA [1]  12 NA [2] 
Resistance to Zidovudine: Week 96 (n= 27, 55, 23) 0 0 0
Resistance to Lamivudine: Week 96 (n= 27, 55, 23) 20 33 8
Resistance to Efavirenz: Week 96 (n= 27, 55, 23) 0 0 13
Resistance to Maraviroc: Week 96 (n= 27, 55, 23) NA [1]  NA [3]  NA [2] 
[1]
Data not summarized since treatment arm was stopped at Week 16 as it failed to meet pre-specified criteria.
[2]
Data not summarized as maraviroc resistance was not relevant to efavirenz activity.
[3]
Data not summarized since Week 96 analysis included participants who experienced TLOVR defined virologic failure in addition to those with treatment failure.
13.Secondary Outcome
Title Number of Participants With NRTI Associated Mutations at Time of Treatment Failure Through Week 48 and 96
Hide Description Genotypic resistance to NRTIs was assessed by identification of relevant mutations at screening using MBPSGT assay and repeated for all participants with HIV-1 viral load more than 500 copies/mL at treatment failure through week 48 and week 96. Following mutations associated with NRTIs were summarized at time of failure: Any zidovudine/lamivudine (Zid/Lam), Any thymidine analogue-associated mutation (TAM), methionine (M) to valine/isoleucine (V/I) substitution at residue (r) 184 (M184V/I), lysine (K) to arginine (R) substitution at residue 65 (K65R) and any other NRTI mutations.
Time Frame Screening, time of failure through Week 48, Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population included all the randomized participants who had taken at least 1 dose of the study medication. ‘n’ is signifying those participants who experienced treatment failure, defined as discontinuation due to insufficient response at specified time points for each arm group respectively.
Arm/Group Title Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL) Maraviroc Twice Daily + CBV (DB) Efavirenz Once Daily + CBV (DB)
Hide Arm/Group Description:
Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.
Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Overall Number of Participants Analyzed 174 360 361
Measure Type: Number
Unit of Measure: participants
Any Zid/Lam Mutation: Week 48 (n= 20, 43, 15) 14 27 3
Any TAM Mutation: Week 48 (n= 20, 43, 15) 1 6 0
K65R Mutation: Week 48 (n= 20, 43, 15) 0 1 0
M184V/I Mutation: Week 48 (n= 20, 43, 15) 14 27 3
Other NRTI Mutation: Week 48 (n= 20, 43, 15) 0 1 0
Any Zid/Lam Mutation: Week 96 (n= 27, 55, 23) 20 33 8
Any TAM Mutation: Week 96 (n= 27, 55, 23) 3 6 2
K65R Mutation: Week 96 (n= 27, 55, 23) 0 1 0
M184V/I Mutation: Week 96 (n= 27, 55, 23) 20 33 8
Other NRTI Mutation: Week 96 (n= 27, 55, 23) 0 1 0
14.Secondary Outcome
Title Number of Participants With Efavirenz Associated Mutations at Time of Treatment Failure Through Week 48 and 96
Hide Description Genotypic resistance: mutations at screening by MBPSGT assay, repeated if viral load >500 copies/mL at treatment failure through week 48, 96. Efavirenz mutation:lysine to aspargine at r103(K103N);tyrosine to cysteine/isoleucine at r181(Y181C/I);tyrosine to cysteine/leucine/histidine at r188(Y188C/L/H);glycine to alanine/serine at r190(G190A/S);valine to alanine to r106(V106A);leucine to isoleucine at r100(L100I);alanine to glycine at r98(A98G);lysine to glutamic acid at r101(K101E);valine to isoleucine at r108(V108I);proline to histidine at r225(P225H);methionine to leucine at r230(M230L).
Time Frame Screening, time of failure through Week 48, Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population; n=participants with treatment failure at specified time points for each arm group respectively. Data not analyzed for participants originally randomized to maraviroc once daily arm since after termination focus shifted from efficacy, safety to only safety as reflected in abbreviated set of efficacy noted in amended planned analysis.
