Combivir And Maraviroc In Antiretroviral Naive Subjects In Russia

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT01275625
First received: January 11, 2011
Last updated: January 13, 2014
Last verified: January 2014
Results First Received: September 23, 2013  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV
Intervention: Drug: HIV therapy

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
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)

Participant Flow:   Overall Study
    Maraviroc+Combivir  
STARTED     77  
Treated     77  
COMPLETED     64  
NOT COMPLETED     13  
Death                 1  
Lack of Efficacy                 2  
Lost to Follow-up                 1  
Withdrawal by Subject                 3  
Protocol Violation                 1  
Adverse Event                 4  
Not specified                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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)

Baseline Measures
    Maraviroc+Combivir  
Number of Participants  
[units: participants]
  77  
Age  
[units: Years]
Mean ± Standard Deviation
  35.2  ± 8.3  
Gender  
[units: Participants]
 
Female     26  
Male     51  



  Outcome Measures
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1.  Primary:   Percentage of Participants With Plasma Human Immuno Deficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) Load <50 Copies/Milliliter (mL) at 48 Weeks.   [ Time Frame: 48 weeks ]

Measure Type Primary
Measure Title Percentage of Participants With Plasma Human Immuno Deficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) Load <50 Copies/Milliliter (mL) at 48 Weeks.
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set (FAS) Population included those participants who had taken at least 1 dose of the study drug.

Reporting Groups
  Description
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)

Measured Values
    Maraviroc+Combivir  
Number of Participants Analyzed  
[units: participants]
  77  
Percentage of Participants With Plasma Human Immuno Deficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) Load <50 Copies/Milliliter (mL) at 48 Weeks.  
[units: Percentage of participants]
Number ( 95% Confidence Interval )
  77.92  
  ( 68.01 to 87.84 )  

No statistical analysis provided for Percentage of Participants With Plasma Human Immuno Deficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) Load <50 Copies/Milliliter (mL) at 48 Weeks.



2.  Secondary:   Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load <50 Copies/mL at Post-baseline Visits.   [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 20, Week 24, Week 36 and Week 48 ]

Measure Type Secondary
Measure Title Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load <50 Copies/mL at Post-baseline Visits.
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS Population included those participants who had taken at least 1 dose of the study drug.

Reporting Groups
  Description
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)

Measured Values
    Maraviroc+Combivir  
Number of Participants Analyzed  
[units: participants]
  77  
Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load <50 Copies/mL at Post-baseline Visits.  
[units: Percentage of participants]
 
Baseline (N= 77)     0.00  
Week 4 (N= 77)     7.79  
Week 8 (N= 75)     26.67  
Week 12 (N= 76)     48.68  
Week 20 (N= 73)     78.08  
Week 24 (N= 73)     83.56  
Week 36 (N= 68)     89.71  
Week 48 (N= 65)     92.31  

No statistical analysis provided for Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load <50 Copies/mL at Post-baseline Visits.



3.  Secondary:   Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load < 400 Copies/mL at Post-baseline Visits.   [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 20, Week 24, Week 36 and Week 48 ]

Measure Type Secondary
Measure Title Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load < 400 Copies/mL at Post-baseline Visits.
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS Population included those participants who had taken at least 1 dose of the study drug.

Reporting Groups
  Description
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)

Measured Values
    Maraviroc+Combivir  
Number of Participants Analyzed  
[units: participants]
  77  
Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load < 400 Copies/mL at Post-baseline Visits.  
[units: Percentage of participants]
 
Baseline (N= 77)     0.00  
Week 4 (N= 77)     41.56  
Week 8 (N= 75)     72.00  
Week 12 (N= 76)     89.47  
Week 20 (N= 73)     91.78  
Week 24 (N= 73)     91.78  
Week 36 (N= 68)     97.06  
Week 48 (N= 65)     95.38  

No statistical analysis provided for Virologic Response: Percentage of Participants With Plasma HIV-1 RNA Load < 400 Copies/mL at Post-baseline Visits.



