Human Immunodeficiency Virus-1
Conditions
Keywords
CCR5-tropic HIV-1 virus
Brief summary
This is a pilot study to examine if the novel treatment regimen maraviroc plus boosted atazanavir can be expected to be safe and efficacious in treatment naive HIV infected patients. Based on the results from this study, a confirmatory phase 3 study may be conducted.
Interventions
DRUGmaraviroc
maraviroc (Selzentry, Celsentri) 150mg QD + atazanavir (Reyataz) /ritonavir (Norvir) (300/100mg) QD OR maraviroc (Selzentry, Celsentri) 150mg QD+ darunavir (Prezista)/ritonavir (Norvir) (800/100 mg) QD (if atazanavir (Reyataz) /ritonavir (Norvir) is replaced by darunavir (Prezista)/ritonavir (Norvir)) OR maraviroc (Selzentry, Celsentri) 150mg QD+ lopinavir/ritonavir (Kaletra, Aluvia) (400/100 mg) BID (if atazanavir (Reyataz) /ritonavir (Norvir) is replaced by lopinavir/ritonavir (Kaletra, Aluvia))
Sponsors
Pfizer
ViiV Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV-1 RNA viral load of ≥1,000 copies/mL measured at the Screening Visit. * CD4 count ≥100 cells/mm3 at Screening. * Have only R5 HIV-1 at Screening as verified by the Monogram Bioscience Trofile® assay with enhanced sensitivity.
Exclusion criteria
* Prior treatment with any other HIV antiretroviral therapy for more than 14 days at any time. * Any evidence of resistance to atazanavir, tenofovir, and emtricitabine. * X4-or dual/mixed-tropic virus by enhanced Trofile assay or repeated assay failure or not reportable results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Plasma Human Immuno Deficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than 50 Copies/Milliliter (mL) | Week 48 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HIV-1 RNA Levels of First 15 Participants at Days 4, 7, 10 and 14 | Baseline , Days 4, 7, 10 and 14 | Plasma HIV-1 RNA levels were evaluated for first 15 participants enrolled at United States (U.S) sites only. |
| Maximum Observed Plasma Concentration (Cmax) of Maraviroc | Day 14 (0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose) | — |
| Minimum Observed Plasma Concentration (Cmin) of Maraviroc | Day 14 (0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose) | — |
| Average Observed Plasma Concentration (Cavg) of Maraviroc | Day 14 (0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose) | Cavg was described as area under the plasma concentration-time profile from time zero to time 24 hours (AUC24) divided by the dosing interval (AUC24/ 24). |
| Change From Baseline in Plasma log10 Viral Load at Weeks 16, 24, 48 and 96 | Baseline, Week 16, Week 24, Week 48, Week 96 | — |
| Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, Week 96 | — |
| Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, Week 96 | — |
| HIV-1 RNA Levels at Baseline | Baseline | — |
| Time-Averaged Difference (TAD) in log10 Viral Load | Week 16, Week 24, Week 48, Week 96 | TAD was calculated as area under the curve of HIV divided by time period minus baseline HIV where HIV was denoted as HIV-1 RNA (log10 copies/mL). |
| Change From Baseline in Cluster of Differentiation 4+T Lymphocyte (CD4) Cell Counts at Weeks 16, 24, 48 and 96 | Baseline, Week 16, Week 24, Week 48, Week 96 | — |
| Change From Baseline in Cluster of Differentiation 8+T Lymphocyte (CD8) Cell Count at Weeks 16, 24, 48 and 96 | Baseline, Week 16, Week 24, Week 48, Week 96 | — |
| Number of Participants With Genotypic Resistance | Week 96 or Time of treatment failure | Genotypic resistance was assessed for all participants at screening and was evaluated for protease inhibitors (PIs), Nucleotide reverse transcriptase inhibitors (NRTIs), and non-NRTIs (NNRTIs) using Monogram GenoSeq and/or PhenoSenseGT assays. This was then repeated for all participants with HIV-1 viral load more than 500 copies/mL either at treatment failure or at early termination, up to Week 96. |
| Number of Participants With Phenotypic Resistance | Week 96 or Time of treatment failure | Phenotypic resistance was assessed for all participants at screening and was evaluated for PIs, NRTIs, and NNRTIs using Monogram GenoSeq and/or PhenoSenseGT assays. This was then repeated for all participants with HIV-1 viral load more than 500 copies/mL either at treatment failure or at early termination, up to Week 96. |
