The Body Covers: The XVI International AIDS Conference
Switching From Lopinavir/Ritonavir to Unboosted Atazanavir May Yield Benefits, but Verdict Remains Uncertain
August 17, 2006
Data from SWAN, a multicenter, randomized, open-label study of 407 patients, were previously reported at the 10th European AIDS Conference in Dublin, Ireland, in 2005.2 The presentation at that conference showed that switching from a stable, virologically suppressive, PI-based regimen to an atazanavir-containing regimen resulted in less virological rebound through 48 weeks, comparable safety and tolerability profiles, and improved lipids. The study presented at AIDS 2006 is a sub-analysis of SWAN,3 in which only the 153 individuals who received lopinavir/ritonavir at baseline were examined.
Of these 153 patients, 100 were randomized to switch to atazanavir (18 of whom received ritonavir-boosted atazanavir, as they were receiving concomitant tenofovir [TDF, Viread] at baseline) and 53 to continue lopinavir/ritonavir. Rates of virological rebound at week 48 were comparable: 11% in the atazanavir arm and 9% in the lopinavir/ritonavir arm. Rates of treatment failure for any reason, which included viral rebound or failure to receive the randomized treatment, were similar in both groups (28% of patients on lopinavir/ritonavir versus 28% on atazanavir).
New onset of gastrointestinal toxicity of any grade was reported in only 2% of patients receiving atazanavir, but in 13% of patients on lopinavir/ritonavir (P < .01). Three percent of individuals on atazanavir and 8% receiving lopinavir/ritonavir used anti-diarrheal medication during the study. Lipids improved in the atazanavir arm, with reduction in non-HDL (high-density lipoprotein) cholesterol of 17% versus 4% in the lopinavir/ritonavir arm (P < .0001). Accordingly, lipid-lowering agents were used less commonly with atazanavir (8% versus 21% with lopinavir/ritonavir, P < .05). Other discontinuations due to ALT (alanine aminotransferase) elevations or grade 3/4 toxicity were similar between the two groups. One percent of individuals receiving atazanavir discontinued the drug due to jaundice/hyperbilirubinemia.
The results of this substudy clearly show that individuals receiving lopinavir/ritonavir who switch to atazanavir have at least as good virological control and less toxicity at 48 weeks. However, these results should be taken with caution.
Firstly, it is clear that ritonavir-boosted PIs have a high barrier to resistance, so that even in individuals who are failing virologically, there are few reports of the development of resistance. This high barrier is not the case with unboosted atazanavir, for which individuals may develop specific mutations, particularly I50L.
Secondly, although there were improvements in lipid profile in the group who received atazanavir, it remains unclear how this impacts the development of heart and other vascular disease. Another poster at this conference showed that, although there were improvements in lipid parameters in individuals switching from lopinavir/ritonavir to atazanavir, the effect of these improvements was negligible, based on the Framingham equation for risk of myocardial infarction.
Thirdly, although it is accepted that lopinavir/ritonavir may have a difficult toxicity profile in some individuals, the development of the new tablet formulation, which was not utilized in this study, may reduce the incidence of toxicity, specifically diarrhea.
This SWAN substudy showed that atazanavir can be an alternative for individuals who are intolerant of lopinavir/ritonavir. But before individuals switch en masse, one must add up the pros and cons of using an unboosted PI. We must also have more clinical trial data from randomized studies involving ritonavir-boosted atazanavir before switching can be widely recommended.
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