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

Sponsor
ViiV Healthcare (Industry)
Overall Status
Completed
CT.gov ID
NCT00098306
Collaborator
Pfizer (Industry)
601
Enrollment
22
Locations
3
Arms
76.9
Duration (Months)
27.3
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Maraviroc (UK-427,857), a selective and reversible CCR5 coreceptor antagonist, has been shown to be active in vitro against a wide range of clinical isolates (including those resistant to existing classes). In HIV-1 infected patients, maraviroc (UK-427,857) given as monotherapy for 10 days reduced HIV-1 viral load by up to 1.6 log, consistent with currently available agents. Safety and toleration have been studied in over 400 subjects for up to 28 days at 300 mg twice daily. No significant effects were seen on the QTc interval. The purpose of this study is to evaluate the antiretroviral activity of maraviroc (UK-427,857) in HIV infected, treatment experienced patients who are failing their current antiretroviral regimen and are infected with R5-tropic virus exclusively. This study will involve more than 100 centers from the US and Canada to achieve a total randomized subject population of 500 subjects. Patients will be randomly (2:2:1) assigned to one of three groups: Optimized Background Therapy [OBT (3-6 drugs based on treatment history and resistance testing)] + maraviroc (UK-427,857) 150 mg taken once daily, OBT + maraviroc (UK-427,857) 150 mg taken twice daily, or OBT alone. The study will enroll over approximately a 9 month period with 48 weeks of treatment. This may be extended for an additional year depending on the results at 48 weeks. Physical examinations will be performed at study entry, weeks 4, 8, 12, 16, 20, 24, 32, 40, and 48. Blood samples will also be taken at study entry, weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48. Additionally, blood samples will be drawn twice, at least 30 minutes apart, at weeks 2 and 24 for maraviroc (UK-427,857) pharmacokinetic analysis. As part of this clinical study a blood sample will also be taken for non-anonymized pharmacogenetic analysis. Patients will undergo a 12-lead electrocardiogram at study entry, weeks 24 and 48.

Condition or Disease Intervention/Treatment Phase
  • Drug: Maraviroc (UK-427,857)
  • Drug: Optimized Background Therapy
  • Drug: Optimized Background Therapy
  • Drug: Placebo
  • Drug: Optimized Background Therapy
 Phase 2/Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
601 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of a Novel CCR5 Antagonist, UK-427,857, in Combination With Optimized Background Therapy Versus Optimized Background Therapy Alone for the Treatment of Antiretroviral-Experienced HIV-1 Infected Subjects.
Study Start Date :
Nov 1, 2004
Actual Primary Completion Date :
Apr 1, 2007
Actual Study Completion Date :
Apr 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1

Drug: Maraviroc (UK-427,857)
Maraviroc was given either once or twice per day with the dose adjusted according to the optimized background therapy
Other Names:
  • Selzentry

    • Drug: Optimized Background Therapy
    Maraviroc was given either once or twice per day with the dose adjusted according to the optimized background therapy
    Experimental: 2

    Drug: Optimized Background Therapy
    Patients will be randomly (2:2:1) assigned to one of three groups: Optimized Background Therapy [OBT (3-6 drugs based on treatment history and resistance testing)] + maraviroc (UK-427,857) 150 mg taken once daily, OBT + maraviroc (UK-427,857) 150 mg taken twice daily, or OBT alone.

    Drug: Placebo
    Patients will be randomly (2:2:1) assigned to one of three groups: Optimized Background Therapy [OBT (3-6 drugs based on treatment history and resistance testing)] + maraviroc (UK-427,857) 150 mg taken once daily, OBT + maraviroc (UK-427,857) 150 mg taken twice daily, or OBT alone.
    Experimental: 3

    Drug: Optimized Background Therapy
    Patients will be randomly (2:2:1) assigned to one of three groups: Optimized Background Therapy [OBT (3-6 drugs based on treatment history and resistance testing)] + maraviroc (UK-427,857) 150 mg taken once daily, OBT + maraviroc (UK-427,857) 150 mg taken twice daily, or OBT alone. The study will enroll over approximately a 9 month period with 48 weeks of treatment.

    Outcome Measures

    Primary Outcome Measures

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

      Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.

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

      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.

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

      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.

    Secondary Outcome Measures

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

    2. Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL or With at Least 0.5 log10 Decrease From Baseline [Week 24 and 48]

    3. Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL or With at Least 1.0 log10 Decrease From Baseline [Week 24 and 48]

    4. Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL [Week 24 and 48]

    5. Cluster of Differentiation 4 (CD4) and Cluster of Differentiation 8 (CD8) Cell Count at Baseline [Baseline]

      Baseline value calculated as average of pre-dose measurements collected at screening and immediately pre-dose.

    6. Change From Baseline in CD4 Cell Count at Week 24 and 48 [Baseline, Week 24 and 48]

      Change from baseline in CD4 cell count measured as cells/µL. Baseline value calculated as the average of pre-dose measurements collected at screening and immediately pre-dose.

    7. Change From Baseline in CD8 Cell Count at Week 24 and 48 [Baseline, Week 24 and 48]

      Change from baseline in CD8 cell count measured as cells/µL. Baseline value calculated as the average of pre-dose measurements collected at screening and immediately pre-dose.

    8. Time to Virological Failure [Week 48]

      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.

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

      TAD from baseline was calculated as area under the curve of HIV-1 RNA load (log10 copies/mL) divided by time period minus baseline HIV-1 RNA load (log10 copies/mL). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.

    10. Number of Participants With Genotypic Susceptibility Scores (GSS) and Phenotypic Susceptibility Score (PSS) at Screening [Screening]

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

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

      Number of participants with GSS and PSS were used as surrogates for assessing genotype and phenotype. Genotypic and phenotypic resistance to PIs, NRTIs and NNRTIs were evaluated at screening and time of treatment failure analyzed through week 24 visit, by Monogram Biosciences PhenoSense GT assay. Score was determined for each drug in OBT, giving 1: drug 'sensitive'/'susceptible' and 0: 'resistant'. GSS and PSS score range:0 to >3. Genotypic enfuvirtide value was used for PSS, no phenotypic enfuvirtide was recorded.

    12. Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure at Week 48 [Screening and time of failure through week 48]

      Number of participants with GSS and PSS were used as surrogates for assessing genotype and phenotype. Genotypic and phenotypic resistance to PIs, NRTIs and NNRTIs were evaluated at screening and time of treatment failure analyzed through week 48 visit, by Monogram Biosciences PhenoSense GT assay. Score was determined for each drug in OBT, giving 1: drug 'sensitive'/'susceptible' and 0: 'resistant'. GSS and PSS score range:0 to >3. Genotypic enfuvirtide value was used for PSS, no phenotypic enfuvirtide was recorded.

    13. Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 24 [Baseline and time of failure through week 24]

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

    14. Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 48 [Baseline and time of failure through week 48]

      Number of participants per tropism status (R5, X4, DM, or NR/NP) at baseline and time of treatment failure analyzed through week 48 visit. Treatment failure defined as insufficient clinical response. HIV-1 RNA viral load <500 copies/mL categorized as BLQ. The assessment for time of treatment failure was defined as the last on treatment assessment.

