and Safety of Boosted Darunavir (Prezista) Are Superior to Lopinavir/ritonavir
(Kaletra) at 96 Weeks: ARTEMIS Trial|
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
darunavir has also been studied in treatment-naive individuals, and earlier
this month received approval for use in this patient population.
previously reported, in the Phase III ARTEMIS trial darunavir/ritonavir demonstrated
safety and efficacy comparable to that of lopinavir/ritonavir
(Kaletra) at 48 weeks.
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.
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.
96 weeks, darunavir/ritonavir remained non-inferior to lopinavir/ritonavir.
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).
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
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).
patients with baseline viral load < 100,000 copies/mL, the corresponding percentages
were 81% and 75%, respectively (not a significant difference).
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).
patients with a baseline CD4 count > 200 cells/mm3, the corresponding percentages
were 79% and 75% (also not a significant difference).
darunavir/ritonavir was generally safe and well tolerated.
patients in the darunavir/ritonavir arm discontinued treatment due to adverse
events (4% vs 9%).
taking darunavir/ritonavir were less likely to have moderate to severe (grade
2-4) treatment-related diarrhea (4% vs 11%; P < 0.001).
2-4 treatment-related rash occurred infrequently in both arms (3% with darunavir/ritonavir
vs 1% with lopinavir/ritonavir; P = 0.273).
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).
darunavir/ritonavir recipients had abnormally high triglycerides (41% vs 56%)
or total cholesterol (37% vs 47%), according to National Cholesterol Education
Program (NCEP) guidelines.
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."
concluded that "Once-daily darunavir/ritonavir offers a new, effective, well-tolerated
once-daily first-line treatment option for treatment-naive patients."
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.
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
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.