HIV Infections
Conditions
Keywords
HIV Infections
Brief summary
To provide access to maraviroc to patients who have limited or no therapeutic treatment options and to collect more safety data in a broader patient population.
Interventions
DRUGmaraviroc
The nominal dose for maraviroc is 300 mg twice a day (BID). However, the dosage of maraviroc should be adjusted based on optimal background therapy (OBT) patient is taking. If OBT includes CYP3A4 inhibitor (with or without inducers) maraviroc dose should be 150 mg BID and if OBT includes CYP3A4 inducer (without inhibitors) maraviroc dose should be 600mg BID. If OBT does not include any CYP3A4 inducers or inhibitors maraviroc dose should be 300 mg BID.
Sponsors
ViiV Healthcare
Study design
Allocation
NON_RANDOMIZED
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must be failing to achieve adequate virologic suppression on their current regimen and have HIV-1 RNA greater than or equal to 1000 copies/ml, at screening * Have only R5 HIV-1 at Screening as verified by the Monogram Biosciences Trofile assay * Minimum age must be 16 years or minimum adult age as determined by local regulatory authorities or directed by local law.
Exclusion criteria
* Failed prior treatment with any CCR5 antagonist, in any ongoing CCR5 trial or having previously prematurely discontinued Maraviroc in trials
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Grade 3 and Grade 4 Adverse Events (AE) | Baseline up to Week 144 | AEs as defined by the Division of AIDS (DAIDS) toxicity grading scale: Grade 3 = severe: interrupted usual daily activity and traditionally required systemic drug therapy or other treatment. Grade 4 = very severe: events that were unacceptable and intolerable or were irreversable or caused imminent danger of death. If same participant had more than 1 occurrence in the same preferred term event category, only the most severe (grade 4) occurrence was taken. Treatment-related = investigator assessment of a reasonable possibility that the investigational product caused or contributed to the AE. |
| Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Baseline up to Week 144 | Laboratory abnormalities as defined by the Division of AIDS (DAIDS) toxicity grading scale: Grade 3, Severe =events that interrupted participants usual daily activity and traditionally required systemic drug therapy or other treatment. |
| Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Baseline up to Week 144 | Laboratory abnormalities as defined by the Division of AIDS (DAIDS) toxicity grading scale: Grade 4, Very Severe = events which were unacceptable and intolerable or were irreversible or caused the participant to be in imminent danger of death. |
| Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | Baseline up to Week 144 | Treatment-emergent 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 30 days after last dose of study drug. |
| Percentage of Participants With Possible Acquired Immunodeficiency Syndrome (AIDS) Related Infections and Malignancies by Baseline Viral Load | Baseline up to Week 144 | — |
| Percentage of Participants With Possible Acquired Immunodeficiency Syndrome (AIDS) Related Infections and Malignancies by Baseline/Nadir CD4 Cell Counts | Baseline up to Week 144 | — |
| Percentage of Participants With Possible Acquired Immunodeficiency Syndrome (AIDS) Related Infections and Malignancies by Time on Therapy | Baseline up to Week 144 | — |
| Percentage of Participants With All Causality Treatment-emergent Adverse (AEs) Events by Gender | Baseline up to Week 144 | Treatment-emergent AEs by gender that occurred up to 30 days after the last dose of study medication. |
| Percentage of Participants With Treatment-emergent Adverse Events (AEs) by Race | Baseline up to Week 144 | Treatment-emergent AEs by race that occurred up to 30 days after the last dose of study medication. |
| Percentage of Participants With Treatment-emergent Adverse Events (AEs) by Age | Baseline up to Week 144 | Treatment-emergent AEs by age that occurred up to 30 days after the last dose of study medication. |
| Percentage of Participants With Treatment-emergent Averse Events (AEs) by Baseline Hepatitis B and Hepatitis C Virus Serology Status | Baseline up to Week 144 | Treatment emergent AEs by hepatis B and hepatitis C serology status that occurred up to 30 days post last dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Baseline up to Week 144 | Defined as HIV-1 RNA levels \< 400 Copies/mL or at least 0.5 Log 10-decrease from baseline in HIV-1 RNA levels. Baseline value calculated as average of the screening and baseline values if both values were within 1 log10 difference. |
| Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Baseline up to Week 144 | Defined as HIV-1 RNA levels \< 400 copies/mL or at least 1.0 Log 10-decrease from baseline in HIV-1 RNA levels. Baseline value calculated as average of the screening and baseline values if both values were within 1 log10 difference. |
| Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Baseline up to Week 144 | Limit of quantification defined as \<400 copies/mL. Baseline value calculated as average of the screening and baseline values if both values were within 1 log 10 difference. |
| Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Baseline up to Week 144 | Limit of quantification defined as \<50 copies/mL. Baseline value calculated as average of the screening and baseline values if both values were within 1 log 10 difference. |
| Change From Baseline in CD4 Cell Count | Baseline up to Week 144 | Change from baseline in cluster of differentiation 4 helper T cells (CD4) cell count. If baseline value was not available, it was taken from immediate preceding non-missing value. |
| Change From Baseline in CD4 Cell Count Percent | Baseline up to Week 144 | Change from baseline in CD4 cell count percent . If baseline value was not available, it was taken from immediate preceding non-missing value. |