Arm/Group Title Maraviroc Twice Daily + CBV (DB) Efavirenz Once Daily + CBV (DB)
Hide Arm/Group Description:
Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Overall Number of Participants Analyzed 360 361
Measure Type: Number
Unit of Measure: participants
L100I Mutation: Week 48 (n= 43, 15) 0 0
K103N Mutation: Week 48 (n= 43, 15) 0 6
V106M Mutation: Week 48 (n= 43, 15) 0 0
V108I Mutation: Week 48 (n= 43, 15) 1 0
Y181C/I Mutation: Week 48 (n= 43, 15) 0 0
Y188L Mutation: Week 48 (n= 43, 15) 0 0
G190S/A Mutation: Week 48 (n= 43, 15) 0 1
P225H Mutation: Week 48 (n= 43, 15) 0 0
L100I Mutation: Week 96 (n= 55, 23) 0 0
K103N Mutation: Week 96 (n= 55, 23) 0 12
V106M Mutation: Week 96 (n= 55, 23) 0 1
V108I Mutation: Week 96 (n= 55, 23) 1 1
Y181C/I Mutation: Week 96 (n= 55, 23) 0 0
Y188L Mutation: Week 96 (n= 55, 23) 0 0
G190S/A Mutation: Week 96 (n= 55, 23) 0 2
P225H Mutation: Week 96 (n= 55, 23) 0 1
15.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL at Week 48 and Week 96 by Overall Susceptibility Score (OSS) at Screening
Hide Description Association between baseline resistance and virological response was assessed as percentage of participants with HIV-1RNA levels less than 50 copies/mL 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.
Time Frame Baseline, Week 48, Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data not analyzed because of insufficient diversity amongst participants with respect to baseline resistance due to the study entry criteria regarding baseline resistance.
Arm/Group Title Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL) Maraviroc Twice Daily + CBV (DB) Efavirenz Once Daily + CBV (DB)
Hide Arm/Group Description:
Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.
Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
16.Other Pre-specified Outcome
Title Percentage of Participants With Viral Load of Less Than 400 Copies/mL and Less Than 50 Copies/mL of HIV-1 RNA at Week 96
Hide Description [Not Specified]
Time Frame Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population included all the randomized participants who had taken at least 1 dose of the study medication. Missing data (MD) imputed as failure (F); that is, participants with missing data classified as not achieving the viral load criterion (MD=F).
Arm/Group Title Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL) Maraviroc Twice Daily + CBV (DB) Efavirenz Once Daily + CBV (DB)
Hide Arm/Group Description:
Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study.
Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Overall Number of Participants Analyzed 174 360 361
Measure Type: Number
Unit of Measure: Percentage of participants
Less than 400 copies/mL 52.9 61.4 64.5
Less than 50 copies/mL 48.3 56.9 62.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Less than 400 copies/mL: Treatment difference in percentage stratified by randomization strata was presented along with the lower bound of the 1-sided 97.5% CI based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Step down procedure used to control for multiple comparisons.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was to be concluded if the lower bound of the 1-sided 97.5% CI was greater than (>) -10%.
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value -3.2
Confidence Interval (1-Sided) 97.5%
-10.2
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Less than 50 copies/mL: Treatment difference in percentage stratified by randomization strata was presented along with the lower bound of the 1-sided 97.5% CI based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Step down procedure used to control for multiple comparisons.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was to be concluded if the lower bound of the 1-sided 97.5% CI was > -10%.
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value -5.8
Confidence Interval (1-Sided) 97.5%
-12.8
Estimation Comments [Not Specified]
17.Post-Hoc Outcome
Title Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 48 for Enhanced Sensitivity Trofile Assay (ESTA) R5 Participants
Hide Description Percentage of participants with HIV-1 RNA levels of less than 400 copies/mL and less than 50 copies/mL were not analyzed for maraviroc once daily, then twice daily arm in order to avoid misinterpretation due to possible bias due to the fact that only a non-random sample of participants in the terminated arm were re-assayed with ESTA.
Time Frame Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population; 'N' number of participants analyzed included ESTA R5 participants who had R5 tropic virus by ESTA at screening. Missing data (MD) imputed as failure (F); that is, participants with missing data classified as not achieving the viral load criterion (MD=F).
