Hemodialysis Does Not Significantly Affect the Pharmacokinetics of Nevirapine in HIV-1-Infected Persons Requiring Hemodialysis: Results From ACTG A5177

Abstract

When characterizing the pharmacokinetics of a therapeutic agent, a key goal is to maximize efficacy while minimizing risk. Because pharmacokinetics studies are difficult to do in populations with severe end organ damage, such as end-stage renal disease, dosing recommendations in these populations may be extrapolated from other data or may be missing. In patients receiving dialysis, the added complexity of clearance by the dialysis process, which depends on the degree to which medications are protein bound, must be taken into account. Nevirapine (NVP) is a commonly used non-nucleoside antiretroviral agent that has only minimal renal elimination. However, hemodialysis may represent a significant route of NVP elimination in patients with end stage renal disease due to its relatively low volume of distribution (1.2 L/kg), low molecular weight, and being only 60% bound to plasma proteins.1 In the one previously published case report of NVP use in a patient receiving hemodialysis,2 the area under the concentration time curve was substantially reduced during dialysis with a 46.5% extraction ratio. However, NVP was dosed at only 200 mg once daily in this patient. Therefore, we examined the potential effects of hemodialysis on the steady-state pharmacokinetics of NVP, in HIV-1-infected subjects with end-stage renal disease requiring hemodialysis, when given at the usual dosing strategy of 200 mg twice daily. ACTG A5177 was a prospective observational study to estimate the steady-state pharmacokinetic (PK) parameters of efavirenz, lopinavir/ritonavir and NVP in HIV-infected subjects requiring hemodialysis. The efavirenz and lopinavir/ritonavir results have been reported elsewhere.3 This letter summarizes the pharmacokinetic results observed in the 3 subjects accrued to the NVP arm.