| Change From Baseline in CD8 Cell Count | Baseline up to Week 144 | Change from baseline in cluster of differentiation 8 suppressor T cells (CD8) cell count. If baseline value was not available, it was taken from immediate preceding non-missing value. |
| Change From Baseline in CD8 Cell Count Percent | Baseline up to Week 144 | Change from baseline in CD8 cell count percent . If baseline value was not available, it was taken from immediate preceding non-missing value. |
| Median Time to Virologic Failure | Day 1 up to Week 144 | Computed as time from the first dose of study medication to the loss of virologic response. Virologic failure defined as: failure to achieve a reduction from baseline (BL) in HIV 1 RNA ≥ 0.5 log10 copies /mL by the second viral load determination (unless viral load was below the lower limit level of quantification \[LLOQ\]); or a ≥ 0.5 log10 increase from nadir in HIV 1 RNA after achieving a HIV 1 RNA reduction from BL \>0.5 log10 copies/mL; or a HIV 1 RNA level of \>1000 copies/mL after having achieved a HIV 1 RNA level below LLOQ. |
| Percentage of Participants With Changes in HIV-1 RNA Level in Participants Meeting the Definition of Virologic Failure | Baseline up to Week 144 | Reasons for virologic failure: A) failure to achieve a reduction in HIV-1 RNA\>=0.5 log10 copies/ml from baseline (BL) by second viral load determination (unless below level of quantification \[LOQ\]); B) \>=0.5 log10 increase from nadir in HIV-1 RNA after achieving an HIV-1 RNA reduction from BL \>0.5 log10 copies/ml ; C) HIV-1 RNA \>1000 copies/ml after having achieved an HIV-1 RNA below LOQ. |
| Percentage of Participants With Change in Chemokine Co-receptor Tropism From Screening to Time of Virologic Failure | Screening up to Week 144 | Tropism status (CCR5 \[R5\], CXCR4 \[X4\], Dual Mixed \[DM\], or Non-reportable \[NR\]) at Screening (Scr) and time of virologic failure (V fail). Virologic failure defined as: failure to achieve a reduction from baseline (BL) in HIV 1 RNA ≥0.5 log10 copies/mL by second viral load determination (unless viral load was below lower limit level of quantification \[LLOQ\]); or a ≥ 0.5 log10 increase from nadir in HIV 1 RNA after achieving HIV 1 RNA reduction from BL \>0.5 log10 copies/mL; or a HIV 1 RNA level of \>1000 copies/mL after having achieved a HIV 1 RNA level below LLOQ. |
| Number of Participants With Reduced Maraviroc Susceptibility as Defined by Change From Baseline to Time of Virologic Failure in Inhibitory Concentration of 50% (IC 50) and Presence of Plateau | Baseline up to Week 144 | Resistance to maravroc in viruses from participants failing therapy with R5 virus was investigated using the in vitro phenotypic (drug susceptibility) assay. The number of participants who failed with R5 virus were assessed successfully for maraviroc susceptibility at Baseline and Last on--treatment (Week 144). Samples were analyzed for change from Baseline to time of virologic failure in IC 50 and presence of plateau. A maximal percent inhibition (MPI) \<95% established as a plateau in inhibition at high concentrations of maraviroc was used to identify viruses which had reduced phenotypic susceptibility to maraviroc. |
| Number of Participants With Emergence of Resistance to Maraviroc as Defined by Genotypic Changes in the V3 Loop of Glycoprotein 120 (gp 120) | Baseline up to Week 144 | Virus from participants who experienced virologic failure was analyzed for resistance to maraviroc. Resistance testing was performed on archived samples of participants which were available pre--treatment at time of virologic failure. For participants who met definition of virologic failure during the trial, the sequencing of the V3 loop of HIV--1 viral envelope gp 120 was evaluated to identify any amino acid changes concomitant with decreased susceptibility to maraviroc. |
Countries
Argentina, Australia, Austria, Belgium, Canada, Chile, Costa Rica, Dominican Republic, France, Germany, Greece, Hong Kong, India, Ireland, Italy, Malaysia, Mexico, Netherlands, Portugal, Puerto Rico, Romania, Spain, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
Of 2584 participants screened, 1047 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Maraviroc Maraviroc 150 milligrams (mg) twice daily (BID), 600 mg BID, or 300 mg BID; dose administered depending on concomitant medications in combination with optimized background therapy (OBT) according to local standard of care. | 1,032 |
| Total | 1,032 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 23 |
| Overall Study | Death | 14 |
| Overall Study | Enrolled Not Treated | 15 |
| Overall Study | Insufficient Clinical Response | 22 |
| Overall Study | Lost to Follow-up | 15 |
| Overall Study | Other | 23 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 18 |
Baseline characteristics
| Characteristic | Maraviroc |
|---|---|
| Age, Continuous | 45.6 years STANDARD_DEVIATION 8.6 |
| Baseline Viral Load: Absolute Value >= 100,000: Absolute (N=250) | 234750.0 copies/mL |
| Baseline Viral Load: Absolute Value < 100,000: Absolute (N=729) | 22395.9 copies/mL STANDARD_DEVIATION 25974.4 |
| Baseline Viral Load: Absolute Value Overall: Absolute (N=979) | 25109.5 copies/mL |
| Baseline Viral Load: : Log Scale >= 100,000: Log Scale (N=250) | 5.371 log10 copies/mL |
| Baseline Viral Load: : Log Scale < 100,000: Log Scale (N=729) | 4.043 log10 copies/mL |
| Baseline Viral Load: : Log Scale Overall: Log Scale (N=979) | 4.400 log10 copies/mL |
| Baseline Viral Load: Log Scale >= 100,000: Log Scale (N=250) | 5.423 log10 copies/mL STANDARD_DEVIATION 0.3496 |
| Baseline Viral Load: Log Scale < 100,000: Log Scale (N=729) | 3.859 log10 copies/mL STANDARD_DEVIATION 0.8517 |
| Baseline Viral Load: Log Scale Overall: Log Scale (N=979) | 4.259 log10 copies/mL STANDARD_DEVIATION 1.0182 |
| Sex: Female, Male Female | 205 Participants |
| Sex: Female, Male Male | 827 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 700 / 1,032 |
| serious Total, serious adverse events | 139 / 1,032 |
Outcome results
Primary
Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses
Treatment-emergent 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 30 days after last dose of study drug.
