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Project Inform
Analysis of CASTLE Finds No Benefit for Once-Daily Dosing

By Paul Dalton

October 27, 2008

A poster presented at the joint 2008 ICAAC/IDSA meeting in Washington, DC suggests that there is no adherence benefit of protease inhibitor treatment given once a day compared to twice a day. In fact, once daily dosing seemed to lead to small increases in forgotten doses. With many drug companies convinced that once daily treatment is easier to market to people with HIV, this study suggests it does not lead to better adherence.

The poster looked at adherence to treatment in the CASTLE study, which compared once daily Reyataz (atazanavir) boosted with Norvir (ritonavir) to twice daily Kaletra (lopinavir + ritonavir). They both were taken with Truvada (tenofovir + emtricitabine/FTC).

Overall, adherence rates were above 80% throughout the study and did not differ between the two groups. While these rates to Reyataz dropped somewhat more (from 88% to 82%) compared to Kaletra (86% to 84%), the difference is not significant. Interestingly, more people reported forgetting to take Reyataz (11%) than Kaletra (6%). This suggests, but does not prove, that there might be a marginal benefit to twice daily dosing in terms of forgotten doses.

There were somewhat higher rates of people stopping Kaletra. After 48 weeks, 91% of people were still taking Reyataz compared to 86.5% of those on Kaletra. This difference is small, but it suggests a possible small benefit in terms of tolerability for once daily dosing. This difference could be due to the drugs themselves rather than how often they were taken each day.

Over the past few years, once daily HIV regimens have become more common particularly since the introduction of Atripla (efavirenz + tenofovir + emtricitabine/FTC), the first full HIV regimen that's taken as one pill once a day. While people with HIV commonly express a preference for simpler regimens, there's little comparative data to show how well they perform compared to twice daily regimens. This CASTLE analysis suggests that once daily dosing does not lead to better adherence and might actually lead to slightly higher rates of forgotten doses.

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