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 Guide Editors
 Editor In Chief
    Joel E. Gallant, MD, MPH

Pharmacology Editor
    Paul Pham, PharmD, BCPS

Zambia Guideline Team
   Peter Mwaba MMed PhD FRCP
   Alywn Mwinga MMed
   Isaac Zulu MMed MPH
   Velepie Mtonga MMed
   Albert Mwango MBChB
   Jabbin Mulwanda MMed FCS



Diagnosis>Complications of Therapy>
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Lactic Acidosis

Richard D. Moore, M.D.

  • 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.


Treatment of Hyperlactatemia and Lactic Acidosis

  • 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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