Time frame: Baseline up to Week 144
Population: Safety analysis set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc | Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | AIDS encephalopathy | 0.1 percentage of participants |
| Maraviroc | Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | Bone tuberculosis | 0.1 percentage of participants |
| Maraviroc | Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | Cytomegalovirus infection | 0.2 percentage of participants |
| Maraviroc | Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | Extrapulmonary tuberculosis | 0.1 percentage of participants |
| Maraviroc | Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | Meningitis cryptococcal | 0.1 percentage of participants |
| Maraviroc | Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | Meningitis tuberculous | 0.1 percentage of participants |
| Maraviroc | Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | Mycobacterium avium complex infection | 0.1 percentage of participants |
| Maraviroc | Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | Mycobacterium kansasii infection | 0.1 percentage of participants |
| Maraviroc | Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | Oesophageal candidiasis | 0.6 percentage of participants |
| Maraviroc | Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | Pancreatitis bacterial | 0.1 percentage of participants |
| Maraviroc | Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | Pneumocystis jiroveci pneumonia | 0.1 percentage of participants |
| Maraviroc | Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | Progressive multifocal leukoencephalopathy | 0.1 percentage of participants |
| Maraviroc | Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | Pulmonary tuberculosis | 0.5 percentage of participants |
| Maraviroc | Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | Toxoplasmosis | 0.1 percentage of participants |
| Maraviroc | Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | B-cell lymphoma | 0.1 percentage of participants |
| Maraviroc | Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | Hodgkin's disease | 0.1 percentage of participants |
| Maraviroc | Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | Kaposi's sarcoma | 0.2 percentage of participants |
| Maraviroc | Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses | Encephalopathy | 0.1 percentage of participants |
Primary
Percentage of Participants With All Causality Treatment-emergent Adverse (AEs) Events by Gender
Treatment-emergent AEs by gender that occurred up to 30 days after the last dose of study medication.
Time frame: Baseline up to Week 144
Population: Safety analysis set; n = number of participants evaluable for adverse events.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc | Percentage of Participants With All Causality Treatment-emergent Adverse (AEs) Events by Gender | Male (n=827) | 69.6 percentage of participants |
| Maraviroc | Percentage of Participants With All Causality Treatment-emergent Adverse (AEs) Events by Gender | Female (n=205) | 73.7 percentage of participants |
Primary
Percentage of Participants With Grade 3 and Grade 4 Adverse Events (AE)
AEs as defined by the Division of AIDS (DAIDS) toxicity grading scale: Grade 3 = severe: interrupted usual daily activity and traditionally required systemic drug therapy or other treatment. Grade 4 = very severe: events that were unacceptable and intolerable or were irreversable or caused imminent danger of death. If same participant had more than 1 occurrence in the same preferred term event category, only the most severe (grade 4) occurrence was taken. Treatment-related = investigator assessment of a reasonable possibility that the investigational product caused or contributed to the AE.
Time frame: Baseline up to Week 144
Population: Safety analysis set: all participants who were randomized and received at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc | Percentage of Participants With Grade 3 and Grade 4 Adverse Events (AE) | Grade 3 AE: all causality | 13.2 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 3 and Grade 4 Adverse Events (AE) | Grade 3 AE: treatment related | 2.4 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 3 and Grade 4 Adverse Events (AE) | Grade 4 AE: all causality | 6.3 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 3 and Grade 4 Adverse Events (AE) | Grade 4 AE: treatment related | 1.6 percentage of participants |
Primary
Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities
Laboratory abnormalities as defined by the Division of AIDS (DAIDS) toxicity grading scale: Grade 3, Severe =events that interrupted participants usual daily activity and traditionally required systemic drug therapy or other treatment.
Time frame: Baseline up to Week 144
Population: Safety analysis set. N = number of participants evaluable for laboratory abnormalities (with at least one observation of a laboratory test while on study treatment or during lag time); n = number of participants with at least one observation of given laboratory test while on study treatment or during lag time.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc | Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Alanine aminotransferase (ALT) (n=1013) | 2.17 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Aspartate aminotransferase (AST) (n=1013) | 2.07 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Absolute Neutrophil Count (n=1004) | 0.70 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Alkaline Phosphatase (n=1014) | 0.39 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Creatinine (n=1014) | 0.49 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Gamma-glutamyl transpeptidase (GGT) (n=1014) | 4.73 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Hemoglobin (n=1005) | 0.20 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Hyperbilirubinemia (n=1013) | 1.28 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Hyperuricemia (n=1014) | 0.69 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Hypophosphatemia (n=1014) | 0.20 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Lipase (n=409) | 4.40 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Platelets (n=997) | 1.50 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Potassium (hyperkalemia) (n=1014) | 0.10 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Serum Amylase (n=1014) | 4.83 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Sodium (hypernatremia) (n=1014) | 0.10 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Triglycerides (n=1014) | 4.73 percentage of participants |
Primary
Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities
Laboratory abnormalities as defined by the Division of AIDS (DAIDS) toxicity grading scale: Grade 4, Very Severe = events which were unacceptable and intolerable or were irreversible or caused the participant to be in imminent danger of death.
Time frame: Baseline up to Week 144
Population: Safety analysis set. N = number of participants evaluable for laboratory abnormalities (with at least one observation of a laboratory test while on study treatment or during lag time); n = number of participants with at least one observation of given laboratory test while on study treatment or during lag time.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc | Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities | ALT (n=1013) | 0.79 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities | AST (n=1013) | 0.39 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Absolute Neutrophil Count (n=1004) | 0.20 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Alkaline Phosphatase (n=1014) | 0.00 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Creatinine (n=1014) | 0.10 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities | GGT (n=1014) | 1.48 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Hemoglobin (n=1005) | 0.10 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Hyperbilirubinemia (n=1013) | 0.30 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Hyperuricemia (n=1014) | 0.10 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Hypophosphatemia (n=1014) | 0.00 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Lipase (n=409) | 1.22 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Platelets (n=997) | 0.30 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Potassium (hyperkalemia) (n=1014) | 0.20 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Serum Amylase (n=1014) | 0.30 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Sodium (hypernatremia) (n=1014) | 0.20 percentage of participants |
| Maraviroc | Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities | Triglycerides (n=1014) | 1.97 percentage of participants |
Primary
Percentage of Participants With Possible Acquired Immunodeficiency Syndrome (AIDS) Related Infections and Malignancies by Baseline/Nadir CD4 Cell Counts
Time frame: Baseline up to Week 144
Population: Safety analysis set. Data not analyzed; the number of possible AIDS-related infections and malignancies and limited data collection during the study in terms of baseline/nadir CD4 cell counts were such that a summary of AIDS-related infections by this parameter was not clinically meaningful.
