A Phase III, Randomized, Open-Label Comparison of Lopinavir/Ritonavir Plus Efavirenz Versus Lopinavir/Ritonavir Plus 2 NRTIs Versus Efavirenz Plus 2 NRTIs as Initial Therapy for HIV-1 Infection

Brief Summary

Detailed Description

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.

Primary Outcomes

Secondary Outcomes

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