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Determining the Effects of Observed and Self-Administered Drug Regimens in HIV Infected 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:
NCT00608569
First received: January 21, 2008
Last updated: November 14, 2013
Last verified: November 2013
Results First Received: September 5, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Condition: HIV Infections
Interventions: Drug: Lopinavir/ritonavir
Drug: Emtricitabine/Tenofovir disoproxil fumarate
Drug: Tenofovir disoproxil fumarate
Drug: Zidovudine
Drug: Emtricitabine

  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 were recruited across 9 study sites (2 in Peru, one each in South Africa, Haiti, Uganda, Botswana, Zimbabwe, Brazil and Zambia) in the AIDS Clinical Trials Group system between April 2009 and September 2011.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Five hundred twenty nine subjects including participants and partners entered the study. Among the 529 subjects, 259 were participants, which included two participants with eligibility violations. Only the 257 eligible participants were included in the analyses. All participants started TDF/FTC +LPV/rtv and stratified by screening HIV-1 RNA only.

Reporting Groups
  Description
mDOT Arm Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.
Non-mDOT Arm Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.

Participant Flow:   Overall Study
    mDOT Arm   Non-mDOT Arm
STARTED   129   128 
COMPLETED   119   119 
NOT COMPLETED   10   9 
Death                4                3 
Lost to Follow-up                4                5 
Withdrawal by Subject                1                0 
Adverse Event                1                0 
Unable to adhere with study requirements                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.
Five hundred twenty nine subjects including participants and partners entered the study. Among the 529 subjects, 259 were participants, which include two participants with eligibility violations. Only the 257 eligible participants were included in the analysis.

Reporting Groups
  Description
mDOT Arm Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.
Non-mDOT Arm Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Total Total of all reporting groups

Baseline Measures
   mDOT Arm   Non-mDOT Arm   Total 
Overall Participants Analyzed 
[Units: Participants]
 129   128   257 
Age 
[Units: Participants]
     
<=18 years   1   0   1 
Between 18 and 65 years   127   123   250 
>=65 years   1   5   6 
Age 
[Units: Years]
Mean (Standard Deviation)
 39.3  (9.7)   39.4  (10.6)   39.4  (10.1) 
Gender 
[Units: Participants]
     
Female   62   65   127 
Male   67   63   130 
Race/Ethnicity, Customized 
[Units: Participants]
     
Black Non-Hispanic   101   103   204 
Hispanic (regardless of race)   27   25   52 
More than one race   1   0   1 
Region of Enrollment 
[Units: Participants]
     
Haiti   37   36   73 
Zambia   4   5   9 
Botswana   4   4   8 
Peru   23   23   46 
Uganda   25   25   50 
South Africa   15   17   32 
Zimbabwe   17   16   33 
Brazil   4   2   6 
CD4 Counts [1] 
[Units: Cells/mm3]
Median (Inter-Quartile Range)
 164 
 (91 to 250) 
 201 
 (97 to 292) 
 179 
 (92 to 269) 
[1] The baseline CD4 count is the average of screening and entry values.
CD4 Count Category 
[Units: Participants]
     
0-50 cells/mm3   17   14   31 
51-100 cells/mm3   20   19   39 
101-200 cells/mm3   40   31   71 
201-350 cells/mm3   35   47   82 
351-500 cells/mm3   9   12   21 
>500 cells/mm3   8   5   13 
Log10 HIV-1 RNA Viral Load [1] 
[Units: Log10 copies/mL]
Median (Inter-Quartile Range)
 4.2 
 (3.8 to 4.9) 
 4.3 
 (3.8 to 4.9) 
 4.3 
 (3.8 to 4.9) 
[1] The baseline HIV-1 RNA value is the result at study entry.
HIV-1 RNA Viral Load Category 
[Units: Participants]
     
<=400 copies/mL   6   5   11 
401-999 copies/mL   4   2   6 
1000-9999 copies/mL   42   38   80 
10000-99999 copies/mL   54   55   109 
100000-499999 copies/mL   17   24   41 
>=500000 copies/mL   6   4   10 


  Outcome Measures
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1.  Primary:   Confirmed Virologic Failure at or Prior to Week 48   [ Time Frame: At or prior to Week 48 ]
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Measure Type Primary
Measure Title Confirmed Virologic Failure at or Prior to Week 48
Measure Description Confirmed virologic failure was defined as two successive HIV-1 RNA measurements at least 24 hours apart that were either:1) <1 log10 copies/mL below the baseline level and >400 copies/mL at the week 12 HIV-1 RNA evaluation (obtained at least 11 weeks after the date of the randomization) 2) >400 copies/mL at or after the week 24 HIV-1 RNA evaluation (obtained at least 23 weeks after the date of randomization). 3) subjects who discontinued the study follow-up for any reason other than study completion, including death, and who did so ≤50 weeks after randomization was considered to be a virologic failure. Number of participants experiencing or not experiencing virologic failure at or prior to week 48 was reported.
Time Frame At or prior to Week 48  
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.
Two hundred fifty seven eligible participants were included in the analysis. Intent to treat analysis was performed.

Reporting Groups
  Description
mDOT Arm Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.
Non-mDOT Arm Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.

Measured Values
   mDOT Arm   Non-mDOT Arm 
Participants Analyzed 
[Units: Participants]
 129   128 
Confirmed Virologic Failure at or Prior to Week 48 
[Units: Participants]
   
No Failure   95   105 
Experienced Failure   34   23 


Statistical Analysis 1 for Confirmed Virologic Failure at or Prior to Week 48
Groups [1] All groups
Method [2] Fisher Exact
P Value [3] 0.133
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Fisher exact test (unstratified)
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Results were considered to be statistically significant if p<0.05



2.  Secondary:   Confirmed Virologic Failure at or Prior to Week 24   [ Time Frame: At or prior to Week 24 ]

3.  Secondary:   CD4 Count at Follow-up Visits   [ Time Frame: At Weeks 4, 12, 24, 36, and 48 ]

4.  Secondary:   CD8 Count at Follow-up Visits   [ Time Frame: At week 4, 12, 24, 36, and 48 ]

5.  Secondary:   Time to First Grade 3 or 4 Lab Event   [ Time Frame: 52 weeks since randomization ]

6.  Secondary:   Time to First Grade 3 or 4 Sign or Symptom   [ Time Frame: 52 weeks since randomization ]

7.  Secondary:   Time to First Grade 3 or 4 Lab or Sign/Symptom Event   [ Time Frame: 52 weeks since randomization ]

8.  Secondary:   Adherence to Second Line HAART Regimen   [ Time Frame: At weeks 4, 8, 12, 24, 36, 48 and 52 ]


  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.


  More Information