    15. Change From Baseline in Viral Load at Week 24 and Week 48 by Overall Susceptibility Score (OSS) at Screening [Baseline, Week 24 and Week 48]

      Association between baseline resistance and virological response was assessed as change in viral load by OSS at screening. OSS categorized as 0, 1, 2, >3 (maximum value of 6) and calculated as the sum of the net assessment of in-vitro phenotypic and genotypic susceptibility using a binary scoring system (0= resistant, 1= sensitive or susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility. Baseline value is the average of the values from screening, randomization and immediately pre-dose.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    16 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Men or women at least 16 years of age (or minimum age as determined by local regulatory authorities)

    • HIV-1 RNA viral load of greater than or equal to 5,000 copies/mL

    • Stable pre-study antiretroviral regimen, or on no antiretroviral agents, for at least 4 weeks

    • Documented genotypic or phenotypic resistance to three of the four antiretroviral drug classes, OR, Antiretroviral-class experience greater than or equal to 6 months (sequential or cumulative) with at least three of the following: One nucleoside or nucleotide reverse transcriptase inhibitor, one non-nucleoside reverse transcriptase inhibitor, two protease inhibitors (excluding low-dose ritonavir) and/or enfuvirtide

    • Be willing to remain on randomized treatment without any changes or additions to the OBT regimen, except for toxicity management or upon meeting criteria for treatment failure

    • A negative urine pregnancy test at the baseline visit for Women of Child Bearing Potential (WOCBP)

    • Effective barrier contraception for WOCBP and males

    Exclusion Criteria:

    • Patients requiring treatment with more than 6 antiretroviral agents (excluding low-dose ritonavir)

    • Prior treatment with maraviroc (UK-427,857) or another experimental HIV entry inhibitor for more than 14 days

    • Suspected or documented active, untreated HIV-1 related opportunistic infection (OI) or other condition requiring acute therapy

    • Treatment for an active opportunistic infection, or unexplained temperature >38.5 degrees Celsius for 7 consecutive days

    • Active alcohol or substance abuse sufficient, in the Investigator's judgement, to prevent adherence to study medication and/or follow up

    • Lactating women, or planned pregnancy during the trial period

    • Significant renal insufficiency

    • Previous therapy with a potentially myelosuppressive, neurotoxic, hepatoxic and/or cytotoxic agent within 30 days prior to randomization or the expected need for such therapy during the study period

    • Documented or suspected acute hepatitis or pancreatitis within 30 days prior to randomization

    • Significantly elevated liver enzymes or cirrhosis

    • Significant neutropenia, anemia or thrombocytopenia

    • Malabsorption or an inability to tolerate oral medications

    • Symptomatic postural hypotension or severe cardiovascular or cerebrovascular disease

    • Certain medications

    • Malignancy requiring parenteral chemotherapy that must be continued for the duration of the trial

    • X4- or dual/mixed-tropic virus or repeated assay failure

    • Any other clinical condition that, in the Investigator's judgement, would potentially compromise study compliance or the ability to evaluate safety/efficacy

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Pfizer Investigational Site Sacramento California United States 95825
    2 Pfizer Investigational Site San Francisco California United States 94115
    3 Pfizer Investigational Site San Francisco California United States 94118
    4 Pfizer Investigational Site San Francisco California United States 94121
    5 Pfizer Investigational Site Auroa Colorado United States 80045
    6 Pfizer Investigational Site Aurora Colorado United States 80045
    7 Pfizer Investigational Site Washington District of Columbia United States 20036
    8 Pfizer Investigational Site Tampa Florida United States 33602
    9 Pfizer Investigational Site Tampa Florida United States 33614
    10 Pfizer Investigational Site Vero Beach Florida United States 32960
    11 Pfizer Investigational Site Atlanta Georgia United States 30308
    12 Pfizer Investigational Site New Orleans Louisiana United States 70112
    13 Pfizer Investigational Site Santa Fe New Mexico United States 87505
    14 Pfizer Investigational Site Bronx New York United States 10467
    15 Pfizer Investigational Site New York New York United States 10003
    16 Pfizer Investigational Site Rochester New York United States 14642
    17 Pfizer Investigational Site Cincinnati Ohio United States 45267-0405
    18 Pfizer Investigational Site Portland Oregon United States 97219
    19 Pfizer Investigational Site Austin Texas United States 78705
    20 Pfizer Investigational Site Annandale Virginia United States 22003
    21 Pfizer Investigational Site Vancouver British Columbia Canada V6Z 1Y6
    22 Pfizer Investigational Site Montreal Quebec Canada H2L 4P9

    Sponsors and Collaborators

    • ViiV Healthcare
    • Pfizer

    Investigators

    • Study Director: Pfizer CT.gov Call Center, Pfizer

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    ViiV Healthcare
    ClinicalTrials.gov Identifier:
    NCT00098306
    Other Study ID Numbers:
    • A4001027
    First Posted:
    Dec 7, 2004
    Last Update Posted:
    Apr 27, 2012
    Last Verified:
    Apr 1, 2012
    Additional relevant MeSH terms:
    HIV Infections
    Maraviroc

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Maraviroc QD, Double Blind Maraviroc BID, Double Blind Placebo, Double Blind Maraviroc BID, Open Label In Study-off Drug (ISOD), Open Label Maraviroc BID, Observation Phase In Study-off Drug (ISOD), Observation Phase
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Participants from maraviroc QD, maraviroc BID and Placebo (double blind phase) who received maraviroc 150 or 300 mg BID in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during open label phase. Participants from maraviroc QD, maraviroc BID and Placebo (double blind phase) who received no study treatment along with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) in during open label phase. Participants continuing from open label phase, who received maraviroc 150 or 300 mg BID in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during observational phase. Participants continuing from open label phase, who received no study treatment along with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during observational phase.
    Period Title: Double Blind
    STARTED 241 240 120 0 0 0 0
    Treated 232 235 118 0 0 0 0
    COMPLETED 0 0 0 0 0 0 0
    NOT COMPLETED 241 240 120 0 0 0 0
    Period Title: Double Blind
    STARTED 0 0 0 327 62 0 0
    COMPLETED 0 0 0 0 0 0 0
    NOT COMPLETED 0 0 0 327 62 0 0
    Period Title: Double Blind
    STARTED 0 0 0 0 0 250 81
    COMPLETED 0 0 0 0 0 204 55
    NOT COMPLETED 0 0 0 0 0 46 26

    Baseline Characteristics

    Arm/Group Title Maraviroc QD Maraviroc BID Placebo Total
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Total of all reporting groups
    Overall Participants 232 235 118 585
    Age, Customized (participants) [Number]
    Less than 18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    18 to 24 years
    1
    0.4%
    0
    0%
    0
    0%
    1
    0.2%
    25 to 34 years
    10
    4.3%
    7
    3%
    5
    4.2%
    22
    3.8%
    35 to 44 years
    97
    41.8%
    108
    46%
    48
    40.7%
    253
    43.2%
    45 to 54 years
    93
    40.1%
    90
    38.3%
    45
    38.1%
    228
    39%
    55 to 64 years
    26
    11.2%
    28
    11.9%
    19
    16.1%
    73
    12.5%
    Greater than or equal to 65 years
    5
    2.2%
    2
    0.9%
    1
    0.8%
    8
    1.4%
    Sex: Female, Male (Count of Participants)
    Female
    22
    9.5%
    23
    9.8%
    12
    10.2%
    57
    9.7%
    Male
    210
    90.5%
    212
    90.2%
    106
    89.8%
    528
    90.3%

