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Comparison of First-Line NNRTI versus PI/r Regimens in ARTEN Study

The ARTEN study compared NVP and ATV/r with TDF/FTC for HIV treatment in ARV-naive patients. The study aimed to show non-inferiority of NVP to ATV/r in achieving HIV RNA suppression. Results demonstrated similar efficacy between NVP BID and QD but higher discontinuations with NVP due to adverse events. NVP showed lower liver toxicity and better lipid profile than ATV/r. Resistance development was higher with NVP at virologic failure.

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Comparison of First-Line NNRTI versus PI/r Regimens in ARTEN Study

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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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