HIV Infections
Conditions
Brief summary
Maraviroc (UK-427,857), a selective and reversible CCR5 co-receptor 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 in the United States, maraviroc (UK-427,857) is approved for use as part of combination antiretroviral treatment in treatment-experienced and treatment-naive adult subjects. At least 50% of treatment-experienced patients are infected with R5-tropic HIV-1 exclusively. However, even in patients infected with a dual tropic (R5 + X4) phenotype, a large proportion of the virus population still uses CCR5 exclusively. Thus, the purpose of this study is to evaluate the antiretroviral activity, and safety, of maraviroc (UK-427,857) (in combination with other agents) in HIV infected, treatment experienced patients who are failing their current antiretroviral regimen and not infected with R5-tropic virus exclusively. This study will involve more than 200 centers globally to achieve a total randomized subject population of 192 subjects. Patients will be randomly (1:1:1) 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. Randomization was stratified by Enfuvirtide use in OBT (yes/no) and Screening HIV-1 RNA level (viral load) (\<100,000/≥ 100, 000 copies per milliliter \[copies per mL\]). The study will enroll over approximately a 9 month period with 48 weeks of treatment. 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.
Detailed description
(i) Subjects remained on their assigned therapy for 48 weeks, unless the subject was discontinued early for protocol-defined treatment failure or other reasons such as adverse event, loss to follow-up, withdrawal of consent, or death. (ii) If a subject met the criteria for treatment failure or discontinued for another reason (eg, pregnancy, adverse event) and required an alternative regimen, the subject was followed until the Week 48 visit according to protocol guidelines. The new regimen, selected by the Investigator based on the results of resistance testing at the time of failure, had to be recorded in the CRF. (iii) Open-label maraviroc (UK-427,857) was provided by the sponsor, until it was commercially available, to subjects who completed 48 weeks of therapy and for whom it was medically appropriate to continue therapy with maraviroc (UK-427,857).
Interventions
OBT (3-6 drugs based on treatment history and resistance testing)
maraviroc (UK-427,857) 150 mg taken once daily
Sponsors
Pfizer
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
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 two of the four antiretroviral drug classes, OR, Antiretroviral-class experience greater than or equal to 3 months (sequential or cumulative) with at least three of the following: One nucleoside or nucleotide reverse transcriptase inhibitor (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 judgment, 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, hepatotoxic 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 * R5 virus phenotype only * No option to use at least one non-nucleoside reverse transcriptase inhibitor or protease inhibitor, or enfuvirtide, based on resistance testing * Any other clinical condition that, in the Investigator's judgment, would potentially compromise study compliance or the ability to evaluate safety/efficacy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA]) | Baseline to Week 24 and Week 48 | Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log 10 copies per milliliter \[log10 copies/mL\]). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels | Baseline, Week 24, Week 48 | Number of subjects with HIV-1 RNA levels \< 400 copies/mL or at least 0.5 log 10-transformed decrease from baseline in HIV-1 RNA levels. Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits. |
| Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels | Baseline, Week 24, Week 48 | Number of subjects with HIV-1 RNA levels \< 400 copies/mL or at least 1.0 log 10-transformed decrease from baseline in HIV-1 RNA levels. Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits. |
| Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL | Baseline, Week 24, Week 48 | — |
| Change From Baseline in CD4 Cell Count | Baseline to Week 24 and Week 48 | Change from baseline in CD4 cell count (measured as cells per microliter \[cells/µL\]). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and baseline visits. |
| Change From Baseline in CD8 Cell Count | Baseline to Week 24 and Week 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, randomization, and baseline visits. |
