Induction/Simplification With Atazanavir + Ritonavir + Abacavir/Lamivudine Fixed-Dose Combination In HIV-1 Infection

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00440947
First received: February 23, 2007
Last updated: March 15, 2012
Last verified: July 2011
Results First Received: May 19, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Infection, Human Immunodeficiency Virus I
HIV Infection
Interventions: Drug: Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV) + ritonavir (/r)
Drug: Abacavir (ABC)/lamivudine (3TC) + atazanavir (ATV)

  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
Participants (PAR) were recruited at 66 centers in the United States of America and Canada. HIV-RNA, human immunodeficiency virus-ribonucleic acid; ml, milliliters.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study had a 36-week Non-randomized Induction Phase, followed by an 84-week Randomized Phase. All PAR completing 84 weeks were eligible to enter an optional 60-week extension phase (EP); some PAR chose not to continue in the EP. PAR whose HIV-RNA wasn't <50 copies/ml before Week 36 weren't allowed to randomize at Week 36 and were withdrawn.

Reporting Groups
  Description
ABC/3TC + ATV/r: Induction Phase Abacavir (ABC) 600 milligrams (mg)/lamivudine (3TC) 300 mg fixed-dose combination tablet (FDC) once a day (QD) plus atazanavir (ATV) 300 mg QD + ritonavir (/r) 100 mg QD during the first 36 weeks of the study (planned interim analysis)
ABC/3TC + ATV: Randomization Phase Simplification regimen of the ABC/3TC FDC tablet administered QD for an additional 48 weeks in combination with 400 mg ATV QD
ABC/3TC + ATV/r: Randomization Phase Continuation of ABC/3TC FDC tablet administered QD for an additional 48 weeks in combination with ATV/r QD
ABC/3TC + ATV: Extension Phase Simplification regimen of the ABC/3TC FDC tablet administered QD for an additional 60 weeks in combination with ATV QD
ABC/3TC + ATV/r: Extension Phase Continuation of ABC/3TC FDC tablet administered QD for an additional 60 weeks in combination with ATV/r QD

Participant Flow for 3 periods

Period 1:   36-Week Induction Phase
    ABC/3TC + ATV/r: Induction Phase     ABC/3TC + ATV: Randomization Phase     ABC/3TC + ATV/r: Randomization Phase     ABC/3TC + ATV: Extension Phase     ABC/3TC + ATV/r: Extension Phase  
STARTED     515     0     0     0     0  
COMPLETED     442 [1]   0     0     0     0  
NOT COMPLETED     73     0     0     0     0  
Adverse Event                 16                 0                 0                 0                 0  
Insufficient Viral Load Response                 11                 0                 0                 0                 0  
Protocol-defined Virologic Failure                 5                 0                 0                 0                 0  
Non-compliance                 10                 0                 0                 0                 0  
Lost to Follow-up                 16                 0                 0                 0                 0  
Withdrawal by Subject                 7                 0                 0                 0                 0  
Kaposi Lesions Requiring Chemotherapy                 1                 0                 0                 0                 0  
Took Exclusionary Medications                 1                 0                 0                 0                 0  
Genotype Had Exclusionary Mutations                 1                 0                 0                 0                 0  
Fleeing Police; Outstanding Warrants                 1                 0                 0                 0                 0  
Incarceration                 3                 0                 0                 0                 0  
Pregnancy                 1                 0                 0                 0                 0  
[1] 23 PAR without confirmed HIV-RNA<50c/mL prior to Wk 36 couldn’t be randomized but weren’t withdrawn.

Period 2:   48-Week Randomization Phase
    ABC/3TC + ATV/r: Induction Phase     ABC/3TC + ATV: Randomization Phase     ABC/3TC + ATV/r: Randomization Phase     ABC/3TC + ATV: Extension Phase     ABC/3TC + ATV/r: Extension Phase  
STARTED     0     210     209     0     0  
COMPLETED     0     194     185     0     0  
NOT COMPLETED     0     16     24     0     0  
Adverse Event                 0                 2                 5                 0                 0  
Protocol-defined Virologic Failure                 0                 1                 1                 0                 0  
Non-compliance                 0                 3                 4                 0                 0  
Lost to Follow-up                 0                 2                 8                 0                 0  
Protocol Violation                 0                 0                 1                 0                 0  
Withdrawal by Subject                 0                 2                 4                 0                 0  
Pregnancy                 0                 0                 1                 0                 0  
Incarceration                 0                 3                 0                 0                 0  
Trying to Get Pregnant                 0                 1                 0                 0                 0  
Physician Decision                 0                 2                 0                 0                 0  

