Efficacy and safety of once-daily darunavir/ritonavir versus lopinavir/ritonavir in treatment-naive HIV-1-infected patients at week 48.

Authors

Ortiz R, Dejesus E, Khanlou H, et al. 

Institution

Orlando Immunology Center, Orlando, Florida, USA. rocuv@aol.com

Source

AIDS 2008 Jul 31; 22(12) :1389-97.

Abstract

BACKGROUND
The present primary analysis of AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects (ARTEMIS) compares the efficacy and safety of once-daily darunavir/ritonavir (DRV/r) with that of lopinavir/ritonavir (LPV/r) in treatment-naive patients.
METHODS
Patients with HIV-1 RNA at least 5000 copies/ml were stratified by HIV-1 RNA and CD4 cell count in a phase III, open-label trial, and randomized to receive DRV/r 800/100 mg qd or LPV/r 800/200 mg total daily dose (bid or qd) plus fixed-dose tenofovir and emtricitabine for 192 weeks. The primary objective was to demonstrate non-inferiority of DRV/r as compared with LPV/r in HIV-1 RNA less than 50 copies/ml per-protocol time-to-loss of virologic response at 48 weeks.
RESULTS
Six hundred and eighty-nine patients were randomized and treated; mean baseline HIV-1 RNA: 4.85 log10 copies/ml and median CD4 count: 225 cells/microl. At 48 weeks, 84% of DRV/r and 78% of LPV/r patients achieved HIV-1 RNA less than 50 copies/ml (estimated difference = 5.6 [95% confidence interval -0.1-11]%), demonstrating non-inferiority of DRV/r as compared with LPV/r (P < 0.001; per-protocol time-to-loss of virologic response). Patients with HIV-1 RNA at least 100 000 copies/ml had a significantly higher response rate with DRV/r (79%) versus LPV/r (67%; P < 0.05). Median CD4 cell count increases (non-completer = failure; cells/mul) were 137 for DRV/r and 141 for LPV/r. DRV/r had a lower incidence of possibly treatment-related grade 2-4 gastrointestinal-related adverse events (7 versus 14%) and treatment-related moderate-to-severe diarrhea (4 versus 10%) than LPV/r. Adverse events leading to discontinuation were DRV/r: 3% and LPV/r: 7%.
CONCLUSION
DRV/r 800/100 mg qd was non-inferior to LPV/r 800/200 mg at 48 weeks, with a more favorable safety profile. Significantly higher response rates were observed with DRV/r in patients with HIV-1 RNA at least 100 000 copies/ml. DRV/r 800/100 mg offers a new effective and well tolerated once-daily, first-line treatment option for treatment-naive patients.

Mesh

Adult
CD4 Lymphocyte Count
Drug Administration Schedule
Drug Combinations
Drug Resistance, Viral
Female
HIV Infections
HIV Protease Inhibitors
HIV-1
Humans
Lipids
Male
Pyrimidinones
RNA, Viral
Ritonavir
Sulfonamides
Treatment Outcome
Viral Load
Weight Gain

Language

eng

Pub Type(s)

Clinical Trial, Phase III Comparative Study Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

PubMed ID

18614861