    Outcome Measures

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

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS) included all the randomized participants who had taken at least one dose of the study medication.
    Arm/Group Title Maraviroc QD Maraviroc BID Placebo
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
    Measure Participants 232 235 118
    Mean (Standard Deviation) [log10 copies/milliliter(log10 copies/mL)]
    4.854
    (0.641)
    4.861
    (0.614)
    4.840
    (0.556)
    2. Primary Outcome
    Title Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 24
    Description Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.
    Time Frame Baseline and Week 24

    Outcome Measure Data

    Analysis Population Description
    FAS included all the randomized participants who had taken at least one dose of the study medication. Missing values for viral load at week 24 have been imputed as baseline value for the participants who discontinued and as Last observation carried forward (LOCF) for participants who did not discontinue.
    Arm/Group Title Maraviroc QD Maraviroc BID Placebo
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
    Measure Participants 232 235 118
    Least Squares Mean (Standard Error) [log10 copies/mL]
    -1.818
    (0.0920)
    -1.952
    (0.0913)
    -1.030
    (0.1287)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
    Comments The difference between the treatment least square means (LS means) adjusted for the randomization strata was presented in addition to 2-sided 97.5% confidence interval (CI) as an adjustment for multiplicity using a Bonferroni correction. Negative value favors maraviroc over placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value -0.788
    Confidence Interval (2-Sided) 97.5%
    -1.141 to -0.435
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.1571
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
    Comments The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 97.5% CI as an adjustment for multiplicity using a Bonferroni correction. Negative value favors maraviroc over placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value -0.922
    Confidence Interval (2-Sided) 97.5%
    -1.275 to -0.570
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.1568
    Estimation Comments
    3. Secondary Outcome
    Title Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL
    Description
    Time Frame Week 24 and 48

    Outcome Measure Data

    Analysis Population Description
    FAS included all the randomized participants who had taken at least one dose of the study medication. Missing data was imputed as "failure" which was defined as not meeting the criteria of less than 400 copies/mL of HIV-1 RNA levels.
    Arm/Group Title Maraviroc QD Maraviroc BID Placebo
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
    Measure Participants 232 235 118
    Week 24
    54.7
    23.6%
    60.4
    25.7%
    31.4
    26.6%
    Week 48
    50.9
    21.9%
    57.5
    24.5%
    22.0
    18.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
    Comments Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (less than [<] 100,000 or greater than or equal to [>=] 100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio greater than (>) 1 favors maraviroc.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.88
    Confidence Interval (2-Sided) 95%
    1.78 to 4.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
    Comments Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.66
    Confidence Interval (2-Sided) 95%
    2.26 to 5.95
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
    Comments Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.96
    Confidence Interval (2-Sided) 95%
    2.36 to 6.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
    Comments Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 5.11
    Confidence Interval (2-Sided) 95%
    3.04 to 8.59
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL or With at Least 0.5 log10 Decrease From Baseline
    Description
    Time Frame Week 24 and 48

    Outcome Measure Data

    Analysis Population Description
    FAS included all the randomized participants who had taken at least one dose of the study medication. Missing data was imputed as "failure" which was defined as not meeting the criteria of less than 400 copies/mL or with at least 0.5 log10 decrease from baseline of HIV-1 RNA levels.
    Arm/Group Title Maraviroc QD Maraviroc BID Placebo
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
    Measure Participants 232 235 118
    Week 24
    67.7
    29.2%
    69.4
    29.5%
    45.8
    38.8%
    Week 48
    59.9
    25.8%
    64.3
    27.4%
    35.6
    30.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
    Comments Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.60
    Confidence Interval (2-Sided) 95%
    1.63 to 4.13
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
    Comments Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.85
    Confidence Interval (2-Sided) 95%
    1.79 to 4.54
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
    Comments Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.93
    Confidence Interval (2-Sided) 95%
    1.83 to 4.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
    Comments Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.33
    Confidence Interval (2-Sided) 95%
    2.08 to 5.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL or With at Least 1.0 log10 Decrease From Baseline
    Description
    Time Frame Week 24 and 48

    Outcome Measure Data

    Analysis Population Description
    FAS included all the randomized participants who had taken at least one dose of the study medication. Missing data was imputed as "failure" which was defined as not meeting the criteria of less than 400 copies/mL or with at least 1.0 log10 decrease from baseline of HIV-1 RNA levels.
    Arm/Group Title Maraviroc QD Maraviroc BID Placebo
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
    Measure Participants 232 235 118
    Week 24
    64.7
    27.9%
    67.7
    28.8%
    38.1
    32.3%
    Week 48
    57.8
    24.9%
    63.0
    26.8%
    31.4
    26.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
    Comments Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.06
    Confidence Interval (2-Sided) 95%
    1.92 to 4.88
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
    Comments Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.55
    Confidence Interval (2-Sided) 95%
    2.22 to 5.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
    Comments Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.30
    Confidence Interval (2-Sided) 95%
    2.05 to 5.31
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
    Comments Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.03
    Confidence Interval (2-Sided) 95%
    2.50 to 6.51
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL
    Description
    Time Frame Week 24 and 48

    Outcome Measure Data

    Analysis Population Description
    FAS included all the randomized participants who had taken at least one dose of the study medication. Missing data was imputed as "failure" which was defined as not meeting the criteria of less than 50 copies/mL of HIV-1 RNA levels.
    Arm/Group Title Maraviroc QD Maraviroc BID Placebo
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
    Measure Participants 232 235 118
    Week 24
    42.2
    18.2%
    48.5
    20.6%
    24.6
    20.8%
    Week 48
    41.8
    18%
    46.8
    19.9%
    16.1
    13.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
    Comments Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0006
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 2.43
    Confidence Interval (2-Sided) 95%
    1.46 to 4.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
    Comments Week 24: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.15
    Confidence Interval (2-Sided) 95%
    1.90 to 5.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
    Comments Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.10
    Confidence Interval (2-Sided) 95%
    2.32 to 7.25
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
    Comments Week 48: Two-sided 95% CI was presented for the odds ratios between treatment groups with placebo as the comparator. CIs were calculated using the Wald-approximation. Logistic model with treatment, screening HIV concentrations (<100,000 or >=100,000), enfuvirtide use (Yes or No) as covariates was used. Odds ratio >1 favors maraviroc.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Regression, Logistic
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.97
    Confidence Interval (2-Sided) 95%
    2.82 to 8.77
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Cluster of Differentiation 4 (CD4) and Cluster of Differentiation 8 (CD8) Cell Count at Baseline
    Description Baseline value calculated as average of pre-dose measurements collected at screening and immediately pre-dose.
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    FAS included all the randomized participants who had taken at least one dose of the study medication. 'N' (number of participants analyzed) signifies participants evaluable for this measure.
    Arm/Group Title Maraviroc QD Maraviroc BID Placebo
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
    Measure Participants 231 235 118
    CD4
    187.5
    (149.88)
    176.5
    (143.93)
    178.5
    (127.09)
    CD8
    941.1
    (556.53)
    880.1
    (547.19)
    880.4
    (489.28)
    8. Secondary Outcome
    Title Change From Baseline in CD4 Cell Count at Week 24 and 48
    Description Change from baseline in CD4 cell count measured as cells/µL. Baseline value calculated as the average of pre-dose measurements collected at screening and immediately pre-dose.
    Time Frame Baseline, Week 24 and 48

