Severe rhabdomyolysis-induced acute kidney injury following concomitant use of Genvoya® (EVG/COBI/FTC/TAF) and simvastatin; a case report

Genvoya® (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) is a recent single regimen for the treatment of Human Immunodeficiency Virus (HIV). However, because of its complexity, it is difficult to predict drug interactions, especially when associated with HMG-CoA reductase inhibitors an...

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Published in:	BMC nephrology Vol. 20; no. 1; p. 69
Main Authors:	Godinho, Rita, Bugnon, Serge, Gracin, Terezija, Tataw, James
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 26-02-2019 BioMed Central BMC
Subjects:	Acquired immune deficiency syndrome Acute kidney failure Acute kidney injury Acute Kidney Injury - chemically induced Acute Kidney Injury - physiopathology Acute Kidney Injury - therapy AIDS Anti-HIV agents Anti-HIV Agents - administration & dosage Anti-HIV Agents - adverse effects Antilipemic agents Atorvastatin Care and treatment Case Report Case reports Case studies Cobicistat Cobicistat - administration & dosage Cobicistat - adverse effects Comorbidity Complications and side effects Cytochrome P-450 Diagnosis Drug Combinations Drug Interactions Drug therapy Dyslipidemias - complications Dyslipidemias - drug therapy Elvitegravir Emtricitabine Emtricitabine - administration & dosage Emtricitabine - adverse effects Enzymes Etravirine Genvoya Hemodialysis Hepatitis Hepatitis A Hepatitis A - complications Hepatitis A - diagnosis Hepatitis A - physiopathology Hepatitis C Hepatitis C - complications Hepatitis C - diagnosis Hepatitis C - physiopathology Highly active antiretroviral therapy HIV HIV Infections - complications HIV Infections - drug therapy HIV patients HMG-CoA reductase inhibitors Human immunodeficiency virus Humans Hydroxymethylglutaryl-CoA reductase Hypolipidemic Agents - administration & dosage Hypolipidemic Agents - adverse effects Infections Kidney diseases Kidneys Laboratories Liver Liver diseases Liver Function Tests Lovastatin Male Middle Aged Nephrology Patients Potassium Quinolones - administration & dosage Quinolones - adverse effects Renal Dialysis - methods Renal replacement therapy Rhabdomyolysis Rhabdomyolysis - chemically induced Rhabdomyolysis - physiopathology Rhabdomyolysis - therapy Simvastatin Simvastatin - administration & dosage Simvastatin - adverse effects Statins Tenofovir Tenofovir - administration & dosage Tenofovir - adverse effects Tenofovir - analogs & derivatives Treatment Outcome Urine Switzerland Genvoya Rhabdomyolysis HIV Acute kidney injury Simvastatin
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Summary:	Genvoya® (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) is a recent single regimen for the treatment of Human Immunodeficiency Virus (HIV). However, because of its complexity, it is difficult to predict drug interactions, especially when associated with HMG-CoA reductase inhibitors and/or in the setting of other comorbidities. We discuss the mechanisms of these potential drug interactions as the cause of rhabdomyolysis and acute kidney injury in the context of prior and current medication therapy with possible underlying liver and kidney dysfunction. We describe the case of a 54-year-old man diagnosed with HIV who developed severe rhabdomyolysis-induced anuric acute kidney injury (AKI) requiring renal replacement therapy following introduction of Genvoya® concomitantly with simvastatin, in the context of recently diagnosed hepatitis C and hepatitis A. Haemodialysis was continued over 5 weeks followed by progressive clinical and biological improvements. Five months later, a new antiretroviral regimen was started and has been well tolerated. Simvastatin, as well as lovastatin, because of their CYP3A4 metabolism, and to a lesser extent atorvastatin, which is only partially metabolized by CYP3A4, are the HMG-CoA reductase inhibitors with the greatest risk of drug interactions and should not be used in patients under HIV-therapy. Patients receiving HMG-CoA reductase inhibitors should be monitored regularly for the occurrence of muscular adverse effects and drug interactions should be considered with each new prescription or change in clinical status. There are many online tools that enable clinicians to rapidly check for drug interactions. We recommend the one from the University of Liverpool for patients under HIV-therapy ( https://www.hiv-druginteractions.org/checker ), while for patients under hepatitis C-therapy, we advise to consult http://www.hep-druginteractions.org/ . This case illustrates the importance of multidisciplinary collaboration in the treatment of HIV-positive patients because of their complexity, associated comorbidities and the potential of multiple drug-drug interactions potentially exacerbated by underlying liver and/or kidney dysfunction.
Bibliography:	ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3
ISSN:	1471-2369 1471-2369
DOI:	10.1186/s12882-019-1257-6