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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:
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 ]

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
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Time Frame 52 weeks since randomization
Additional 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).

Frequency Threshold
Threshold above which other adverse events are reported   5%  

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.

Other Adverse Events
    mDOT Arm     Non-mDOT Arm  
Total, other (not including serious) adverse events      
# participants affected / at risk     94/129     98/128  
Gastrointestinal disorders      
Abdominal pain † 1    
# participants affected / at risk     4/129 (3.10%)     9/128 (7.03%)  
Diarrhoea † 1    
# participants affected / at risk     16/129 (12.40%)     18/128 (14.06%)  
Vomiting † 1    
# participants affected / at risk     6/129 (4.65%)     9/128 (7.03%)  
General disorders      
Chest pain † 1    
# participants affected / at risk     7/129 (5.43%)     5/128 (3.91%)  
Pyrexia † 1    
# participants affected / at risk     11/129 (8.53%)     15/128 (11.72%)  
Infections and infestations      
Urinary tract infection † 1    
# participants affected / at risk     4/129 (3.10%)     10/128 (7.81%)  
Investigations      
Aspartate aminotransferase increased † 1    
# participants affected / at risk     13/129 (10.08%)     14/128 (10.94%)  
Blood alkaline phosphatase increased † 1    
# participants affected / at risk     15/129 (11.63%)     8/128 (6.25%)  
Blood bicarbonate abnormal † 1    
# participants affected / at risk     9/129 (6.98%)     8/128 (6.25%)  
Blood cholesterol † 1    
# participants affected / at risk     0/129 (0.00%)     7/128 (5.47%)  
Blood glucose increased † 1    
# participants affected / at risk     14/129 (10.85%)     9/128 (7.03%)  
Blood sodium decreased † 1    
# participants affected / at risk     28/129 (21.71%)     19/128 (14.84%)  
Blood sodium increased † 1    
# participants affected / at risk     8/129 (6.20%)     3/128 (2.34%)  
Haemoglobin decreased † 1    
# participants affected / at risk     8/129 (6.20%)     14/128 (10.94%)  
Neutrophil count decreased † 1    
# participants affected / at risk     40/129 (31.01%)     48/128 (37.50%)  
Weight decreased † 1    
# participants affected / at risk     8/129 (6.20%)     8/128 (6.25%)  
White blood cell count decreased † 1    
# participants affected / at risk     24/129 (18.60%)     21/128 (16.41%)  
Nervous system disorders      
Headache † 1    
# participants affected / at risk     7/129 (5.43%)     9/128 (7.03%)  
Respiratory, thoracic and mediastinal disorders      
Cough † 1    
# participants affected / at risk     13/129 (10.08%)     15/128 (11.72%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 16.0



  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
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