| Time (50% Quartile Point Estimate) to Virologic Failure | Day 1 through Week 24 and through Week 48 | Time to virologic failure based on observed HIV-1 RNA levels and failure events (death; permanent discontinuation of test drug \[perm DC\]; lost to follow-up \[LTFU\]; new anti-retroviral drug added (except background drug change to drug of same class); or on open label for early non-response or rebound). Failure: at Time 0 if level not \<400 copies/mL (2 consecutive visits) before event(s) or last available visit; at time of earliest event if level \<400 copies/mL (on 2 consecutive visits); failure if level ≥400 copies/mL (2 consecutive visits) or 1 visit ≥400 copies/mL followed by perm DC or LTFU. |
| Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA | Baseline to Week 24 and Week 48 | Change from baseline of TAD in log10 HIV-1 RNA viral load calculated as \[AUC of HIV-1 RNA viral load (log10 copies/mL) / time period\] - Baseline HIV-1 RNA viral load (log10 copies/mL). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and baseline visits. |
| Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL | Week 24, Week 48 | — |
| Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Screening through Week 24 | Number of subjects per Tropism status (CCR5 \[R5\], CXCR4 \[X4\], Dual Mixed \[DM\], or Non-reportable/Non-phenotypable \[NR/NP\]) at Screening (Scr) and at time of treatment failure (Tx fail). Treatment failure defined as insufficient clinical response. HIV-1 RNA viral load \<500 copies/ml categorized as below lower limit of quantification (BLQ). Tropism may have been assessed at either the Screening or Baseline visit. The assessment for time of treatment failure is defined as the last on-treatment assessment. |
| Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Screening through Week 48 | Number of subjects per Tropism status (CCR5 \[R5\], CXCR4 \[X4\], Dual Mixed \[DM\], or Non-reportable/Non-phenotypable \[NR/NP\]) at Screening (Scr) and at time of treatment failure (Tx fail). Treatment failure defined as insufficient clinical response. HIV-1 RNA viral load \<500 copies/ml categorized as below lower limit of quantification (BLQ). Tropism may have been assessed at either the Screening or Baseline visit. The assessment for time of treatment failure is defined as the last on-treatment assessment. |
| Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening | Screening, Week 24 | Number of subjects for association between screening resistance and virologic response as determined by treatment failure and OSS at screening. OSS categorized as 0-1, 2-4, \>4 (maximum value of 6) and calculated as the sum of the net assessment of in vitro phenotypic and genotypic susceptibility using a binary scoring system (0= reduced susceptibility, 1=susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility. |
| Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening | Screening, Week48 | Number of subjects for association between screening resistance and virologic response as determined by treatment failure and OSS at screening. OSS categorized as 0, 1, 2, or ≥3 (maximum value of 6) and calculated as the sum of the net assessment of in vitro phenotypic and genotypic susceptibility using a binary scoring system (0= reduced susceptibility, 1=susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility. |
| Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Baseline through Week 24 | Number of subjects with AIDS-defining opportunistic illnesses based on investigator classification guided by a predefined list of clinical Category C Adverse Events per Center for Disease Control (CDC) HIV Classification System. Includes events occurring up to 7 days after last dose of study drug. |
| Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Baseline through Week 48 | Number of subjects with AIDS-defining opportunistic illnesses based on investigator classification guided by a predefined list of clinical Category C Adverse Events per CDC HIV Classification System. Includes events occurring up to 7 days after last dose of study drug. |
| Number of Subjects Per Genotype and Phenotype at Baseline and at Time of Failure | Baseline through Week 48 | Number of subjects per genotype and phenotype (tests for presence of non CCR5-tropic HIV-1 and for resistance to reverse transcriptase, protease, and fusion inhibitors) at baseline and at time of failure through Week 48 visit. Sensitivity to drug categorized as 0-1, 2-4, \>4; scores defined as 0=resistance, 1=sensitive or susceptible with higher number indicating greater sensitivity or susceptibility. |
Countries
Australia, Belgium, Canada, Germany, Netherlands, Spain, Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Maraviroc QD Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening. | 63 |
| Maraviroc BID Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening. | 61 |
| Placebo Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening. | 62 |
| Total | 186 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Assigned to Study Treatment | Randomized, but not treated | 0 | 2 | 2 |
| Continued on Open-Label Treatment | Adverse Event | 0 | 1 | 0 |
| Continued on Open-Label Treatment | Lack of Efficacy | 1 | 2 | 0 |
