• Poster 56: Hyperlactatemia in 20 Patients Receiving NRTI Combination Regimens (Authored by J.T. Lonergan, D. Havlir, C. Behling, H. Pfander, T. Hassanein, and W.C. Mathews. Univ. California San Diego Med. Ctr.)
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• Poster 59: Four Cases of Fatal Lactic Acidosis Due to Mitochondrial Toxicity of NRTI Treatment: Analysis of Clinical Features and Risk Factors (Authored by H. Ter Hofstede, S. De Marie, N. Foudraine, S. Danner, and K. Brinkman. Univ. Hosp. Nijmegen; Univ. Med. Ctr. Rotterdam; Academic Med. Ctr., Univ. of Amsterdam; and Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands)
  Click here to view the original abstract

Lactic acidosis is another metabolic complication associated with antiretroviral therapy (ART) that is poorly understood. A range of possible presentations is possible as demonstrated by two papers. Lonergan from San Diego reported on 20 patients who developed mild elevations of lactic acid (hyperlactatemia) in the blood without frank acidosis. All of these patients had a combination of syndromes involving abdominal pain as well as nausea and abdominal distention. Abnormal elevations of liver enzymes were also commonly seen. However, the cause of the hyperlactatemia was unclear -- no concurrent illnesses, no excessive short or long-term alcohol use, and no recent strenuous physical activity. All 20 patients were taking nucleosides (with or without NNRTI or PI). Every patient was on d4T. Nineteen of the 20 patients resumed ART without d4T and three had mild relapses of hyperlactatemia. Seven patients underwent liver biopsy because of the liver abnormalities; six of these revealed steatosis (fatty infiltration).

Hofstede from the Netherlands reported on a more extreme form of hyperlactatemia, four cases of fatal lactic acidosis. All four of these patients had been receiving ART for from 6-20 months. d4T was being taken by all four, with ddI in three of the cases and 3TC in the other. All developed GI symptoms (nausea and vomiting) with tachypnea the first sign of acidosis. This presentation occurred rapidly, as did the subsequent deterioration to death: 6-22 days after admission.

So what does this mean? We can certainly add severe lactic acidosis as well as nonacidotic mild hyperlactatemia to our list of metabolic complications associated with ART. These complications seem to be rare and more associated with NRTI therapy than with either NNRTI or PI. The role of d4T and mitochondrial toxicity remains controversial, but possible.

As a physician, I will now make sure I look for elevated lactic acid levels even in patients without obvious evidence of acidosis, especially when vague abdominal or GI symptoms occur. In the past I thought serum electrolyte determinations were sufficient for this evaluation, but now I'm not so sure.