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- Incidence: Mild, asymptomatic hyperlactatemia: 8-15%; Symptomatic hyperlactatemia: 0.5-12%
- Symptoms: Fatigue, weakness, myalgias, and GI distress, including abdominal pain, abdominal distention, nausea/vomiting, diarrhea. Later can advance to dyspnea, orthostasis, organ failure (hepatic, renal), cardiovascular collapse and death.
- Mortality: 7% with lactate 5-10 mM, 20-30% with lactate 10-15 mM, 50-60% with lactate >15 mM
- Caused by NRTI use: d4TddI, AZT. May not occur with 3TC, FTC, ABC, TDF, though listed in package insert as a class effect.
- Associated with mitochondrial DNA gamma polymerase inhibition, and decrease in mitochondrial DNA
- May be accompanied by hepatic steatosis (fatty liver), pancreatitis. Fatal liver failure can occur (earliest reports in AZT-treated patients)
- Increased risk with lower CD4, older age, female sex. Do not use ddI + d4T in pregnancy (FDA warning)