Risk of Biktarvy Use in Metabolic Acidosis
Biktarvy should be suspended immediately in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or metabolic acidosis, as lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with nucleoside analogs contained in this medication. 1
Mechanism of Acidosis Risk
Biktarvy contains emtricitabine and tenofovir alafenamide (TAF), both nucleoside analogs that can cause lactic acidosis through mitochondrial DNA polymerase gamma inhibition. 1 This enzyme is critical for mitochondrial replication, and its inhibition leads to impaired mitochondrial function, increased anaerobic metabolism, and subsequent lactic acid accumulation. 2
The previous tenofovir formulation (tenofovir disoproxil fumarate) was more commonly associated with severe lactic acidosis, while TAF has significantly decreased this incidence. 3 However, severe lactic acidosis with TAF-containing products remains a documented risk, particularly in overdose situations or with inappropriate dosing. 3, 2
Absolute Contraindications and When to Avoid
Do not initiate or continue Biktarvy in patients with:
Active metabolic acidosis or lactic acidosis - Treatment must be suspended immediately if clinical or laboratory findings suggest lactic acidosis or pronounced hepatotoxicity. 1
Severe renal impairment (creatinine clearance 15 to <30 mL/min) or end-stage renal disease not on chronic hemodialysis - These patients are at increased risk for tenofovir-related adverse events including metabolic complications. 1
High-Risk Clinical Scenarios
Exercise extreme caution or avoid Biktarvy in patients with:
Liver cirrhosis, chronic kidney disease, or hepatitis B/C coinfection - These are established risk factors for nucleoside analog-induced lactic acidosis. 3
Concomitant metformin use - This combination increases the risk of lactic acidosis. 3
Septic shock or tissue hypoperfusion - Do not use sodium bicarbonate to treat metabolic acidosis arising from tissue hypoperfusion, as acidosis may have protective effects and bicarbonate effectiveness is uncertain. 4 In a case report, inappropriate high-dose Biktarvy in septic shock led to persistent lactic acidosis despite clinical improvement. 2
Patients taking nephrotoxic agents including NSAIDs - These patients have increased risk of developing renal-related adverse reactions that can predispose to metabolic complications. 1
Monitoring Requirements Before and During Treatment
Prior to initiating Biktarvy, assess:
- Serum creatinine and estimated creatinine clearance 1
- Urine glucose and urine protein 1
- Serum phosphorus in patients with chronic kidney disease 1
- Baseline serum bicarbonate and electrolytes 4
During treatment, monitor every 3 months:
- Serum bicarbonate and electrolytes for early identification of increased anion gap 4
- Serum creatinine and estimated creatinine clearance 1
- Clinical symptoms of lactic acidosis (fatigue, nausea, vomiting, abdominal pain, dyspnea, tachypnea) 4
Clinical Presentation and Management
Warning signs of lactic acidosis include:
- Nonspecific gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea) with or without serum transaminase abnormalities 4
- Fatigue, dyspnea, and tachypnea progressing to respiratory failure 4
- Hepatomegaly and hepatic steatosis 4
If lactic acidosis is suspected:
- Measure serum venous lactate level immediately; if abnormal, repeat measurement and obtain arterial blood gas 4
- For lactate 2-5 mmol/L, close monitoring is advised 4
- Suspend Biktarvy immediately for any clinical or laboratory findings suggestive of lactic acidosis 1
- Intensive therapeutic strategies may include bicarbonate infusions and hemodialysis 4
- Consider thiamine and riboflavin supplementation based on pathophysiologic rationale, though efficacy requires clinical validation 4
Real-World Evidence
In a case of acute Biktarvy overdose, severe lactic acidosis developed requiring continuous renal replacement therapy (CRRT) for three days before resolution. 3
Another case demonstrated persistent lactic acidosis from inappropriately high Biktarvy dosing in septic shock, which resolved only after the medication was held. 2
In large real-world studies (BICSTaR), serious adverse events potentially related to Biktarvy occurred in <0.1% of patients, with excellent overall tolerability. 5 However, these studies excluded patients with active metabolic complications.
Key Clinical Pitfall
The most critical error is continuing Biktarvy in a patient with unexplained metabolic acidosis or elevated lactate. 1 Always maintain a high index of suspicion for drug-induced lactic acidosis in patients on nucleoside analogs presenting with nonspecific symptoms, and perform thorough medication reconciliation. 2 Unlike acidosis from tissue hypoperfusion where bicarbonate is not recommended 4, drug-induced lactic acidosis may warrant bicarbonate therapy and dialysis while the offending agent is discontinued. 4, 3