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Objectif :

• Non inferiority of TDF + FTC + EFV vs ZDV/3TC + EFV at W48: % HIV RNA < 400 c/mL, TLOVR algorithm (lower margin of the 95% CI for the difference = -13%, 85% power)

Design :

Baseline characteristics :

* Excluded from primary endpoint analysis

Note : TDF, FTC and EFV taken without regards to meals and preferably at bed time; Substitution of NVP for EFV allowed if EFV intolerance; not considered as treatment failure

Response to treatment at week 48 :

Safety and tolerability: TDF + FTC vs ZDV/3TC :

• Similar frequency of clinical adverse events grade 2 to 4 and laboratory abnormalities grade 2 to 4 in both groups, respectively 63% vs 63% and 56% vs 57%
• Significantly more discontinuations for adverse events in the ZDV/3TC group: 9% vs 4% (p = 0.02); mainly for anemia (N = 14 vs 0)
• Renal safety was similar in both groups and no patients discontinued because of renal events. Change in median GFR (MDRD) at W48 was similar in both groups (< - 1 mL/min/1.73 m2). No Fanconi's syndrome occurred
• Mean increase significantly lower in the TDF + FTC group for total cholesterol, LDL-cholesterol and HDL-cholesterol; increase in triglycerides modest and not different between groups
• At week 48, DEXA substudy in 100 patients (no baseline evaluation): significantly less total limb fat with ZDV/3TC (mean 6.9 vs 8.9 kg; p = 0.03)

Resistance data :

• Genotypic analysis was done in patients without baseline NNRTI resistance if
  • viral rebound
  • consecutive HIV RNA > 400 c/mL after achieving < 400 c/mL HIV RNA > 400 c/mL at W48
  • discontinuation before W48 with HIV RNA > 400 c/mL at the last visit
• Patients with baseline resistance (11 in each group) were excluded from this analysis of resistance

* 1 technical failure; ** K103N mutation developed in 21 of 25 patients

Study extended to 3 years of follow-up (W144) :

• At week 96, patients on TDF + FTC swithed to fixed-dose combination TDF/FTC

* No discontinuation for renal events