    Outcome Measure Data

    Analysis Population Description
    FAS included all the randomized participants who had taken at least one dose of the study medication. 'N' (number of participants analyzed) signifies participants evaluable for this measure. Missing values were imputed using LOCF.
    Arm/Group Title Maraviroc QD Maraviroc BID Placebo
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
    Measure Participants 227 233 116
    Week 24
    106.63
    (7.255)
    111.08
    (7.148)
    52.14
    (10.140)
    Week 48
    112.53
    (7.390)
    122.44
    (7.284)
    53.97
    (10.341)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
    Comments Week 24: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value 54.49
    Confidence Interval (2-Sided) 95%
    30.07 to 78.92
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 12.435
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
    Comments Week 24: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value 58.94
    Confidence Interval (2-Sided) 95%
    34.63 to 83.26
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 12.378
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
    Comments Week 48: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value 58.56
    Confidence Interval (2-Sided) 95%
    33.66 to 83.46
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 12.677
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
    Comments Week 48: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value 68.47
    Confidence Interval (2-Sided) 95%
    43.69 to 93.25
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 12.617
    Estimation Comments
    9. Secondary Outcome
    Title Change From Baseline in CD8 Cell Count at Week 24 and 48
    Description Change from baseline in CD8 cell count measured as cells/µL. Baseline value calculated as the average of pre-dose measurements collected at screening and immediately pre-dose.
    Time Frame Baseline, Week 24 and 48

    Outcome Measure Data

    Analysis Population Description
    FAS included all the randomized participants who had taken at least one dose of the study medication. 'N' (number of participants analyzed) signifies participants evaluable for this measure. Missing values were imputed using LOCF.
    Arm/Group Title Maraviroc QD Maraviroc BID Placebo
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
    Measure Participants 227 233 116
    Week 24
    283.48
    (30.206)
    302.33
    (29.745)
    -0.74
    (42.198)
    Week 48
    198.00
    (28.962)
    220.40
    (28.532)
    -15.34
    (40.503)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
    Comments Week 24: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value 284.21
    Confidence Interval (2-Sided) 95%
    182.51 to 385.92
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 51.779
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
    Comments Week 24: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value 303.07
    Confidence Interval (2-Sided) 95%
    201.90 to 404.23
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 51.507
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
    Comments Week 48: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value 213.34
    Confidence Interval (2-Sided) 95%
    115.77 to 310.92
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 49.679
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
    Comments Week 48: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Positive value favors maraviroc over placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value 235.74
    Confidence Interval (2-Sided) 95%
    138.68 to 332.80
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 49.416
    Estimation Comments
    10. Secondary Outcome
    Title Time to Virological Failure
    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

    Outcome Measure Data

    Analysis Population Description
    FAS included all the randomized participants who had taken at least one dose of the study medication.
    Arm/Group Title Maraviroc QD Maraviroc BID Placebo
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
    Measure Participants 232 235 118
    Median (95% Confidence Interval) [days]
    344.00
    NA
    0.00
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
    Comments P-value was calculated using Log rank test controlling for the effect of the randomization strata. Hazard ratio calculated by fitting a Cox proportional hazards model including treatment group and randomization strata. Hazard ratio <1 favors maraviroc.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.45
    Confidence Interval (2-Sided) 95%
    0.34 to 0.60
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
    Comments P-value was calculated using Log rank test controlling for the effect of the randomization strata. Hazard ratio calculated by fitting a Cox proportional hazards model including treatment group and randomization strata. Hazard ratio <1 favors maraviroc.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.38
    Confidence Interval (2-Sided) 95%
    0.28 to 0.50
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    11. Secondary Outcome
    Title Time-Averaged Difference (TAD) From Baseline in log10 Transformed HIV-1 RNA Levels
    Description TAD from baseline was calculated as area under the curve of HIV-1 RNA load (log10 copies/mL) divided by time period minus baseline HIV-1 RNA load (log10 copies/mL). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.
    Time Frame Baseline to Week 24 and Week 48

    Outcome Measure Data

    Analysis Population Description
    FAS included all the randomized participants who had taken at least one dose of the study medication. Missing data imputed as 0 for participants who discontinued and through last available observation for participants who did not discontinue.
    Arm/Group Title Maraviroc QD Maraviroc BID Placebo
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
    Measure Participants 232 235 118
    Week 24
    -1.636
    (0.0789)
    -1.741
    (0.0783)
    -0.939
    (0.1103)
    Week 48
    -1.556
    (0.0876)
    -1.720
    (0.0870)
    -0.788
    (0.1227)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
    Comments Week 24: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Negative value favors maraviroc over placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value -0.697
    Confidence Interval (2-Sided) 95%
    -0.961 to -0.432
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.1347
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
    Comments Week 24: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Negative value favors maraviroc over placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value -0.802
    Confidence Interval (2-Sided) 95%
    -1.065 to -0.538
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.1344
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
    Comments Week 48: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Negative value favors maraviroc over placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value -0.767
    Confidence Interval (2-Sided) 95%
    -1.061 to -0.474
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.1497
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
    Comments Week 48: The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 95% CI. Negative value favors maraviroc over placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value -0.931
    Confidence Interval (2-Sided) 95%
    -1.225 to -0.638
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.1494
    Estimation Comments
    12. Primary Outcome
    Title Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 48
    Description Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization and immediately pre-dose.
    Time Frame Baseline and Week 48