Period 3:   Optional 60-Week Extension Phase
    ABC/3TC + ATV/r: Induction Phase     ABC/3TC + ATV: Randomization Phase     ABC/3TC + ATV/r: Randomization Phase     ABC/3TC + ATV: Extension Phase     ABC/3TC + ATV/r: Extension Phase  
STARTED     0     0     0     189     180  
COMPLETED     0     0     0     160     154  
NOT COMPLETED     0     0     0     29     26  
Adverse Event                 0                 0                 0                 1                 3  
Insufficient Viral Load Response                 0                 0                 0                 1                 1  
Protocol-defined Virologic Failure                 0                 0                 0                 3                 2  
Non-compliance                 0                 0                 0                 1                 1  
Lost to Follow-up                 0                 0                 0                 9                 9  
Protocol Violation                 0                 0                 0                 1                 0  
Withdrawal by Subject                 0                 0                 0                 4                 3  
Pregnancy                 0                 0                 0                 3                 0  
Participant Moved                 0                 0                 0                 1                 1  
Sponsor Request                 0                 0                 0                 1                 1  
Sponsor Terminated Site                 0                 0                 0                 3                 3  
Unknown                 0                 0                 0                 1                 0  
Physician Decision                 0                 0                 0                 0                 1  
Participant Remained in Cuba                 0                 0                 0                 0                 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
ABC/3TC + ATV/r All participants starting the Induction Phase: ABC 600 mg/3TC 300 mg FDC tablet QD plus ATV 300 mg QD + /r 100 mg QD during the first 36 weeks of the study (planned interim analysis)

Baseline Measures
    ABC/3TC + ATV/r  
Number of Participants  
[units: participants]
  515  
Age  
[units: Years]
Mean ± Standard Deviation
  38.3  ± 10.03  
Gender  
[units: Participants]
 
Female     86  
Male     429  
Race/Ethnicity, Customized  
[units: participants]
 
African American/African Heritage     167  
American Indian or Alaskan Native     9  
Asian - Central/South Asian Heritage     4  
Asian - East Asian Heritage     3  
Asian - Japanese Heritage     1  
Asian - South East Asian Heritage     3  
Native Hawaiian or Other Pacific Islander     1  
White - Arabic/North African Heritage     5  
White - White/Caucasian/European Heritage     316  
Mixed Race     6  
Number of participants with the indicated baseline HIV-RNA level [1]
[units: participants]
 
HIV-1 RNA <100,000     227  
HIV-1 RNA 100,000-<250,000     143  
HIV-1 RNA 250,000-<500,000     73  
HIV-1 RNA >=500,000     72  
Number of participants with the indicated Baseline CD4+ Cell Count [2]
[units: participants]
 
CD4+ cells <50     69  
CD4+ cells 50-<200     190  
CD4+ cells >=200     256  
Number of participants with the indicated Center for Disease Control (CDC) Classification [3]
[units: participants]
 
Asymptomatic HIV Infection     353  
Symptomatic (non-AIDS) condition     97  
AIDS     65  
Median Baseline CD4+ Cell Count  
[units: cells per cubic millimeter]
Median ( Full Range )
  199  
  ( 19 to 754 )  
Median Baseline HIV-1 RNA Level  
[units: log10 copies/ml]
Median ( Full Range )
  5.076  
  ( 2.989 to 6.620 )  
[1] HIV-1 RNA, Human Immunodeficiency Virus type 1 Ribonucleic acid. HIV-1 viral load was measured as virus copies per milliliter (ml) at baseline.
[2] A CD4+ cell is a T lymphocyte that carries the CD4 antigen. Immunologic response was assessed by CD4+ counts.
[3] AIDS, Acquired Immunodeficiency Syndrome CDC classifications are Asymptomatic, Symptomatic, or AIDs.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants (PAR) Who Achieved Plasma HIV-1 RNA <50 Copies (c) /Milliliter (ml) at the Week 84 Visit   [ Time Frame: Week 84 ]

2.  Secondary:   Mean Age at Baseline of Participants Randomized to Treatment for the 48-Week Randomized Phase   [ Time Frame: Baseline of Randomized Phase ]

3.  Secondary:   Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 36 Visit   [ Time Frame: Week 36 ]

4.  Secondary:   Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 84 Visit   [ Time Frame: Week 84 ]

5.  Secondary:   Percentage of Participants Who Achieved Plasma HIV-1 RNA <50 c/ml at the Week 144 Visit   [ Time Frame: Week 144 ]

6.  Secondary:   Percentage of Participants Who Achieved Plasma HIV-1 RNA <400 c/ml at the Week 36 Visit   [ Time Frame: Week 36 ]