Primary
Percentage of Participants With Possible Acquired Immunodeficiency Syndrome (AIDS) Related Infections and Malignancies by Baseline Viral Load
Time frame: Baseline up to Week 144
Population: Safety analysis set. Data not analyzed; the number of possible AIDS-related infections and malignancies and limited data collection during the study in terms of baseline viral load were such that a summary of AIDS-related infections by this parameter was not clinically meaningful.
Primary
Percentage of Participants With Possible Acquired Immunodeficiency Syndrome (AIDS) Related Infections and Malignancies by Time on Therapy
Time frame: Baseline up to Week 144
Population: Safety analysis set. Data not analyzed; the number of possible AIDS-related infections and malignancies and limited data collection during the study by time on therapy were such that a summary of AIDS-related infections by this parameter was not clinically meaningful.
Primary
Percentage of Participants With Treatment-emergent Adverse Events (AEs) by Age
Treatment-emergent AEs by age that occurred up to 30 days after the last dose of study medication.
Time frame: Baseline up to Week 144
Population: Safety analysis set; n = number of participants evaluable for adverse events.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by Age | <18 years (n=1) | 100.0 percentage of participants |
| Maraviroc | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by Age | 18 to 44 years (n=515) | 71.7 percentage of participants |
| Maraviroc | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by Age | 45 to 64 years (n=493) | 68.6 percentage of participants |
| Maraviroc | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by Age | >=65 years (n=23) | 82.6 percentage of participants |
Primary
Percentage of Participants With Treatment-emergent Adverse Events (AEs) by Race
Treatment-emergent AEs by race that occurred up to 30 days after the last dose of study medication.
Time frame: Baseline up to Week 144
Population: Safety analysis set; n = number of participants evaluable for adverse events.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by Race | White (n=817) | 68.5 percentage of participants |
| Maraviroc | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by Race | Black (n=106) | 67.9 percentage of participants |
| Maraviroc | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by Race | Asian (n=54) | 88.9 percentage of participants |
| Maraviroc | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by Race | Other Unspecified (n=55) | 85.5 percentage of participants |
Primary
Percentage of Participants With Treatment-emergent Averse Events (AEs) by Baseline Hepatitis B and Hepatitis C Virus Serology Status
Treatment emergent AEs by hepatis B and hepatitis C serology status that occurred up to 30 days post last dose.
Time frame: Baseline up to Week 144
Population: Safety analysis set; n = number of participants evaluable for adverse events. Abbreviations: HBV = hepatitis B virus, HBC = hepatitis C virus.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc | Percentage of Participants With Treatment-emergent Averse Events (AEs) by Baseline Hepatitis B and Hepatitis C Virus Serology Status | HBV: negative (n=897) | 71.3 percentage of participants |
| Maraviroc | Percentage of Participants With Treatment-emergent Averse Events (AEs) by Baseline Hepatitis B and Hepatitis C Virus Serology Status | HBV: positive (n=60) | 65.0 percentage of participants |
| Maraviroc | Percentage of Participants With Treatment-emergent Averse Events (AEs) by Baseline Hepatitis B and Hepatitis C Virus Serology Status | HBV: missing: (n=75) | 64.0 percentage of participants |
| Maraviroc | Percentage of Participants With Treatment-emergent Averse Events (AEs) by Baseline Hepatitis B and Hepatitis C Virus Serology Status | HCV: negative (n=794) | 72.7 percentage of participants |
| Maraviroc | Percentage of Participants With Treatment-emergent Averse Events (AEs) by Baseline Hepatitis B and Hepatitis C Virus Serology Status | HCV: positive (n=158) | 62.7 percentage of participants |
| Maraviroc | Percentage of Participants With Treatment-emergent Averse Events (AEs) by Baseline Hepatitis B and Hepatitis C Virus Serology Status | HCV: missing (n=80) | 63.8 percentage of participants |
Secondary
Change From Baseline in CD4 Cell Count
Change from baseline in cluster of differentiation 4 helper T cells (CD4) cell count. If baseline value was not available, it was taken from immediate preceding non-missing value.