| Number of Participants With HIV-1 RNA Tropism Status Using Trofile Assay | Baseline to Week 96 or Time of treatment Failure | Viral tropism was determined using the trofile assay with enhanced sensitivity for participants with HIV-1 RNA greater than equal to 1000 copies/mL. The enhanced trofile assay had the sensitivity to detect 100 percent of spiked samples when C-X-C chemokine receptor type 4 {CXCR4} \[X4\]-using HIV-1 RNA represented 0.3 percent of the total viral population. |
| Time to Loss of Virological Response (TLOVR) | Baseline through Week 96 | TLOVR (virological failure) was defined as the time from first dose of study treatment (Day 1) until the time of virologic failure using the time to loss of virologic response algorithm. |
Countries
Germany, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Maraviroc+ Atazanavir / Ritonavir Maraviroc 150 milligram (mg) tablets once daily along with atazanavir/ritonavir 300 mg/100 mg tablets once daily were orally administered for 96 weeks. | 60 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir Atazanavir/ritonavir 300 mg/100 mg tablets once daily along with emtricitabine/tenofovir 200 mg/245 mg tablets once daily were orally administered for 96 weeks. | 61 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Lack of Efficacy | 2 | 0 |
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Other | 1 | 3 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Randomized but not treated | 5 | 3 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Maraviroc+ Atazanavir / Ritonavir | Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Total |
|---|---|---|---|
| Age Continuous | 38.3 Years STANDARD_DEVIATION 10.2 | 35.3 Years STANDARD_DEVIATION 10.5 | 36.8 Years STANDARD_DEVIATION 10.4 |
| Sex: Female, Male Female | 4 Participants | 9 Participants | 13 Participants |
| Sex: Female, Male Male | 56 Participants | 52 Participants | 108 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 55 / 60 | 58 / 61 |
| serious Total, serious adverse events | 13 / 60 | 11 / 61 |
Outcome results
Primary
Percentage of Participants With Plasma Human Immuno Deficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than 50 Copies/Milliliter (mL)
Time frame: Week 48
Population: Full Analysis Set (FAS) population included those participants who had taken at least one dose of the study drug, had baseline and at least one post baseline measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Plasma Human Immuno Deficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than 50 Copies/Milliliter (mL) | 74.60 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Plasma Human Immuno Deficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than 50 Copies/Milliliter (mL) | 83.60 Percentage of participants |
Secondary
Average Observed Plasma Concentration (Cavg) of Maraviroc
Cavg was described as area under the plasma concentration-time profile from time zero to time 24 hours (AUC24) divided by the dosing interval (AUC24/ 24).
Time frame: Day 14 (0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose)
Population: PK parameter analysis population included first 15 participants treated with maraviroc.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc+ Atazanavir / Ritonavir | Average Observed Plasma Concentration (Cavg) of Maraviroc | 185.10 ng/mL | Standard Deviation 71.08 |
Secondary
Change From Baseline in Cluster of Differentiation 4+T Lymphocyte (CD4) Cell Counts at Weeks 16, 24, 48 and 96
Time frame: Baseline, Week 16, Week 24, Week 48, Week 96
Population: FAS population included those participants who had taken at least one dose of the study drug, had a baseline and at least one post baseline measurement. Here n signified participants who received the study drug and evaluated at the time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in Cluster of Differentiation 4+T Lymphocyte (CD4) Cell Counts at Weeks 16, 24, 48 and 96 | Change at Week 16 (n= 54, 58) | 169.60 cells/microliter (cells/mcL) | Standard Deviation 117.2 |
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in Cluster of Differentiation 4+T Lymphocyte (CD4) Cell Counts at Weeks 16, 24, 48 and 96 | Change at Week 48 (n= 52, 53) | 215.70 cells/microliter (cells/mcL) | Standard Deviation 166.59 |
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in Cluster of Differentiation 4+T Lymphocyte (CD4) Cell Counts at Weeks 16, 24, 48 and 96 | Change at Week 24 (n= 54, 57) | 188.90 cells/microliter (cells/mcL) | Standard Deviation 125.14 |
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in Cluster of Differentiation 4+T Lymphocyte (CD4) Cell Counts at Weeks 16, 24, 48 and 96 | Change at Week 96 (n= 50, 51) | 287.50 cells/microliter (cells/mcL) | Standard Deviation 173.23 |
