Bristol-Myers Squibb Company said results from the CASTLE study, evaluating 300 mg of once-daily Reyataz (atazanavir sulfate) taken with 100 mg of ritonavir (Reyataz/r) showed similar antiviral efficacy to twice-daily lopinavir 400 mg and ritonavir 100 mg (lopinavir/r) in previously untreated adult HIV-1 infected patients at 48 weeks, as part of HIV combination therapy.
In this study, 78 per cent of the 440 patients in the Reyataz/r arm met the primary endpoint of achieving undetectable viral load (defined as HIV-1 RNA less than 50 copies/mL) at 48 weeks, compared with 76 per cent of the 443 patients in the lopinavir/r arm.
CASTLE is the first large-scale, open-label, randomized study designed to demonstrate the non-inferiority of Reyataz/r to lopinavir/r in previously untreated HIV-1 infected adult patients. Data from the CASTLE study were presented for the first time at the 15th Conference on Retroviruses and Opportunistic Infections (CROI) this week in Boston, Mass.
"The CASTLE study provides important additional data to inform the use of a once-daily regimen including Reyataz and ritonavir in antiretroviral-naive HIV-infected patients," said Jean-Michel Molina, M.D., Hopital Saint Louis, Paris, France. "When choosing a treatment in previously untreated patients it is important to ensure antiviral activity as well as tolerability to optimise the management of HIV infection over the long term."
The most common grade 2-4 adverse events occurring in greater than or equal to three percent of patients in the once-daily Reyataz (atazanavir sulfate)/r arm or the twice-daily lopinavir/r arm were diarrhea (two per cent and eleven percent, respectively) nausea (four per cent and eight per cent, respectively), jaundice (four percent and zero per cent, respectively) and rash (three percent and two percent, respectively).
The Reyataz/r arm was associated with significantly lower increases from baseline compared to the lopinavir/r arm in total cholesterol, triglycerides and non-HDL cholesterol at 48 weeks (p<0.0001). Two per cent of patients in the Reyataz/r arm and seven percent of patients in the lopinavir/r arm required initiation of lipid-lowering therapy in the study.
Safety events in this study were consistent with prior experience. Four deaths were reported in each treatment arm at 48 weeks; none were attributed to the study medications. Twelve percent of patients in the Reyataz/r arm and ten percent of patients in the lopinavir/r arm experienced a serious adverse event.
Nine per cent of patients in the Reyataz/r arm and thirteen percent of patients in the lopinavir/r arm discontinued the study therapy before week 48.
The international, multi-centre, open-label, 96-week CASTLE study randomised 883 treatment-naive patients infected with HIV-1. Four hundred and forty patients were randomised to receive Reyataz 300 mg and ritonavir 100 mg once daily and 443 patients were randomised to receive lopinavir 400 mg and ritonavir 100 mg twice daily, each in combination with a once-daily, fixed- dose combination of emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg. All patients had a baseline viral load of greater than or equal to 5,000 copies/mL; there was no CD4+ cell count restriction for study entry. The primary endpoint for the study was the proportion of patients with viral load of less than 50 copies/mL at 48 weeks.
A number of secondary endpoints were also measured with regard to efficacy, lipid effects, safety and tolerability, the company said.
Reyataz (atazanavir sulfate) is a protease inhibitor that has been studied extensively in both treatment-naive and treatment-experienced HIV- infected patients and is administered once-daily in all patient populations.
Reyataz (atazanavir sulfate) is a prescription medicine used in combination with other medicines to treat people who are infected with the human immunodeficiency virus (HIV). Reyataz has been studied in 48-week trials in both patients who have taken or have never taken anti-HIV medicines.