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Comparison of PI vs PI

Comparison of PI vs PI. ATV vs ATV/r BMS 089 LPV/r mono vs LPV/r + ZDV/3TC MONARK LPV/r QD vs BID M02-418 M05-730 A5073 LPV/r + 3TC vs LPV/r + 2 NRTI GARDEL ATV/r vs FPV/r ALERT ATV/r vs DRV/r ATADAR FPV/r vs LPV/r KLEAN SQV/r vs LPV/r GEMINI ATV/r vs LPV/r CASTLE

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Comparison of PI vs PI

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  1. Comparison of PI vs PI • ATV vs ATV/r BMS 089 • LPV/r mono vs LPV/r + ZDV/3TC MONARK • LPV/r QD vs BIDM02-418M05-730A5073 • LPV/r + 3TC vs LPV/r + 2 NRTI GARDEL • ATV/r vs FPV/r ALERT • ATV/r vs DRV/r ATADAR • FPV/r vs LPV/r KLEAN • SQV/r vs LPV/r GEMINI • ATV/r vs LPV/r CASTLE • DRV/r vs LPV/rARTEMIS

  2. ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD),in combination with TDF/FTC ARTEMIS • Design Randomisation* 1 : 1 Open-label W48 W192 N = 343 > 18 years ARV-naïve HIV RNA > 5,000 c/mL Any CD4 cell count N = 346 *Randomisation was stratified by HIV RNA (< or > 100,000 c/mL)and CD4 (< or > 200/mm3) at screening • Objective • Non inferiority of DRV/r vs LPV/r at W48: % HIV RNA < 50 c/mL by per-protocol TLOVR analysis (lower margin of the 2-sided 95% CI for the difference = - 12%, 90% power). Superiority tested by ITT if non inferiority established Ortiz R. AIDS 2008;22:1389-97

  3. ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD),in combination with TDF/FTC ARTEMIS Baseline characteristics and patient disposition * 3 patients excluded for the per-protocol analysis (did not received study medication or received disallowed therapy for more than 1 week) ** LPV/r was administered BID or QD according to investigator and/or patient preference (77% received BID, 15% QD and 8% both; 15% received soft-gel capsules, 2% tablets and 83% switched from SGC to tablets) Ortiz R. AIDS 2008;22:1389-97

  4. ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD),in combination with TDF/FTC ARTEMIS Response to treatment at week 48 HIV RNA < 50 c/mL (TLOVR) HIV RNA < 50 c/mL at W48 (per-protocol, TLOVR) by baseline stratification factors % Per protocol ITT 100 84 84 78 78 75 50 25 * P < 0.05 N = 343 346 343 346 0 DRV/r LPV/r DRV/r LPV/r Median CD4/mm3 increase at W48 (ITT, NC = F): 137 (DRV/r) vs 141 (LPV/r) 95% CI for the difference = (- 0.1; 11) (P < 0.001)  Non inferiority • 95% CI for the difference • = (- 0.3; 11) • Test for superiority • (P = 0.062) Ortiz R. AIDS 2008;22:1389-97

  5. ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD),in combination with TDF/FTC Virologic failure at Week 48 Definition: HIV RNA never suppressed below 50 c/mL at W24 or confirmed HIV RNA > 50 c/mL after achieving < 50 c/mL or last observed HIV RNA > 50 c/mL followed by discontinuation ARTEMIS Resistance data * 1 patient with HIV RNA > 1,000 c/mL did not have genotype available ** A71T and V77I Ortiz R. AIDS 2008;22:1389-97

  6. W48 Safety: DRV/r vs LPV/r Discontinuations for adverse events (AE) were significantly less frequent in the DRV/r group: 3% vs 7% (P < 0.05) Rate of serious AE was not significantly different: 7% vs 12% Incidence of grade 2 to 4 gastrointestinal AE was significantly lower in the DRV/r group: 7% vs 14% (P < 0.01); these were mainly diarrhoea: 4% vs 10% (P < 0.01) Rash incidence was not significantly different: 3% vs 1%; 1 case of Stevens-Johnson occurred in the DRV/r group No patients discontinued because of renal events Mean increases in triglycerides and total cholesterol were less pronounced with DRV/r; grade 2 to 4 elevations in triglycerides and total cholesterol were significantly less frequent with DRV/r: 3% vs 11% and 13% vs 23%, respectively Hepatic safety was similar in both groups ARTEMIS ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD),in combination with TDF/FTC Ortiz R. AIDS 2008;22:1389-97

  7. ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD),in combination with TDF/FTC • Summary – Conclusion (W48) • DRV/r QD is non inferior to LPV/r, when co-administered with TDF/FTC(1) • Greater virologic response, at W48 (HIV RNA < 50 c/mL), of DRV/ras compared with LPV/r in patients with high pre treatment HIV RNA (significant difference) or low CD4 count • Lower incidence of diarrhoea with DRV/r vs LPV/r • Lipid elevations were less pronounced with DRV/r Ortiz R. AIDS 2008;22:1389-97

  8. ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD),in combination with TDF/FTC • Overview at week 96 • At W96(2), significantly more DRV/r (79%) than LPV/r (71%) patients had HIV RNA < 50 c/mL confirming non inferiority and superiority (P = 0.012; ITT) in virologic response • Safety outcomes confirmed W48 results: more favourable gastrointestinal and lipid profile of DRV/r QD • Lipid-lowering agents use by W96: 8% LPV/r vs 7% DRV/r • Overall, discontinuation for adverse events occurred in 4% of DRV/r patients vs 9% of LPV/r patients Mills AM. AIDS 2009;23:1679-88

  9. ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD),in combination with TDF/FTC ARTEMIS Patient disposition at W96 and W192 Ortiz R. AIDS 2008;22:1389-97 ; Mills AM. AIDS 2009;23:1679-88 ; Orkin C. HIV Med 2012;14:49-59

  10. ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD),in combination with TDF/FTC ARTEMIS Final (week 192) analysis % HIV RNA < 50 c/mL (TLOVR) HIV RNA < 50 c/mL (ITT, TLOVR) by baseline stratification factors 100 Per protocol ITT 69.1 68.8 75 57.1 57.2 50 25 N = 340 345 343 346 0 DRV/r LPV/r DRV/r LPV/r Median CD4/mm3 increase at W192 (ITT, NC = F): + 258 (DRV/r) vs + 263 (LPV/r) Difference (95% CI) = 12.0% (4.8 ; 19.2) (P < 0.001)  Superiority Difference (95% CI) = 11.6% (4.4 ; 18.8) (P < 0.001)  Superiority Orkin C. HIV Med 2012;14:49-59

  11. ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD),in combination with TDF/FTC ARTEMIS Resistance data at W192 * At endpoint = last time point : with available genotype ** L10V, N = 1 ; V11I, N = 1 ; I13V, N = 1 ; I13V + G16E, N = 1 Orkin C. HIV Med 2012;14:49-59

  12. Safety – W192 analysis Data similar to that seen at W96 No new emerging AE with longer-term follow-up Grade 2-4 treatment-related diarrhoea was significantly less frequent with DRV/r than with LPV/r (5.0% vs. 11.3%, respectively; P = 0.003) DRV/r was associated with smaller median increases in total cholesterol and triglyceride levels than LPV/r. Changes in low- and high-density lipoprotein cholesterol were similar between groups Similar increases in aspartate aminotransferase and alanine aminotransferase for DRV/r and LPV/r were observed ARTEMIS Study: DRV/r QD vs LPV/r (BID or QD),in combination with TDF/FTC ARTEMIS Orkin C. HIV Med 2012;14:49-59

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