ARTEMIS: 192-week efficacy and safety of once-daily darunavir/ritonavir (DRV/r) vs lopinavir/r (LPV/r) in treatment-naïve HIV-1-infected adults

Abstract

Background ARTEMIS was a Phase III, randomised, open-label study assessing efficacy and safety of DRV/r 800/100mg qd versus LPV/r 800/200mg total daily dose (qd or bid) in treatment-naïve HIV-1-infected adults. At 96 wks, DRV/r demonstrated non-inferiority and superiority to LPV/r in virological response. Wk 192 results are reported. Methods Patients stratified by baseline (BL) viral load (VL [HIV-1 RNA] < or ≥100,000 copies/mL [cpm]) and CD4 cell count (< or ≥200 cells/mm3) were randomised 1:1 to DRV/r qd or LPV/r. Primary efficacy parameter: non-inferiority (≤ –12%) of DRV/r to LPV/r in virological response (VL <50 cpm, ITT-TLOVR). DRV/r superiority ( ≤ 0%) was assessed if non-inferiority was demonstrated. Results 689 patients (30% female; mean BL VL 4.85 log10 cpm; median CD4 225 cells/mm3) were randomised. Overall, significantly more DRV/r than LPV/r patients had VL <50 cpm at Wk 192, confirming DRV/r qd non-inferiority (p<0.001) and superiority (p=0.002) (Table 1). In patients with virological failure (VF; TLOVR non-VF censored) no developing primary PI mutations were identified in either arm; all VFs with paired BL/endpoint phenotypes that were susceptible at BL to amprenavir, atazanavir, indinavir, lopinavir, saquinavir or tipranavir remained susceptible after treatment. Table 1 DRV/r LPV/r DRV/r-LPV/r [95% CI] N % N % VL <50cpm (ITT-TLOVR) All patients 343 68.8 346 57.2 11.6 [4.4-18.8] BL VL <100,000 226 69.5 226 60.2 9.3 [0.5-18.1] BL VL ≥100,000 117 67.5 120 51.7 15.9 [3.5-28.3] BL CD4 <200 141 65.2 148 54.1 11.2 [-0.1-22.5] BL CD4 ≥200 202 71.3 198 59.6 11.7 [2.4-21.0] VL <50cpm (sensitivity analyses) TLOVR non-VF censored 270 87.4 245 80.8 6.6 [0.3-12.9] On protocol TLOVR 340 69.1 345 57.1 12.0 [4.8-19.2] Missing=failure 343 68.5 346 60.1 8.4 [1.3-15.5] FDA snapshot 343 68.5 346 59.8 8.7 [1.5-15.8] Treatment-emergent adverse events (AEs) AEs leading to permanent stop of study medication 343 7.6 346 14.5 p=0.005* Grade 2-4 treatment-related diarrhoea 343 5.0 346 11.3 p=0.003* Changes in lipid parameters, median increase mmol/L (min; max) Triglycerides‡ 254 0.1 (-5; 3) 228 0.6 (-3; 10) p<0.0001¶ Total cholesterol§ 254 0.6 (-2; 4) 228 1.0 (-1; 4) p<0.0001¶ *Fisher's Exact test; ‡NCEP normal level <1.69mmol/L; §NCEP normal level <5.17mmol/L; ¶Wilcoxon Rank Sum test Conclusions DRV/r qd demonstrated sustained efficacy with non-inferiority and superiority to LPV/r over 192 wks. Development of resistance was low in both arms. DRV/r was associated with smaller median increases in total cholesterol and triglycerides than LPV/r, and a lower incidence of grade 2–4 diarrhoea.