From the Guidelines
HIV patients with an elevated anion gap should be immediately evaluated for lactic acidosis, particularly if they are taking nucleoside reverse transcriptase inhibitors (NRTIs), and the implicated drug should be stopped and replaced with an alternative antiretroviral with less mitochondrial toxicity, such as tenofovir or abacavir, as recommended by the guidelines for using antiretroviral agents among HIV-infected adults and adolescents 1.
Key Considerations
- Lactic acidosis is a common cause of elevated anion gap in HIV patients, often due to mitochondrial toxicity from NRTIs, especially older agents like stavudine and didanosine.
- Symptoms of lactic acidosis include fatigue, nausea, abdominal pain, and dyspnea, and can progress to severe lactic acidosis with significant mortality risk if not promptly recognized and treated.
- Other causes of elevated anion gap in HIV patients include opportunistic infections causing sepsis, renal tubular acidosis from HIV-associated nephropathy, or ketoacidosis from poor nutritional status.
- Management involves identifying and treating the underlying cause, discontinuing offending medications if present, and providing supportive care, including monitoring of serum lactate levels and electrolytes.
- Clinicians should periodically check electrolytes, especially in those with risk factors like female gender, obesity, or prolonged NRTI exposure, as recommended by the guidelines for the management of chronic kidney disease in HIV-infected patients 1.
Monitoring and Prevention
- Monitoring of serum bicarbonate and electrolytes is recommended every 3 months to identify an increased anion gap early, as suggested by certain persons knowledgeable in HIV treatment 1.
- Early recognition of lactic acidosis is crucial, and clinicians should be aware of the risk factors and symptoms to provide prompt treatment and prevent severe lactic acidosis.
- The use of alternative antiretrovirals with less mitochondrial toxicity, such as tenofovir or abacavir, can help prevent lactic acidosis in HIV patients, as recommended by the primary care guidelines for the management of persons infected with human immunodeficiency virus 1.
From the Research
HIV and Anion Gap
- The anion gap (AG) is an important tool in the evaluation of metabolic acidosis, and it can be affected by various factors including serum albumin and globulin concentrations 2.
- In HIV patients, the serum globulin concentration is often higher, which can lead to a lower anion gap 2.
- A study found that the average anion gap in HIV patients was significantly lower than in normal controls (9.4 +/- 1.9 mmol/L vs. 10.8 +/- 2.7 mmol/L) 2.
- The study also suggested that the anion gap can be adjusted for abnormal serum globulin levels using the formula: adjusted anion gap = anion gap + 0.147 x (globulin - 29) 2.
Lactic Acidosis and HIV
- Lactic acidosis is a life-threatening complication of antiretroviral therapy in HIV patients, with an incidence of about 1% per year 3.
- It is often caused by nucleoside analogue reverse transcriptase inhibitors, such as didanosine, stavudine, and zalcitabine, which can inhibit the replication of mitochondrial DNA 3.
- Lactic acidosis can also be associated with other mitochondrial toxins, such as valproic acid and acetylsalicylic acid 3.
- Treatment of lactic acidosis in HIV patients typically involves discontinuing the offending medication and supplementing with uridine, vitamins, L-carnitine, and coenzyme Q10 3.
Relationship between Anion Gap and Lactic Acidosis
- A high serum anion gap metabolic acidosis may be masked by a deceitfully normal anion gap in patients with elevated serum globulin concentrations 2.
- Therefore, calculation of the corrected anion gap is important to avoid a delay in diagnosis and treatment of lactic acidosis in HIV patients 2.
- Other factors, such as riboflavin deficiency, can also contribute to the development of lactic acidosis in HIV patients, and screening and treatment of riboflavin deficiency may be important in patients on nucleoside analogues 4.