Arm/Group Title Maraviroc Twice Daily + CBV (DB) Efavirenz Once Daily + CBV (DB)
Hide Arm/Group Description:
Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Overall Number of Participants Analyzed 311 303
Measure Type: Number
Unit of Measure: Percentage of participants
Less than 400 copies/mL 73.3 72.3
Less than 50 copies/mL 68.5 68.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Less than 400 copies/mL: Treatment difference in percentage stratified by randomization strata was presented along with the lower bound of the 1-sided 97.5% CI based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Due to its post-hoc nature, this analysis was considered descriptive only rather than inferential.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value 0.6
Confidence Interval (1-Sided) 97.5%
-6.4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Less than 50 copies/mL: Treatment difference in percentage stratified by randomization strata was presented along with the lower bound of the 1-sided 97.5% CI based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Due to its post-hoc nature, this analysis was considered descriptive only rather than inferential.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value -0.2
Confidence Interval (1-Sided) 97.5%
-7.4
Estimation Comments [Not Specified]
18.Post-Hoc Outcome
Title Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 96 for Enhanced Sensitivity Trofile Assay (ESTA) R5 Participants
Hide Description Percentage of participants with HIV-1 RNA levels of less than 400 copies/mL and less than 50 copies/mL were not analyzed for maraviroc once daily, then twice daily arm in order to avoid misinterpretation due to possible bias due to the fact that only a non-random sample of participants in the terminated arm were re-assayed with ESTA.
Time Frame Week 96
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS population; 'N' number of participants analyzed included ESTA R5 participants who had R5 tropic virus by ESTA at screening. Missing data (MD) imputed as failure (F); that is, participants with missing data classified as not achieving the viral load criterion (MD=F).
Arm/Group Title Maraviroc Twice Daily + CBV (DB) Efavirenz Once Daily + CBV (DB)
Hide Arm/Group Description:
Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase.
Overall Number of Participants Analyzed 311 303
Measure Type: Number
Unit of Measure: Percentage of participants
Less than 400 copies/mL 64.0 64.4
Less than 50 copies/mL 58.8 62.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Less than 400 copies/mL: Treatment difference in percentage stratified by randomization strata was presented along with the lower bound of the 1-sided 97.5% CI based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Due to its post-hoc nature, this analysis was considered descriptive only rather than inferential.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value -0.4
Confidence Interval (1-Sided) 97.5%
-7.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maraviroc Twice Daily + CBV (DB), Efavirenz Once Daily + CBV (DB)
Comments Less than 50 copies/mL: Treatment difference in percentage stratified by randomization strata was presented along with the lower bound of the 1-sided 97.5% CI based on the normal approximation to the binomial distribution. Positive value would favor maraviroc. Due to its post-hoc nature, this analysis was considered descriptive only rather than inferential.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value -3.9
Confidence Interval (1-Sided) 97.5%
-11.5
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL) Maraviroc Twice Daily + CBV (DB and OL) Efavirenz Once Daily + CBV (DB and OL) Maraviroc Twice Daily + CBV (SP)
Hide Arm/Group Description Maraviroc 300 milligram (mg) tablet orally once daily in the evening along with placebo matched to maraviroc 300 mg tablet orally once daily in the morning and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase prior to the termination of the treatment arm based on the recommendation of the DSMB following a planned interim analysis. Eligible participants then switched to open-label maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily for the remainder of the study. Maraviroc 300 mg tablet orally twice daily and placebo matched to efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase. DB phase nominally ended at last participant’s Week 96 visit. Maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the open-label (OL) phase. OL phase continued for at least 3 years after DB phase. Placebo matched to maraviroc 300 mg tablet orally twice daily and efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the DB phase. DB phase nominally ended at last participant’s Week 96 visit. Efavirenz 600 mg tablet orally once daily in the evening co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily, during the OL phase. OL phase continued for at least 3 years after DB phase. Participants who remained on mararviroc until their open-label phase End-of-Study visit and for whom maraviroc was commercially or otherwise unavailable entered an additional supplemental phase (SP) (initially planned for 6 months and subsequently extended for another 6 months) which consisted of study visits at 3-month intervals and received maraviroc 300 mg tablet orally twice daily co-administered with combination therapy containing zidovudine 300 mg and lamivudine 150 mg (combivir [CBV]) tablet orally twice daily until maraviroc was commercially or otherwise available.