| Continued on Open-Label Treatment | Lost to Follow-up | 1 | 1 | 0 |
| Continued on Open-Label Treatment | Other reason includes protocol violation | 6 | 7 | 0 |
| Continued on Open-Label Treatment | Withdrawal by Subject | 0 | 4 | 0 |
| Received Study Treatment | Adverse Event | 1 | 2 | 5 |
| Received Study Treatment | Death | 2 | 1 | 2 |
| Received Study Treatment | Lack of Efficacy | 40 | 27 | 27 |
| Received Study Treatment | Other | 2 | 2 | 6 |
| Received Study Treatment | Subject defaulted | 3 | 4 | 4 |
Baseline characteristics
| Characteristic | Maraviroc QD | Maraviroc BID | Placebo | Total |
|---|---|---|---|---|
| Age Continuous | 42.7 years FULL_RANGE 8.4 | 42.5 years FULL_RANGE 8 | 44.6 years FULL_RANGE 8.3 | 43.3 years FULL_RANGE 8.2 |
| Age, Customized <18 years | 2 participants | 2 participants | 0 participants | 4 participants |
| Age, Customized ≥65 years | 0 participants | 0 participants | 1 participants | 1 participants |
| Age, Customized Between 18 and 24 years | 1 participants | 1 participants | 1 participants | 3 participants |
| Age, Customized Between 25 and 34 years | 2 participants | 3 participants | 2 participants | 7 participants |
| Age, Customized Between 35 and 44 years | 30 participants | 31 participants | 31 participants | 92 participants |
| Age, Customized Between 45 and 54 years | 25 participants | 21 participants | 20 participants | 66 participants |
| Age, Customized Between 55 and 64 years | 3 participants | 3 participants | 7 participants | 13 participants |
| Sex: Female, Male Female | 10 Participants | 6 Participants | 9 Participants | 25 Participants |
| Sex: Female, Male Male | 53 Participants | 55 Participants | 53 Participants | 161 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 46 / 63 | 51 / 62 | 42 / 61 |
| serious Total, serious adverse events | 13 / 63 | 14 / 62 | 13 / 61 |
Outcome results
Primary
Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA])
Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log 10 copies per milliliter \[log10 copies/mL\]). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time frame: Baseline to Week 24 and Week 48
Population: Full Analysis Set (FAS)-as treated: all randomized subjects classified as dual-tropic by phenotype assay; received at least 1 dose of study treatment. Missing values: discontinuations (DC) imputed as baseline value (change from baseline=0); missing data imputed as Last Observation Carried Forward (LOCF).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc QD | Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA]) | Week 24 | -0.890 log10 copies/mL | Standard Error 0.1706 |
| Maraviroc QD | Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA]) | Week 48 | -0.604 log10 copies/mL | Standard Error 0.1596 |
| Maraviroc BID | Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA]) | Week 24 | -1.194 log10 copies/mL | Standard Error 0.206 |
| Maraviroc BID | Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA]) | Week 48 | -1.105 log10 copies/mL | Standard Error 0.2071 |
| Placebo | Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA]) | Week 24 | -0.953 log10 copies/mL | Standard Error 0.1795 |
| Placebo | Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA]) | Week 48 | 0.839 log10 copies/mL | Standard Error 0.1851 |
Comparison: Maraviroc (MVC) QD versus placebo (PBO) treatment (TX) difference at Week 24. If upper bound of 97.5% confidence interval is \<0, it is concluded that dose is superior to PBO. If upper bound is \<0.25, it is concluded that MVC is non-inferior to PBO. Assumption: 79% of subjects are dual-tropic; total N=192 needed to be randomized to get N=150 dual-tropic. Standard deviation=0.8 with 2-sided p-value=0.025: 80% power for TX difference of 0.5 for change from baseline in log10-transformed viral load.97.5% CI: [-0.528, 0.638]ANCOVA
Comparison: MVC BID vs PBO treatment difference at Week 24.97.5% CI: [-0.829, 0.364]ANCOVA
Comparison: MVC QD vs PBO treatment difference at Week 48.97.5% CI: [-0.351, 0.81]ANCOVA
Comparison: MVC BID vs PBO treatment difference at Week 48.97.5% CI: [-0.856, 0.333]ANCOVA
Secondary
Change From Baseline in CD4 Cell Count
Change from baseline in CD4 cell count (measured as cells per microliter \[cells/µL\]). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time frame: Baseline to Week 24 and Week 48
Population: FAS - as treated dual-tropic subjects. Placebo N: 4 subjects did not have on-treatment information. Missing data imputed using LOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc QD | Change From Baseline in CD4 Cell Count | Week 24 | 59.237 cells/µL | Standard Error 8.9661 |
| Maraviroc QD | Change From Baseline in CD4 Cell Count | Week 48 | 65.86 cells/µL | Standard Error 10.822 |
| Maraviroc BID | Change From Baseline in CD4 Cell Count | Week 24 | 62.651 cells/µL | Standard Error 10.0234 |
| Maraviroc BID | Change From Baseline in CD4 Cell Count | Week 48 | 78.87 cells/µL | Standard Error 11.566 |
