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AIDS 2008: Boosted Atazanavir and Lopinavir/ritonavir Have Similar Efficacy, Side Effects Differ across Racial/ethnic Groups

Race-based differences in efficacy and safety have been reported among HIV positive individuals on HAART. However, data on this issue are limited. It is widely known that rates of obesity, diabetes, and the metabolic syndrome are increasing. In addition, studies suggest that certain racial/ethnic groups may be more susceptible to the risks associated with these conditions.

Ritonavir-boosted atazanavir (Reyataz) is a potent and generally well-tolerated once-daily HIV protease inhibitor (PI) that has been extensively studied in both treatment-naive and treatment-experienced individuals.

At the XVII International AIDS Conference last week in Mexico City (August 3-8, 2008), researchers presented results of the CASTLE trial, which assessed the potential differences in treatment effectiveness and safety in treatment-naive patients with a variety of racial/ethnic backgrounds.

The primary objective of this substudy was to analyze the 48-week CASTLE efficacy and safety data by racial/ethnic group and to assess the virologic, immunologic, and safety profiles of both an atazanavir/ritonavir-based regimen and a lopinavir/ritonavir (Kaletra)-based regimen.

CASTLE is a randomized, open label, prospective study comparing once-daily atazanavir/ritonavir vs twice-daily lopinavir/ritonavir, both in combination with fixed-dose tenofovir/emtricitabine (Truvada) in treatment-naive HIV patients.

The primary endpoint of the study was the proportion of patients with HIV RNA < 50 copies/mL at week 48. For this analysis, the proportion of patients with < 50 copies/mL (confirmed virological response, non-completer equals failure), CD4 cell count changes, adverse events (AEs), and fasting lipid changes were presented by race/ethnicity (classified as white, black, Asian, or other) through week 48.

Results

• In the overall study population, 78% of those on atazanavir/ritonavir and 76% on lopinavir/ritonavir achieved HIV RNA < 50 copies/mL.

• Overall, median CD4 cell count increases from baseline to week 48 were 191 cells/mm3 for the atazanavir/ritonavir group vs 200 cells mm3 for the atazanavir/ritonavir group.

• Among blacks, the median increase was 142 cells mm3 for the atazanavir/ritonavir group vs 190 cells mm3 for the lopinavir/ritonavir group.

• Adverse events were not treatment limiting in most cases.

• More patients receiving atazanavir/ritonavir discontinued due to jaundice or hyperbilirubinemia (<1% vs 0), while more people receiving lopinavir/ritonavir discontinued due to diarrhea (<1% vs 0).

• As expected, patients taking atazanavir/ritonavir had fewer gastrointestinal (GI) AEs, regardless of race/ethnicity.

• Patients receiving atazanavir/ritonavir had less elevation in total cholesterol, non-HDL ("bad") cholesterol and triglycerides regardless of ethnicity.

• In the lopinavir/ritonavir group, whites had a 27% increase in total cholesterol and patients in the other racial/ethnic groups had a 30% increase, compared with increases of 15% and 17%, respectively, for whites and other racial/ethnic groups receiving atazanavir/ritonavir.

• In contrast, triglyceride levels increased by 17% in whites, 0% in blacks, 21% in Asians, and 11% in the other racial/ethnic groups receiving atazanavir/ritonavir.

In conclusion, the study investigators noted:

• In the primary analysis, once-daily boosted atazanavir was non-inferior to twice-daily lopinavir/ritonavir.

• The rates of direct hyperbilirubinemia (all grades and grade 3-4) were slightly higher among whites than other racial/ethnic groups, but were consistent with prior studies of atazanavir/ritonavir.

• These differences provide important information for clinicians to consider when selecting regimens intended for long-term control of HIV infection.

8/12/08

Sources

D McGrath, J Uy, R Yang, and others. Efficacy and Safety by Racial Group in ARV-naïve Subjects Treated with Atazanavir/ritonavir or Lopinavir/ritonavir: 48-week Results of the CASTLE Study. XVII International AIDS Conference (AIDS 2008). Mexico City. August 3-8, 2008. Poster TUPE0058.

Abbott Laboratories. Abbott's Kaletra Tablet Dosed Once-Daily or Twice-Daily Demonstrated Similar Clinical Results across Race and Gender Lines. Press Release. August 5, 2008.