Determining the Effects of Observed and Self-Administered Drug Regimens in HIV Infected Adults

This study has been completed.
Sponsor:
Collaborator:
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  
Number of Participants  
[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 )  
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 [2]
[units: log10┬ácopies/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 )  
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  
[1] The baseline CD4 count is the average of screening and entry values.
[2] The baseline HIV-1 RNA value is the result at study entry.



  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 ]

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  
Number of 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  
Number of 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  
Number of 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  
Number of 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  
Number of Participants Analyzed  
[units: participants]
  129     128  
Time to First Grade 3 or 4 Lab Event  
[units: weeks]
Number ( 95% Confidence Interval )
   
5th percentile     24  
  ( 1.3 to NA ) [1]
  NA  
  ( 12 to NA ) [2]
10th percentile     NA  
  ( 12 to NA ) [3]
  NA  
  ( 36.9 to NA ) [3]
[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  
Number of 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  
  ( 12 to NA ) [1]
  48.9  
  ( 12 to NA ) [2]
[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  
Number of 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  
  ( 12 to NA ) [1]
[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  
Number of 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.


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