Sierra-Madero J. J Acquir Immune Defic Syndr. 2010 Apr;53(5):582-8
Type of ARV Trial
Head-to-head comparative trials for first line ART since 2006
» NNRTI vs PI/r
» EFV + ZDV/3TC vs LPV/r + ZDV/3TC
Head-to-head comparative trials for first line ART since 2006
» NNRTI vs PI/r
» EFV + ZDV/3TC vs LPV/r + ZDV/3TC
Drugs
LPV/r, EFV 600, ZDV/3TC, 3TC, ZDV
LPV/r, EFV 600, ZDV/3TC, 3TC, ZDV
- In this very advanced HIV-infected antiretroviral-naïve population with a median CD4 closed to 50/mm3, EFV was virologically superior to LPV/r BID, when combined with ZDV/3TC
- EFV superiority was due to both a higher rate of virologic failure and of discontinuations due to adverse event in the LPV/r group
- Limits
- Single country study, limited sample size (underpowered)
- LPV/r soft-gel capsules and high pill burden associated with low tolerability and poor adherence in advanced HIV disease
- NRTI backbone: ZDV/3TC
Design :
Objective :
-
Non inferiority of EFV vs LPV/r at W48: % HIV RNA < 50 c/mL by intention
to treat, missing equals failure, TLOVR analysis (lower margin of the 2-sided 95% CI for the difference =Â - 12%)
Baseline characteristics, patient disposition and primary endpoint at W48 :
Secondary endpoints :
- HIV RNA < 50 c/mL at W48 according to baseline CD4
- Baseline CD4 < 100/mm3 : EFV > LPV/r (p = 0.03)
- Baseline CD4 > 100/mm3 : virologic response to EFV and LPV/r not different (p = 0.11)
- Similar CD4+ cell count increase in both groups
- Incidence of grade 2 to 4 adverse events similar between groups: 68%
- Significantly greater increase in triglyceride levels in LPV/r arm vs EFV (p < 0.01)
- Changes in total cholesterol, HDL, and LDL similar between groups
- At virologic failure, only few patients were genotyped:
- LPV/r, N = 5/17: no PI resistance, NRTI resistance in 1
- EFV, N = 3/7: NNRTI resistance in 3, NRTI resistance in 2