7.  Secondary:   Percentage of Participants Who Achieved HIV-1 RNA <400 c/ml at the Week 84 Visit   [ Time Frame: Week 84 ]

8.  Secondary:   Percentage of Participants Who Achieved HIV-1 RNA <400 c/ml at the Week 144 Visit   [ Time Frame: Week 144 ]

9.  Secondary:   Number of Participants Who Met the Protocol-defined Virologic Failure (PDVF) Criteria at Week 36   [ Time Frame: Week 36 ]

10.  Secondary:   Number of Participants Who Met the PDVF Criteria at Week 84   [ Time Frame: Week 84 ]

11.  Secondary:   Number of Participants Who Met the PDVF Criteria at Week 144   [ Time Frame: Week 144 ]

12.  Secondary:   Change From Baseline in HIV-1 RNA at Week 36   [ Time Frame: Baseline and Week 36 ]

13.  Secondary:   Change From Baseline in HIV-1 RNA at Week 84   [ Time Frame: Baseline and Week 84 ]

14.  Secondary:   Change From Baseline in HIV-1 RNA at Week 144   [ Time Frame: Baseline and Week 144 ]

15.  Secondary:   Change From Baseline in CD4+ Cell Count at Week 36   [ Time Frame: Baseline and Week 36 ]

16.  Secondary:   Change From Baseline in CD4+ Cell Count at Week 84   [ Time Frame: Baseline and Week 84 ]

17.  Secondary:   Change From Baseline in CD4+ Cell Count at Week 144   [ Time Frame: Baseline and Week 144 ]

18.  Secondary:   Number of Confirmed Virologic Failure Participants With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Baseline Through Week 36   [ Time Frame: Baseline through Week 36 ]

19.  Secondary:   Number of Confirmed Virologic Failure Participants With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Randomization at Week 36 Through Week 84   [ Time Frame: Randomization at Week 36 through Week 84 ]

20.  Secondary:   Number of Confirmed Virologic Failure Participants With Treatment-emergent HIV Genotypic Resistance in Reverse Transcriptase and Protease From Week 84 Through Week 144   [ Time Frame: Week 84 through Week 144 ]

21.  Secondary:   Number of Confirmed Virologic Failure Participants From Baseline Through Week 36 With Treatment-emergent Reductions in Susceptibility to Abacavir, Lamivudine, Atazanavir, or Ritonavir   [ Time Frame: Baseline through Week 36 ]

22.  Secondary:   Number of Confirmed Virologic Failure Participants From Randomization at Week 36 Through Week 84 With Treatment-emergent Reductions in HIV Susceptibility to Abacavir, Lamivudine, Atazanavir, or Ritonavir   [ Time Frame: Randomization at Week 36 through Week 84 ]

23.  Secondary:   Number of Confirmed Virologic Failure Participants From Week 84 Through Week 144 With Treatment-emergent Reductions in HIV Susceptibility to Abacavir, Lamivudine, Atazanavir, or Ritonavir   [ Time Frame: Week 84 through Week 144 ]

24.  Secondary:   Mean Percent Compliance at Week 36   [ Time Frame: Week 36 ]
  Hide Outcome Measure 24

Measure Type Secondary
Measure Title Mean Percent Compliance at Week 36
Measure Description Percent compliance is defined as the total number of pills taken divided by the total number of pills prescribed. The total number of pills taken was calculated by subtracting any returned pills from the total number of pills that were dispensed to each participant during this period. Compliance was calculated for each medication in the regimen.
Time Frame Week 36  
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.
ITT-E Population, Induction Phase. Participants with an unknown number of pills returned (including those whose pill bottles were not returned) were not included in this analysis.

Reporting Groups
  Description
ABC/3TC + ATV/r: Induction Phase Induction Phase: ABC 600 mg/3TC 300 mg FDC tablet QD plus ATV 300 mg QD + /r 100 mg QD during the first 36 weeks of the study (planned interim analysis)

Measured Values
    ABC/3TC + ATV/r: Induction Phase  
Number of Participants Analyzed  
[units: participants]
  503  
Mean Percent Compliance at Week 36  
[units: percent compliance]
Mean ± Standard Deviation
 
Abacavir/Lamivudine     92.2  ± 13.05  
Ritonavir     92.3  ± 12.15  
Atazanavir     92.7  ± 12.50  

No statistical analysis provided for Mean Percent Compliance at Week 36



25.  Secondary:   Mean Percent Compliance at Week 84   [ Time Frame: Week 84 ]

26.  Secondary:   Mean Percent Compliance at Week 144   [ Time Frame: Week 144 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
No text entered.


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