Time frame: Baseline up to Week 144
Population: Safety analysis set; n = number of participants contributing to summary statistic at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc | Change From Baseline in CD4 Cell Count | Day 2-7 (n=6) | 28.5 cells/uL | Standard Deviation 76.18 |
| Maraviroc | Change From Baseline in CD4 Cell Count | Week 2 (n=213) | 49.7 cells/uL | Standard Deviation 93.15 |
| Maraviroc | Change From Baseline in CD4 Cell Count | Week 4 (n=762) | 68.9 cells/uL | Standard Deviation 124.31 |
| Maraviroc | Change From Baseline in CD4 Cell Count | Week 8 (n=739) | 94.5 cells/uL | Standard Deviation 122.94 |
| Maraviroc | Change From Baseline in CD4 Cell Count | Week 12 (n=738) | 95.7 cells/uL | Standard Deviation 124.42 |
| Maraviroc | Change From Baseline in CD4 Cell Count | Week 16 (n=149) | 85.9 cells/uL | Standard Deviation 124.37 |
| Maraviroc | Change From Baseline in CD4 Cell Count | Week 20 (n=130) | 106.6 cells/uL | Standard Deviation 112.26 |
| Maraviroc | Change From Baseline in CD4 Cell Count | Week 24 (n=552) | 127.8 cells/uL | Standard Deviation 139.42 |
| Maraviroc | Change From Baseline in CD4 Cell Count | Week 32 (n=197) | 124.1 cells/uL | Standard Deviation 150.44 |
| Maraviroc | Change From Baseline in CD4 Cell Count | Week 40 (n=232) | 129.2 cells/uL | Standard Deviation 144.31 |
| Maraviroc | Change From Baseline in CD4 Cell Count | Week 48 (n=222) | 140.5 cells/uL | Standard Deviation 154.46 |
| Maraviroc | Change From Baseline in CD4 Cell Count | Week 60 (n=161) | 134.0 cells/uL | Standard Deviation 151.52 |
| Maraviroc | Change From Baseline in CD4 Cell Count | Week 72 (n=124) | 147.0 cells/uL | Standard Deviation 160.92 |
| Maraviroc | Change From Baseline in CD4 Cell Count | Week 84 (n=72) | 141.1 cells/uL | Standard Deviation 147.55 |
| Maraviroc | Change From Baseline in CD4 Cell Count | Week 96 (n=50) | 160.3 cells/uL | Standard Deviation 160.78 |
| Maraviroc | Change From Baseline in CD4 Cell Count | Week 108 (n=19) | 242.9 cells/uL | Standard Deviation 167.06 |
| Maraviroc | Change From Baseline in CD4 Cell Count | Week 120 (n=8) | 117.9 cells/uL | Standard Deviation 203.49 |
| Maraviroc | Change From Baseline in CD4 Cell Count | Week 132 (n=4) | 179.0 cells/uL | Standard Deviation 109.94 |
| Maraviroc | Change From Baseline in CD4 Cell Count | Week 144 (n=1) | 93.0 cells/uL | — |
Secondary
Change From Baseline in CD4 Cell Count Percent
Change from baseline in CD4 cell count percent . If baseline value was not available, it was taken from immediate preceding non-missing value.
Time frame: Baseline up to Week 144
Population: Safety analysis set; n = number of participants contributing to summary statistic at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Days 2-7 (n=6) | -1.3 percentage of lymphocytes | Standard Deviation 1.56 |
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Week 2 (n=206) | 1.8 percentage of lymphocytes | Standard Deviation 3.79 |
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Week 4 (n=733) | 1.6 percentage of lymphocytes | Standard Deviation 4.84 |
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Week 8 (n=722) | 1.4 percentage of lymphocytes | Standard Deviation 6.12 |
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Week 12 (n=708) | 1.6 percentage of lymphocytes | Standard Deviation 5.45 |
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Week 16 (n=141) | 1.9 percentage of lymphocytes | Standard Deviation 4.63 |
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Week 20 (n=125) | 2.2 percentage of lymphocytes | Standard Deviation 6.17 |
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Week 24 (n=531) | 2.8 percentage of lymphocytes | Standard Deviation 4.55 |
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Week 32 (n=191) | 3.2 percentage of lymphocytes | Standard Deviation 5.38 |
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Week 40 (n=218) | 3.7 percentage of lymphocytes | Standard Deviation 4.97 |
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Week 48 (n=210) | 3.5 percentage of lymphocytes | Standard Deviation 5.87 |
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Week 60 (n=148) | 4.5 percentage of lymphocytes | Standard Deviation 6.1 |
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Week 72 (n=116) | 5.0 percentage of lymphocytes | Standard Deviation 6.33 |
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Week 84 (n=64) | 5.7 percentage of lymphocytes | Standard Deviation 6.73 |
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Week 96 (n=41) | 3.9 percentage of lymphocytes | Standard Deviation 6.36 |
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Week 108 (n=19) | 6.3 percentage of lymphocytes | Standard Deviation 6.86 |
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Week 120 (n=7) | 5.7 percentage of lymphocytes | Standard Deviation 9.07 |
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Week 132 (n=4) | 8.5 percentage of lymphocytes | Standard Deviation 8.35 |
| Maraviroc | Change From Baseline in CD4 Cell Count Percent | Week 144 (n=1) | 1.0 percentage of lymphocytes | Standard Deviation 0 |
Secondary
Change From Baseline in CD8 Cell Count
Change from baseline in cluster of differentiation 8 suppressor T cells (CD8) cell count. If baseline value was not available, it was taken from immediate preceding non-missing value.
