Efficacy and safety of once-daily atazanavir/ritonavir compared to twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, in antiretroviral naive HIV-1 infected subjects. The CASTLE Study (AI424138) 48-week results
Abstract number: O524
Molina J-M., Andrade-Villaneuva J., Echevarria J., Chetchotisakd P., Corral J., David N., Moyle G., Mancini M., Percival L., Thiry A., McGrath D.
Objectives: Atazanavir/Ritonavir (ATV/r) is as effective as Lopinavir/Ritonavir (LPV/r) with more favourable lipid and GI profiles in treatment-experienced HIV-infected patients. Comparative data in antiretroviral (ARV)-naive patients are needed.
Methods: CASTLE is a randomised, open-label, multicentre, ongoing 96 week study to assess non-inferiority (10% margin) of ATV/r 300 mg/100 mg once-daily (QD) versus LPV/r 400 mg/100mg twice-daily, both in combination with fixed-dose tenofovir (TDF) 300mg/emtricitabine (FTC) 200 mg QD, in treatment-naive patients. The primary endpoint was the proportion of patients with HIV RNA <50 c/mL at week 48; planned secondary assessments included percent with HIV RNA <400 c/mL, CD4 cell count change, and safety.
Results: 883 patients randomised, 878 treated. Baseline (BL) demographics and characteristics were well balanced. Median CD4 205 cells/mm3; median plasma HIV RNA 4.98 log10 c/mL. At week 48, mean CD4 increases from BL for ATV/r and LPV/r were 203 and 219 cells/mm3, respectively. Fewer patients on ATV/r (2%) than LPV/r (8%) initiated lipid lowering therapy. The proportion of patients with a TC: HDL ratio >5 at week 48 was 12% and 20% on ATV/r and LPV/r, respectively. Patients on ATV/r had a lower incidence of Grade 24 treatment-related diarrhoea (2% vs 11%) and nausea (4% vs 8%) than LPV/r. Grade 34 ALT/AST elevations were low ( 2%) on both arms. Discontinuations prior to week 48 were: ATV/r, 9%; LPV/r, 13%. AE-related discontinuations were 2% and 3% on ATV/r and LPV/r, respectively. Three patients (<1%) discontinued ATV/r due to jaundice/hyperbilirubinaemia.
Conclusions: In treatment-naive patients, ATV/r demonstrated similar efficacy, a lower incidence of GI-related AEs, and a significantly better lipid profile (TC, TG, non-HDL) compared to LPV/r. In combination with TDF and FTC, both ATV/r and LPV/r were well tolerated with few discontinuations through 48 weeks.
These data have been accepted for oral presentation at the 15th Conference on Retroviruses and Opportunistic Infections, February, 2008. ECCMID would be the first European presentation of these important data.
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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