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in Cluster of Differentiation 4+T Lymphocyte (CD4) Cell Counts at Weeks 16, 24, 48 and 96 | Baseline (n= 59, 61) | 357.70 cells/microliter (cells/mcL) | Standard Deviation 123.53 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in Cluster of Differentiation 4+T Lymphocyte (CD4) Cell Counts at Weeks 16, 24, 48 and 96 | Change at Week 96 (n= 50, 51) | 298.50 cells/microliter (cells/mcL) | Standard Deviation 160.54 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in Cluster of Differentiation 4+T Lymphocyte (CD4) Cell Counts at Weeks 16, 24, 48 and 96 | Baseline (n= 59, 61) | 390.00 cells/microliter (cells/mcL) | Standard Deviation 152.34 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in Cluster of Differentiation 4+T Lymphocyte (CD4) Cell Counts at Weeks 16, 24, 48 and 96 | Change at Week 16 (n= 54, 58) | 139.80 cells/microliter (cells/mcL) | Standard Deviation 102.62 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in Cluster of Differentiation 4+T Lymphocyte (CD4) Cell Counts at Weeks 16, 24, 48 and 96 | Change at Week 24 (n= 54, 57) | 173.30 cells/microliter (cells/mcL) | Standard Deviation 130.55 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in Cluster of Differentiation 4+T Lymphocyte (CD4) Cell Counts at Weeks 16, 24, 48 and 96 | Change at Week 48 (n= 52, 53) | 226.60 cells/microliter (cells/mcL) | Standard Deviation 138.04 |
Secondary
Change From Baseline in Cluster of Differentiation 8+T Lymphocyte (CD8) Cell Count at Weeks 16, 24, 48 and 96
Time frame: Baseline, Week 16, Week 24, Week 48, Week 96
Population: FAS population included those participants who had taken at least one dose of the study drug, had a baseline and at least one post baseline measurement. Here n signified participants who received the study drug and evaluated at the time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in Cluster of Differentiation 8+T Lymphocyte (CD8) Cell Count at Weeks 16, 24, 48 and 96 | Change at Week 16 (n= 54, 58) | 63.70 cells/mcL | Standard Deviation 290.49 |
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in Cluster of Differentiation 8+T Lymphocyte (CD8) Cell Count at Weeks 16, 24, 48 and 96 | Change at Week 48 (n= 52, 53) | -76.80 cells/mcL | Standard Deviation 354.48 |
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in Cluster of Differentiation 8+T Lymphocyte (CD8) Cell Count at Weeks 16, 24, 48 and 96 | Change at Week 24 (n= 54, 57) | 6.20 cells/mcL | Standard Deviation 334.89 |
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in Cluster of Differentiation 8+T Lymphocyte (CD8) Cell Count at Weeks 16, 24, 48 and 96 | Change at Week 96 (n= 50, 51) | -63.00 cells/mcL | Standard Deviation 355.6 |
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in Cluster of Differentiation 8+T Lymphocyte (CD8) Cell Count at Weeks 16, 24, 48 and 96 | Baseline (n= 59, 61) | 931.10 cells/mcL | Standard Deviation 446.26 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in Cluster of Differentiation 8+T Lymphocyte (CD8) Cell Count at Weeks 16, 24, 48 and 96 | Change at Week 96 (n= 50, 51) | -231.40 cells/mcL | Standard Deviation 516.99 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in Cluster of Differentiation 8+T Lymphocyte (CD8) Cell Count at Weeks 16, 24, 48 and 96 | Baseline (n= 59, 61) | 1125.60 cells/mcL | Standard Deviation 735.08 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in Cluster of Differentiation 8+T Lymphocyte (CD8) Cell Count at Weeks 16, 24, 48 and 96 | Change at Week 16 (n= 54, 58) | -153.80 cells/mcL | Standard Deviation 473.96 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in Cluster of Differentiation 8+T Lymphocyte (CD8) Cell Count at Weeks 16, 24, 48 and 96 | Change at Week 24 (n= 54, 57) | -178.00 cells/mcL | Standard Deviation 508.75 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in Cluster of Differentiation 8+T Lymphocyte (CD8) Cell Count at Weeks 16, 24, 48 and 96 | Change at Week 48 (n= 52, 53) | -267.60 cells/mcL | Standard Deviation 574.22 |
Secondary
Change From Baseline in HIV-1 RNA Levels of First 15 Participants at Days 4, 7, 10 and 14
Plasma HIV-1 RNA levels were evaluated for first 15 participants enrolled at United States (U.S) sites only.
Time frame: Baseline , Days 4, 7, 10 and 14
Population: First 15 participants who were enrolled at U.S sites and had taken the study drug .