| Placebo | Change From Baseline in CD4 Cell Count | Week 24 | 36.367 cells/µL | Standard Error 8.4477 |
| Placebo | Change From Baseline in CD4 Cell Count | Week 48 | 51.29 cells/µL | Standard Error 12.523 |
Comparison: MVC QD vs PBO treatment difference at Week 24.95% CI: [-1.359, 49.213]ANCOVA
Comparison: MVC BID vs PBO treatment difference at Week 24.95% CI: [0.869, 52.49]ANCOVA
Comparison: MVC QD vs PBO treatment difference at Week 48.95% CI: [-17.8, 47.03]ANCOVA
Comparison: MVC BID vs PBO treatment difference at Week 48.95% CI: [-5.38, 60.8]ANCOVA
Secondary
Change From Baseline in CD8 Cell Count
Change from baseline in CD8 cell count (measured as cells/µL). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time frame: Baseline to Week 24 and Week 48
Population: FAS - as treated dual-tropic subjects. Placebo N: 4 subjects did not have on-treatment information. Missing data imputed using LOCF.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc QD | Change From Baseline in CD8 Cell Count | Week 24 | 391.061 cells/µL | Standard Error 57.0135 |
| Maraviroc QD | Change From Baseline in CD8 Cell Count | Week 48 | 351.23 cells/µL | Standard Error 54.653 |
| Maraviroc BID | Change From Baseline in CD8 Cell Count | Week 24 | 322.683 cells/µL | Standard Error 68.3315 |
| Maraviroc BID | Change From Baseline in CD8 Cell Count | Week 48 | 342.87 cells/µL | Standard Error 72.222 |
| Placebo | Change From Baseline in CD8 Cell Count | Week 24 | 154.293 cells/µL | Standard Error 46.81 |
| Placebo | Change From Baseline in CD8 Cell Count | Week 48 | 192.30 cells/µL | Standard Error 62.578 |
Comparison: MVC QD vs PBO treatment difference at Week 24.95% CI: [74.913, 394.084]ANCOVA
Comparison: MVC BID vs PBO treatment difference at Week 24.95% CI: [23.999, 353.635]ANCOVA
Comparison: MVC QD vs PBO treatment difference at Week 48.95% CI: [-16.49, 328.37]ANCOVA
Comparison: MVC BID vs PBO treatment difference at Week 48.95% CI: [4.81, 361.02]ANCOVA
Secondary
Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA
Change from baseline of TAD in log10 HIV-1 RNA viral load calculated as \[AUC of HIV-1 RNA viral load (log10 copies/mL) / time period\] - Baseline HIV-1 RNA viral load (log10 copies/mL). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time frame: Baseline to Week 24 and Week 48
Population: FAS - as treated dual-tropic subjects. Discontinuations prior to time point of analysis imputed as 0.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc QD | Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA | Week 24 | -0.850 log10 copies/mL | Standard Error 0.151 |
| Maraviroc QD | Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA | Week 48 | -0.561 log10 copies/mL | Standard Error 0.1475 |
| Maraviroc BID | Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA | Week 24 | -1.151 log10 copies/mL | Standard Error 0.1895 |
| Maraviroc BID | Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA | Week 48 | -1.066 log10 copies/mL | Standard Error 0.1962 |
| Placebo | Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA | Week 24 | -0.926 log10 copies/mL | Standard Error 0.1679 |
| Placebo | Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA | Week 48 | -0.776 log10 copies/mL | Standard Error 0.17 |
Comparison: MVC QD vs PBO treatment difference at Week 24.95% CI: [-0.396, 0.535]ANCOVA
Comparison: MVC BID vs PBO treatment difference at Week 24.95% CI: [-0.694, 0.258]ANCOVA
Comparison: MVC QD vs PBO treatment difference at Week 48.95% CI: [-0.262, 0.681]ANCOVA
Comparison: MVC BID vs PBO treatment difference at Week 48.95% CI: [-0.767, 0.199]ANCOVA
Secondary
Number of Subjects Per Genotype and Phenotype at Baseline and at Time of Failure
Number of subjects per genotype and phenotype (tests for presence of non CCR5-tropic HIV-1 and for resistance to reverse transcriptase, protease, and fusion inhibitors) at baseline and at time of failure through Week 48 visit. Sensitivity to drug categorized as 0-1, 2-4, \>4; scores defined as 0=resistance, 1=sensitive or susceptible with higher number indicating greater sensitivity or susceptibility.
Time frame: Baseline through Week 48
Population: FAS-as treated dual-tropic subjects. Genotype and phenotype at screening and at time of failure were not summarized as planned.
Secondary
Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24)
Number of subjects per Tropism status (CCR5 \[R5\], CXCR4 \[X4\], Dual Mixed \[DM\], or Non-reportable/Non-phenotypable \[NR/NP\]) at Screening (Scr) and at time of treatment failure (Tx fail). Treatment failure defined as insufficient clinical response. HIV-1 RNA viral load \<500 copies/ml categorized as below lower limit of quantification (BLQ). Tropism may have been assessed at either the Screening or Baseline visit. The assessment for time of treatment failure is defined as the last on-treatment assessment.
