Case 5: Antiretrovirals and Statins

Question | Discussion | References | CME Credit

Case last updated: May 31, 2005

A 34-year-old HIV-infected man with a CD4 count of 189 cell/mm3 and long-standing, well-controlled hyperlipidemia presents to the clinic complaining of a four day history of diarrhea, fatigue, leg weakness, total body aches, and muscle pain. He has noticed his urine has been darker than normal. Three weeks prior, he started a new antiretroviral regimen after having virologic breakthrough on a regimen consisting of zidovudine plus lamivudine (Combivir) plus efavirenz (Sustiva). His physical examination shows a T = 38.4°C, HR = 110, and diffuse muscle tenderness. Laboratory studies show a serum creatinine of 5.2 mg/dL (baseline = 1.0 mg/dl), serum urea nitrogen = 67 mg/dL (baseline = 10 mg/dL), aspartate aminotransferase (AST) level of 632 U/L (baseline = 56 U/L), alanine aminotransferase (ALT) level of 400 U/L (baseline = 25 U/L), creatine kinase = 9700 U/L and slightly elevated amylase level.

Current Medications:
Tenofovir (Viread): 300 mg PO qd
Lamivudine (Epivir): 300 mg PO qd
Lopinavir-Ritonavir (Kaletra): 3 PO bid
Trimethoprim-Sulfamethoxazole (Bactrim): 160 mg/800 mg PO qd
Simvastatin (Zocor): 40mg PO qd

Which of the following statements is the MOST accurate related to this patient's clinical presentation?

	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 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.
	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.