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

• Confirmed Virologic Failure at or Prior to Week 48 [ Time Frame: At or prior to Week 48 ] [ Designated as safety issue: Yes ]
  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.
  
  

• Confirmed Virologic Failure at or Prior to Week 24 [ Time Frame: At or prior to Week 24 ] [ Designated as safety issue: Yes ]
  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.
  
  
• CD4 Count at Follow-up Visits [ Time Frame: At Weeks 4, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
  CD4 cell count (median, inter-quartile range)
  
  
• CD8 Count at Follow-up Visits [ Time Frame: At week 4, 12, 24, 36, and 48 ] [ Designated as safety issue: No ]
  CD8 cell count (median, inter-quartile range)
  
  
• Time to First Grade 3 or 4 Lab Event [ Time Frame: 52 weeks since randomization ] [ Designated as safety issue: Yes ]
  5th and 10th percentiles in weeks from randomization to first grade 3 or 4 lab event
  
  
• Time to First Grade 3 or 4 Sign or Symptom [ Time Frame: 52 weeks since randomization ] [ Designated as safety issue: Yes ]
  5th and 10th percentiles in weeks from randomization to first grade 3 or 4 sign or symptom
  
  
• Time to First Grade 3 or 4 Lab or Sign/Symptom Event [ Time Frame: 52 weeks since randomization ] [ Designated as safety issue: Yes ]
  5th and 10th percentiles in weeks from randomization to first grade 3 or 4 lab or sign/ symptom event
  
  
• Adherence to Second Line HAART Regimen [ Time Frame: At weeks 4, 8, 12, 24, 36, 48 and 52 ] [ Designated as safety issue: No ]
  Number of participants with self-reported 100% adherence over the week prior to study visit
  
  

Poor adherence to HAART is usually associated with resistant virus. Poor adherence to HAART can have serious consequences, including limited treatment options for HIV infected individuals if they become infected with resistant HIV. The purpose of this study was to examine the effectiveness of modified directly observed therapy (mDOT) and compare it with the effectiveness of self-administered therapy (non-mDOT) in HIV infected individuals with first virologic failure on an NNRTI-based HAART regimen who were starting a PI-based HAART regimen at study entry.

mDOT was defined in this study as the daily observation of lopinavir/ritonavir (LPV/r) being taken on a regular basis. Observation consisted of an mDOT partner being present at the time the study participant took the observed dose. Half of the participants in this study were required to choose an mDOT partner to supervise adherence for the first 24 weeks of the study. Each mDOT partner completed the study-administered mDOT training program and was required to record all observed doses in an mDOT diary log. All participants and partners received health education through the study. Adherence was measured using Medication Event Monitoring System (MEMS) caps and self-report questionnaires.

This study lasted 52 weeks. Per protocol, participants were to be stratified according to their screening viral load and the proposed study treatment. The study treatment each participant received was based on their treatment history. At entry, participants were to start one of the two PI-based HAART regimens, either FTC/Tenofovir Disoproxil Fumarate (TDF) 200/300 mg once daily (QD) and Lopinavir/Ritonavir (LPV/RTV) 400/100 mg twice a day (BID) or TDF 300 mg QD and zidovudine (ZDV) 300 mg BID and LPV/RTV 400/100 mg BID. mDOT was used for the first 24 weeks of the study, followed by self-administration of study medications from week 25 to week 52. ZDV was not provided by the study. All enrolled participants except one who did not start study regimen initiated FTC/TDF and LPV/rtv after randomization. No participants started ZDV containing regimen on study. Thus, participants in this study were stratified by screening HIV-1 RNA only.

There were eight visits during the study. Medical and medication history, blood collection, and clinical assessment were required at all visits. A quality of life questionnaire and an adherence tools assessment were collected at most visits. For the mDOT arm, medication diary logs and mDOT partner monitoring were reviewed at most visits. An mDOT exit questionnaire and exit interview were required at the end of the study.