All-Cause Mortality
Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL) Maraviroc Twice Daily + CBV (DB and OL) Efavirenz Once Daily + CBV (DB and OL) Maraviroc Twice Daily + CBV (SP)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL) Maraviroc Twice Daily + CBV (DB and OL) Efavirenz Once Daily + CBV (DB and OL) Maraviroc Twice Daily + CBV (SP)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   47/174 (27.01%)   77/360 (21.39%)   82/361 (22.71%)   4/127 (3.15%) 
Blood and lymphatic system disorders         
Anaemia * 1  6/174 (3.45%)  7/360 (1.94%)  6/361 (1.66%)  0/127 (0.00%) 
Leukocytosis * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Neutropenia * 1  3/174 (1.72%)  2/360 (0.56%)  2/361 (0.55%)  0/127 (0.00%) 
Pancytopenia * 1  0/174 (0.00%)  0/360 (0.00%)  2/361 (0.55%)  0/127 (0.00%) 
Cardiac disorders         
Acute myocardial infarction * 1  0/174 (0.00%)  1/360 (0.28%)  2/361 (0.55%)  0/127 (0.00%) 
Angina unstable * 1  1/174 (0.57%)  1/360 (0.28%)  1/361 (0.28%)  0/127 (0.00%) 
Cardiopulmonary failure * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Myocardial infarciton * 1  0/174 (0.00%)  2/360 (0.56%)  1/361 (0.28%)  0/127 (0.00%) 
Pericardial effusion * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Pulseless electrical activity * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Congenital, familial and genetic disorders         
Bicuspid aortic valve * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Tinnitus * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Vertigo * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Ear and labyrinth disorders         
Haematotympanum * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Eye disorders         
Diabetic eye disease * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Uveitis * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Gastrointestinal disorders         
Abdominal pain * 1  1/174 (0.57%)  4/360 (1.11%)  1/361 (0.28%)  0/127 (0.00%) 
Abdominal pain lower * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Anal fistula * 1  0/174 (0.00%)  1/360 (0.28%)  2/361 (0.55%)  0/127 (0.00%) 
Ascites * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Colitis * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Diarrhoea * 1  2/174 (1.15%)  2/360 (0.56%)  0/361 (0.00%)  0/127 (0.00%) 
Duodenal ulcer * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Gastric ulcer * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Gastritis * 1  0/174 (0.00%)  1/360 (0.28%)  1/361 (0.28%)  0/127 (0.00%) 
Gastrointestinal haemorrhage * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Haemorrhoids * 1  1/174 (0.57%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Ileus * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Inguinal hernia * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Mesenteric vein thrombosis * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Nausea * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Pancreatitis * 1  0/174 (0.00%)  1/360 (0.28%)  1/361 (0.28%)  0/127 (0.00%) 
Rectal haemorrhage * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Rectal polyp * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Small intestinal obstruction * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Vomiting * 1  0/174 (0.00%)  2/360 (0.56%)  0/361 (0.00%)  0/127 (0.00%) 
Umbilical hernia * 1  0/174 (0.00%)  0/360 (0.00%)  0/361 (0.00%)  1/127 (0.79%) 
General disorders         
Asthenia * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Chest pain * 1  2/174 (1.15%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Influenza like illness * 1  0/174 (0.00%)  0/360 (0.00%)  2/361 (0.55%)  0/127 (0.00%) 
Pyrexia * 1  4/174 (2.30%)  4/360 (1.11%)  5/361 (1.39%)  0/127 (0.00%) 
Sudden cardiac death * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Hepatobiliary disorders         
Biliary colic * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Cholelithiasis * 1  0/174 (0.00%)  2/360 (0.56%)  2/361 (0.55%)  0/127 (0.00%) 
Hepatitis * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Hepatitis toxic * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Hypertransaminasaemia * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Immune system disorders         
Anaphylactic shock * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Drug hypersensitivity * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Hypersensitivity * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Infections and infestations         
