• Time from study entry to virologic failure
  
• time from study entry to regimen completion
  

• 20 % or more loss in peripheral fat
  
• increase in lactic acid levels at least 2-4old above the upper limit of normal (ULN)
  
• 20 % or more increase in truncal fat accumulation
  
• fasting cholesterol level equal to or greater than 240 mg/dl
  
• Grade 3 or greater elevation in fasting triglyceride levels
  
• change from baseline in insulin resistance [ Time Frame: at Weeks 24, 48 and 96 ]
  
• change from baseline of whole-body bone density and whole-body bone mineral content [ Time Frame: at Weeks 48 and 96 ]
  
• time to confirmed virologic failure while on Steps I (initial randomized regimen) or II (within class substitutes for initial regimen toxicity) OR treatment-limiting toxicity on Steps I or II
  
• number of antiretroviral classes with resistance mutations at virologic failure
  
• number of missed medication doses [ Time Frame: 4 days prior ]
  
• change from baseline in self-reported symptoms OR occurrence of reporting an increase in symptoms [ Time Frame: at Weeks 4, 48, 72 and 96 ]
  
• change from baseline in body image OR occurrence of reporting body image distress [ Time Frame: at Weeks 24, 48, 72 and 96 ]
  
• time until treatment-limiting toxicity OR occurrence of Grades 3 or 4 toxicity
  

Numerous treatment options are available to HIV infected patients who are antiretroviral (ARV) therapy naive, but an optimal regimen has not yet been established. This study will compare a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen, a ritonavir (RTV)-enhanced protease inhibitor (PI)-based regimen, and a nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimen for the initial treatment of HIV infection.

Patients will be randomly assigned to one of three study arms. In Arm A, patients will receive lopinavir/ritonavir (LPV/r) twice daily and efavirenz (EFV) once daily before bed. Arm B patients will receive LPV/r twice daily, lamivudine (3TC) once daily, plus either stavudine extended release (d4T XR) once daily, zidovudine (ZDV) twice daily, or tenofovir disoproxil fumarate (TDF) once daily. Patients in Arm C will receive EFV once daily before bed and 3TC plus either d4T XR once daily before bed, ZDV twice daily, or TDF once daily before bed.

Study visits will occur every 4 weeks until Week 24, then every 8 weeks thereafter for a maximum of 96 weeks. Blood will be drawn at every visit and a urine sample will be collected every 8 weeks. Body measurements will be taken at Weeks 24, 48, 72, and 96. Whole body dual-energy x-ray absorptiometry (DEXA) scans will be done at Weeks 48 and 96. Patients must fast before study visits at Weeks 12, 24, 48, 72, and 96. Women in the study will have gynecological assessments every 24 weeks.

Inclusion Criteria for Step 1:

• HIV infected
• HIV viral load of 2000 copies/ml or greater within 60 days prior to study entry
• Willing to use acceptable means of contraception
• d4T XR, TDF, or ZDV chosen as part of an initial regimen prior to randomization to a study arm
• Coenrolled in ACTG A5152s

Exclusion Criteria for Step 1:

• On ARV therapy for 7 days or more any time prior to study entry
• NNRTIs or 3TC at any time prior to study entry
• Current peripheral neuropathy of Grade 2 or higher
• Pregnancy or breastfeeding
• Immunomodulators, vaccines, or investigational therapies within 30 days of study entry. Patients taking a stable or tapering dose of prednisone at less than 10 mg are not excluded.
• Human growth hormone within 30 days prior to study entry
• Initiation of testosterone or anabolic steroids within 30 days prior to study entry
• Certain other medications within 30 days of study entry
• Hypersensitivity to components of the study drug formulations
• Drug or alcohol use or dependence that would interfere with adherence to study requirements
• Acute therapy for serious medical illnesses requiring systemic treatment and/or hospitalization within 14 days prior to study entry
• Recent infection with drug-resistant HIV