Portal de Periódicos da CAPES

Final 192‐week efficacy and safety of once‐daily darunavir/ritonavir compared with lopinavir/ritonavir in HIV ‐1‐infected treatment‐naïve patients in the ARTEMIS trial

2012; Wiley; Volume: 14; Issue: 1 Linguagem: Inglês

10.1111/j.1468-1293.2012.01060.x

1468-1293

Chloe Orkin, E DeJesus, Homayoon Khanlou, Albrecht Stoehr, K Supparatpinyo, Erkki Lathouwers, Éric Lefebvre, Magda Opsomer, Tom Van de Casteele, FL Tomaka,

HIV/AIDS Research and Interventions

Objective This paper presents the final analysis of once‐daily darunavir/ritonavir ( DRV /r) vs . lopinavir/ritonavir ( LPV /r) in treatment‐naïve HIV ‐1‐infected adults. Methods ARTEMIS ( AntiRetroviral T herapy with TMC 114 ExaMined I n naïve S ubjects; NCT 00258557) was a randomized, open‐label, phase‐ III , 192‐week trial. Patients were stratified by baseline HIV ‐1 RNA and CD 4 count, and randomized to once‐daily DRV /r 800/100 mg or LPV /r 800/200 mg total daily dose (either once or twice daily) plus tenofovir/emtricitabine. Results Of 689 randomized patients receiving treatment ( DRV /r: 343; LPV /r: 346), 85 and 114 patients in the DRV /r and LPV /r arms, respectively, had discontinued by week 192. Noninferiority was shown in the primary endpoint of virological response ( HIV ‐1 RNA < 50 copies/ mL ) [ DRV /r: 68.8%; LPV /r: 57.2%; P < 0.001; intent to treat ( ITT )/time to loss of virological response; estimated difference in response 11.6% (95% confidence interval 4.4–18.8%)]. Statistical superiority in virological response of DRV /r over LPV /r was demonstrated for the primary endpoint ( P = 0.002) and for the ITT non‐virological‐failure‐censored analysis (87.4% vs . 80.8%, respectively; P = 0.040). No protease inhibitor ( PI ) primary mutations developed and only low levels of nucleoside reverse transcriptase inhibitor ( NRTI ) resistance developed in virological failures in both groups. Significantly fewer discontinuations because of adverse events were observed with DRV /r (4.7%) than with LPV /r (12.7%; P = 0.005). 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. Conclusion Over 192 weeks, once‐daily DRV /r was noninferior and statistically superior in virological response to LPV /r, with a more favourable gastrointestinal profile, demonstrating its suitability for long‐term use in treatment‐naïve patients.