Anal abscess * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Anal fistula infection * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Anogenital warts * 1  1/174 (0.57%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Appendicitis * 1  0/174 (0.00%)  3/360 (0.83%)  3/361 (0.83%)  0/127 (0.00%) 
Appendicitis perforated * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Bronchitis * 1  1/174 (0.57%)  0/360 (0.00%)  2/361 (0.55%)  1/127 (0.79%) 
Bronchopneumonia * 1  1/174 (0.57%)  1/360 (0.28%)  1/361 (0.28%)  0/127 (0.00%) 
Cellulitis * 1  0/174 (0.00%)  1/360 (0.28%)  1/361 (0.28%)  0/127 (0.00%) 
Cryptosporidiosis infection * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Disseminated tuberculosis * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Diverticulitis * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Hepatitis A * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Hepatitis C * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Herpes zoster * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Intervertebral discitis * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Lobar pneumonia * 1  0/174 (0.00%)  2/360 (0.56%)  2/361 (0.55%)  0/127 (0.00%) 
Localised infection * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Lower respiratory tract infection * 1  0/174 (0.00%)  1/360 (0.28%)  1/361 (0.28%)  0/127 (0.00%) 
Meningitis * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Meningitis bacterial * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Neurosyphilis * 1  0/174 (0.00%)  1/360 (0.28%)  1/361 (0.28%)  0/127 (0.00%) 
Orchitis * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Osteomyelitis * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Parasitic gastroenteritis * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Pelvic inflamatory disease * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Penile infection * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Peritoneal abscess * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Pneumocystis jiroveci infection * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Pneumocystis jiroveci pneumonia * 1  1/174 (0.57%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Pneumonia * 1  1/174 (0.57%)  3/360 (0.83%)  5/361 (1.39%)  0/127 (0.00%) 
Pneumonia staphylococcal * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Pulmonary tuberculosis * 1  0/174 (0.00%)  2/360 (0.56%)  3/361 (0.83%)  0/127 (0.00%) 
Sepsis * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Sinobronchitis * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Sinusitis * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Staphylococcal bacteraemia * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Staphylococcal infection * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Subcutaneous abscess * 1  0/174 (0.00%)  0/360 (0.00%)  2/361 (0.55%)  0/127 (0.00%) 
Syphilis * 1  0/174 (0.00%)  2/360 (0.56%)  0/361 (0.00%)  0/127 (0.00%) 
Upper respiratory tract infection * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Urinary tract infection * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Injury, poisoning and procedural complications         
Ankle fracture * 1  1/174 (0.57%)  1/360 (0.28%)  1/361 (0.28%)  0/127 (0.00%) 
Chest injury * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Concussion * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Femoral neck fracture * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Head injury * 1  0/174 (0.00%)  2/360 (0.56%)  0/361 (0.00%)  0/127 (0.00%) 
Heart injury * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Hip fracture * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Human bite * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Injury * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Jaw fracture * 1  2/174 (1.15%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Laceration * 1  0/174 (0.00%)  0/360 (0.00%)  2/361 (0.55%)  0/127 (0.00%) 
Limb injury * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Multiple fracture * 1  0/174 (0.00%)  1/360 (0.28%)  1/361 (0.28%)  0/127 (0.00%) 
Overdose * 1  0/174 (0.00%)  0/360 (0.00%)  2/361 (0.55%)  1/127 (0.79%) 
Pubis fracture * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Rib fracture * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Skull fracture * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Soft tissue injury * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Spinal compression fracture * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Tendon rupture * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Whiplash injury * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Injury * 1  0/174 (0.00%)  0/360 (0.00%)  0/361 (0.00%)  1/127 (0.79%) 
