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

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ClinicalTrials.gov Identifier: NCT00608569
Recruitment Status : Completed
First Posted : February 6, 2008
Results First Posted : November 15, 2013
Last Update Posted : October 12, 2018
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (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
Enrollment 529
Recruitment Details 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 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.
Arm/Group Title mDOT Arm Non-mDOT Arm
Hide Arm/Group Description 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. Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Period Title: Overall Study
Started 129 128
Completed 119 119
Not Completed 10 9
Reason Not Completed
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
Arm/Group Title mDOT Arm Non-mDOT Arm Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 129 128 257
Hide Baseline Analysis Population Description
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.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 129 participants 128 participants 257 participants
<=18 years
1
   0.8%
0
   0.0%
1
   0.4%
Between 18 and 65 years
127
  98.4%
123
  96.1%
250
  97.3%
>=65 years
1
   0.8%
5
   3.9%
6
   2.3%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 129 participants 128 participants 257 participants
39.3  (9.7) 39.4  (10.6) 39.4  (10.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 129 participants 128 participants 257 participants
Female
62
  48.1%
65
  50.8%
127
  49.4%
Male
67
  51.9%
63
  49.2%
130
  50.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 129 participants 128 participants 257 participants
Black Non-Hispanic 101 103 204
Hispanic (regardless of race) 27 25 52
More than one race 1 0 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 129 participants 128 participants 257 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] 
Median (Inter-Quartile Range)
Unit of measure:  Cells/mm3
Number Analyzed 129 participants 128 participants 257 participants
164
(91 to 250)
201
(97 to 292)
179
(92 to 269)
[1]
Measure Description: The baseline CD4 count is the average of screening and entry values.
CD4 Count Category  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 129 participants 128 participants 257 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] 
Median (Inter-Quartile Range)
Unit of measure:  Log10 copies/mL
Number Analyzed 129 participants 128 participants 257 participants
4.2
(3.8 to 4.9)
4.3
(3.8 to 4.9)
4.3
(3.8 to 4.9)
[1]
Measure Description: The baseline HIV-1 RNA value is the result at study entry.
HIV-1 RNA Viral Load Category  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 129 participants 128 participants 257 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.Primary Outcome
Title Confirmed Virologic Failure at or Prior to Week 48
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Two hundred fifty seven eligible participants were included in the analysis. Intent to treat analysis was performed.
Arm/Group Title mDOT Arm Non-mDOT Arm
Hide Arm/Group Description:
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.
Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Overall Number of Participants Analyzed 129 128
Measure Type: Number
Unit of Measure: participants
No Failure 95 105
Experienced Failure 34 23
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection mDOT Arm, Non-mDOT Arm
Comments Fisher exact test (unstratified)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.133
Comments Results were considered to be statistically significant if p<0.05
Method Fisher Exact
Comments [Not Specified]
2.Secondary Outcome
Title Confirmed Virologic Failure at or Prior to Week 24
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Two hundred fifty seven eligible participants were included in the analysis. Intent to treat analysis was performed.
Arm/Group Title mDOT Arm Non-mDOT Arm
Hide Arm/Group Description:
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.
Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Overall Number of Participants Analyzed 129 128
Measure Type: Number
Unit of Measure: participants
No Failure 105 111
Experienced Failure 24 17
3.Secondary Outcome
Title CD4 Count at Follow-up Visits
Hide Description CD4 cell count (median, inter-quartile range)
Time Frame At Weeks 4, 12, 24, 36, and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title mDOT Arm Non-mDOT Arm
Hide Arm/Group Description:
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.
Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Overall Number of Participants Analyzed 129 128
Median (Inter-Quartile Range)
Unit of Measure: cells/mm3
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)
4.Secondary Outcome
Title CD8 Count at Follow-up Visits
Hide Description CD8 cell count (median, inter-quartile range)
Time Frame At week 4, 12, 24, 36, and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title mDOT Arm Non-mDOT Arm
Hide Arm/Group Description:
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.
Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Overall Number of Participants Analyzed 129 128
Median (Inter-Quartile Range)
Unit of Measure: cells/mm3
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)
5.Secondary Outcome
Title Time to First Grade 3 or 4 Lab Event
Hide Description 5th and 10th percentiles in weeks from randomization to first grade 3 or 4 lab event
Time Frame 52 weeks since randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Two hundred fifty seven eligible participants were included in the analysis. As-treated analysis was performed.
Arm/Group Title mDOT Arm Non-mDOT Arm
Hide Arm/Group Description:
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.
Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Overall Number of Participants Analyzed 129 128
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: weeks
5th percentile
24 [1] 
(1.3 to NA)
NA [2] 
(12 to NA)
10th percentile
NA [3] 
(12 to NA)
NA [3] 
(36.9 to NA)
[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%
6.Secondary Outcome
Title Time to First Grade 3 or 4 Sign or Symptom
Hide Description 5th and 10th percentiles in weeks from randomization to first grade 3 or 4 sign or symptom
Time Frame 52 weeks since randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Two hundred fifty seven eligible participants were included in the analysis. As-treated analysis was performed.