Time frame: Screening through Week 24
Population: FAS-as treated; N=subjects with TX failure due to insufficient clinical response and who had a tropism assessment at Screening. Subjects with DC prior to timepoint not included; LOCF if no result (viral load too low for analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc QD | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr: X4, Tx fail: X4 | 1 participants |
| Maraviroc QD | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr: X4, Tx fail: DM | 1 participants |
| Maraviroc QD | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr: DM, Tx fail: R5 | 1 participants |
| Maraviroc QD | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr: DM, Tx fail: X4 | 12 participants |
| Maraviroc QD | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr: DM, Tx fail: DM | 19 participants |
| Maraviroc QD | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr DM, Tx fail: NR/NP | 0 participants |
| Maraviroc QD | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr DM, Tx fail: BLQ | 1 participants |
| Maraviroc QD | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr NR/NP, Tx fail: NR/NP | 0 participants |
| Maraviroc BID | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr: DM, Tx fail: R5 | 0 participants |
| Maraviroc BID | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr DM, Tx fail: BLQ | 0 participants |
| Maraviroc BID | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr: DM, Tx fail: X4 | 12 participants |
| Maraviroc BID | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr: DM, Tx fail: DM | 9 participants |
| Maraviroc BID | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr DM, Tx fail: NR/NP | 0 participants |
| Maraviroc BID | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr: X4, Tx fail: X4 | 1 participants |
| Maraviroc BID | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr: X4, Tx fail: DM | 1 participants |
| Maraviroc BID | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr NR/NP, Tx fail: NR/NP | 1 participants |
| Placebo | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr: DM, Tx fail: R5 | 4 participants |
| Placebo | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr: X4, Tx fail: DM | 0 participants |
| Placebo | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr: X4, Tx fail: X4 | 1 participants |
| Placebo | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr: DM, Tx fail: X4 | 2 participants |
| Placebo | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr DM, Tx fail: BLQ | 0 participants |
| Placebo | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr DM, Tx fail: NR/NP | 1 participants |
| Placebo | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr: DM, Tx fail: DM | 16 participants |
| Placebo | Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24) | Scr NR/NP, Tx fail: NR/NP | 0 participants |
Secondary
Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48)
Number of subjects per Tropism status (CCR5 \[R5\], CXCR4 \[X4\], Dual Mixed \[DM\], or Non-reportable/Non-phenotypable \[NR/NP\]) at Screening (Scr) and at time of treatment failure (Tx fail). Treatment failure defined as insufficient clinical response. HIV-1 RNA viral load \<500 copies/ml categorized as below lower limit of quantification (BLQ). Tropism may have been assessed at either the Screening or Baseline visit. The assessment for time of treatment failure is defined as the last on-treatment assessment.
Time frame: Screening through Week 48
Population: FAS-as treated; N=subjects with TX failure due to insufficient clinical response and who had a tropism assessment at Screening. Subjects with DC prior to timepoint not included; LOCF if no result (viral load too low for analysis).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc QD | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: X4, Tx fail: X4 | 1 participants |
| Maraviroc QD | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: X4, Tx fail: DM | 1 participants |
| Maraviroc QD | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: DM, Tx fail: R5 | 1 participants |
| Maraviroc QD | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: DM, Tx fail: X4 | 12 participants |
| Maraviroc QD | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: DM, Tx fail: DM | 24 participants |
| Maraviroc QD | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: DM, Tx fail: NR/NP | 0 participants |
| Maraviroc QD | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: DM, Tx fail: BLQ | 1 participants |
| Maraviroc QD | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: NR/NP, Tx fail: NR/NP | 0 participants |
| Maraviroc BID | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: DM, Tx fail: R5 | 1 participants |
| Maraviroc BID | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: DM, Tx fail: BLQ | 0 participants |
| Maraviroc BID | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: DM, Tx fail: X4 | 12 participants |
| Maraviroc BID | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: DM, Tx fail: DM | 10 participants |
| Maraviroc BID | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: DM, Tx fail: NR/NP | 1 participants |
| Maraviroc BID | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: X4, Tx fail: X4 | 1 participants |
| Maraviroc BID | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: X4, Tx fail: DM | 1 participants |
| Maraviroc BID | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: NR/NP, Tx fail: NR/NP | 1 participants |
| Placebo | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: DM, Tx fail: R5 | 5 participants |
| Placebo | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: X4, Tx fail: DM | 0 participants |
| Placebo | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: X4, Tx fail: X4 | 1 participants |
| Placebo | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: DM, Tx fail: X4 | 2 participants |
| Placebo | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: DM, Tx fail: BLQ | 0 participants |
| Placebo | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: DM, Tx fail: NR/NP | 1 participants |
| Placebo | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: DM, Tx fail: DM | 18 participants |
| Placebo | Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48) | Scr: NR/NP, Tx fail: NR/NP | 0 participants |
Secondary
Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24)
Number of subjects with AIDS-defining opportunistic illnesses based on investigator classification guided by a predefined list of clinical Category C Adverse Events per Center for Disease Control (CDC) HIV Classification System. Includes events occurring up to 7 days after last dose of study drug.