    Outcome Measure Data

    Analysis Population Description
    FAS included all the randomized participants who had taken at least one dose of the study medication. Missing values for viral load at week 48 have been imputed as the baseline value for participants who discontinued and as LOCF for participants who did not discontinue.
    Arm/Group Title Maraviroc QD Maraviroc BID Placebo
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
    Measure Participants 232 235 118
    Least Squares Mean (Standard Error) [log10 copies/mL]
    -1.656
    (0.0949)
    -1.824
    (0.0942)
    -0.803
    (0.1329)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Maraviroc QD, Placebo
    Comments The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 97.5% CI as an adjustment for multiplicity using a Bonferroni correction. Negative value favors maraviroc over placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value -0.853
    Confidence Interval (2-Sided) 97.5%
    -1.217 to -0.489
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.1621
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Maraviroc BID, Placebo
    Comments The difference between the treatment LS means adjusted for the randomization strata was presented in addition to 2-sided 97.5% CI as an adjustment for multiplicity using a Bonferroni correction. Negative value favors maraviroc over placebo.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter LS mean difference
    Estimated Value -1.021
    Confidence Interval (2-Sided) 97.5%
    -1.385 to -0.658
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.1618
    Estimation Comments
    13. Secondary Outcome
    Title Number of Participants With Genotypic Susceptibility Scores (GSS) and Phenotypic Susceptibility Score (PSS) at Screening
    Description Number of participants with GSS and PSS were used as surrogates for assessing genotype and phenotype. Genotypic and phenotypic resistance to protease inhibitors(PIs), nucleoside reverse transcriptase inhibitors(NRTIs), non-nucleoside reverse transcriptase inhibitors(NNRTIs) were evaluated at screening (not at baseline), by Monogram Biosciences PhenoSense genotyping (GT) assay. Score was determined for each drug in OBT, giving 1:drug 'sensitive'/'susceptible' and 0:'resistant'. GSS and PSS score range:0 to >3. Genotypic enfuvirtide value was used for PSS, no phenotypic enfuvirtide was recorded.
    Time Frame Screening

    Outcome Measure Data

    Analysis Population Description
    FAS included all the randomized participants who had taken at least one dose of the study medication.
    Arm/Group Title Maraviroc QD Maraviroc BID Placebo
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
    Measure Participants 232 235 118
    GSS: 0
    52
    22.4%
    59
    25.1%
    31
    26.3%
    GSS: 1
    82
    35.3%
    80
    34%
    29
    24.6%
    GSS: 2
    38
    16.4%
    48
    20.4%
    21
    17.8%
    GSS: greater than or equal to 3
    57
    24.6%
    47
    20%
    34
    28.8%
    GSS: missing
    3
    1.3%
    1
    0.4%
    3
    2.5%
    PSS: 0
    25
    10.8%
    24
    10.2%
    17
    14.4%
    PSS: 1
    70
    30.2%
    73
    31.1%
    18
    15.3%
    PSS: 2
    51
    22%
    69
    29.4%
    35
    29.7%
    PSS: greater than or equal to 3
    83
    35.8%
    66
    28.1%
    45
    38.1%
    PSS: missing
    3
    1.3%
    3
    1.3%
    3
    2.5%
    14. Secondary Outcome
    Title Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 24
    Description Number of participants with GSS and PSS were used as surrogates for assessing genotype and phenotype. Genotypic and phenotypic resistance to PIs, NRTIs and NNRTIs were evaluated at screening and time of treatment failure analyzed through week 24 visit, by Monogram Biosciences PhenoSense GT assay. Score was determined for each drug in OBT, giving 1: drug 'sensitive'/'susceptible' and 0: 'resistant'. GSS and PSS score range:0 to >3. Genotypic enfuvirtide value was used for PSS, no phenotypic enfuvirtide was recorded.
    Time Frame Screening and time of failure through week 24

    Outcome Measure Data

    Analysis Population Description
    FAS; 'N' (number of participants analyzed) is signifying those participants who experienced treatment failure defined as discontinuation due to insufficient response. 'n' is number of participants who were evaluable for the given change in GSS and PSS score for each arm group respectively.
    Arm/Group Title Maraviroc QD Maraviroc BID Placebo
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
    Measure Participants 42 46 53
    Change in GSS by less than -3 (n= 35 ,40, 47)
    0
    0%
    0
    0%
    1
    0.8%
    Change in GSS by -3 (n= 35 ,40, 47)
    0
    0%
    0
    0%
    0
    0%
    Change in GSS by -2 (n= 35 ,40, 47)
    3
    1.3%
    0
    0%
    1
    0.8%
    Change in GSS by -1 (n= 35 ,40, 47)
    9
    3.9%
    13
    5.5%
    11
    9.3%
    Change in GSS by 0 (n= 35 ,40, 47)
    23
    9.9%
    26
    11.1%
    32
    27.1%
    Change in GSS by 1 (n= 35 ,40, 47)
    0
    0%
    1
    0.4%
    1
    0.8%
    Change in GSS by 2 (n= 35 ,40, 47)
    0
    0%
    0
    0%
    0
    0%
    Change in GSS by 3 (n= 35 ,40, 47)
    0
    0%
    0
    0%
    1
    0.8%
    Change in GSS by greater than 3 (n= 35 ,40, 47)
    0
    0%
    0
    0%
    0
    0%
    Change in PSS by less than -3 (n= 35 ,40, 45)
    0
    0%
    0
    0%
    1
    0.8%
    Change in PSS by -3 (n= 35 ,40, 45)
    4
    1.7%
    1
    0.4%
    1
    0.8%
    Change in PSS by -2 (n= 35 ,40, 45)
    4
    1.7%
    1
    0.4%
    4
    3.4%
    Change in PSS by -1 (n= 35 ,40, 45)
    10
    4.3%
    18
    7.7%
    12
    10.2%
    Change in PSS by 0 (n= 35 ,40, 45)
    15
    6.5%
    17
    7.2%
    25
    21.2%
    Change in PSS by 1 (n= 35 ,40, 45)
    2
    0.9%
    3
    1.3%
    2
    1.7%
    Change in PSS by 2 (n= 35 ,40, 45)
    0
    0%
    0
    0%
    0
    0%
    Change in PSS by 3 (n= 35 ,40, 45)
    0
    0%
    0
    0%
    0
    0%
    Change in PSS by greater than 3 (n= 35 ,40, 45)
    0
    0%
    0
    0%
    0
    0%
    15. Secondary Outcome
    Title Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure at Week 48
    Description Number of participants with GSS and PSS were used as surrogates for assessing genotype and phenotype. Genotypic and phenotypic resistance to PIs, NRTIs and NNRTIs were evaluated at screening and time of treatment failure analyzed through week 48 visit, by Monogram Biosciences PhenoSense GT assay. Score was determined for each drug in OBT, giving 1: drug 'sensitive'/'susceptible' and 0: 'resistant'. GSS and PSS score range:0 to >3. Genotypic enfuvirtide value was used for PSS, no phenotypic enfuvirtide was recorded.
    Time Frame Screening and time of failure through week 48