Arm/Group Title mDOT Arm Non-mDOT Arm
Hide Arm/Group Description:
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.
Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Overall Number of Participants Analyzed 129 128
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: weeks
5th percentile
13.7
(0 to 48)
26.7
(0.3 to 48.9)
10th percentile
NA [1] 
(12 to NA)
48.9 [2] 
(12 to NA)
[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%
7.Secondary Outcome
Title Time to First Grade 3 or 4 Lab or Sign/Symptom Event
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Two hundred fifty seven eligible participants were included in the analysis. As-treated analysis was performed.
Arm/Group Title mDOT Arm Non-mDOT Arm
Hide Arm/Group Description:
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.
Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Overall Number of Participants Analyzed 129 128
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: weeks
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 NA)
[1]
Not estimable as the upper limit for survival function at all weeks is above 90%
8.Secondary Outcome
Title Adherence to Second Line HAART Regimen
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title mDOT Arm Non-mDOT Arm
Hide Arm/Group Description:
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.
Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
Overall Number of Participants Analyzed 129 128
Measure Type: Number
Unit of Measure: 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
Time Frame 52 weeks since randomization
Adverse Event Reporting Description Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities, requiring hospitalization, and ≥grade 3 AEs (where grade 1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death).
 
Arm/Group Title mDOT Arm Non-mDOT Arm
Hide Arm/Group Description 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. Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.
All-Cause Mortality
mDOT Arm Non-mDOT Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
mDOT Arm Non-mDOT Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   6/129 (4.65%)   7/128 (5.47%) 
Gastrointestinal disorders     
Diarrhoea  1  0/129 (0.00%)  1/128 (0.78%) 
Pancreatitis  1  0/129 (0.00%)  1/128 (0.78%) 
General disorders     
Death  1  2/129 (1.55%)  0/128 (0.00%) 
Infections and infestations     
Bronchopneumonia  1  0/129 (0.00%)  1/128 (0.78%) 
Metabolism and nutrition disorders     
Dehydration  1  0/129 (0.00%)  1/128 (0.78%) 
Diabetes mellitus  1  1/129 (0.78%)  0/128 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Neoplasm  1  1/129 (0.78%)  0/128 (0.00%) 
Pregnancy, puerperium and perinatal conditions     
Abortion spontaneous  1  0/129 (0.00%)  1/128 (0.78%) 
Ruptured ectopic pregnancy  1  0/129 (0.00%)  1/128 (0.78%) 
Psychiatric disorders     
Delirium  1  0/129 (0.00%)  1/128 (0.78%) 
Renal and urinary disorders     
Renal failure  1  2/129 (1.55%)  0/128 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Respiratory distress  1  0/129 (0.00%)  1/128 (0.78%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
mDOT Arm Non-mDOT Arm
Affected / at Risk (%) Affected / at Risk (%)
Total   94/129 (72.87%)   98/128 (76.56%) 
Gastrointestinal disorders     
Abdominal pain  1  4/129 (3.10%)  9/128 (7.03%) 
Diarrhoea  1  16/129 (12.40%)  18/128 (14.06%) 
Vomiting  1  6/129 (4.65%)  9/128 (7.03%) 
General disorders     
Chest pain  1  7/129 (5.43%)  5/128 (3.91%) 
Pyrexia  1  11/129 (8.53%)  15/128 (11.72%) 
Infections and infestations     
Urinary tract infection  1  4/129 (3.10%)  10/128 (7.81%) 
Investigations     
Aspartate aminotransferase increased  1  13/129 (10.08%)  14/128 (10.94%) 
Blood alkaline phosphatase increased  1  15/129 (11.63%)  8/128 (6.25%) 
Blood bicarbonate abnormal  1  9/129 (6.98%)  8/128 (6.25%) 
Blood cholesterol  1  0/129 (0.00%)  7/128 (5.47%) 
Blood glucose increased  1  14/129 (10.85%)  9/128 (7.03%) 
Blood sodium decreased  1  28/129 (21.71%)  19/128 (14.84%) 
Blood sodium increased  1  8/129 (6.20%)  3/128 (2.34%) 
Haemoglobin decreased  1  8/129 (6.20%)  14/128 (10.94%) 
Neutrophil count decreased  1  40/129 (31.01%)  48/128 (37.50%) 
Weight decreased  1  8/129 (6.20%)  8/128 (6.25%) 
White blood cell count decreased  1  24/129 (18.60%)  21/128 (16.41%) 
Nervous system disorders     
Headache  1  7/129 (5.43%)  9/128 (7.03%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  13/129 (10.08%)  15/128 (11.72%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights".
Results Point of Contact
Name/Title: ACTG ClinicalTrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
Phone: (301) 628-3313
Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00608569     History of Changes
Other Study ID Numbers: ACTG A5234
1U01AI068636 ( U.S. NIH Grant/Contract )
First Submitted: January 21, 2008
First Posted: February 6, 2008
Results First Submitted: September 5, 2013
Results First Posted: November 15, 2013
Last Update Posted: October 12, 2018