• Confirmed virologic failure [ Time Frame: At or prior to Week 48 ] [ Designated as safety issue: Yes ]
  

• Confirmed virologic failure [ Time Frame: At or prior to Week 24 ] [ Designated as safety issue: Yes ]
  
• CD4 count [ Time Frame: At Weeks 4, 12, 14, 36, and 48 ] [ Designated as safety issue: Yes ]
  
• Occurence of adverse events [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• Grade 2, 3, or 4 signs and symptoms; Grade 3 or 4 laboratory test abnormal values; new diagnoses [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• Acceptability and feasibility of mDot [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  
• Adherence and resistance to second line HAART regimen [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  

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 is to examine the effectiveness of modified directly observed therapy (mDOT) and compare it with the effectiveness of self-administered therapy in HIV infected individuals with first virologic failure on an NNRTI-based HAART regimen who are starting a PI-based HAART regimen.

mDOT is defined in this study as the daily observation of lopinavir/ritonavir (LPV/r) being taken on a regular basis. Observation consists of an mDOT partner being present at the time the study participant takes the observed dose. Half of the participants in this study will be required to choose an mDOT partner to supervise adherence for the first 28 weeks of the study. Each mDOT partner will complete the study-administered mDOT training program and must record all observed doses in an mDOT diary log. All participants and partners will receive health education through the study. Adherence will be measured using Medication Event Monitoring System (MEMS) caps and self-report questionnaires.

This study will last approximately 52 weeks. Participants will be stratified according to their viral load into one of four arms. The arm in which each participant is placed by the clinician is based on the treatment history of the participant. Participants in Arms 1 and 3 will receive emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and lopinavir/ritonavir (LPV/r) for the duration of the study. Participants in Arms 2 and 4 will receive LPV/r, TDF, and zidovudine (ZDF) for the duration of the study. mDOT will be used for the first 24 weeks of the study. For the remaining 28 weeks, participants in Arms 1 and 2 will use self-administration without mDOT. Participants in Arms 3 and 4 will self-administer study medications without mDOT for all 52 weeks. ZDV will not be provided by the study.

There will be eight visits during the study. Medical and medication history, blood collection, and adherence monitoring will occur at all visits. A quality of life questionnaire and an adherence tools assessment will occur at most visits. For Arms 1 and 2, medication diary logs and mDOT partner monitoring will be reviewed at most visits. An mDOT exit questionnaire and exit interview will occur at the end of the study for each partner.