Back injury * 1  0/174 (0.00%)  0/360 (0.00%)  0/361 (0.00%)  1/127 (0.79%) 
Investigations         
Alanine aminotransferase increased * 1  1/174 (0.57%)  1/360 (0.28%)  1/361 (0.28%)  0/127 (0.00%) 
Aspartate aminotransferase increased * 1  0/174 (0.00%)  1/360 (0.28%)  2/361 (0.55%)  0/127 (0.00%) 
Blood creatine phosphokinase increased * 1  1/174 (0.57%)  2/360 (0.56%)  3/361 (0.83%)  0/127 (0.00%) 
Blood lactate dehydrogenase increased * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Blood sodium decreased * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Gama-glutamytransferase increased * 1  1/174 (0.57%)  0/360 (0.00%)  2/361 (0.55%)  0/127 (0.00%) 
Haemoglobin decreased * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Hepatic enzyme increased * 1  1/174 (0.57%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Transaminases increased * 1  0/174 (0.00%)  1/360 (0.28%)  1/361 (0.28%)  0/127 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite * 1  1/174 (0.57%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Dehydration * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Hyperkalaemia * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Back pain * 1  0/174 (0.00%)  2/360 (0.56%)  0/361 (0.00%)  0/127 (0.00%) 
Flank pain * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Myalgia * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Osteoarthritis * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Pain in extremity * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Rhabdomyolysis * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Basal cell carcinoma * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Breast cancer in situ * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Castleman's disease * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Diffuse large B-cell lymphoma * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Fibroma * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Hoadgkin's disease * 1  0/174 (0.00%)  2/360 (0.56%)  3/361 (0.83%)  0/127 (0.00%) 
Kaposi's sarcoma * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Metastases to bone * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Metastatic neoplasm * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Multiple myeloma * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Nasopharyngeal cancer * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Neoplasm * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Non-Hodgkin's lymphoma * 1  1/174 (0.57%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Non-small cell lung cancer * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Rectal cancer * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Squamous cell carcinoma * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Thyroid cancer * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Thyroid neoplasm * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Vulval neoplasm * 1  0/174 (0.00%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Nervous system disorders         
Ataxia * 1  0/174 (0.00%)  0/360 (0.00%)  2/361 (0.55%)  0/127 (0.00%) 
Balance disorder * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Cerebrovascular accident * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Convulsion * 1  1/174 (0.57%)  1/360 (0.28%)  2/361 (0.55%)  0/127 (0.00%) 
Cranial nerve paralysis * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Dysarthria * 1  0/174 (0.00%)  1/360 (0.28%)  1/361 (0.28%)  0/127 (0.00%) 
Dyspraxia * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Encephalitis * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Grand mal convulsion * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Headache * 1  1/174 (0.57%)  1/360 (0.28%)  1/361 (0.28%)  0/127 (0.00%) 
Ischaemic stroke * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Loss of consciousness * 1  0/174 (0.00%)  2/360 (0.56%)  0/361 (0.00%)  0/127 (0.00%) 
Monoparesis * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Syncope * 1  1/174 (0.57%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Thoracic outlet syndrome * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Transient ischaemic attack * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Vascular demetia * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Pregnancy, puerperium and perinatal conditions         