4.  Secondary:   Virologic Response: Rate of Virologic Failure at Week 48.   [ Time Frame: 48 weeks ]

Measure Type Secondary
Measure Title Virologic Response: Rate of Virologic Failure at Week 48.
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS Population included those participants who had taken at least 1 dose of the study drug.

Reporting Groups
  Description
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)

Measured Values
    Maraviroc+Combivir  
Number of Participants Analyzed  
[units: participants]
  77  
Virologic Response: Rate of Virologic Failure at Week 48.  
[units: Participants]
 
Responders     60  
Rebounders     1  
Non-response     15  
Death     1  
Discontinued before Week 48 due to Adverse Events     4  
Discontinued before Week 48 for other reasons     9  

No statistical analysis provided for Virologic Response: Rate of Virologic Failure at Week 48.



5.  Secondary:   Immunological Response at Week 48: Absolute Change From Baseline in Absolute Cluster of Differentiation 4 (CD4)   [ Time Frame: Week 48 ]

Measure Type Secondary
Measure Title Immunological Response at Week 48: Absolute Change From Baseline in Absolute Cluster of Differentiation 4 (CD4)
Measure Description Immunological Response was summarized using absolute change from Baseline to Week 48 in absolute CD4+ cell count
Time Frame Week 48  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS Population included those participants who had taken at least 1 dose of the study drug.

Reporting Groups
  Description
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)

Measured Values
    Maraviroc+Combivir  
Number of Participants Analyzed  
[units: participants]
  64  
Immunological Response at Week 48: Absolute Change From Baseline in Absolute Cluster of Differentiation 4 (CD4)  
[units: cells/microliter (cells/mcL)]
Mean ± Standard Deviation
  165.53  ± 163.65  

No statistical analysis provided for Immunological Response at Week 48: Absolute Change From Baseline in Absolute Cluster of Differentiation 4 (CD4)



6.  Secondary:   Immunological Response at Week 48: Percentage Change From Baseline in Absolute Cluster of Differentiation 4 (CD4)   [ Time Frame: Week 48 ]

Measure Type Secondary
Measure Title Immunological Response at Week 48: Percentage Change From Baseline in Absolute Cluster of Differentiation 4 (CD4)
Measure Description Immunological Response was summarized using percentage change from Baseline to Week 48 in absolute CD4+ cell count
Time Frame Week 48  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS Population included those participants who had taken at least 1 dose of the study drug.

Reporting Groups
  Description
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)

Measured Values
    Maraviroc+Combivir  
Number of Participants Analyzed  
[units: participants]
  64  
Immunological Response at Week 48: Percentage Change From Baseline in Absolute Cluster of Differentiation 4 (CD4)  
[units: Percent]
Mean ± Standard Deviation
  8.07  ± 7.14  

No statistical analysis provided for Immunological Response at Week 48: Percentage Change From Baseline in Absolute Cluster of Differentiation 4 (CD4)



7.  Secondary:   Immunological Response at Week 48: Absolute Change From Baseline in Absolute Cluster of Differentiation 8 (CD8)   [ Time Frame: Week 48 ]

Measure Type Secondary
Measure Title Immunological Response at Week 48: Absolute Change From Baseline in Absolute Cluster of Differentiation 8 (CD8)
Measure Description Immunological Response was summarized using absolute change from Baseline to Week 48 in absolute CD8+ cell count.
Time Frame Week 48  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS Population included those participants who had taken at least 1 dose of the study drug.