Time frame: Baseline through Week 24
Population: FAS - as randomized; N=number of subjects with Category C Adverse Events for maraviroc QD, maraviroc BID, and placebo, respectively. Week 48 results reflect subsequent updates to data originally reported at Week 24.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc QD | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Histoplasmosis | 1 participants |
| Maraviroc QD | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Encephalitis | 0 participants |
| Maraviroc QD | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Oesophageal candidiasis | 0 participants |
| Maraviroc QD | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Mycobacterium avium complex infection | 1 participants |
| Maraviroc QD | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Candidiasis | 0 participants |
| Maraviroc QD | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Pneumonia | 0 participants |
| Maraviroc QD | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Herpes simplex | 1 participants |
| Maraviroc QD | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Cytomegalovirus chorioretinitis | 1 participants |
| Maraviroc QD | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Pneumocystis jiroveci pneumonia | 3 participants |
| Maraviroc BID | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Mycobacterium avium complex infection | 0 participants |
| Maraviroc BID | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Candidiasis | 0 participants |
| Maraviroc BID | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Cytomegalovirus chorioretinitis | 0 participants |
| Maraviroc BID | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Herpes simplex | 0 participants |
| Maraviroc BID | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Histoplasmosis | 0 participants |
| Maraviroc BID | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Oesophageal candidiasis | 2 participants |
| Maraviroc BID | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Pneumocystis jiroveci pneumonia | 1 participants |
| Maraviroc BID | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Pneumonia | 0 participants |
| Maraviroc BID | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Encephalitis | 0 participants |
| Placebo | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Herpes simplex | 0 participants |
| Placebo | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Candidiasis | 1 participants |
| Placebo | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Pneumocystis jiroveci pneumonia | 0 participants |
| Placebo | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Cytomegalovirus chorioretinitis | 0 participants |
| Placebo | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Encephalitis | 1 participants |
| Placebo | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Mycobacterium avium complex infection | 0 participants |
| Placebo | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Histoplasmosis | 0 participants |
| Placebo | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Pneumonia | 1 participants |
| Placebo | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24) | Oesophageal candidiasis | 0 participants |
Secondary
Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48)
Number of subjects with AIDS-defining opportunistic illnesses based on investigator classification guided by a predefined list of clinical Category C Adverse Events per CDC HIV Classification System. Includes events occurring up to 7 days after last dose of study drug.
Time frame: Baseline through Week 48
Population: FAS - as randomized; N=number of subjects with Category C Adverse Events for maraviroc QD, maraviroc BID, and placebo, respectively. Week 48 results reflect subsequent updates to data originally reported at Week 24.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc QD | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Candidiasis | 0 participants |
| Maraviroc QD | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Cytomegalovirus chorioretinitis | 1 participants |
| Maraviroc QD | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Histoplasmosis | 1 participants |
| Maraviroc QD | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Oesophageal candidiasis | 0 participants |
| Maraviroc QD | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Pneumococcal Sepsis | 0 participants |
| Maraviroc QD | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Pneumocystis jiroveci pneumonia | 3 participants |
| Maraviroc QD | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Pneumonia | 0 participants |
| Maraviroc QD | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Encephalitis | 0 participants |
| Maraviroc BID | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Histoplasmosis | 0 participants |
| Maraviroc BID | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Pneumonia | 1 participants |
| Maraviroc BID | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Oesophageal candidiasis | 2 participants |
| Maraviroc BID | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Pneumococcal Sepsis | 1 participants |
| Maraviroc BID | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Pneumocystis jiroveci pneumonia | 0 participants |
| Maraviroc BID | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Candidiasis | 1 participants |
| Maraviroc BID | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Cytomegalovirus chorioretinitis | 0 participants |
| Maraviroc BID | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Encephalitis | 0 participants |
| Placebo | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Histoplasmosis | 0 participants |
| Placebo | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Cytomegalovirus chorioretinitis | 0 participants |
| Placebo | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Candidiasis | 1 participants |
| Placebo | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Oesophageal candidiasis | 0 participants |