Abortion * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Abortion spontaneous * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Pregnancy * 1  3/174 (1.72%)  5/360 (1.39%)  8/361 (2.22%)  0/127 (0.00%) 
Psychiatric disorders         
Completed suicide * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Depression * 1  1/174 (0.57%)  2/360 (0.56%)  0/361 (0.00%)  0/127 (0.00%) 
Depression suicidal * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Drug abuse * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Drug dependence * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Intentional self-injury * 1  0/174 (0.00%)  1/360 (0.28%)  1/361 (0.28%)  0/127 (0.00%) 
Major depression * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Mental status changes * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Post-traumatic stress disorder * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Suicidal ideation * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Suicide attempt * 1  2/174 (1.15%)  0/360 (0.00%)  2/361 (0.55%)  0/127 (0.00%) 
Renal and urinary disorders         
Calculus bladder * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Haematuria * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Nephrolithiasis * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Renal failure * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Renal failure acute * 1  1/174 (0.57%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Reproductive system and breast disorders         
Cervix haemorrhage uterine * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Epididymitis * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Ovarian cyst * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Testicular pain * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Uterine cervical laceration * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Atelectasis * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Haemoptysis * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Pleural effusion * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Pneumothorax * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Pulmonary embolism * 1  1/174 (0.57%)  3/360 (0.83%)  0/361 (0.00%)  0/127 (0.00%) 
Skin and subcutaneous tissue disorders         
Dermal cyst * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Drug eruption * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Penile ulceration * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Rash * 1  1/174 (0.57%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Rash erythematous * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Rash pruritic * 1  0/174 (0.00%)  0/360 (0.00%)  1/361 (0.28%)  0/127 (0.00%) 
Stevens-Johnson syndrome * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Social circumstances         
Drug abuser * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
Pregnancy of partner * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Surgical and medical procedures         
Cholecystectomy * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Finger amputation * 1  0/174 (0.00%)  1/360 (0.28%)  0/361 (0.00%)  0/127 (0.00%) 
Vascular disorders         
Deep vein thrombosis * 1  0/174 (0.00%)  1/360 (0.28%)  1/361 (0.28%)  0/127 (0.00%) 
Hypertension * 1  1/174 (0.57%)  0/360 (0.00%)  0/361 (0.00%)  0/127 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL) Maraviroc Twice Daily + CBV (DB and OL) Efavirenz Once Daily + CBV (DB and OL) Maraviroc Twice Daily + CBV (SP)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   151/174 (86.78%)   319/360 (88.61%)   327/361 (90.58%)   0/127 (0.00%) 
Blood and lymphatic system disorders         
Anaemia * 1  12/174 (6.90%)  27/360 (7.50%)  18/361 (4.99%)  0/127 (0.00%) 
Eye disorders         
Conjunctivitis * 1  11/174 (6.32%)  11/360 (3.06%)  25/361 (6.93%)  0/127 (0.00%) 
Gastrointestinal disorders         
Abdominal distension * 1  12/174 (6.90%)  21/360 (5.83%)  20/361 (5.54%)  0/127 (0.00%) 
Abdominal pain * 1  30/174 (17.24%)  53/360 (14.72%)  53/361 (14.68%)  0/127 (0.00%) 
Abdominal pain upper * 1  7/174 (4.02%)  22/360 (6.11%)  23/361 (6.37%)  0/127 (0.00%) 
Constipation * 1  13/174 (7.47%)  37/360 (10.28%)  20/361 (5.54%)  0/127 (0.00%) 
Diarrhoea * 1  46/174 (26.44%)  90/360 (25.00%)  111/361 (30.75%)  0/127 (0.00%) 
Dyspepsia * 1  9/174 (5.17%)  26/360 (7.22%)  38/361 (10.53%)  0/127 (0.00%) 