Time frame: Baseline up to Week 144
Population: Safety analysis set; n = number of participants contributing to summary statistic at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc | Change From Baseline in CD8 Cell Count | Day 2-7 (n=6) | 268.5 cells/uL | Standard Deviation 262.5 |
| Maraviroc | Change From Baseline in CD8 Cell Count | Week 2 (n=201) | 78.2 cells/uL | Standard Deviation 343.85 |
| Maraviroc | Change From Baseline in CD8 Cell Count | Week 4 (n=701) | 205.6 cells/uL | Standard Deviation 509.7 |
| Maraviroc | Change From Baseline in CD8 Cell Count | Week 8 (n=692) | 345.6 cells/uL | Standard Deviation 599.98 |
| Maraviroc | Change From Baseline in CD8 Cell Count | Week 12 (n=696) | 309.4 cells/uL | Standard Deviation 578.91 |
| Maraviroc | Change From Baseline in CD8 Cell Count | Week 16 (n=129) | 259.6 cells/uL | Standard Deviation 430.78 |
| Maraviroc | Change From Baseline in CD8 Cell Count | Week 20 (n=119) | 325.2 cells/uL | Standard Deviation 621.46 |
| Maraviroc | Change From Baseline in CD8 Cell Count | Week 24 (n=523) | 251.3 cells/uL | Standard Deviation 498.85 |
| Maraviroc | Change From Baseline in CD8 Cell Count | Week 32 (n=185) | 185.2 cells/uL | Standard Deviation 484.74 |
| Maraviroc | Change From Baseline in CD8 Cell Count | Week 40 (n=222) | 160.9 cells/uL | Standard Deviation 471.99 |
| Maraviroc | Change From Baseline in CD8 Cell Count | Week 48 (n=214) | 153.2 cells/uL | Standard Deviation 464.73 |
| Maraviroc | Change From Baseline in CD8 Cell Count | Week 60 (n=157) | 76.9 cells/uL | Standard Deviation 467.64 |
| Maraviroc | Change From Baseline in CD8 Cell Count | Week 72 (n=120) | 68.7 cells/uL | Standard Deviation 502.73 |
| Maraviroc | Change From Baseline in CD8 Cell Count | Week 84 (n=70) | -11.6 cells/uL | Standard Deviation 548.85 |
| Maraviroc | Change From Baseline in CD8 Cell Count | Week 96 (n=45) | 56.6 cells/uL | Standard Deviation 403.1 |
| Maraviroc | Change From Baseline in CD8 Cell Count | Week 108 (n=19) | 147.5 cells/uL | Standard Deviation 600.55 |
| Maraviroc | Change From Baseline in CD8 Cell Count | Week 120 (n=8) | -135.1 cells/uL | Standard Deviation 517.02 |
| Maraviroc | Change From Baseline in CD8 Cell Count | Week 132 (n=4) | -363.3 cells/uL | Standard Deviation 882.3 |
| Maraviroc | Change From Baseline in CD8 Cell Count | Week 144 (n=1) | 642.0 cells/uL | Standard Deviation 0 |
Secondary
Change From Baseline in CD8 Cell Count Percent
Change from baseline in CD8 cell count percent . If baseline value was not available, it was taken from immediate preceding non-missing value.
Time frame: Baseline up to Week 144
Population: Safety analysis set; n = number of participants contributing to summary statistic at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Week 120 (n=6) | -14.5 percentage of lymphocytes | Standard Deviation 13.41 |
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Day 2-7 (n=6) | 3.0 percentage of lymphocytes | Standard Deviation 3.42 |
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Week 2 (n=197) | -1.5 percentage of lymphocytes | Standard Deviation 7.68 |
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Week 4 (n=689) | -0.3 percentage of lymphocytes | Standard Deviation 8.08 |
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Week 8 (n=683) | 0.4 percentage of lymphocytes | Standard Deviation 9.62 |
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Week 12 (n=675) | -0.9 percentage of lymphocytes | Standard Deviation 9.95 |
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Week 16 (n=125) | 0.7 percentage of lymphocytes | Standard Deviation 8.66 |
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Week 20 (n=115) | -0.7 percentage of lymphocytes | Standard Deviation 10.08 |
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Week 24 (n=510) | -3.2 percentage of lymphocytes | Standard Deviation 8.92 |
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Week 32 (n=184) | -4.0 percentage of lymphocytes | Standard Deviation 9.09 |
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Week 40 (n=215) | -4.5 percentage of lymphocytes | Standard Deviation 8.9 |
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Week 48 (n=202) | -5.1 percentage of lymphocytes | Standard Deviation 10.63 |
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Week 60 (n=146) | -5.0 percentage of lymphocytes | Standard Deviation 11.9 |
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Week 72 (n=113) | -6.2 percentage of lymphocytes | Standard Deviation 9.87 |
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Week 84 (n=64) | -8.2 percentage of lymphocytes | Standard Deviation 15.52 |
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Week 96 (n=40) | -9.5 percentage of lymphocytes | Standard Deviation 10.18 |
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Week 108 (n=19) | -14.5 percentage of lymphocytes | Standard Deviation 9.99 |
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Week 132 (n=4) | -16.8 percentage of lymphocytes | Standard Deviation 12.89 |
| Maraviroc | Change From Baseline in CD8 Cell Count Percent | Week 144 (n=1) | -2.0 percentage of lymphocytes | Standard Deviation 0 |
Secondary
Median Time to Virologic Failure
Computed as time from the first dose of study medication to the loss of virologic response. Virologic failure defined as: failure to achieve a reduction from baseline (BL) in HIV 1 RNA ≥ 0.5 log10 copies /mL by the second viral load determination (unless viral load was below the lower limit level of quantification \[LLOQ\]); or a ≥ 0.5 log10 increase from nadir in HIV 1 RNA after achieving a HIV 1 RNA reduction from BL \>0.5 log10 copies/mL; or a HIV 1 RNA level of \>1000 copies/mL after having achieved a HIV 1 RNA level below LLOQ.
Time frame: Day 1 up to Week 144
Population: Safety analysis set. N = number of participants with virologic failure. For the calculation of the time to virologic failure, any visits with no data were excluded. Participants who were not virologic failures were censored at the last available observation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Median Time to Virologic Failure | 86.5 days |
95% CI: [135, 178]
95% CI: [82, 92]
95% CI: [57, 62]
Secondary
Number of Participants With Emergence of Resistance to Maraviroc as Defined by Genotypic Changes in the V3 Loop of Glycoprotein 120 (gp 120)
Virus from participants who experienced virologic failure was analyzed for resistance to maraviroc. Resistance testing was performed on archived samples of participants which were available pre--treatment at time of virologic failure. For participants who met definition of virologic failure during the trial, the sequencing of the V3 loop of HIV--1 viral envelope gp 120 was evaluated to identify any amino acid changes concomitant with decreased susceptibility to maraviroc.
Time frame: Baseline up to Week 144
Population: Safety analysis set. Here, number of participants analyzed signifies those participants who were assessed for genotypic changes in the V3 Loop of glycoprotein 120 (gp 120).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maraviroc | Number of Participants With Emergence of Resistance to Maraviroc as Defined by Genotypic Changes in the V3 Loop of Glycoprotein 120 (gp 120) | NA participants |
Secondary
Number of Participants With Reduced Maraviroc Susceptibility as Defined by Change From Baseline to Time of Virologic Failure in Inhibitory Concentration of 50% (IC 50) and Presence of Plateau
Resistance to maravroc in viruses from participants failing therapy with R5 virus was investigated using the in vitro phenotypic (drug susceptibility) assay. The number of participants who failed with R5 virus were assessed successfully for maraviroc susceptibility at Baseline and Last on--treatment (Week 144). Samples were analyzed for change from Baseline to time of virologic failure in IC 50 and presence of plateau. A maximal percent inhibition (MPI) \<95% established as a plateau in inhibition at high concentrations of maraviroc was used to identify viruses which had reduced phenotypic susceptibility to maraviroc.
