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Efavirenz or Atazanavir/Ritonavir Given With Emtricitabine/Tenofovir Disoproxil Fumarate or Abacavir/Lamivudine in HIV Infected Treatment-Naive Adults

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00118898
First received: July 7, 2005
Last updated: February 15, 2011
Last verified: February 2011
Results First Received: January 8, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: Abacavir/Lamivudine
Drug: Atazanavir
Drug: Efavirenz
Drug: Emtricitabine/Tenofovir disoproxil fumarate
Drug: Ritonavir
Drug: Abacavir/Lamivudine placebo
Drug: Emtricitabine/Tenofovir disoproxil fumarate placebo

  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
Recruited at AIDS Clinical Trials Units in the United States and Puerto Rico. Recruitment occurred between September 21, 2005 (date first subject was randomized) and November 20, 2007 (date last subject was randomized).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
1864 were randomized. Results reported for 1857 eligible participants; 7 were subsequently found ineligible and excluded from all analyses.

Reporting Groups
  Description
EFV, FTC/TDF, and Placebo ABC/3TC Participants will receive EFV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks
EFV, Placebo FTC/TDF, and ABC/3TC Participants will receive EFV, placebo for FTC/TDF, and ABC/3TC for at least 96 weeks
RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC Participants will receive RTV-boosted ATV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks
RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC Participants will receive RTV-boosted ATV, placebo for FTC/TDF, and ABC/3TC for at least 96 weeks

Participant Flow:   Overall Study
    EFV, FTC/TDF, and Placebo ABC/3TC     EFV, Placebo FTC/TDF, and ABC/3TC     RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC     RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC  
STARTED     464     465     465     463  
Initiated Treatment     461     461     464     462  
COMPLETED     343     324     342     322  
NOT COMPLETED     121     141     123     141  
Death                 6                 11                 6                 8  
Lost to Follow-up                 26                 34                 33                 33  
Withdrawal by Subject                 10                 5                 8                 8  
Site Closure                 33                 31                 28                 37  
Severe debilitation                 1                 4                 6                 4  
Not compliant with requirements                 11                 13                 11                 11  
Not able to get to clinic                 34                 43                 31                 40  



  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
EFV, FTC/TDF, and Placebo ABC/3TC Participants will receive EFV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks
EFV, Placebo FTC/TDF, and ABC/3TC Participants will receive EFV, placebo for FTC/TDF, and ABC/3TC for at least 96 weeks
RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC Participants will receive RTV-boosted ATV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks
RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC Participants will receive RTV-boosted ATV, placebo for FTC/TDF, and ABC/3TC for at least 96 weeks
Total Total of all reporting groups

Baseline Measures
    EFV, FTC/TDF, and Placebo ABC/3TC     EFV, Placebo FTC/TDF, and ABC/3TC     RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC     RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC     Total  
Number of Participants  
[units: participants]
  464     465     465     463     1857  
Age  
[units: participants]
         
<=18 years     2     3     2     3     10  
Between 18 and 65 years     461     454     461     458     1834  
>=65 years     1     8     2     2     13  
Age  
[units: years]
Mean ± Standard Deviation
  38.2  ± 9.6     38.4  ± 10.5     38.9  ± 10.4     38.0  ± 9.8     38.4  ± 10.1  
Gender  
[units: participants]
         
Female     71     98     78     75     322  
Male     393     367     387     388     1535  
Race/Ethnicity, Customized [1]
[units: participants]
         
White Non-Hispanic     197     174     186     189     746  
Black Non-Hispanic     151     164     147     153     615  
Hispanic (Regardless of Race)     104     106     111     108     429  
Asian, Pacific Islander     5     8     12     7     32  
Native American, Alaskan Native     4     5     3     2     14  
More than One Race     2     5     5     4     16  
Unknown     1     3     1     0     5  
Region of Enrollment  
[units: participants]
         
United States     451     452     452     450     1805  
Puerto Rico     13     13     13     13     52  
Baseline HIV-1 RNA [2]
[units: log10┬ácopies/mL]
Mean ± Standard Deviation
  4.7  ± 0.7     4.7  ± 0.7     4.7  ± 0.7     4.7  ± 0.7     4.7  ± 0.7  
Screening HIV-1 RNA  
[units: participants]
         
<100,000 copies/mL     265     266     265     264     1060  
>=100,000 copies/mL     199     199     200     199     797  
Baseline CD4+ count [3]
[units: cells/mm3]
Median ( Inter-Quartile Range )
  233.5  
  ( 102.5 to 333.5 )  
  225  
  ( 103 to 324 )  
  224  
  ( 87.0 to 326.5 )  
  236  
  ( 71.5 to 345.5 )  
  229.5  
  ( 89.5 to 333.8 )  
[1] Race/Ethnicity is collected prior to study entry, participants may opt out of reporting.
[2] Baseline RNA is calculated as the mean of the log10 pre-entry and entry values
[3] Baseline CD4 count is the average (mean) of 2 measures taken at pre-entry and entry visits.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Time From Randomization to Virologic Failure   [ Time Frame: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details ]

