Nephrotoxicity Associated with Concomitant Use of Ledipasvir‐Sofosbuvir and Tenofovir in a Patient with Hepatitis C Virus and Human Immunodeficiency Virus Coinfection

Abstract

Direct-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV) infection, with superior efficacy and safety compared to interferon-based therapies. Despite these improvements, drug interactions with DAAs exist and may be clinically relevant in human immunodeficiency virus (HIV)-coinfected patients. We present a case of nephrotoxicity associated with concomitant use of tenofovir disoproxil fumarate (TDF) and ledipasvir-sofosbuvir (LDV-SOF). A 56-year-old woman with HIV infection who had been taking efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC) for 6 years developed acute kidney injury 8 weeks after initiating LDV-SOF for the treatment of HCV infection. Her serum creatinine concentration peaked at 10 mg/dL, compared with her baseline concentration of 0.9-1 mg/dL. Kidney biopsy revealed acute tubular necrosis and acute interstitial nephritis. Both LDV-SOF and TDF were discontinued, and the patient's serum creatinine concentration decreased to 1.3 mg/dL over the following 6 weeks. We postulate that this adverse drug reaction may have been secondary to the known interaction between ledipasvir and TDF, which results in increased TDF exposure. Despite knowledge of this interaction, LDV-SOF is commonly prescribed in patients with HIV-HCV coinfection, as patients who received LDV-SOF- and TDF-containing regimens in trials have not demonstrated adverse clinical consequences related to this interaction. This case highlights the rare but potentially serious nephrotoxicity that can result from TDF toxicity and serves as a reminder to clinicians to implement close renal function monitoring in patients receiving both LDV-SOF and TDF. Clinicians prescribing LDV-SOF to HCV-HIV-coinfected patients receiving TDF should be cautious about use with concomitant nephrotoxic medications and monitor markers of tubular dysfunction, including urinary phosphorus excretion, and renal injury at baseline and week 4 of therapy. Tenofovir alafenamide and alternative DAAs may also have a role in the management of patients at high risk for renal adverse effects from TDF.

Efficacy and safety of combined directly acting antivirals for treatment of Chinese chronic hepatitis C patients in a real-world setting

“…In this study, 83.3% (45/54) of patients achieved RVR 2 and 94.4% (51/54) of patients achieved SVR 24 which had no significant difference with those reported in previous studies[30-33]. With the application of DAAs, some cases were reported with nephrotoxicity and hepatotoxicity due to DAAs treatment[34,35]. Thus, our study analyzed the changes of hemogram and hepatorenal function indices and the frequency of AEs associated with combined DAAs treatment.…”

Acute Kidney Injury in Patients Undergoing Chronic Hepatitis C Virus Treatment With Ledipasvir/Sofosbuvir

“…Currently, there are limited published data suggesting the risk of AKI during oral direct acting antiviral treatment. (11)(12)(13) These case reports and retrospective studies suggest an intrinsic cause of renal injury, with most of the available biopsies showing acute tubular necrosis (ATN) and acute interstitial nephritis (AIN). Most of these patients had returned to baseline renal function on cessation of LDV/SOF combination therapy.…”

Lack of clinically important PK interaction between coformulated ledipasvir/sofosbuvir and rilpivirine/emtricitabine/tenofovir alafenamide

“…, ; Mathias ; Bunnell et al. ). This led to updates in the labeling of TDF‐containing products globally, recommending the monitoring for TDF adverse reactions when LDV/SOF is coadministered or using alternative HCV or HIV therapy.…”

“…; Mathias ; Bunnell et al. ). The highest absolute TFV exposures were observed when the fixed‐dose combination (FDC) LDV/sofosbuvir (SOF) and ritonavir‐boosted HIV protease inhibitors with emtricitabine (FTC)/TDF were coadministered (German et al.…”