HIV
Conditions
Keywords
maraviroc, naive, hiv, zidovudine, lamivudine, combivir, Clade A
Brief summary
One hundred subjects in Russia will be treated with a combination of Combivir (zidovudine and lamivudine) and maraviroc as their first line HIV therapy. The aim is to assess the efficacy and safety of this combination in a Russian population of patients.
Interventions
DRUGHIV therapy
Combivir one tablet BD with maraviroc 300mg BD for 48 weeks
Sponsors
Pfizer
ViiV Healthcare
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Over 18 years of age. * R5 HIV infection on screening tropism test. * Viral load \>1,000 copies/mL. * Never previously treated with anti-HIV medicines.
Exclusion criteria
* Previously treated with anti-HIV medicines. * Hepatitis B co-infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Plasma Human Immuno Deficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) Load <50 Copies/Milliliter (mL) at 48 Weeks. | 48 weeks | Participants' responder status at Week 48 was assessed according to Missing, discontinuation= Failure (MDF) algorithm. This algorithm treats all participants with HIV 1 RNA data missing at the time of interest or discontinuation of study drug as failures or non responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load < 400 Copies/mL at Post-baseline Visits. | Baseline, Week 4, Week 8, Week 12, Week 20, Week 24, Week 36 and Week 48 | Participants' responder status at Week 48 was assessed according to MDF algorithm. This algorithm treats all participants with HIV 1 RNA data missing at the time of interest or discontinuation of study drug as failures or non responders. |
| Virologic Response: Rate of Virologic Failure at Week 48. | 48 weeks | Virologic failure defined as: failure to achieve a reduction from baseline 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. Participants with Time to loss of virologic response (defined by level of \<50 copies/mL) failure were classified as rebounders or non-responders. |
| Immunological Response at Week 48: Absolute Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) | Week 48 | Immunological Response was summarized using absolute change from Baseline to Week 48 in absolute CD4+ cell count |
| Immunological Response at Week 48: Percentage Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) | Week 48 | Immunological Response was summarized using percentage change from Baseline to Week 48 in absolute CD4+ cell count |
| Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load <50 Copies/mL at Post-baseline Visits. | Baseline, Week 4, Week 8, Week 12, Week 20, Week 24, Week 36 and Week 48 | Participants' responder status at Week 48 was assessed according to MDF algorithm. This algorithm treats all participants with HIV 1 RNA data missing at the time of interest or discontinuation of study drug as failures or non responders. |
| Immunological Response at Week 48: Percentage Change From Baseline in Absolute Cluster of Differentiation 8 (CD8) | Week 48 | Immunological Response was summarized using percentage change from Baseline to Week 48 in absolute CD8+ cell count. |
| Immunological Response at Week 48: Change From Baseline in Absolute Cluster of Differentiation 4 (CD4)/ Cluster of Differentiation 8 (CD8) Ratio. | Week 48 | Immunological Response was summarized using absolute change from Baseline to Week 48 in absolute CD4+/ CD8+ ratio. |
| Number of Participants With Genotypic Resistance. | Screening to Week 48 or Time of treatment Failure | The viral genotypes were captured at Baseline and at treatment failure or Early termination and any resistance-associated mutations summarized descriptively at Week 48 for the Nucleotide reverse transcriptase inhibitors (NRTIs), and non-NRTIs (NNRTIs)drug classes. |
| Number of Participants With HIV-1 RNA Tropism Status Using Genotyping Assay at Screening and at the Time of Virologic Failure. | Screening to Week 48 or Time of treatment Failure | Change in tropism were summarized at the time of treatment failure or Early Termination (note: this was performed for participants with viral load \> 400 copies/mL only). |
| Immunological Response at Week 48: Absolute Change From Baseline in Absolute Cluster of Differentiation 8 (CD8) | Week 48 | Immunological Response was summarized using absolute change from Baseline to Week 48 in absolute CD8+ cell count. |
Countries
Russia
Participant flow
Recruitment details
This report presents results of a 48 week study conducted at 8 centers in Russia. A total of 98 subjects were enrolled in the study; however, one site was closed and data from this site was deemed unusable, thus in total 77 subjects were included in the analysis.
Pre-assignment details
Treatment naïve Human Immuno Deficiency Virus (HIV) infected participants aged 18 years at screening were enrolled. Participants were required to meet all eligibility criteria prior to randomization into the study.
Participants by arm
| Arm | Count |
|---|---|
| Maraviroc+Combivir All participants received Maraviroc (300 milligram \[mg\] twice daily) in combination with Combivir (fixed dose combination of zidovudine 300 mg and lamivudine 150 mg) | 77 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Death | 1 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Maraviroc+Combivir |
|---|---|
| Age, Continuous | 35.2 Years STANDARD_DEVIATION 8.3 |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 51 / 77 |
| serious Total, serious adverse events | 2 / 77 |
Outcome results
Primary
Percentage of Participants With Plasma Human Immuno Deficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) Load <50 Copies/Milliliter (mL) at 48 Weeks.