Reporting Groups
  Description
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)

Measured Values
    Maraviroc+Combivir  
Number of Participants Analyzed  
[units: participants]
  64  
Immunological Response at Week 48: Absolute Change From Baseline in Absolute Cluster of Differentiation 8 (CD8)  
[units: cells/mcL]
Mean ± Standard Deviation
  -112.96  ± 361.85  

No statistical analysis provided for Immunological Response at Week 48: Absolute Change From Baseline in Absolute Cluster of Differentiation 8 (CD8)



8.  Secondary:   Immunological Response at Week 48: Percentage Change From Baseline in Absolute Cluster of Differentiation 8 (CD8)   [ Time Frame: Week 48 ]

Measure Type Secondary
Measure Title Immunological Response at Week 48: Percentage Change From Baseline in Absolute Cluster of Differentiation 8 (CD8)
Measure Description Immunological Response was summarized using percentage change from Baseline to Week 48 in absolute CD8+ cell count.
Time Frame Week 48  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS Population included those participants who had taken at least 1 dose of the study drug.

Reporting Groups
  Description
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)

Measured Values
    Maraviroc+Combivir  
Number of Participants Analyzed  
[units: participants]
  64  
Immunological Response at Week 48: Percentage Change From Baseline in Absolute Cluster of Differentiation 8 (CD8)  
[units: Percent]
Mean ± Standard Deviation
  -8.59  ± 9.28  

No statistical analysis provided for Immunological Response at Week 48: Percentage Change From Baseline in Absolute Cluster of Differentiation 8 (CD8)



9.  Secondary:   Immunological Response at Week 48: Change From Baseline in Absolute Cluster of Differentiation 4 (CD4)/ Cluster of Differentiation 8 (CD8) Ratio.   [ Time Frame: Week 48 ]

Measure Type Secondary
Measure Title Immunological Response at Week 48: Change From Baseline in Absolute Cluster of Differentiation 4 (CD4)/ Cluster of Differentiation 8 (CD8) Ratio.
Measure Description Immunological Response was summarized using absolute change from Baseline to Week 48 in absolute CD4+/ CD8+ ratio.
Time Frame Week 48  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS Population included those participants who had taken at least 1 dose of the study drug.

Reporting Groups
  Description
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)

Measured Values
    Maraviroc+Combivir  
Number of Participants Analyzed  
[units: participants]
  64  
Immunological Response at Week 48: Change From Baseline in Absolute Cluster of Differentiation 4 (CD4)/ Cluster of Differentiation 8 (CD8) Ratio.  
[units: Ratio]
Mean ± Standard Deviation
  0.33  ± 0.90  

No statistical analysis provided for Immunological Response at Week 48: Change From Baseline in Absolute Cluster of Differentiation 4 (CD4)/ Cluster of Differentiation 8 (CD8) Ratio.



10.  Secondary:   Number of Participants With Genotypic Resistance.   [ Time Frame: Screening to Week 48 or Time of treatment Failure ]

Measure Type Secondary
Measure Title Number of Participants With Genotypic Resistance.
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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)

Measured Values
    Maraviroc+Combivir  
Number of Participants Analyzed  
[units: participants]
  77  
Number of Participants With Genotypic Resistance.  
[units: Participants]
 
Participants with genotype reported     8  
Participants with Emergent NRTI mutations     5  

No statistical analysis provided for Number of Participants With Genotypic Resistance.



11.  Secondary:   Number of Participants With HIV-1 RNA Tropism Status Using Genotyping Assay at Screening and at the Time of Virologic Failure.   [ Time Frame: Screening to Week 48 or Time of treatment Failure ]

Measure Type Secondary
Measure Title Number of Participants With HIV-1 RNA Tropism Status Using Genotyping Assay at Screening and at the Time of Virologic Failure.
Measure Description 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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)

Measured Values
    Maraviroc+Combivir  
Number of Participants Analyzed  
[units: participants]
  77  
Number of Participants With HIV-1 RNA Tropism Status Using Genotyping Assay at Screening and at the Time of Virologic Failure.  
[units: Participants]
 
Tropism change (n= 8)     0  
Reduced Maraviroc susceptibility (n= 3)     0  

No statistical analysis provided for Number of Participants With HIV-1 RNA Tropism Status Using Genotyping Assay at Screening and at the Time of Virologic Failure.




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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