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in HIV-1 RNA Levels of First 15 Participants at Days 4, 7, 10 and 14 | Change at Day 4 | 1800.00 copies/mL | Standard Deviation 37351.09 |
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in HIV-1 RNA Levels of First 15 Participants at Days 4, 7, 10 and 14 | Change at Day 7 | -36947.90 copies/mL | Standard Deviation 28463.8 |
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in HIV-1 RNA Levels of First 15 Participants at Days 4, 7, 10 and 14 | Change at Day 10 | -58595.80 copies/mL | Standard Deviation 66157.66 |
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in HIV-1 RNA Levels of First 15 Participants at Days 4, 7, 10 and 14 | Change at Day 14 | -47271.60 copies/mL | Standard Deviation 38234.34 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in HIV-1 RNA Levels of First 15 Participants at Days 4, 7, 10 and 14 | Change at Day 14 | -55449.90 copies/mL | Standard Deviation 71207.16 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in HIV-1 RNA Levels of First 15 Participants at Days 4, 7, 10 and 14 | Change at Day 4 | -46479.40 copies/mL | Standard Deviation 62259.15 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in HIV-1 RNA Levels of First 15 Participants at Days 4, 7, 10 and 14 | Change at Day 10 | -54925.90 copies/mL | Standard Deviation 70846.93 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in HIV-1 RNA Levels of First 15 Participants at Days 4, 7, 10 and 14 | Change at Day 7 | -52137.10 copies/mL | Standard Deviation 68684.14 |
Secondary
Change From Baseline in Plasma log10 Viral Load at Weeks 16, 24, 48 and 96
Time frame: Baseline, Week 16, Week 24, Week 48, Week 96
Population: FAS population included those participants who had taken at least one dose of the study drug, had a baseline and at least one post baseline measurement. Here n signified participants who received the study drug and evaluated at the time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in Plasma log10 Viral Load at Weeks 16, 24, 48 and 96 | Change at Week 16 (n= 54, 58) | -89859.1 log10 copies/ml | Standard Deviation 131317.35 |
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in Plasma log10 Viral Load at Weeks 16, 24, 48 and 96 | Change at Week 48 (n= 53, 54) | -82343.4 log10 copies/ml | Standard Deviation 119356.62 |
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in Plasma log10 Viral Load at Weeks 16, 24, 48 and 96 | Change at Week 24 (n= 56, 58) | -87241.2 log10 copies/ml | Standard Deviation 129638.57 |
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in Plasma log10 Viral Load at Weeks 16, 24, 48 and 96 | Change at Week 96 (n= 49, 51) | -80117.7 log10 copies/ml | Standard Deviation 121443.5 |
| Maraviroc+ Atazanavir / Ritonavir | Change From Baseline in Plasma log10 Viral Load at Weeks 16, 24, 48 and 96 | Baseline (n= 59, 61) | 84982 log10 copies/ml | Standard Deviation 127008 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in Plasma log10 Viral Load at Weeks 16, 24, 48 and 96 | Change at Week 96 (n= 49, 51) | -99662.6 log10 copies/ml | Standard Deviation 116525.87 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in Plasma log10 Viral Load at Weeks 16, 24, 48 and 96 | Baseline (n= 59, 61) | 114827 log10 copies/ml | Standard Deviation 149638 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in Plasma log10 Viral Load at Weeks 16, 24, 48 and 96 | Change at Week 16 (n= 54, 58) | -107684.6 log10 copies/ml | Standard Deviation 149476.47 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in Plasma log10 Viral Load at Weeks 16, 24, 48 and 96 | Change at Week 24 (n= 56, 58) | -110498.1 log10 copies/ml | Standard Deviation 149836.29 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Change From Baseline in Plasma log10 Viral Load at Weeks 16, 24, 48 and 96 | Change at Week 48 (n= 53, 54) | -115582.9 log10 copies/ml | Standard Deviation 153705.26 |
Secondary
HIV-1 RNA Levels at Baseline
Time frame: Baseline
Population: FAS population included those participants who had taken at least one dose of the study drug, had baseline and at least one post baseline measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc+ Atazanavir / Ritonavir | HIV-1 RNA Levels at Baseline | 84982 copies/mL | Standard Deviation 127008 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | HIV-1 RNA Levels at Baseline | 114827 copies/mL | Standard Deviation 149638 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Maraviroc
Time frame: Day 14 (0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose)
Population: Pharmacokinetic (PK) parameter analysis population included first 15 participants treated with maraviroc.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc+ Atazanavir / Ritonavir | Maximum Observed Plasma Concentration (Cmax) of Maraviroc | 650 nanogram (ng)/mL |
Secondary
Minimum Observed Plasma Concentration (Cmin) of Maraviroc
Time frame: Day 14 (0, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose)
Population: PK parameter analysis population included first 15 participants treated with maraviroc.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc+ Atazanavir / Ritonavir | Minimum Observed Plasma Concentration (Cmin) of Maraviroc | 37.0 ng/mL |
Secondary
Number of Participants With Genotypic Resistance
Genotypic resistance was assessed for all participants at screening and was evaluated for protease inhibitors (PIs), Nucleotide reverse transcriptase inhibitors (NRTIs), and non-NRTIs (NNRTIs) using Monogram GenoSeq and/or PhenoSenseGT assays. This was then repeated for all participants with HIV-1 viral load more than 500 copies/mL either at treatment failure or at early termination, up to Week 96.