Flatulence * 1  10/174 (5.75%)  26/360 (7.22%)  13/361 (3.60%)  0/127 (0.00%) 
Gastritis * 1  5/174 (2.87%)  16/360 (4.44%)  22/361 (6.09%)  0/127 (0.00%) 
Haemorrhoids * 1  6/174 (3.45%)  25/360 (6.94%)  16/361 (4.43%)  0/127 (0.00%) 
Nausea * 1  60/174 (34.48%)  138/360 (38.33%)  132/361 (36.57%)  0/127 (0.00%) 
Vomiting * 1  28/174 (16.09%)  53/360 (14.72%)  61/361 (16.90%)  0/127 (0.00%) 
General disorders         
Asthenia * 1  17/174 (9.77%)  29/360 (8.06%)  40/361 (11.08%)  0/127 (0.00%) 
Chest pain * 1  6/174 (3.45%)  17/360 (4.72%)  25/361 (6.93%)  0/127 (0.00%) 
Fatigue * 1  37/174 (21.26%)  64/360 (17.78%)  60/361 (16.62%)  0/127 (0.00%) 
Influenza like illness * 1  14/174 (8.05%)  21/360 (5.83%)  22/361 (6.09%)  0/127 (0.00%) 
Pyrexia * 1  16/174 (9.20%)  21/360 (5.83%)  30/361 (8.31%)  0/127 (0.00%) 
Infections and infestations         
Bronchitis * 1  28/174 (16.09%)  64/360 (17.78%)  49/361 (13.57%)  0/127 (0.00%) 
Gastroenteritis * 1  10/174 (5.75%)  27/360 (7.50%)  33/361 (9.14%)  0/127 (0.00%) 
Herpes zoster * 1  4/174 (2.30%)  18/360 (5.00%)  16/361 (4.43%)  0/127 (0.00%) 
Influenza * 1  15/174 (8.62%)  56/360 (15.56%)  50/361 (13.85%)  0/127 (0.00%) 
Nasopharyngitis * 1  24/174 (13.79%)  70/360 (19.44%)  48/361 (13.30%)  0/127 (0.00%) 
Pharyngitis * 1  15/174 (8.62%)  24/360 (6.67%)  33/361 (9.14%)  0/127 (0.00%) 
Sinusitis * 1  4/174 (2.30%)  29/360 (8.06%)  28/361 (7.76%)  0/127 (0.00%) 
Syphilis * 1  10/174 (5.75%)  16/360 (4.44%)  13/361 (3.60%)  0/127 (0.00%) 
Upper respiratory tract infection * 1  32/174 (18.39%)  82/360 (22.78%)  78/361 (21.61%)  0/127 (0.00%) 
Urinary tract infection * 1  7/174 (4.02%)  15/360 (4.17%)  25/361 (6.93%)  0/127 (0.00%) 
Investigations         
Alanine aminotransferase increased * 1  15/174 (8.62%)  20/360 (5.56%)  11/361 (3.05%)  0/127 (0.00%) 
Aspartate aminotransferase increased * 1  12/174 (6.90%)  13/360 (3.61%)  12/361 (3.32%)  0/127 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite * 1  18/174 (10.34%)  34/360 (9.44%)  36/361 (9.97%)  0/127 (0.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia * 1  17/174 (9.77%)  37/360 (10.28%)  30/361 (8.31%)  0/127 (0.00%) 
Back pain * 1  18/174 (10.34%)  44/360 (12.22%)  44/361 (12.19%)  0/127 (0.00%) 
Muscle spasms * 1  9/174 (5.17%)  16/360 (4.44%)  22/361 (6.09%)  0/127 (0.00%) 
Myalgia * 1  14/174 (8.05%)  29/360 (8.06%)  28/361 (7.76%)  0/127 (0.00%) 
Pain in extremity * 1  15/174 (8.62%)  27/360 (7.50%)  23/361 (6.37%)  0/127 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Skin papilloma * 1  10/174 (5.75%)  6/360 (1.67%)  14/361 (3.88%)  0/127 (0.00%) 
Nervous system disorders         
Dizziness * 1  25/174 (14.37%)  62/360 (17.22%)  116/361 (32.13%)  0/127 (0.00%) 
Dysgeusia * 1  10/174 (5.75%)  10/360 (2.78%)  11/361 (3.05%)  0/127 (0.00%) 
Headache * 1  44/174 (25.29%)  109/360 (30.28%)  105/361 (29.09%)  0/127 (0.00%) 
Paraesthesia * 1  7/174 (4.02%)  19/360 (5.28%)  13/361 (3.60%)  0/127 (0.00%) 
Somnolence * 1  6/174 (3.45%)  18/360 (5.00%)  13/361 (3.60%)  0/127 (0.00%) 
Psychiatric disorders         
Abnormal dreams * 1  20/174 (11.49%)  22/360 (6.11%)  46/361 (12.74%)  0/127 (0.00%) 
Anxiety * 1  8/174 (4.60%)  21/360 (5.83%)  26/361 (7.20%)  0/127 (0.00%) 
Depression * 1  18/174 (10.34%)  40/360 (11.11%)  28/361 (7.76%)  0/127 (0.00%) 
Insomnia * 1  20/174 (11.49%)  48/360 (13.33%)  44/361 (12.19%)  0/127 (0.00%) 
Sleep disorder * 1  7/174 (4.02%)  12/360 (3.33%)  19/361 (5.26%)  0/127 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough * 1  22/174 (12.64%)  51/360 (14.17%)  66/361 (18.28%)  0/127 (0.00%) 
Oropharyngeal pain * 1  9/174 (5.17%)  30/360 (8.33%)  21/361 (5.82%)  0/127 (0.00%) 
Skin and subcutaneous tissue disorders         
Eczema * 1  6/174 (3.45%)  9/360 (2.50%)  22/361 (6.09%)  0/127 (0.00%) 
Lipodystrophy acquired * 1  7/174 (4.02%)  12/360 (3.33%)  21/361 (5.82%)  0/127 (0.00%) 
Pruritus * 1  9/174 (5.17%)  8/360 (2.22%)  26/361 (7.20%)  0/127 (0.00%) 
Rash * 1  25/174 (14.37%)  38/360 (10.56%)  56/361 (15.51%)  0/127 (0.00%) 
Vascular disorders         
Hypertension * 1  6/174 (3.45%)  25/360 (6.94%)  23/361 (6.37%)  0/127 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 14.0
Following DSMB decision to discontinue maraviroc 300 mg once daily, inferential statistical analyses was performed between maraviroc 300 mg twice daily and efavirenz 600 mg once daily only. Data at Week 24 was not analyzed as planned in protocol.
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.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021