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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:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00118898
First received: July 7, 2005
Last updated: January 4, 2016
Last verified: January 2016
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 
Overall Participants Analyzed 
[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 
[1] Race/Ethnicity is collected prior to study entry, participants may opt out of reporting.
Region of Enrollment 
[Units: Participants]
         
United States   451   452   452   450   1805 
Puerto Rico   13   13   13   13   52 
Baseline HIV-1 RNA [1] 
[Units: Log10 copies/mL]
Mean (Standard Deviation)
 4.7  (0.7)   4.7  (0.7)   4.7  (0.7)   4.7  (0.7)   4.7  (0.7) 
[1] Baseline RNA is calculated as the mean of the log10 pre-entry and entry values
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 [1] 
[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] 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 ]
  Hide Outcome Measure 9

Measure Type Secondary
Measure Title Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events.
Measure Description

AIDS-defining illnesses were defined per CDC category C definition. HIV-1 related events were defined per CDC category B definition. Events underwent study chair review for classification. See link below for more details.

http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm

Time Frame Follow-up time was variable, median follow-up was 138 weeks; see 'Amount of study follow-up' outcome for details  
Safety Issue Yes  

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 
Participants Analyzed 
[Units: Participants]
 464   465   465   463 
Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events. 
[Units: Participants]
       
Death   6   11   6   8 
AIDS-defining illness   14   25   20   23 
HIV-1 relatated event   56   61   57   63 

No statistical analysis provided for Number of Participants Experiencing Certain Targeted Clinical Events, Including Death, AIDS-defining Illness, and HIV-1 Related Events.



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 ]

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