Time frame: Week 96 or Time of treatment failure
Population: FAS population included those participants who had taken at least one dose of the study drug, had a baseline and at least one post baseline measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maraviroc+ Atazanavir / Ritonavir | Number of Participants With Genotypic Resistance | 0 Participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Number of Participants With Genotypic Resistance | 0 Participants |
Secondary
Number of Participants With HIV-1 RNA Tropism Status Using Trofile Assay
Viral tropism was determined using the trofile assay with enhanced sensitivity for participants with HIV-1 RNA greater than equal to 1000 copies/mL. The enhanced trofile assay had the sensitivity to detect 100 percent of spiked samples when C-X-C chemokine receptor type 4 {CXCR4} \[X4\]-using HIV-1 RNA represented 0.3 percent of the total viral population.
Time frame: Baseline to Week 96 or Time of treatment Failure
Population: FAS population included those participants who had taken at least one dose of the study drug, had a baseline and at least one post baseline measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc+ Atazanavir / Ritonavir | Number of Participants With HIV-1 RNA Tropism Status Using Trofile Assay | Baseline | 60 Participants |
| Maraviroc+ Atazanavir / Ritonavir | Number of Participants With HIV-1 RNA Tropism Status Using Trofile Assay | Week 96 or Time of treatment Failure | 0 Participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Number of Participants With HIV-1 RNA Tropism Status Using Trofile Assay | Baseline | 61 Participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Number of Participants With HIV-1 RNA Tropism Status Using Trofile Assay | Week 96 or Time of treatment Failure | 0 Participants |
Secondary
Number of Participants With Phenotypic Resistance
Phenotypic resistance was assessed for all participants at screening and was evaluated for PIs, NRTIs, and NNRTIs using Monogram GenoSeq and/or PhenoSenseGT assays. This was then repeated for all participants with HIV-1 viral load more than 500 copies/mL either at treatment failure or at early termination, up to Week 96.
Time frame: Week 96 or Time of treatment failure
Population: FAS population included those participants who had taken at least one dose of the study drug, had a baseline and at least one post baseline measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maraviroc+ Atazanavir / Ritonavir | Number of Participants With Phenotypic Resistance | 0 Participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Number of Participants With Phenotypic Resistance | 0 Participants |
Secondary
Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA
Time frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, Week 96
Population: FAS population included those participants who had taken at least one dose of the study drug, had a baseline and at least one post baseline measurement. Here n signified participants who received the study drug and evaluated at the time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 2 (n= 55, 60) | 27.12 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 4 (n= 57, 60) | 50.85 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 8 (n= 57, 59) | 79.66 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 12 (n= 55, 59) | 89.83 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 16 (n= 54, 58) | 88.14 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 20 (n= 56, 57) | 89.83 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 24 (n= 56, 58) | 91.53 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 32 (n= 55, 57) | 89.83 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 40 (n= 54, 55) | 91.53 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 48 (n= 53, 54) | 89.83 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 60 (n= 52, 53) | 86.44 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 72 (n= 52, 53) | 86.44 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 84 (n= 50, 52) | 81.36 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 96 (n= 49, 51) | 77.97 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 60 (n= 52, 53) | 86.89 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 2 (n= 55, 60) | 34.43 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 32 (n= 55, 57) | 93.44 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 4 (n= 57, 60) | 52.46 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 84 (n= 50, 52) | 85.25 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 8 (n= 57, 59) | 77.05 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 40 (n= 54, 55) | 90.16 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 12 (n= 55, 59) | 88.52 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 72 (n= 52, 53) | 85.25 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 16 (n= 54, 58) | 91.80 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 48 (n= 53, 54) | 86.89 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 20 (n= 56, 57) | 93.44 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 96 (n= 49, 51) | 83.61 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 400 Copies/mL of HIV-1 RNA | Week 24 (n= 56, 58) | 93.44 Percentage of participants |