| Placebo | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Pneumonia | 0 participants |
| Placebo | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Pneumocystis jiroveci pneumonia | 0 participants |
| Placebo | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Pneumococcal Sepsis | 0 participants |
| Placebo | Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48) | Encephalitis | 1 participants |
Secondary
Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL
Time frame: Week 24, Week 48
Population: FAS - as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc QD | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL | Week 24 | 14 participants |
| Maraviroc QD | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL | Week 48 | 13 participants |
| Maraviroc BID | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL | Week 48 | 16 participants |
| Maraviroc BID | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL | Week 24 | 16 participants |
| Placebo | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL | Week 24 | 14 participants |
| Placebo | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL | Week 48 | 13 participants |
Comparison: MVC QD vs PBO treatment difference in proportions at Week 24.95% CI: [-0.12, 0.18]
Comparison: MVC BID vs PBO treatment difference in proportions at Week 24.95% CI: [-0.08, 0.23]
Comparison: MVC QD vs PBO treatment difference in proportions at Week 48.95% CI: [-0.12, 0.17]
Comparison: MVC BID vs PBO treatment difference in proportions at Week 48.95% CI: [-0.07, 0.25]
Secondary
Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels
Number of subjects with HIV-1 RNA levels \< 400 copies/mL or at least 0.5 log 10-transformed decrease from baseline in HIV-1 RNA levels. Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time frame: Baseline, Week 24, Week 48
Population: FAS-as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc QD | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels | Week 24 | 24 participants |
| Maraviroc QD | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels | Week 48 | 14 participants |
| Maraviroc BID | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels | Week 24 | 25 participants |
| Maraviroc BID | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels | Week 48 | 22 participants |
| Placebo | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels | Week 24 | 23 participants |
| Placebo | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels | Week 48 | 18 participants |
Comparison: MVC QD vs PBO treatment difference in proportions at Week 24.95% CI: [-0.15, 0.2]
Comparison: MVC BID vs PBO treatment difference in proportions at Week 24.95% CI: [-0.1, 0.26]
Comparison: MVC QD vs PBO treatment difference in proportions at Week 48.95% CI: [-0.22, 0.1]
Comparison: MVC BID vs PBO treatment difference in proportions at Week 48.95% CI: [-0.07, 0.28]
Secondary
Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels
Number of subjects with HIV-1 RNA levels \< 400 copies/mL or at least 1.0 log 10-transformed decrease from baseline in HIV-1 RNA levels. Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time frame: Baseline, Week 24, Week 48
Population: FAS-as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc QD | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels | Week 24 | 18 participants |
| Maraviroc QD | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels | Week 48 | 13 participants |
| Maraviroc BID | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels | Week 24 | 23 participants |
| Maraviroc BID | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels | Week 48 | 20 participants |
| Placebo | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels | Week 24 | 21 participants |
| Placebo | Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels | Week 48 | 15 participants |
Comparison: MVC QD vs PBO treatment difference in proportions at Week 24.95% CI: [-0.21, 0.12]
Comparison: MVC BID vs PBO treatment difference in proportions at Week 24.95% CI: [-0.1, 0.26]
Comparison: MVC QD vs PBO treatment difference in proportions at Week 48.95% CI: [-0.18, 0.13]
Comparison: MVC BID vs PBO treatment difference in proportions at Week 48.95% CI: [-0.04, 0.29]
Secondary
Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL
Time frame: Baseline, Week 24, Week 48
Population: FAS - as treated dual-tropic subjects. Missing values counted as failures/non-responders (counted as not achieving the stated criterion).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc QD | Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL | Week 24 | 12 participants |
| Maraviroc QD | Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL | Week 48 | 10 participants |
| Maraviroc BID | Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL | Week 48 | 14 participants |
| Maraviroc BID | Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL | Week 24 | 14 participants |
| Placebo | Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL | Week 48 | 13 participants |
| Placebo | Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL | Week 24 | 9 participants |
Comparison: MVC QD vs PBO treatment difference in proportions at Week 24.95% CI: [-0.07, 0.2]
Comparison: MVC BID vs PBO difference in proportions at Week 24.95% CI: [-0.03, 0.26]
Comparison: MVC QD vs PBO treatment difference in proportions at Week 48.95% CI: [-0.18, 0.1]
Comparison: MVC BID vs PBO treatment difference in proportions at Week 48.95% CI: [-0.1, 0.21]
Secondary
Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening
Number of subjects for association between screening resistance and virologic response as determined by treatment failure and OSS at screening. OSS categorized as 0-1, 2-4, \>4 (maximum value of 6) and calculated as the sum of the net assessment of in vitro phenotypic and genotypic susceptibility using a binary scoring system (0= reduced susceptibility, 1=susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility.