2.  Primary:   Time From Treatment Dispensation to a Grade 3/4 Safety Event   [ Time Frame: All follow-up while on initially assigned regimen; the median (25th, 75th percentile) follow-up while on initial regimen was 120 (54, 156) weeks and the range was 0 to 205 weeks. ]

3.  Primary:   Time From Treatment Dispensation to Treatment Modification   [ Time Frame: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details ]

4.  Secondary:   Time From Treatment Dispensation to Regimen Failure (First Occurrence of Virologic Failure or Treatment Modification)   [ Time Frame: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details ]

5.  Secondary:   The Number of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL   [ Time Frame: At Weeks 48 and 96 ]

6.  Secondary:   Number of Participants With HIV-1 RNA Levels Less Than 200 Copies/mL   [ Time Frame: At Weeks 48 and 96 ]

7.  Secondary:   Change in CD4 Count (Cells/mm3) From Baseline   [ Time Frame: At Weeks 48 and 96 ]

8.  Secondary:   Number of Participants With Virologic Failure and Emergence of Major Resistance   [ Time Frame: Follow-up time was variable,median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details ]

9.  Secondary:   Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events.   [ Time Frame: Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details ]

10.  Secondary:   Change in Fasting Total Cholesterol Level From Baseline   [ Time Frame: At Weeks 48 and 96 ]

11.  Secondary:   Change in Fasting High-density Lipoprotein (HDL) Cholesterol Level From Baseline   [ Time Frame: At Weeks 48 and 96 ]

12.  Secondary:   Change in Fasting Non-high Density Lipoprotein (Non-HDL) Cholesterol Level From Baseline   [ Time Frame: At Weeks 48 and 96 ]

13.  Secondary:   Change in Fasting Triglyceride Level From Baseline   [ Time Frame: At Weeks 48 and 96 ]

14.  Other Pre-specified:   Amount of Study Follow-up   [ Time Frame: Follow-up time was variable, median follow-up was 138 weeks ]

15.  Other Pre-specified:   Number of Participants With Virologic Failure   [ Time Frame: Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details ]
  Hide Outcome Measure 15

Measure Type Other Pre-specified
Measure Title Number of Participants With Virologic Failure
Measure Description Blood samples for determining virologic failure were obtained at 16 and 24 weeks, and every 12 weeks thereafter. Virologic failure was defined as a confirmed plasma HIV-1 RNA level >= 1000 copies/mL at or after 16 weeks and before 24 weeks or >=200 copies/mL at or after 24 weeks.
Time Frame Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details  
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.
Intention to treat: All eligible participants were included in the analysis, participants were analyzed per originally assigned regimen.

Reporting Groups
  Description
EFV, FTC/TDF, and Placebo ABC/3TC Participants will receive EFV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks
EFV, Placebo FTC/TDF, and ABC/3TC Participants will receive EFV, placebo for FTC/TDF, and ABC/3TC for at least 96 weeks
RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC Participants will receive RTV-boosted ATV, FTC/TDF, and placebo for ABC/3TC for at least 96 weeks
RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC Participants will receive RTV-boosted ATV, placebo for FTC/TDF, and ABC/3TC for at least 96 weeks

Measured Values
    EFV, FTC/TDF, and Placebo ABC/3TC     EFV, Placebo FTC/TDF, and ABC/3TC     RTV-boosted ATV, FTC/TDF, and Placebo ABC/3TC     RTV-boosted ATV, Placebo FTC/TDF, and ABC/3TC  
Number of Participants Analyzed  
[units: participants]
  464     465     465     463  
Number of Participants With Virologic Failure  
[units: participants]
  57     72     57     83  

No statistical analysis provided for Number of Participants With Virologic Failure



16.  Other Pre-specified:   Cumulative Probability of Not Experiencing Virologic Failure   [ Time Frame: At week 48 and 96 ]

17.  Other Pre-specified:   Number of Participants With a Grade 3/4 Safety Event   [ Time Frame: Over all study follow-up while on initially assigned treatment, median follow-up was 120 weeks ]

18.  Other Pre-specified:   Cumulative Probability of Not Experiencing a Grade 3/4 Safety Event   [ Time Frame: At week 48 and 96 ]

19.  Other Pre-specified:   Number of Participants With Treatment Modification   [ Time Frame: Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details ]

20.  Other Pre-specified:   Cumulative Probability of Not Experiencing Treatment Modification   [ Time Frame: At week 48 and 96 ]

21.  Other Pre-specified:   Number of Participants With Regimen Failure   [ Time Frame: Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details ]

22.  Other Pre-specified:   Cumulative Probability of Not Experiencing Regimen Failure   [ Time Frame: At week 48 and 96 ]


  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
HIV-1 drug resistance testing and HLA-B*5701 testing were not standard of care during enrollment. EFV and RTV-boosted ATV were open-label, and blinded FTC/TDF vs. ABC/3TC were unblinded in the >=100,000 cp/mL screening viral load stratum Feb 2008.


  More Information