Secondary
Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA
Time frame: Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, Week 96
Population: FAS population included those participants who had taken at least one dose of the study drug, had a baseline and at least one post baseline measurement. Here n signified participants who received the study drug and evaluated at the time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 2 (n= 55, 60) | 0 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 4 (n= 57, 60) | 8.50 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 8 (n= 57, 59) | 47.50 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 12 (n= 55, 59) | 61.00 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 16 (n= 54, 58) | 72.90 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 20 (n= 56, 57) | 71.20 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 24 (n= 56, 58) | 81.36 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 32 (n= 55, 57) | 79.66 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 40 (n= 54, 55) | 81.36 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 48 (n= 53, 54) | 74.58 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 60 (n= 52, 53) | 67.80 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 72 (n= 52, 53) | 74.58 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 84 (n= 50, 52) | 76.27 Percentage of participants |
| Maraviroc+ Atazanavir / Ritonavir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 96 (n= 49, 51) | 67.80 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 60 (n= 52, 53) | 85.25 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 2 (n= 55, 60) | 6.60 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 32 (n= 55, 57) | 88.52 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 4 (n= 57, 60) | 21.30 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 84 (n= 50, 52) | 83.61 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 8 (n= 57, 59) | 42.60 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 40 (n= 54, 55) | 88.52 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 12 (n= 55, 59) | 62.30 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 72 (n= 52, 53) | 81.97 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 16 (n= 54, 58) | 73.80 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 48 (n= 53, 54) | 83.61 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 20 (n= 56, 57) | 83.61 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 96 (n= 49, 51) | 81.97 Percentage of participants |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Percentage of Participants With Less Than 50 Copies/mL of HIV-1 RNA | Week 24 (n= 56, 58) | 88.52 Percentage of participants |
Secondary
Time-Averaged Difference (TAD) in log10 Viral Load
TAD was calculated as area under the curve of HIV divided by time period minus baseline HIV where HIV was denoted as HIV-1 RNA (log10 copies/mL).
Time frame: Week 16, Week 24, Week 48, Week 96
Population: FAS population included those participants who had taken at least one dose of the study drug, had a baseline and at least one post baseline measurement. Here N (Number of participants analyzed) signified participants evaluable for the measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc+ Atazanavir / Ritonavir | Time-Averaged Difference (TAD) in log10 Viral Load | Week 16 | -2.459 log10 copies/mL | Standard Error 0.046 |
| Maraviroc+ Atazanavir / Ritonavir | Time-Averaged Difference (TAD) in log10 Viral Load | Week 24 | -2.663 log10 copies/mL | Standard Error 0.048 |
| Maraviroc+ Atazanavir / Ritonavir | Time-Averaged Difference (TAD) in log10 Viral Load | Week 48 | -2.897 log10 copies/mL | Standard Error 0.046 |
| Maraviroc+ Atazanavir / Ritonavir | Time-Averaged Difference (TAD) in log10 Viral Load | Week 96 | -2.998 log10 copies/mL | Standard Error 0.055 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Time-Averaged Difference (TAD) in log10 Viral Load | Week 96 | -3.001 log10 copies/mL | Standard Error 0.053 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Time-Averaged Difference (TAD) in log10 Viral Load | Week 16 | -2.402 log10 copies/mL | Standard Error 0.045 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Time-Averaged Difference (TAD) in log10 Viral Load | Week 48 | -2.868 log10 copies/mL | Standard Error 0.05 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Time-Averaged Difference (TAD) in log10 Viral Load | Week 24 | -2.626 log10 copies/mL | Standard Error 0.046 |
Secondary
Time to Loss of Virological Response (TLOVR)
TLOVR (virological failure) was defined as the time from first dose of study treatment (Day 1) until the time of virologic failure using the time to loss of virologic response algorithm.
Time frame: Baseline through Week 96
Population: FAS population included those participants who had taken at least one dose of the study drug, had a baseline and at least one post baseline measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc+ Atazanavir / Ritonavir | Time to Loss of Virological Response (TLOVR) | 436.2 Days | Standard Error 22.5 |
| Atazanavir / Ritonavir + Emtricitabine / Tenofovir | Time to Loss of Virological Response (TLOVR) | 463.8 Days | Standard Error 16.1 |