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Comparison of NNRTI vs PI/r

Comparison of NNRTI vs PI/r. EFV vs LPV/r vs EFV + LPV/r A5142 Mexican Study NVP vs ATV/r ARTEN EFV vs ATV/r A5202. ARTEN Study : [NVP (QD or BID) vs ATV/r] + TDF/FTC. Design. Randomisation* 1:1:1 Open-label. W48. W144. > 18 years, ARV-naïve CD4 cell count

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Comparison of NNRTI vs PI/r

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  1. Comparison of NNRTI vs PI/r • EFV vs LPV/r vs EFV + LPV/r • A5142 • MexicanStudy • NVP vs ATV/r • ARTEN • EFV vs ATV/r • A5202

  2. ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC • Design Randomisation* 1:1:1 Open-label W48 W144 > 18 years, ARV-naïve CD4 cell count < 400/mm3 for males, <250/mm3 for females Creatinine clearance > 50 mL/min N = 188 N = 188 N = 193 * Randomisation stratified by HIV RNA (< or > 100,000 c/mL) and CD4 (> or < 50/mm3) at screening ** Lead-in of NVP 200 mg QD for the first 2 weeks • Objective • Non inferiority of NVP (combined groups) compared to ATV/r for primary endpoint: % HIV RNA < 50 c/mL at W24, W36 and W48 by intention to treat with non completers equals failures, (2-sided significance level of 5%, lower margin of the 95% CI for the difference = -12%, 80% power) ARTEN Soriano V. Antiviral Therapy 2011;16:339-48

  3. ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC Baseline characteristics and patient disposition ARTEN Soriano V. Antiviral Therapy 2011;16:339-48

  4. ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC Response to treatment at week 48 HIV RNA < 50 c/mL NVP (QD + BID) + TDF/FTC Primary analysis (W24, W36 and W48) % ATV/r + TDF/FTC 100 • Treatment response similar for NVP BID (66.5%) and QD (67%) • ITT, snapshot : response rate • NVP : 67.3% • ATV/r : 78.8% • difference – 11.1% (95%CI : -18.4 ; - 3.9 ; P = 0.003) 74 70 67 75 65 50 25 Mean CD4/mm3 increase at W48 : + 170 for NVP + 186 for ATV/r 0 ITT, NC=F ITT, TLOVR Adjusted difference (95% CI)= 1.9% (-5.9% ; 9.8%) Adjusted difference (95% CI)= - 2.9% (-10.4% ; 4.5%) ARTEN Soriano V. Antiviral Therapy 2011;16:339-48

  5. ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC • Adverse events through week 48 The majority of rash in NVP groups occurred during the lead-in phase No Grade 4 rashes ARTEN Soriano V. Antiviral Therapy 2011;16:339-48

  6. ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC • Grade 3 and 4 adverse events and liver enzyme increases ARTEN Soriano V. Antiviral Therapy 2011;16:339-48

  7. ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC • Mean lipid values at baseline, W48 (LOCF) and change from baseline (LOCF) * ANCOVA controlling for screeening viral load and CD4 cell count ARTEN Podzamczer D. HIV Medicine 2011;12:374-82

  8. Safety Incidence of discontinuation due to adverse event: 13.6% NVP vs 3.6% ATV/r Rash: 16% NVP vs 12.4% ATV/r (discontinuation due to rash : 5.1% vs 0%) Hepatitis: 1.9% NVP vs 0% ATV/r Grade 3-4 liver enzyme elevations: 4% NVP vs 1.5% ATV/r Grade 3-4 hyperbilirubinemia:3.2% NVP vs 54.4% ATV/r No cases of Stevens-Johnson, toxic epidermal necrolysis, or death due to liver or skin toxicity ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC Mean change in lipid parameters (mg/dL) at week 48 (LOCF) p < 0.0001 NVP 30 P = 0.041 ATV/r 28.1 25 24.3 20 P = 0.011 19.6 15 P < 0.0001 15.0 10 10.5 9.7 5 -0.2 3.9 0 Totalcholesterol LDL-C HDL-C Triglycerides - 5 0.2 0.1 0.13 Mean change in TC:HDL ratio at week 48(LOCF) 0 -0.1 -0.24 P = 0.0001 -0.2 Soriano V, Antivir Ther. 2011;16(3):339-48 -0.25 ARTEN

  9. ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC • Resistance data • Virologic failure : 2 consecutive HIV RNA > 50 copies/mL at least 2 weeks apart ARTEN Soriano V. Antiviral Therapy 2011;16:339-48

  10. Conclusion NVP demonstrated at week 48 non-inferior antiviral efficacy compared with ATV/r when given along with TDF/FTC, despite more drug-related discontinuations with NVP than ATV/r NVP BID and QD had similar efficacy and tolerability The application of the recommended CD4+ T-cell thresholds when initiating first-line NVP therapy probably explain relative low rate of liver enzymes increases and discontinuations for liver toxicity NVP was associated with a lower atherogenic lipid profile than ATV/r At virologic failure, there was a high rate of resistance mutations selected by NVP and none with ATV/r ARTEN Study: [NVP (QD or BID) vs ATV/r] + TDF/FTC ARTEN Soriano V. Antiviral Therapy 2011;16:339-48

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