    Outcome Measure Data

    Analysis Population Description
    FAS; 'N' (number of participants analyzed) is signifying those participants who experienced treatment failure defined as discontinuation due to discontinuation due to insufficient response. 'n' is number of participants who were evaluable for the given change in GSS and PSS score for each arm group respectively.
    Arm/Group Title Maraviroc QD Maraviroc BID Placebo
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
    Measure Participants 51 58 62
    Change in GSS by less than -3 (n= 44 ,52, 55)
    0
    0%
    0
    0%
    1
    0.8%
    Change in GSS by -3 (n= 44 ,52, 55)
    0
    0%
    0
    0%
    1
    0.8%
    Change in GSS by -2 (n= 44 ,52, 55)
    5
    2.2%
    1
    0.4%
    2
    1.7%
    Change in GSS by -1 (n= 44 ,52, 55)
    12
    5.2%
    17
    7.2%
    15
    12.7%
    Change in GSS by 0 (n= 44 ,52, 55)
    26
    11.2%
    31
    13.2%
    33
    28%
    Change in GSS by 1 (n= 44 ,52, 55)
    1
    0.4%
    2
    0.9%
    1
    0.8%
    Change in GSS by 2 (n= 44 ,52, 55)
    0
    0%
    1
    0.4%
    1
    0.8%
    Change in GSS by 3 (n= 44 ,52, 55)
    0
    0%
    0
    0%
    1
    0.8%
    Change in GSS by greater than 3 (n= 44 ,52, 55)
    0
    0%
    0
    0%
    0
    0%
    Change in PSS by less than -3 (n= 44 , 52, 53)
    0
    0%
    1
    0.4%
    1
    0.8%
    Change in PSS by -3 (n= 44 , 52, 53)
    4
    1.7%
    1
    0.4%
    3
    2.5%
    Change in PSS by -2 (n= 44 , 52, 53)
    6
    2.6%
    3
    1.3%
    6
    5.1%
    Change in PSS by -1 (n= 44 , 52, 53)
    13
    5.6%
    21
    8.9%
    12
    10.2%
    Change in PSS by 0 (n= 44 , 52, 53)
    17
    7.3%
    23
    9.8%
    26
    22%
    Change in PSS by 1 (n= 44 , 52, 53)
    3
    1.3%
    3
    1.3%
    4
    3.4%
    Change in PSS by 2 (n= 44 , 52, 53)
    0
    0%
    0
    0%
    1
    0.8%
    Change in PSS by 3 (n= 44 , 52, 53)
    1
    0.4%
    0
    0%
    0
    0%
    Change in PSS by greater than 3 (n= 44 , 52, 53)
    0
    0%
    0
    0%
    0
    0%
    16. Secondary Outcome
    Title Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 24
    Description Number of participants per tropism status (C-X-C chemokine receptor 5 {CCR5} [R5], C-X-C chemokine receptor type 4 {CXCR4} [X4], Dual/mixed [DM], or Non-reportable/Non-phenotypable [NR/NP]) at baseline and time of treatment failure analyzed through week 24 visit. Treatment failure defined as discontinuation due to insufficient clinical response. HIV-1 RNA viral load <500 copies/mL categorized as below lower limit of quantification (BLQ). The assessment for time of treatment failure was defined as the last on treatment assessment.
    Time Frame Baseline and time of failure through week 24

    Outcome Measure Data

    Analysis Population Description
    FAS; 'N' (number of participants analyzed) is signifying those participants who experienced treatment failure, defined as discontinuation due to insufficient response and had tropism assessment at baseline.
    Arm/Group Title Maraviroc QD Maraviroc BID Placebo
    Arm/Group Description Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
    Measure Participants 42 46 53
    Baseline: R5; Treatment failure: R5
    10
    4.3%
    10
    4.3%
    44
    37.3%
    Baseline: R5; Treatment failure: X4
    6
    2.6%
    5
    2.1%
    0
    0%
    Baseline: R5; Treatment failure: DM
    18
    7.8%
    19
    8.1%
    1
    0.8%
    Baseline: R5; Treatment failure: NR/NP
    1
    0.4%
    3
    1.3%
    3
    2.5%
    Baseline: DM; Treatment failure: R5
    0
    0%
    0
    0%
    1
    0.8%
    Baseline: DM; Treatment failure: X4
    1
    0.4%
    4
    1.7%
    1
    0.8%
    Baseline: DM; Treatment failure: DM
    3
    1.3%
    4
    1.7%
    1
    0.8%
    Baseline: DM; Treatment failure: NR/NP
    1
    0.4%
    1
    0.4%
    0
    0%
    17. Secondary Outcome
    Title Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 48
    Description Number of participants per tropism status (R5, X4, DM, or NR/NP) at baseline and time of treatment failure analyzed through week 48 visit. Treatment failure defined as insufficient clinical response. HIV-1 RNA viral load <500 copies/mL categorized as BLQ. The assessment for time of treatment failure was defined as the last on treatment assessment.
    Time Frame Baseline and time of failure through week 48

    Outcome Measure Data

    Analysis Population Description
    FAS; 'N' (number of participants analyzed) is signifying those participants who experienced treatment failure, defined as discontinuation due to insufficient response and had tropism assessment at baseline.
    Arm/Group Title Maraviroc QD Maraviroc BID Placebo
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
    Measure Participants 51 58 62
    Baseline: R5, Treatment failure: R5
    16
    6.9%
    15
    6.4%
    49
    41.5%
    Baseline: R5, Treatment failure: X4
    6
    2.6%
    7
    3%
    0
    0%
    Baseline: R5, Treatment failure: DM
    19
    8.2%
    22
    9.4%
    3
    2.5%
    Baseline: R5, Treatment failure: NR/NP
    1
    0.4%
    3
    1.3%
    3
    2.5%
    Baseline: DM, Treatment failure: R5
    0
    0%
    0
    0%
    2
    1.7%
    Baseline: DM, Treatment failure: X4
    2
    0.9%
    4
    1.7%
    1
    0.8%
    Baseline: DM, Treatment failure: DM
    4
    1.7%
    5
    2.1%
    1
    0.8%
    Baseline: DM, Treatment failure: NR/NP
    2
    0.9%
    1
    0.4%
    0
    0%
    18. Secondary Outcome
    Title Change From Baseline in Viral Load at Week 24 and Week 48 by Overall Susceptibility Score (OSS) at Screening
    Description Association between baseline resistance and virological response was assessed as change in viral load by OSS at screening. OSS categorized as 0, 1, 2, >3 (maximum value of 6) and calculated as the sum of the net assessment of in-vitro phenotypic and genotypic susceptibility using a binary scoring system (0= resistant, 1= sensitive or susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility. Baseline value is the average of the values from screening, randomization and immediately pre-dose.
    Time Frame Baseline, Week 24 and Week 48

    Outcome Measure Data

    Analysis Population Description
    FAS; 'N' (number of participants analyzed) is signifying those participants who were evaluable for this measure. 'n' is number of participants with given OSS score at screening for each treatment arm at particular time-point. LOCF was used to impute missing values.
    Arm/Group Title Maraviroc QD Maraviroc BID Placebo
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
    Measure Participants 228 234 116
    Week 24; Screening OSS 0 (n= 29, 27, 19)
    -0.945
    (0.905)
    -1.524
    (1.331)
    -0.083
    (0.472)
    Week 24; Screening OSS 1 (n= 76, 86, 21)
    -1.911
    (1.229)
    -1.895
    (1.395)
    -0.350
    (0.784)
    Week 24; Screening OSS 2 (n= 51, 65, 38)
    -2.093
    (1.3402)
    -2.220
    (1.0900)
    -1.251
    (1.0800)
    Week 24; Screening OSS >=3 (n= 68, 53, 35)
    -2.536
    (1.1599)
    -2.672
    (1.1836)
    -2.471
    (0.9200)
    Week 24; Screening OSS= Missing (n= 4, 3, 3)
    -2.070
    (1.3832)
    -3.075
    (0.5705)
    -0.530
    (0.1726)
    Week 48; Screening OSS 0 (n= 29, 27, 19)
    -0.876
    (0.8448)
    -1.419
    (1.3042)
    -0.088
    (0.4541)
    Week 48; Screening OSS 1 (n= 77, 86, 20)
    -1.843
    (1.2452)
    -1.868
    (1.4078)
    -0.262
    (0.7048)
    Week 48; Screening OSS 2 (n= 51, 64, 38)
    -2.146
    (1.4208)
    -2.182
    (1.1096)
    -1.147
    (0.9681)
    Week 48; Screening OSS >=3 (n= 67, 54, 36)
    -2.427
    (1.3136)
    -2.634
    (1.1628)
    -2.205
    (1.0870)
    Week 48; Screening OSS= Missing (n= 4, 3, 3)
    -2.106
    (1.4461)
    -2.698
    (1.2056)
    -0.370
    (0.1471)