Time frame: Baseline up to Week 144
Population: Safety analysis set. Here, number of participants analyzed signifies those participants who were assessed for maraviroc susceptibility.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maraviroc | Number of Participants With Reduced Maraviroc Susceptibility as Defined by Change From Baseline to Time of Virologic Failure in Inhibitory Concentration of 50% (IC 50) and Presence of Plateau | 14 participants |
Secondary
Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA)
Defined as HIV-1 RNA levels \< 400 Copies/mL or at least 0.5 Log 10-decrease from baseline in HIV-1 RNA levels. Baseline value calculated as average of the screening and baseline values if both values were within 1 log10 difference.
Time frame: Baseline up to Week 144
Population: Safety analysis set; n = number of participants contributing to summary statistic at given timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Day 2-7 (n=26) | 46.2 percentage of participants |
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Week 2 (n=226) | 93.8 percentage of participants |
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Week 4 (n=773) | 93 percentage of participants |
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Week 8 (n=761) | 93.2 percentage of participants |
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Week 12 (n=756) | 94 percentage of participants |
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Week 16 (n=155) | 87.7 percentage of participants |
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Week 20 (n=131) | 93.1 percentage of participants |
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Week 24 (n=557) | 91.9 percentage of participants |
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Week 32 (n=202) | 93.1 percentage of participants |
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Week 40 (n=227) | 91.2 percentage of participants |
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Week 48 (n=228) | 89 percentage of participants |
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Week 60 (n=160) | 90 percentage of participants |
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Week 72 (n=125) | 88 percentage of participants |
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Week 84 (n=79) | 84.8 percentage of participants |
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Week 96 (n=48) | 91.7 percentage of participants |
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Week 108 (n=18) | 100 percentage of participants |
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Week 120 (n=9) | 100 percentage of participants |
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Week 132 (n=4) | 100 percentage of participants |
| Maraviroc | Percentage of Participants With ≥0.5 log10 Reduction From Baseline in Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV 1 RNA) | Week 144 (n=1) | 100 percentage of participants |
Secondary
Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA
Defined as HIV-1 RNA levels \< 400 copies/mL or at least 1.0 Log 10-decrease from baseline in HIV-1 RNA levels. Baseline value calculated as average of the screening and baseline values if both values were within 1 log10 difference.
Time frame: Baseline up to Week 144
Population: Safety analysis set; n = number of participants contributing to summary statistic at given timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Day 2-7 (n=26) | 30.8 percentage of participants |
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Week 2 (n=226) | 90.3 percentage of participants |
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Week 4 (n=773) | 90.2 percentage of participants |
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Week 8 (n=761) | 91.2 percentage of participants |
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Week 12 (n=756) | 91.3 percentage of participants |
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Week 16 (n=155) | 82.6 percentage of participants |
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Week 20 (n=131) | 89.3 percentage of participants |
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Week 24 (n=557) | 89 percentage of participants |
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Week 32 (n=202) | 90.1 percentage of participants |
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Week 40 (n=227) | 87.7 percentage of participants |
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Week 48 (n=228) | 86.4 percentage of participants |
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Week 60 (n=160) | 85.6 percentage of participants |
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Week 72 (n=125) | 83.2 percentage of participants |
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Week 84 (n=79) | 79.7 percentage of participants |
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Week 96 (n=48) | 85.4 percentage of participants |
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Week 108 (n=18) | 100 percentage of participants |
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Week 120 (n=9) | 100 percentage of participants |
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Week 132 (n=4) | 100 percentage of participants |
| Maraviroc | Percentage of Participants With ≥1.0 log10 Reduction From Baseline in HIV 1 RNA | Week 144 (n=1) | 100 percentage of participants |
Secondary
Percentage of Participants With Change in Chemokine Co-receptor Tropism From Screening to Time of Virologic Failure
Tropism status (CCR5 \[R5\], CXCR4 \[X4\], Dual Mixed \[DM\], or Non-reportable \[NR\]) at Screening (Scr) and time of virologic failure (V fail). Virologic failure defined as: failure to achieve a reduction from baseline (BL) in HIV 1 RNA ≥0.5 log10 copies/mL by second viral load determination (unless viral load was below lower limit level of quantification \[LLOQ\]); or a ≥ 0.5 log10 increase from nadir in HIV 1 RNA after achieving HIV 1 RNA reduction from BL \>0.5 log10 copies/mL; or a HIV 1 RNA level of \>1000 copies/mL after having achieved a HIV 1 RNA level below LLOQ.
