Castle Study Shows Boosted Reyataz(R) (Atazanavir) Is A Well Tolerated And Effective Option For Treatment-Naïve Patients

Main Category: HIV / AIDS
Also Included In: Clinical Trials / Drug Trials
Article Date: 13 Feb 2008 - 3:00 PDT

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The week-48 results of the CASTLE study were announced at the 15th Conference on Retroviruses and Opportunistic Infections (CROI) and showed boosted atazanavir to be as efficacious in antiretroviral-naive HIV-1 patients as lopinavir/ritonavir. In this study, 78 percent of patients (n=343/440) taking once-daily boosted atazanavir met the primary endpoint of achieving and maintaining an undetectable viral load (defined as less than 50 copies/mL) at 48 weeks, compared with 76 percent of patients (n=337/443) taking twice-daily lopinavir/ritonavir. Atazanavir is currently only licensed in the treatment of HIV-1 infected, antiretroviral treatment-experienced adults, in combination with other antiretroviral medicinal products.

This 96-week international study, being conducted at more than 130 sites in 30 countries, is comparing the antiretroviral efficacy and safety of once-daily boosted atazanavir (ATV/r) with twice-daily boosted lopinavir (LPV/r). Both treatments are being given concurrently with ritonavir, and each in combination with fixed-dose tenofovir (TDF) and emtricitabine (FTC) as a background therapy.

In the study, 74 percent of patients with high baseline viral load (greater than or equal to 100,000 copies/mL) who received once-daily ATV/r achieved and maintained an undetectable viral load at 48 weeks, versus 72 percent of patients who received twice-daily LPV/r. In a post hoc analysis of virologic responses by baseline CD4+ count, there was a statistically significant trend toward a lower response rate with lower CD4+ counts for LPV/r (p=0.0085). This trend did not occur with ATV/r.

Patients taking once-daily ATV/r experienced lower rates of diarrhoea and nausea compared with patients taking twice-daily LPV/r at 48 weeks (diarrhoea: 2% vs.11%; nausea: 4% vs. 8%, respectively). The results also demonstrated more favourable lipid effects with once-daily ATV/r as compared to the LPV/r arm. Treatment with once-daily ATV/r was associated with significantly lower mean percentage changes from baseline in total cholesterol (12% with ATV/r vs. 24% with LPV/r), triglycerides (13% vs. 51%) and non-HDL (7% vs. 21%) at 48 weeks (p<0.0001). Two percent of patients taking once-daily ATV/r and seven percent of patients taking twice-daily LPV/r required lipid-lowering therapy in the study.

Mark Nelson, Director of HIV services at Chelsea & Westminster Hospital, London said "The CASTLE study has demonstrated that ATV/r is as efficacious as LPV/r and could therefore be used in early lines of treatment to maximise efficacy and minimise side effects such as diarrhea and nausea, which affect patients' quality of life."

About the study

CASTLE - Efficacy and Safety of Once-Daily Atazanavir/Ritonavir (ATV/r) Compared to Twice-Daily Lopinavir/Ritonavir (LPV/r), Each in Combination with Tenofovir (TDF) and Emitricitabine (FTC), in Antiretroviral (ARV) Naïve HIV-1 Infected Subjects - is the first largescale, randomised, comparative study of ATV/r and LPV/r in the HIV treatment-naïve patient population. It is an open-label study in antiretroviral-naïve HIV-infected subjects. Four hundred and forty patients were randomised to receive ATV/r treatment, and four hundred and forty three patients to receive LPV/r. The study was designed to compare the efficacy and safety of oncedaily ATV/r with twice-daily LPV/r, each in combination with fixed-dose tenofovir and emtricitabine.

Important Information About Atazanavir

In the UK, atazanavir with ritonavir is indicated for the treatment of HIV-1 infected, antiretroviral treatment-experienced adults, in combination with other antiretroviral medicinal products1. In antiretroviral treatment-experienced patients, the demonstration of efficacy is based on study AI424-045 which compared atazanavir 300 mg once daily in combination with ritonavir 100 mg once daily with lopinavir/ritonavir, each regimen in combination with tenofovir and one NRTI. Based on available virological and clinical data, no benefit is expected in patients with strains resistant to multiple protease inhibitors (≥ 4 PI mutations). The choice of atazanavir should be based on individual viral resistance testing and the patient's treatment history1. Bristol-Myers Squibb is a global pharmaceutical and related health care products company whose mission is to extend and enhance human life.

References

1. Reyataz Summary of Product Characteristics, May, 2007 (accessible at http://www.medicines.org.uk)

Bristol-Myers Squibb