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

Abstract

A 46-year-old female with a history of generalized anxiety disorder was admitted after intentional ingestion of an unknown amount of emtricitabine/tenofovir alafenamide (Descovy®) in a suicidal attempt. Patient was emergently intubated secondary to severe agitation and inability to protect airways. Patient developed severe lactic acidosis early in the admission, secondary as to a possible mitochondrial toxicity. Failed attempts to fluid resuscitation with Lactate Ringer®, eventually warranted to start the patient on norepinephrine infusion. Metabolic acidosis remained refractory to bicarbonate bolus and infusion. Hypothermia and hypoglycemia were corrected. Despite the initial approach, the patient remained acidotic, and the nephrology was consulted for emergent continuous renal replacement therapy (CRRT). After three days of intensive care unit stay and CRRT, the patient improved and was successfully decannulated. Her metabolic profile also showed remarkable improvement and the metabolic lactic acidosis resolved. The previous formulation of tenofovir with disoproxil fumarate is associated with severe lactic acidosis due to inhibition of mammalian mitochondrial DNA polymerase. Risk factors include liver cirrhosis, chronic kidney disease, hepatitis B and C coinfection, and metformin use. The new pharmaceutical formulation of tenofovir with alafenamide (TAF) has caused a significant decrease in the incidence of lactic acidosis. However, its real incidence and the usual plasma level to induce toxicity and mitochondrial dysfunction are unknown. The aim of this report is to highlight the risk of severe lactic acidosis with the use of TAF.

Oxidative phosphorylation in HIV-1 infection: impacts on cellular metabolism and immune function

“…Recent studies highlight the role of purinergic signaling, particularly the interaction between extracellular ATP and P2X receptors, in HIV-1 pathogenesis ( 112 , 113 ). These receptors, activated by ATP released from stressed cells, influence the HIV-1 life cycle and contribute to immunometabolic dysfunction ( 96 , 106 , 109 ).…”

“…Advancements in understanding HIV-1 pathogenesis highlight the role of purinergic signaling, particularly the involvement of extracellular ATP and P2X receptors. These receptors play a significant role in the inflammatory response and immune modulation in HIV-1 infection ( 112 , 113 ). This growing body of research underlines the importance of understanding the metabolic and mitochondrial aspects of HIV-1 infection and ART.…”

“…Metformin, a diabetes medication, has shown varying effects on HIV-1 replication in studies by Rezai et al and Guo et al (106,111). There is an additive effect of risk of metformin-associated lactic acidosis when used with NRTIs like tenofovir, which calls for caution in its clinical application (112,113). Research on the antioxidant properties of plant flavonoids, such as naringin, is gaining attention for their potential to mitigate oxidative damage induced by NRTIs (114,115).…”

Severe Lactic Acidosis Due to Inappropriate Use of Biktarvy in a Patient With AIDS

“…Our case presents an uncommon presentation of severe lactic acidosis in the setting of inappropriately high dosing of Biktarvy in a patient suffering from AIDS. NRTIs can cause overproduction of lactic acid through mitochondrial impairment [ 3 ]. Mitochondria depend on the enzyme DNA polymerase gamma (pol gamma) for replication.…”

“…Curiously, this enzyme is structurally similar to the reverse transcriptase enzyme utilized by the HIV. Because of this similarity, NRTIs can reduce mitochondrial replication [ 3 ]. The decreased mitochondrial production results in a reduction of oxidative phosphorylation and the production of ATP.…”