Participants' responder status at Week 48 was assessed according to Missing, discontinuation= Failure (MDF) algorithm. This algorithm treats all participants with HIV 1 RNA data missing at the time of interest or discontinuation of study drug as failures or non responders.
Time frame: 48 weeks
Population: Full Analysis Set (FAS) Population included those participants who had taken at least 1 dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maraviroc+Combivir | Percentage of Participants With Plasma Human Immuno Deficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) Load <50 Copies/Milliliter (mL) at 48 Weeks. | 77.92 Percentage of participants |
Secondary
Immunological Response at Week 48: Absolute Change From Baseline in Absolute Cluster of Differentiation 4 (CD4)
Immunological Response was summarized using absolute change from Baseline to Week 48 in absolute CD4+ cell count
Time frame: Week 48
Population: FAS Population included those participants who had taken at least 1 dose of the study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc+Combivir | Immunological Response at Week 48: Absolute Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) | 165.53 cells/microliter (cells/mcL) | Standard Deviation 163.65 |
Secondary
Immunological Response at Week 48: Absolute Change From Baseline in Absolute Cluster of Differentiation 8 (CD8)
Immunological Response was summarized using absolute change from Baseline to Week 48 in absolute CD8+ cell count.
Time frame: Week 48
Population: FAS Population included those participants who had taken at least 1 dose of the study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc+Combivir | Immunological Response at Week 48: Absolute Change From Baseline in Absolute Cluster of Differentiation 8 (CD8) | -112.96 cells/mcL | Standard Deviation 361.85 |
Secondary
Immunological Response at Week 48: Change From Baseline in Absolute Cluster of Differentiation 4 (CD4)/ Cluster of Differentiation 8 (CD8) Ratio.
Immunological Response was summarized using absolute change from Baseline to Week 48 in absolute CD4+/ CD8+ ratio.
Time frame: Week 48
Population: FAS Population included those participants who had taken at least 1 dose of the study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc+Combivir | Immunological Response at Week 48: Change From Baseline in Absolute Cluster of Differentiation 4 (CD4)/ Cluster of Differentiation 8 (CD8) Ratio. | 0.33 Ratio | Standard Deviation 0.9 |
Secondary
Immunological Response at Week 48: Percentage Change From Baseline in Absolute Cluster of Differentiation 4 (CD4)
Immunological Response was summarized using percentage change from Baseline to Week 48 in absolute CD4+ cell count
Time frame: Week 48
Population: FAS Population included those participants who had taken at least 1 dose of the study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc+Combivir | Immunological Response at Week 48: Percentage Change From Baseline in Absolute Cluster of Differentiation 4 (CD4) | 8.07 Percent | Standard Deviation 7.14 |
Secondary
Immunological Response at Week 48: Percentage Change From Baseline in Absolute Cluster of Differentiation 8 (CD8)
Immunological Response was summarized using percentage change from Baseline to Week 48 in absolute CD8+ cell count.
Time frame: Week 48
Population: FAS Population included those participants who had taken at least 1 dose of the study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc+Combivir | Immunological Response at Week 48: Percentage Change From Baseline in Absolute Cluster of Differentiation 8 (CD8) | -8.59 Percent | Standard Deviation 9.28 |
Secondary
Number of Participants With Genotypic Resistance.
The viral genotypes were captured at Baseline and at treatment failure or Early termination and any resistance-associated mutations summarized descriptively at Week 48 for the Nucleotide reverse transcriptase inhibitors (NRTIs), and non-NRTIs (NNRTIs)drug classes.
Time frame: Screening to Week 48 or Time of treatment Failure
Population: All participants who discontinued therapy early or who reached Week 48 with sufficient plasma HIV 1 RNA for analysis (500 copies/mL) were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc+Combivir | Number of Participants With Genotypic Resistance. | Participants with genotype reported | 8 Participants |
| Maraviroc+Combivir | Number of Participants With Genotypic Resistance. | Participants with Emergent NRTI mutations | 5 Participants |
Secondary
Number of Participants With HIV-1 RNA Tropism Status Using Genotyping Assay at Screening and at the Time of Virologic Failure.
Change in tropism were summarized at the time of treatment failure or Early Termination (note: this was performed for participants with viral load \> 400 copies/mL only).
