Once-Daily Atazanavir/Ritonavir Compared With Twice-Daily Lopinavir/Ritonavir, Each in Combination With Tenofovir and Emtricitabine, for Management of Antiretroviral-Naive HIV-1-Infected Patients: 96-Week Efficacy and Safety Results of the CASTLE Study

Department of Infectious Diseases, Hopital Saint-Louis 1, Av. C. Vellefaux, 75475 Paris, Cedex 10, France.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 03/2010; 53(3):323-32. DOI: 10.1097/QAI.0b013e3181c990bf
Source: PubMed


Once-daily atazanavir/ritonavir demonstrated similar antiviral efficacy to twice-daily lopinavir/ritonavir over 48 weeks, with less gastrointestinal disturbance and a better lipid profile, in treatment-naive patients.
International, multicenter, open-label, 96-week noninferiority randomized trial of atazanavir/ritonavir 300/100 mg once daily vs lopinavir/ritonavir 400/100 mg twice daily, each in combination with fixed-dose tenofovir/emtricitabine 300/200 mg once daily, in antiretroviral-naive, HIV-1-infected patients. The primary end point was the proportion of patients with HIV RNA <50 copies/mL at 48 weeks. Results through 96 weeks are reported.
Of 883 patients enrolled, 440 were randomized to atazanavir/ritonavir and 443 to lopinavir/ritonavir. At week 96, more patients receiving atazanavir/ritonavir achieved HIV RNA <50 copies/mL (74% vs 68%, P < 0.05) in the intent-to-treat analysis. On both regimens, 7% of subjects were virologic failures by 96 weeks. Bilirubin-associated disorders were greater in patients taking atazanavir/ritonavir. Treatment-related gastrointestinal adverse events were greater in patients taking lopinavir/ritonavir. Mean changes from baseline in fasting total cholesterol, non-high-density lipoprotein cholesterol, and triglycerides at week 96 were significantly higher with lopinavir/ritonavir (P < 0.0001).
Noninferiority of atazanavir/ritonavir to lopinavir/ritonavir was confirmed at 96 weeks. Atazanavir/ritonavir had a better lipid profile and fewer gastrointestinal adverse events than lopinavir/ritonavir.

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Available from: Victoria Wirtz, May 01, 2014
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    • "In addition, although the comparison of the incidence rate of AIDS events in Aquitaine and IPEC initially suggested that AIDS events occurred at much higher frequency in the latter, after adjustments for other characteristics (immunological and virological profile as well as time since first HIV positive test), this finding did not hold, suggesting that environment is not a primary determinant of the occurrence of AIDS severe diseases in a population highly exposed to effective antiretroviral combinations [16]. Universal access to cART in both settings as well as more potent and user-friendly cART regimens readily available along the study period [17-20] have indeed contributed to these findings. "
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    BMC Infectious Diseases 05/2014; 14(1):278. DOI:10.1186/1471-2334-14-278 · 2.61 Impact Factor
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    • "Of the protease inhibitors, darunavir-ritonavir and atazanavir-ritonavir are the most widely recommended, owing to their once-daily dosing and favorable efficacy and safety profiles versus lopinavir-ritonavir shown in randomized trials.22,23 "
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    ClinicoEconomics and Outcomes Research 07/2012; 4(1):193-200. DOI:10.2147/CEOR.S12496
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    • "In the CASTLE study, patients treated with lopinavir/ritonavir had significantly raised fasting total cholesterol and triglyceride levels compared to patients given atazanavir/ritonavir (Molina et al., 2010). Other studies have now demonstrated that boosted lopinavir appears to elicit a worse lipid profile compared to other PI-containing regimens (Molina et al., 2010; Mills et al., 2009). "
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