Case 5: Antiretrovirals and Statins

Question | Discussion | References | CME Credit

You answered:

	The patient's acute renal failure is most likely caused by tenofovir. Although the patient has a clinical presentation that suggests a diagnosis of acute rhabdomyolysis, this diagnosis could not explain the development of renal failure.

This answer is incorrect. Although it is possible that tenofovir could have caused the patient's renal failure, tenofovir-associated renal toxicity rarely occurs this rapidly in a patient with previously normal renal function. The more likely scenario is that lopinavir-ritonavir caused a marked increase in simvastatin levels, leading to rhabdomyolysis and subsequent renal failure. Several processes contribute to the renal failure associated with rhabdomyolysis, including volume depletion, tubular obstruction caused by heme pigment casts, and tubular injury caused by excess free chelatable iron.

	Tenofovir causes a marked increase in the intracellular levels of simvastatin. Thus this combination of medications likely triggered statin-induced acute rhabdomyolysis and renal failure. This combination of tenofovir and a statin drug should be avoided in all patients.
	Discontinuation of efavirenz most likely caused simvastatin-induced rhabdomyolysis and renal failure. Stopping efavirenz would lead to normalization of previously induced cytochrome P450 3A4 isozymes, thus leading to a dramatic increase in blood levels of simvastatin.
	The patient's clinical presentation is best explained by drug-induced rhabdomyolysis and acute renal failure caused by elevated blood levels of simvastatin. The increased simvastatin levels resulted from co-administration of simvastatin with lopinavir-ritonavir.

[Back to Case 5 Question | Go to Correct Answer]