Tenofovir alafenamide associated fatal lactic acidosis in an autologous hematopoietic stem cell transplant recipient

Abstract

Fatal lactic acidosis has been reported while on the treatment with Nucleoside/nucleotide analogues (NA) for the treatment of hepatitis B, C and HIV. No cases of such a complication have been reported in hematopoietic stem cell transplant (HSCT) recipients. We present a 65-year male who underwent autologous HSCT for the treatment of multiple myeloma. Prior to transplant he was started on single agent tenofovir alafenamide (TAF) for treatment of resolved hepatitis B infection. He presented few weeks later with severe lactic acidosis. Other causes of lactic acidosis were excluded. The patient died of multi-organ failure despite stopping TAF and aggressive supportive care. The case demonstrates the need for increased awareness of this potential complication of NA treatment in the course of transplantation.

Successful Treatment of Tenofovir Alafenamide-Induced Lactic Acidosis: A Case Report

“…1 All current NAs used in the treatment of HBV-entecavir, lamivudine, tenofovir, adefovir, and telbivudine-have a potential to cause mitochondrial toxicity. 7 Because of its lower affinity for DNA polymerase-γ, tenofovir disoproxil fumarate (TDF) has traditionally been thought of as less toxic to mitochondria when administered as monotherapy, particularly when compared to older therapies for HIV such as the thymidine analogues zidovudine and stavudine, or combination NA therapy. [11][12][13] However, case reports of lactic acidosis with TDF monotherapy are reported in the literature, including several fatalities.…”

“…This syndrome occurred 6 weeks into therapy, in contrast with our patient where it occurred after only 2 doses. 7 The onset of NALA has been reported in the literature to occur as early as one month and as late as 20 months after NA initiation. 1 It is unusual how early it manifested in our patient; however, we hypothesize that his severity of liver dysfunction and critical illness imparted a greater baseline predisposition to mitochondrial dysfunction.…”

“…[1][2][3] The primary reported NA offenders are zidovudine, stavudine, and didanosine, whereas newer agents such as entecavir and tenofovir alafenamide (TAF) have demonstrated less interference with mitochondrial function in vitro. [4][5][6][7] Patients may be asymptomatic, have mild non-specific symptoms, or present in multisystem organ failure. The majority of cases of hyperlactatemia are asymptomatic, reported to occur in 8-21% of patients on NA therapy.…”

Severe Lactic Acidosis Due to Acute Intoxication by Emtricitabine/Tenofovir Alafenamide

“…However, it can be associated with severe lactic acidosis as demonstrated by this case report. In 2018, Alsunaid et al reported a 65-year-old male status post-hematopoietic stem cell transplant due to multiple myeloma, who received treatment for hepatitis B with TAF and died of severe lactic acidosis [ 15 ]. Our report is the first case associated with severe lactic acidosis due to intentional acute intoxication by TAF/emtricitabine (Descovy®) in an attempt at suicide.…”

“…Hemodialysis in our patient was thought to play a major role in the elimination of medication with resolution of lactic acidosis. In the case reports listed, only four of the 14 patients survived after intoxication by tenofovir [ 5 , 9 , 11 , 15 , 16 , 21 - 25 , 27 ]. Our patient also had a favorable outcome without progression to chronic kidney disease.…”