    Adverse Events

    Time Frame
    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 QD, Double Blind Maraviroc BID, Double Blind Placebo, Double Blind Maraviroc BID, Open Label In Study-off Drug (ISOD), Open Label Maraviroc BID, Observation Phase In Study-off Drug (ISOD), Observation Phase
    Arm/Group Description Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning. Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Participants from maraviroc QD, maraviroc BID and Placebo (double blind phase) who received maraviroc 150 or 300 mg BID in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during open label phase. Participants from maraviroc QD, maraviroc BID and Placebo (double blind phase) who received no study treatment along with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) in during open label phase. Participants continuing from open label phase, who received maraviroc 150 or 300 mg BID in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during observational phase. Participants continuing from open label phase, who received no study treatment along with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during observational phase.
    All Cause Mortality
    Maraviroc QD, Double Blind Maraviroc BID, Double Blind Placebo, Double Blind Maraviroc BID, Open Label In Study-off Drug (ISOD), Open Label Maraviroc BID, Observation Phase In Study-off Drug (ISOD), Observation Phase
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Maraviroc QD, Double Blind Maraviroc BID, Double Blind Placebo, Double Blind Maraviroc BID, Open Label In Study-off Drug (ISOD), Open Label Maraviroc BID, Observation Phase In Study-off Drug (ISOD), Observation Phase
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 42/232 (18.1%) 53/235 (22.6%) 20/118 (16.9%) 33/327 (10.1%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Blood and lymphatic system disorders
    Anaemia 2/232 (0.9%) 1/235 (0.4%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Febrile neutropenia 0/232 (0%) 1/235 (0.4%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Lymphadenopathy 0/232 (0%) 0/235 (0%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Splenomegaly 0/232 (0%) 1/235 (0.4%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Thrombotic thrombocytopenic purpura 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Neutropenia 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Thrombocytopenia 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Cardiac disorders
    Acute myocardial infarction 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Angina pectoris 1/232 (0.4%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Angina unstable 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Myocardial ischaemia 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Tachycardia 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Cardiac arrest 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Cardiac failure congestive 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Coronary artery disease 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Myocardial infarction 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Eye disorders
    Blindness unilateral 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Visual impairment 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Gastrointestinal disorders
    Abdominal discomfort 0/232 (0%) 0/235 (0%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Abdominal pain 2/232 (0.9%) 1/235 (0.4%) 2/118 (1.7%) 2/327 (0.6%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Ascites 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Colitis 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Diarrhoea 2/232 (0.9%) 1/235 (0.4%) 0/118 (0%) 3/327 (0.9%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Diarrhoea haemorrhagic 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Diverticulum intestinal haemorrhagic 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Dysphagia 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Haematochezia 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Nausea 2/232 (0.9%) 1/235 (0.4%) 1/118 (0.8%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Odynophagia 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Oesophageal stenosis 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Oesophagitis 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Pancreatitis 2/232 (0.9%) 0/235 (0%) 1/118 (0.8%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Proctalgia 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Small intestinal obstruction 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Varices oesophageal 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Vomiting 3/232 (1.3%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Proctitis 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Rectal haemorrhage 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Abdominal pain upper 1/232 (0.4%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    General disorders
    Asthenia 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Chest pain 3/232 (1.3%) 1/235 (0.4%) 2/118 (1.7%) 2/327 (0.6%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Malaise 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Pyrexia 2/232 (0.9%) 5/235 (2.1%) 1/118 (0.8%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Hepatobiliary disorders
    Cholecystitis 0/232 (0%) 2/235 (0.9%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Cholelithiasis 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Hepatic cirrhosis 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Hepatic failure 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Hepatomegaly 0/232 (0%) 0/235 (0%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Hepatotoxicity 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Hyperbilirubinaemia 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Portal vein thrombosis 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Immune system disorders
    Antiphospholipid syndrome 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Drug hypersensitivity 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Infections and infestations
    Abscess 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Abscess limb 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Appendicitis 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Arthritis bacterial 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Arthritis gonococcal 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Bronchitis 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Cavernous sinus thrombosis 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Cellulitis 1/232 (0.4%) 2/235 (0.9%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Clostridium difficile colitis 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Cystitis 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Cytomegalovirus chorioretinitis 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Diverticulitis 0/232 (0%) 1/235 (0.4%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Fungal infection 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Gangrene 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Gastric infection 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Gastroenteritis 2/232 (0.9%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Gastroenteritis bacterial 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Gastroenteritis viral 1/232 (0.4%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Genital herpes 0/232 (0%) 0/235 (0%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Groin abscess 0/232 (0%) 0/235 (0%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    HIV wasting syndrome 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Herpes simplex 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Infective myositis 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Meningitis viral 0/232 (0%) 2/235 (0.9%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Oesophageal candidiasis 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Pharyngitis 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/0 (NaN) 0/81 (0%)
    Pneumonia 7/232 (3%) 2/235 (0.9%) 4/118 (3.4%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Progressive multifocal leukoencephalopathy 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Pyelonephritis 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Rectal abscess 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Sepsis 0/232 (0%) 0/235 (0%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Sinusitis 1/232 (0.4%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Staphylococcal infection 0/232 (0%) 0/235 (0%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Upper respiratory tract infection 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Urethral abscess 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Abdominal wall abscess 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    HIV infection 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Lung infection 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Mycobacterium avium complex infection 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Osteomyelitis 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Pneumonia bacterial 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Urinary tract infection 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Injury, poisoning and procedural complications
    Drug toxicity 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Fall 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Hip fracture 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Heat exhaustion 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Intentional overdose 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Investigations
    Alanine aminotransferase increased 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Aspartate aminotransferase increased 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Blood amylase increased 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Gamma-glutamyltransferase increased 0/232 (0%) 0/235 (0%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Lipase increased 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Transaminases increased 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Blood creatine phosphokinase increased 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Nuclear magnetic resonance imaging brain 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Weight decreased 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Metabolism and nutrition disorders
