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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
  Hide All Outcome Measures

1.  Primary:   Confirmed Virologic Failure at or Prior to Week 48   [ Time Frame: At or prior to Week 48 ]

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 ]

Measure Type Secondary
Measure Title Confirmed Virologic Failure at or Prior to Week 24
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 ≤30 weeks after randomization was considered to be a virologic failure. Number of participants experiencing or not experiencing virologic failure at or prior to week 24 was reported.
Time Frame At or prior to Week 24  
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 24 
[Units: Participants]
   
No Failure   105   111 
Experienced Failure   24   17 

No statistical analysis provided for Confirmed Virologic Failure at or Prior to Week 24



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

Measure Type Secondary
Measure Title CD4 Count at Follow-up Visits
Measure Description CD4 cell count (median, inter-quartile range)
Time Frame At Weeks 4, 12, 24, 36, and 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.
No text entered.

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 
CD4 Count at Follow-up Visits 
[Units: Cells/mm3]
Median (Inter-Quartile Range)
   
Week 4   212 
 (129 to 309) 
 219 
 (158 to 289) 
Week 12   225 
 (168 to 359) 
 235 
 (174 to 337) 
Week 24   268 
 (177 to 382) 
 266 
 (181 to 395) 
Week 36   281 
 (189 to 395) 
 294 
 (214 to 418) 
Week 48   301 
 (198 to 432) 
 347 
 (234 to 466) 

No statistical analysis provided for CD4 Count at Follow-up Visits



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

Measure Type Secondary
Measure Title CD8 Count at Follow-up Visits
Measure Description CD8 cell count (median, inter-quartile range)
Time Frame At week 4, 12, 24, 36, and 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.
No text entered.

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 
CD8 Count at Follow-up Visits 
[Units: Cells/mm3]
Median (Inter-Quartile Range)
   
Week 4   776 
 (557 to 1048) 
 859 
 (557 to 1141) 
Week 12   895 
 (625 to 1155) 
 916 
 (635 to 1290) 
Week 24   816 
 (586 to 1071) 
 818 
 (547 to 1126) 
Week 36   787 
 (539 to 1034) 
 833 
 (598 to 1131) 
Week 48   815 
 (566 to 1037) 
 823 
 (573 to 1125) 

No statistical analysis provided for CD8 Count at Follow-up Visits



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

Measure Type Secondary
Measure Title Time to First Grade 3 or 4 Lab Event
Measure Description 5th and 10th percentiles in weeks from randomization to first grade 3 or 4 lab event
Time Frame 52 weeks since randomization  
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. As-treated 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 
Time to First Grade 3 or 4 Lab Event 
[Units: Weeks]
Number (95% Confidence Interval)
   
5th percentile   24 [1] 
 (1.3 to N/A) 
 NA [2] 
 (12 to N/A) 
10th percentile   NA [3] 
 (12 to N/A) 
 NA [3] 
 (36.9 to N/A) 
[1] Not estimable as the upper limit for survival function at all weeks is above 95%
[2] Not estimable as the estimates for survival function at all weeks is above 95%
[3] Not estimable as the estimates for survival function at all weeks is above 90%

No statistical analysis provided for Time to First Grade 3 or 4 Lab Event



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

Measure Type Secondary
Measure Title Time to First Grade 3 or 4 Sign or Symptom
Measure Description 5th and 10th percentiles in weeks from randomization to first grade 3 or 4 sign or symptom
Time Frame 52 weeks since randomization  
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. As-treated 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 
Time to First Grade 3 or 4 Sign or Symptom 
[Units: Weeks]
Number (95% Confidence Interval)
   
5th percentile   13.7 
 (0 to 48) 
 26.7 
 (0.3 to 48.9) 
10th percentile   NA [1] 
 (12 to N/A) 
 48.9 [2] 
 (12 to N/A) 
[1] Not estimable as the estimates for survival function at all weeks is above 90%
[2] Not estimable as the upper limit for survival function at all weeks is above 90%

No statistical analysis provided for Time to First Grade 3 or 4 Sign or Symptom



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

Measure Type Secondary
Measure Title Time to First Grade 3 or 4 Lab or Sign/Symptom Event
Measure Description 5th and 10th percentiles in weeks from randomization to first grade 3 or 4 lab or sign/ symptom event
Time Frame 52 weeks since randomization  
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. As-treated 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 
Time to First Grade 3 or 4 Lab or Sign/Symptom Event 
[Units: Weeks]
Number (95% Confidence Interval)
   
5th percentile   6.4 
 (0 to 13.7) 
 24 
 (0.3 to 32.1) 
10th percentile   24 
 (4.4 to 48) 
 32.6 [1] 
 (12 to N/A) 
[1] Not estimable as the upper limit for survival function at all weeks is above 90%

No statistical analysis provided for Time to First Grade 3 or 4 Lab or Sign/Symptom Event



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

Measure Type Secondary
Measure Title Adherence to Second Line HAART Regimen
Measure Description Number of participants with self-reported 100% adherence over the week prior to study visit
Time Frame At weeks 4, 8, 12, 24, 36, 48 and 52  
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.
Only the 257 eligible participants were included in the analysis. Self-reported adherence was collected face-to-face or by self-report on the Adherence/Quality of Life/Psychosocial Interview form. Only adherence to LPV/rtv was collected.

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 
Adherence to Second Line HAART Regimen 
[Units: Participants]
   
Week 4   105   117 
Week 8   108   115 
Week 12   114   116 
Week 24   107   116 
Week 48   103   109 
Week 52   104   109 

No statistical analysis provided for Adherence to Second Line HAART Regimen




  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
No text entered.


  More Information