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ICAAC 2008: Efficacy and Safety of Boosted Darunavir (Prezista) Are Comparable to Lopinavir/ritonavir (Kaletra) at 96 Weeks: ARTEMIS Trial

Tibotec's second-generation protease inhibitor darunavir (Prezista) was approved in June 2006 for treatment-experienced HIV patients, to be administered at 600 mg boosted with 100 mg ritonavir twice-daily. As previously reported, in the Phase III ARTEMIS trial darunavir/ritonavir demonstrated safety and efficacy comparable to that of lopinavir/ritonavir (Kaletra) at 48 weeks. In a late-breaker session at the 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008), taking place this week in Washington, DC, researchers presented longer-term 96-week data from the study. Follow-up is scheduled to continue through 192 weeks.Boosted darunavir has also been studied in treatment-naive individuals, and earlier this month received approval for use in this patient population.

Briefly, ARTEMIS includes 689 treatment-naive participants with a baseline viral load of at least 5000 copies/mL who were randomly assigned to receive 800/100 mg once-daily darunavir/ritonavir or 800/200 mg lopinavir/ritonavir given once- or twice-daily, both with fixed-dose tenofovir/emtricitabine (Truvada coformulation). Patients were stratified according to baseline viral load (mean 4.85 log10 copies/mL) and CD4 cell count (median 225 cells/mm3). At 48 weeks, 84% of patients taking darunavir/ritonavir and 78% taking lopinavir/ritonavir achieved HIV RNA < 50 copies/mL.

Results

• At 96 weeks, darunavir/ritonavir remained non-inferior to lopinavir/ritonavir.

• In an intent-to-treat analysis, significantly more patients in the darunavir/ritonavir arm achieved HIV RNA < 50 copies/mL compared with the lopinavir/ritonavir arm (79% vs 71%; P = 0.012).

• Response rates in the darunavir/ritonavir arm were statistically superior to those in the lopinavir/ritonavir arm for patients with high baseline viral load and low baseline CD4 count.

• Among patients with baseline viral load > 100,000 copies/mL, 76% of patients in the darunavir/ritonavir arm and 63% in the lopinavir/ritonavir arm achieved HIV RNA < 50 copies/mL (P = 0.023).

• Among patients with baseline viral load < 100,000 copies/mL, the corresponding percentages were 81% and 75%, respectively (not a significant difference).

• Among patients with a baseline CD4 count < 200 cells/mm3, 79% in the darunavir/ritonavir arm and 65% in the lopinavir/ritonavir arm achieved HIV RNA < 50 copies/mL (P = 0.009).

• Among patients with a baseline CD4 count > 200 cells/mm3, the corresponding percentages were 79% and 75% (also not a significant difference).

• Once-daily darunavir/ritonavir was generally safe and well tolerated.

• Fewer patients in the darunavir/ritonavir arm discontinued treatment due to adverse events (4% vs 9%).

• Patients taking darunavir/ritonavir were less likely to have moderate to severe (grade 2-4) treatment-related diarrhea (4% vs 11%; P < 0.001).

• Grade 2-4 treatment-related rash occurred infrequently in both arms (3% with darunavir/ritonavir vs 1% with lopinavir/ritonavir; P = 0.273).

• Patients taking darunavir/ritonavir had smaller average increases in triglycerides (0.1 vs 0.8 mmol/L, or 12% vs 50%) and total cholesterol (0.6 vs 0.9 mmol/L, or 15% vs 23%) (both P < 0.0001).

• Fewer darunavir/ritonavir recipients had abnormally high triglycerides (41% vs 56%) or total cholesterol (37% vs 47%), according to National Cholesterol Education Program (NCEP) guidelines.

At 96 weeks, "darunavir/ritonavir 800/100mg [once-daily] proved non-inferior and statistically superior to lopinavir/ritonavir in treatment-naive patients," the investigators stated. "Darunavir/ritonavir was associated with lower rates of diarrhea and smaller mean increases in triglycerides and total cholesterol."

They concluded that "Once-daily darunavir/ritonavir offers a new, effective, well-tolerated once-daily first-line treatment option for treatment-naive patients."

"This study offers the healthcare provider community long-term efficacy and safety data for Prezista in treatment-naive adult patients," added ARTEMIS clinical investigator Tony Mills in a press release issued by Tibotec.

Private Practice, Los Angeles, CA; Chelsea and Westminster Hospital, London, UK; University of Miami, Miami, FL; HIVNAT, Thai Red Cross AIDS Research Centre and Chulalongkorn University, Bangkok, Thailand; Helios Salud, Buenos Aires, Argentina; Hôpital Saint-Antoine, Paris, France; Ground Zero Medical Centre, Darlinghurst, Australia; Tibotec BVBA, Mechelen, Belgium; Tibotec Inc., Yardley, PA.

10/28/08

Reference

A Mills, M Nelson, D Jayaweera, and others. ARTEMIS: Efficacy and Safety of Darunavir/ritonavir (DRV/r) 800/100 mg Once-daily vs Lopinavir/ritonavir (LPV/r) in Treatment-naive, HIV-1-infected Patients at 96 Wks. 48th International Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2008). Washington, DC. October 25-28, 2008. Abstract H-1250c.

Other source

Tibotec. Long-Term Study Evaluates Boosted PREZISTA(R) vs. Lopinavir/Ritonavir as Part of HIV Combination Therapy in Treatment-Naive Adults. Press release. October 26, 2008.