    Dehydration 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Hyperglycaemia 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Lactic acidosis 0/232 (0%) 0/235 (0%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/232 (0%) 2/235 (0.9%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Intervertebral disc degeneration 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Intervertebral disc protrusion 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Joint range of motion decreased 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Joint swelling 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Joint warmth 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Musculoskeletal pain 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Osteonecrosis 1/232 (0.4%) 2/235 (0.9%) 0/118 (0%) 2/327 (0.6%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Pain in extremity 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Rhabdomyolysis 0/232 (0%) 2/235 (0.9%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Spinal disorder 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Anal cancer 2/232 (0.9%) 2/235 (0.9%) 1/118 (0.8%) 2/327 (0.6%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    B-cell lymphoma 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 2/327 (0.6%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Diffuse large B-cell lymphoma 0/232 (0%) 0/235 (0%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Hodgkin's disease 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Lymphoma 1/232 (0.4%) 0/235 (0%) 1/118 (0.8%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Oesophageal carcinoma 1/232 (0.4%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Rectal cancer 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Squamous cell carcinoma 0/232 (0%) 1/235 (0.4%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Sweat gland tumour 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    T-cell lymphoma 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Leukaemia 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Nervous system disorders
    Cerebrovascular accident 2/232 (0.9%) 2/235 (0.9%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Convulsion 1/232 (0.4%) 1/235 (0.4%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Encephalopathy 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Headache 1/232 (0.4%) 0/235 (0%) 1/118 (0.8%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Hypoaesthesia 0/232 (0%) 0/235 (0%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Memory impairment 0/232 (0%) 0/235 (0%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Paraesthesia 0/232 (0%) 0/235 (0%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Sedation 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Speech disorder 0/232 (0%) 0/235 (0%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Syncope 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Transient ischaemic attack 0/232 (0%) 0/235 (0%) 2/118 (1.7%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Cerebral infarction 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Dizziness 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Pneumocephalus 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Pregnancy, puerperium and perinatal conditions
    Pregnancy 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Psychiatric disorders
    Anxiety 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Confusional state 0/232 (0%) 0/235 (0%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Schizophrenia 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Suicide attempt 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Psychotic disorder 0/232 (0%) 0/235 (0%) 0/118 (0%) 2/327 (0.6%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Renal and urinary disorders
    Nephrolithiasis 1/232 (0.4%) 2/235 (0.9%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Renal failure 1/232 (0.4%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Renal failure acute 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Respiratory, thoracic and mediastinal disorders
    Bronchial hyperreactivity 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Cough 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Dyspnoea 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Hypoxia 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Lung infiltration 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Pneumonia aspiration 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Pneumonitis 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Pneumothorax 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Pulmonary embolism 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Skin and subcutaneous tissue disorders
    Erythema 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Rash 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Rash generalised 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Surgical and medical procedures
    Hip surgery 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Plasmapheresis 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Stent placement 0/232 (0%) 0/235 (0%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Toe operation 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Vascular disorders
    Deep vein thrombosis 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Hypertension 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Hypotension 1/232 (0.4%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Peripheral embolism 0/232 (0%) 1/235 (0.4%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Infarction 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Thrombophlebitis 0/232 (0%) 0/235 (0%) 0/118 (0%) 1/327 (0.3%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Other (Not Including Serious) Adverse Events
    Maraviroc QD, Double Blind Maraviroc BID, Double Blind Placebo, Double Blind Maraviroc BID, Open Label In Study-off Drug (ISOD), Open Label Maraviroc BID, Observation Phase In Study-off Drug (ISOD), Observation Phase
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 170/232 (73.3%) 192/235 (81.7%) 89/118 (75.4%) 19/327 (5.8%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Gastrointestinal disorders
    Abdominal distension 13/232 (5.6%) 9/235 (3.8%) 4/118 (3.4%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Abdominal pain 12/232 (5.2%) 13/235 (5.5%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Constipation 12/232 (5.2%) 16/235 (6.8%) 0/118 (0%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Diarrhoea 58/232 (25%) 53/235 (22.6%) 30/118 (25.4%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Nausea 45/232 (19.4%) 48/235 (20.4%) 23/118 (19.5%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Vomiting 20/232 (8.6%) 15/235 (6.4%) 12/118 (10.2%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    General disorders
    Fatigue 36/232 (15.5%) 46/235 (19.6%) 22/118 (18.6%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Injection site reaction 20/232 (8.6%) 24/235 (10.2%) 14/118 (11.9%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Malaise 3/232 (1.3%) 1/235 (0.4%) 6/118 (5.1%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Oedema peripheral 13/232 (5.6%) 9/235 (3.8%) 3/118 (2.5%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Pyrexia 19/232 (8.2%) 32/235 (13.6%) 13/118 (11%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Infections and infestations
    Bronchitis 20/232 (8.6%) 20/235 (8.5%) 9/118 (7.6%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Folliculitis 5/232 (2.2%) 12/235 (5.1%) 3/118 (2.5%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Nasopharyngitis 14/232 (6%) 19/235 (8.1%) 9/118 (7.6%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Sinusitis 15/232 (6.5%) 24/235 (10.2%) 5/118 (4.2%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Upper respiratory tract infection 36/232 (15.5%) 35/235 (14.9%) 10/118 (8.5%) 19/327 (5.8%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Investigations
    Weight decreased 14/232 (6%) 8/235 (3.4%) 2/118 (1.7%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 19/232 (8.2%) 17/235 (7.2%) 4/118 (3.4%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 19/232 (8.2%) 20/235 (8.5%) 3/118 (2.5%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Back pain 11/232 (4.7%) 20/235 (8.5%) 8/118 (6.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Muscle spasms 14/232 (6%) 6/235 (2.6%) 5/118 (4.2%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Pain in extremity 12/232 (5.2%) 11/235 (4.7%) 5/118 (4.2%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Nervous system disorders
    Dizziness 27/232 (11.6%) 25/235 (10.6%) 9/118 (7.6%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Headache 34/232 (14.7%) 35/235 (14.9%) 19/118 (16.1%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Hypoaesthesia 12/232 (5.2%) 9/235 (3.8%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Psychiatric disorders
    Depression 15/232 (6.5%) 14/235 (6%) 4/118 (3.4%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Insomnia 22/232 (9.5%) 25/235 (10.6%) 7/118 (5.9%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 31/232 (13.4%) 37/235 (15.7%) 8/118 (6.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Nasal congestion 10/232 (4.3%) 15/235 (6.4%) 4/118 (3.4%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Oropharyngeal pain 14/232 (6%) 16/235 (6.8%) 4/118 (3.4%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Sinus congestion 11/232 (4.7%) 12/235 (5.1%) 2/118 (1.7%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Skin and subcutaneous tissue disorders
    Night sweats 10/232 (4.3%) 16/235 (6.8%) 3/118 (2.5%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Rash 19/232 (8.2%) 24/235 (10.2%) 6/118 (5.1%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)
    Vascular disorders
    Hypertension 6/232 (2.6%) 12/235 (5.1%) 1/118 (0.8%) 0/327 (0%) 0/62 (0%) 0/250 (0%) 0/81 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    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
    Email ClinicalTrials.gov_Inquiries@pfizer.com
    Responsible Party:
    ViiV Healthcare
    ClinicalTrials.gov Identifier:
    NCT00098306
    Other Study ID Numbers:
    • A4001027
    First Posted:
    Dec 7, 2004
    Last Update Posted:
    Apr 27, 2012
    Last Verified:
    Apr 1, 2012