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Home > Treatment > HIV Meds Quarterly > Fall 2009 > Atazanavir
Atazanavir and Lopinavir/Ritonavir in Hemodialysis
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Renal function has minimal effect on the elimination of protease inhibitors (PIs), and dosage adjustments are not required for patients with chronic kidney disease. Hemodialysis also does not typically affect serum levels of drugs that are hepatically cleared, such as PIs. Despite this, and for reasons that are not understood, patients on hemodialysis appear to have reduced serum levels of the PIs atazanavir, lopinavir, and ritonavir.

Atazanavir and hemodialysis
Whereas atazanavir is minimally (2%) removed by hemodialysis, one study of atazanavir (unboosted) levels in hemodialysis patients demonstrated substantially lower plasma atazanavir concentrations compared with controls (geometric mean AUC, Cmin , and Cmax were 25-43% lower).(1)

Management recommendations for patients receiving hemodialysis include the following:

transparent gifgrey bulletUnboosted atazanavir should not be used.
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transparent gifgrey bulletFor treatment-naive patients, atazanavir must be boosted by ritonavir.
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transparent gifgrey bulletFor treatment-experienced patients, atazanavir (boosted or unboosted) is not recommended.
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Lopinavir/ritonavir and hemodialysis
Lopinavir and ritonavir also are not cleared by hemodialysis, but a pharmacokinetic study showed that hemodialysis patients receiving lopinavir/ritonavir had lower concentrations of both lopinavir and ritonavir than did historical controls with normal renal function. The lopinavir AUC was 19% lower and Cmin was 44% lower; the ritonavir Cmin was 45% lower.(2)

Management recommendations for patients receiving hemodialysis include the following:

transparent gifgrey bulletOnce-daily lopinavir/ritonavir should not be used.
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transparent gifgrey bulletCaution should be exercised with patients whose HIV virus has PI resistance mutations; lopinavir and ritonavir levels may not be adequate for viral suppression.
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Other PIs
Pharmacokinetic evaluations of most other PIs in hemodialysis patients have not been conducted, and it is not known whether other PIs cause lower-than-expected drug levels in hemodialysis patients. Further studies are needed to define dosing recommendations for PIs in the setting of hemodialysis. For additional information, see (Dosing of Antiretroviral Drugs in Adults with Chronic Kidney Disease and Hemodialysis).

References

1. Reyataz [package insert]. Princeton, NJ: Bristol-Myers Squibb; April 2009.

2. Gupta SK, Rosenkranz SL, Cramer YS, et al. The pharmacokinetics and pharmacogenomics of efavirenz and lopinavir/ritonavir in HIV-infected persons requiring hemodialysis. AIDS. 2008 Oct 1;22(15):1919-27.

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