Time frame: Screening, Week 24
Population: FAS - as treated dual-tropic subjects. Missing values imputed as LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc QD | Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening | Scr score: 2-4 | 35 participants |
| Maraviroc QD | Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening | Scr score: 0-1 | 21 participants |
| Maraviroc QD | Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening | Scr score: missing | 1 participants |
| Maraviroc BID | Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening | Scr score: 2-4 | 35 participants |
| Maraviroc BID | Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening | Scr score: 0-1 | 12 participants |
| Maraviroc BID | Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening | Scr score: missing | 1 participants |
| Placebo | Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening | Scr score: 0-1 | 17 participants |
| Placebo | Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening | Scr score: missing | 1 participants |
| Placebo | Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening | Scr score: 2-4 | 40 participants |
Secondary
Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening
Number of subjects for association between screening resistance and virologic response as determined by treatment failure and OSS at screening. OSS categorized as 0, 1, 2, or ≥3 (maximum value of 6) and calculated as the sum of the net assessment of in vitro phenotypic and genotypic susceptibility using a binary scoring system (0= reduced susceptibility, 1=susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility.
Time frame: Screening, Week48
Population: FAS - as treated dual-tropic subjects. Missing values imputed as LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc QD | Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening | Scr score: ≥3 | 15 particpants |
| Maraviroc QD | Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening | Scr score: 2 | 21 particpants |
| Maraviroc QD | Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening | Scr score: 0 | 1 particpants |
| Maraviroc QD | Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening | Scr score: 1 | 19 particpants |
| Maraviroc QD | Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening | Scr score: missing | 1 particpants |
| Maraviroc BID | Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening | Scr score: 2 | 14 particpants |
| Maraviroc BID | Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening | Scr score: 0 | 2 particpants |
| Maraviroc BID | Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening | Scr score: 1 | 11 particpants |
| Maraviroc BID | Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening | Scr score: ≥3 | 24 particpants |
| Maraviroc BID | Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening | Scr score: missing | 1 particpants |
| Placebo | Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening | Scr score: missing | 1 particpants |
| Placebo | Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening | Scr score: ≥3 | 27 particpants |
| Placebo | Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening | Scr score: 0 | 2 particpants |
| Placebo | Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening | Scr score: 2 | 13 particpants |
| Placebo | Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening | Scr score: 1 | 15 particpants |
Secondary
Time (50% Quartile Point Estimate) to Virologic Failure
Time to virologic failure based on observed HIV-1 RNA levels and failure events (death; permanent discontinuation of test drug \[perm DC\]; lost to follow-up \[LTFU\]; new anti-retroviral drug added (except background drug change to drug of same class); or on open label for early non-response or rebound). Failure: at Time 0 if level not \<400 copies/mL (2 consecutive visits) before event(s) or last available visit; at time of earliest event if level \<400 copies/mL (on 2 consecutive visits); failure if level ≥400 copies/mL (2 consecutive visits) or 1 visit ≥400 copies/mL followed by perm DC or LTFU.
Time frame: Day 1 through Week 24 and through Week 48
Population: FAS - as treated dual-tropic subjects; (n)=number of subjects with virologic failure at observation for maraviroc QD, maraviroc BID, and placebo, respectively; Week 48 result values (0.00)=virologic failure at Day 0.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Maraviroc QD | Time (50% Quartile Point Estimate) to Virologic Failure | Week 24 (n=35, 23, 29) | 88.00 days |
| Maraviroc QD | Time (50% Quartile Point Estimate) to Virologic Failure | Week 48 (n=45, 37, 44) | 0.00 days |
| Maraviroc BID | Time (50% Quartile Point Estimate) to Virologic Failure | Week 24 (n=35, 23, 29) | 189.00 days |
| Maraviroc BID | Time (50% Quartile Point Estimate) to Virologic Failure | Week 48 (n=45, 37, 44) | 0.00 days |
| Placebo | Time (50% Quartile Point Estimate) to Virologic Failure | Week 24 (n=35, 23, 29) | 100.00 days |
| Placebo | Time (50% Quartile Point Estimate) to Virologic Failure | Week 48 (n=45, 37, 44) | 0.00 days |
Comparison: MVC QD vs PBO at Week 24. Kaplan-Meier survival estimates. TX difference evaluated by log-rank test.p-value: 0.7524Log Rank
Comparison: MVC BID vs PBO at Week 24. Kaplan-Meier survival estimates. TX difference evaluated by log-rank test.p-value: 0.254Log Rank
Comparison: MVC QD vs PBO at Week 48. Kaplan-Meier survival estimates. TX difference evaluated by log-rank test.p-value: 0.8243Log Rank
Comparison: MVC BID vs PBO at Week 48. Kaplan-Meier survival estimates. TX difference evaluated by log-rank test.p-value: 0.6657Log Rank