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Richard D. Moore, M.D.
07-03-2008
- Lactic acidosis is significant concern in Zambia due to frequent use of d4T- and AZT-based regimens.
- Female gender in Africans has been shown to be significant risk factor for lactic acidosis, particularly in combination with obesity.
- Given limited testing options for lactic acidosis in Zambia, high clinical index of suspicion is necessary, with rapid discontinuation of all ARVs in symptomatic pts.
- Point-of-care testing for lactate may be useful diagnostic tool, but availability limited in Zambia.
- In Zambia, if a pt develops lactic acidosis while on d4T or AZT, substitution with TDF recommended for subsequent regimens.
- New regimen should typically not be started until at least 4 weeks from the end of last regimen and only in pts with normalized lactate levels or resolution of clinical disease.
Zambia Information Author: Larry William Chang, MD, MPH
- 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: d4T > ddI, 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)
- Lactate >2 mM. Venous blood drawn without tourniquet into chilled fluoride-oxelate tube. Blood must be put on ice after phlebotomy, processed in lab within 4 hrs. Should not exercise 24 hrs before level drawn.
- Low bicarb, anion gap >16 (Na -[Cl + CO2)]),elevated CPK, LDH, amylase, lipase, AST, ALT. These tests not sensitive or specific. Can have hyperlactatemia with normal bicarb and anion gap
- Ultrasound or CT of liver may show steatosis
- Asymptomatic elevation of lactate to 2-5 mM range does not reliably predict higher elevations and symptoms. Most with mild elevation do not progress.
- Mild Sx may not correlate well with lactate levels.
- Lactate <5 mM may not require treatment in absence of Sx (routine lactate monitoring not recommended)
- Symptomatic pts (lactate typically >5 mM) should discontinue NRTIs
- Consider switch to ABC or TDF if on d4T, ddI, or AZT with mild lactate elevation and minimal Sx. Combination of TDF and full-dose ddI has been associated with severe lactic acidosis.
- Lactate >10-15 mM may require urgent supportive management. Seriously ill persons may require IV hydration, mechanical ventilation, pressors, dialysis
- Anecdotal reports of benefit from L-carnitine (50-100 mg/kg/d IV in divided doses q4hrs by slow infusion), thiamine (100 mg IV), riboflavin (100 mg PO once daily), vitamin C (500 mg PO or IV once daily), coenzyme Q (1.5 mg/kg IV once daily) but no clinical trials of efficacy
- Monitor lactate initially if alternative NRTIs restarted.
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