Time frame: Screening up to Week 144
Population: Safety analysis set; N = participants with virologic failure (VF). Abbreviations: Scr = screening, R5 = CCR5 tropic HIV-1, X4=CXCR4 tropic HIV-1, DM = dual mixed, NR = non-reportable, Missing = participants with VF who did not have tropism result within specified screening period (Scr missing: -42 days to Day 0) or at the time of VF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc | Percentage of Participants With Change in Chemokine Co-receptor Tropism From Screening to Time of Virologic Failure | Scr: Missing; V fail: R5 | 5.73 percentage of participants |
| Maraviroc | Percentage of Participants With Change in Chemokine Co-receptor Tropism From Screening to Time of Virologic Failure | Scr: Missing; V fail: X4 | 0.52 percentage of participants |
| Maraviroc | Percentage of Participants With Change in Chemokine Co-receptor Tropism From Screening to Time of Virologic Failure | Scr: Missing; V fail: DM | 1.04 percentage of participants |
| Maraviroc | Percentage of Participants With Change in Chemokine Co-receptor Tropism From Screening to Time of Virologic Failure | Scr: Missing; V fail: NR | 7.29 percentage of participants |
| Maraviroc | Percentage of Participants With Change in Chemokine Co-receptor Tropism From Screening to Time of Virologic Failure | Scr: Missing; V fail: Missing | 1.56 percentage of participants |
| Maraviroc | Percentage of Participants With Change in Chemokine Co-receptor Tropism From Screening to Time of Virologic Failure | Scr: NR; V fail: R5 | 0.52 percentage of participants |
| Maraviroc | Percentage of Participants With Change in Chemokine Co-receptor Tropism From Screening to Time of Virologic Failure | Scr: R5; V fail: R5 | 31.25 percentage of participants |
| Maraviroc | Percentage of Participants With Change in Chemokine Co-receptor Tropism From Screening to Time of Virologic Failure | Scr: R5; V fail: X4 | 4.17 percentage of participants |
| Maraviroc | Percentage of Participants With Change in Chemokine Co-receptor Tropism From Screening to Time of Virologic Failure | Scr: R5; V fail: DM | 18.75 percentage of participants |
| Maraviroc | Percentage of Participants With Change in Chemokine Co-receptor Tropism From Screening to Time of Virologic Failure | Scr: R5; V fail: NR | 22.92 percentage of participants |
| Maraviroc | Percentage of Participants With Change in Chemokine Co-receptor Tropism From Screening to Time of Virologic Failure | Scr: R5; V fail: Missing | 6.25 percentage of participants |
Secondary
Percentage of Participants With Changes in HIV-1 RNA Level in Participants Meeting the Definition of Virologic Failure
Reasons for virologic failure: A) failure to achieve a reduction in HIV-1 RNA\>=0.5 log10 copies/ml from baseline (BL) by second viral load determination (unless below level of quantification \[LOQ\]); B) \>=0.5 log10 increase from nadir in HIV-1 RNA after achieving an HIV-1 RNA reduction from BL \>0.5 log10 copies/ml ; C) HIV-1 RNA \>1000 copies/ml after having achieved an HIV-1 RNA below LOQ.
Time frame: Baseline up to Week 144
Population: Safety analysis set; N = number of participants with virologic failure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc | Percentage of Participants With Changes in HIV-1 RNA Level in Participants Meeting the Definition of Virologic Failure | Reduction in HIV-1 RNA<0.5 log10 copies/ml | 43.75 percentage of participants |
| Maraviroc | Percentage of Participants With Changes in HIV-1 RNA Level in Participants Meeting the Definition of Virologic Failure | >=0.5 log10 increase from nadir in HIV-1 RNA | 31.77 percentage of participants |
| Maraviroc | Percentage of Participants With Changes in HIV-1 RNA Level in Participants Meeting the Definition of Virologic Failure | HIV-1 RNA >1000 copies/ml | 18.75 percentage of participants |
| Maraviroc | Percentage of Participants With Changes in HIV-1 RNA Level in Participants Meeting the Definition of Virologic Failure | Reduction <0.5 log10 + HIV-1 RNA >1000 copies/ml | 3.13 percentage of participants |
| Maraviroc | Percentage of Participants With Changes in HIV-1 RNA Level in Participants Meeting the Definition of Virologic Failure | >=0.5 log10 increase from nadir + HIV-1 RNA >1000 | 2.60 percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL
Limit of quantification defined as \<400 copies/mL. Baseline value calculated as average of the screening and baseline values if both values were within 1 log 10 difference.
Time frame: Baseline up to Week 144
Population: Safety analysis set; n = number of participants contributing to summary statistic at given timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Baseline (n=979) | 6.7 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Day 2-7 (n=26) | 3.8 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Week 2 (n=226) | 58.8 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Week 4 (n=773) | 72.7 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Week 8 (n=761) | 78.8 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Week 12 (n=756) | 82.5 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Week 16 (n=155) | 75.5 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Week 20 (n=131) | 83.2 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Week 24 (n=557) | 84.4 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Week 32 (n=202) | 83.7 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Week 40 (n=227) | 81.1 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Week 48 (n=228) | 80.7 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Week 60 (n=160) | 78.1 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Week 72 (n=125) | 72.8 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Week 84 (n=79) | 74.7 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Week 96 (n=48) | 75.0 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Week 108 (n=18) | 88.9 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Week 120 (n=9) | 77.8 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Week 132 (n=4) | 100 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <400 Copies/mL | Week 144 (n=1) | 100 percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL
Limit of quantification defined as \<50 copies/mL. Baseline value calculated as average of the screening and baseline values if both values were within 1 log 10 difference.
Time frame: Baseline up to Week 144
Population: Safety analysis set; n = number of participants contributing to summary statistic at given timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Baseline (n=979) | 1.7 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Day 2-7 (n=26) | 0.0 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Week 2 (n=226) | 19.9 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Week 4 (n=773) | 30.1 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Week 8 (n=761) | 43.1 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Week 12 (n=756) | 45.8 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Week 16 (n=155) | 37.4 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Week 20 (n=131) | 42.7 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Week 24 (n=557) | 55.8 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Week 32 (n=202) | 57.4 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Week 40 (n=227) | 54.6 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Week 48 (n=228) | 54.8 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Week 60 (n=160) | 51.9 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Week 72 (n=125) | 49.6 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Week 84 (n=79) | 55.7 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Week 96 (n=48) | 54.2 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Week 108 (n=18) | 77.8 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Week 120 (n=9) | 44.4 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Week 132 (n=4) | 75.0 percentage of participants |
| Maraviroc | Percentage of Participants With HIV-1 RNA Levels Below the Limit of Quantification: <50 Copies/mL | Week 144 (n=1) | 100 percentage of participants |