Time frame: Screening to Week 48 or Time of treatment Failure
Population: All participants who discontinued therapy early or who reached Week 48 with sufficient plasma HIV 1 RNA for analysis (500 copies/mL) were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc+Combivir | Number of Participants With HIV-1 RNA Tropism Status Using Genotyping Assay at Screening and at the Time of Virologic Failure. | Tropism change (n= 8) | 0 Participants |
| Maraviroc+Combivir | Number of Participants With HIV-1 RNA Tropism Status Using Genotyping Assay at Screening and at the Time of Virologic Failure. | Reduced Maraviroc susceptibility (n= 3) | 0 Participants |
Secondary
Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load < 400 Copies/mL at Post-baseline Visits.
Participants' responder status at Week 48 was assessed according to MDF algorithm. This algorithm treats all participants with HIV 1 RNA data missing at the time of interest or discontinuation of study drug as failures or non responders.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 20, Week 24, Week 36 and Week 48
Population: FAS Population included those participants who had taken at least 1 dose of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc+Combivir | Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load < 400 Copies/mL at Post-baseline Visits. | Baseline (N= 77) | 0.00 Percentage of participants |
| Maraviroc+Combivir | Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load < 400 Copies/mL at Post-baseline Visits. | Week 4 (N= 77) | 41.56 Percentage of participants |
| Maraviroc+Combivir | Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load < 400 Copies/mL at Post-baseline Visits. | Week 8 (N= 75) | 72.00 Percentage of participants |
| Maraviroc+Combivir | Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load < 400 Copies/mL at Post-baseline Visits. | Week 12 (N= 76) | 89.47 Percentage of participants |
| Maraviroc+Combivir | Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load < 400 Copies/mL at Post-baseline Visits. | Week 20 (N= 73) | 91.78 Percentage of participants |
| Maraviroc+Combivir | Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load < 400 Copies/mL at Post-baseline Visits. | Week 24 (N= 73) | 91.78 Percentage of participants |
| Maraviroc+Combivir | Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load < 400 Copies/mL at Post-baseline Visits. | Week 36 (N= 68) | 97.06 Percentage of participants |
| Maraviroc+Combivir | Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load < 400 Copies/mL at Post-baseline Visits. | Week 48 (N= 65) | 95.38 Percentage of participants |
Secondary
Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load <50 Copies/mL at Post-baseline Visits.
Participants' responder status at Week 48 was assessed according to MDF algorithm. This algorithm treats all participants with HIV 1 RNA data missing at the time of interest or discontinuation of study drug as failures or non responders.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 20, Week 24, Week 36 and Week 48
Population: FAS Population included those participants who had taken at least 1 dose of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc+Combivir | Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load <50 Copies/mL at Post-baseline Visits. | Baseline (N= 77) | 0.00 Percentage of participants |
| Maraviroc+Combivir | Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load <50 Copies/mL at Post-baseline Visits. | Week 4 (N= 77) | 7.79 Percentage of participants |
| Maraviroc+Combivir | Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load <50 Copies/mL at Post-baseline Visits. | Week 8 (N= 75) | 26.67 Percentage of participants |
| Maraviroc+Combivir | Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load <50 Copies/mL at Post-baseline Visits. | Week 12 (N= 76) | 48.68 Percentage of participants |
| Maraviroc+Combivir | Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load <50 Copies/mL at Post-baseline Visits. | Week 20 (N= 73) | 78.08 Percentage of participants |
| Maraviroc+Combivir | Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load <50 Copies/mL at Post-baseline Visits. | Week 24 (N= 73) | 83.56 Percentage of participants |
| Maraviroc+Combivir | Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load <50 Copies/mL at Post-baseline Visits. | Week 36 (N= 68) | 89.71 Percentage of participants |
| Maraviroc+Combivir | Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load <50 Copies/mL at Post-baseline Visits. | Week 48 (N= 65) | 92.31 Percentage of participants |
Secondary
Virologic Response: Rate of Virologic Failure at Week 48.
Virologic failure defined as: failure to achieve a reduction from baseline 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. Participants with Time to loss of virologic response (defined by level of \<50 copies/mL) failure were classified as rebounders or non-responders.
Time frame: 48 weeks
Population: FAS Population included those participants who had taken at least 1 dose of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc+Combivir | Virologic Response: Rate of Virologic Failure at Week 48. | Responders | 60 Participants |
| Maraviroc+Combivir | Virologic Response: Rate of Virologic Failure at Week 48. | Rebounders | 1 Participants |
| Maraviroc+Combivir | Virologic Response: Rate of Virologic Failure at Week 48. | Non-response | 15 Participants |
| Maraviroc+Combivir | Virologic Response: Rate of Virologic Failure at Week 48. | Death | 1 Participants |
| Maraviroc+Combivir | Virologic Response: Rate of Virologic Failure at Week 48. | Discontinued before Week 48 due to Adverse Events | 4 Participants |
| Maraviroc+Combivir | Virologic Response: Rate of Virologic Failure at Week 48. | Discontinued before Week 48 for other reasons | 9 Participants |