3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 23-26 October 2001, Athens, Greece

INVESTIGATING LACTATE METABOLISM TO ESTIMATE MITOCHONDRIAL STATUS

Antiviral Therapy 2001; 6(Suppl. 4):16 (abstract no. 21)

P Leclercq, H Roth, A Bosseray and X Leverve
DMAS, CHU Grenoble, France

BACKGROUND: We need to identify earlier forms of nucleoside reverse transcriptase inhibitor (NRTI)- induced lactic acidosis/hepatic steatosis. Lactatemia is a weak parameter, since it gives a steady-state concentration between production and utilization. We propose to measure in vitro lactate flow by using an exogenous lactate challenge test (ELCT).

METHODS: ELCT: fasted subjects, at rest; 2 h measurements of lactatemia after a 15 min Na-lactate infusion; with a pharmacodynamic approach, we obtain clearance and endogenous production of lactate. Twenty ELCT were done in 13 HIV patients under highly active antiretroviral therapy (HAART); 25 ELCT in controls. ELCT was proposed to patients in case of muscular weakness, abnormal asthenia or unexplained elevated ALT level.

RESULTS: Basal lactate (L; mmol/l): 2.1±0.8 (HIV) versus 1.0±0.3 (controls); lactate clearance (ml/kg/min): 10.3±3 versus 14.1±2; endogenous production (EP) (μmol/kg/min):20.7±9 versus 14±4. For six ELCT with L<2 mmolll, EP was normal. For six with 1.5<L<2, EP was increased (20 μmol/kg/min) and in eight cases with 2<L<4, EP was markedly increased (30). Five patients had hepatic and muscular biopsies: one had typical muscular abnormalities, four had hepatic steatosis and two had signs of NASH. Four patients had been investigated with ELCT before and after discontinuation of NRTI: L before/after: 3.1 versus 1.6; lactate clearance: 10 versus 10; EP: 32 versus 16. In the same time, they had clinical improvement and normalization of ALT levels.

CONCLUSIONS: These preliminary results indicate that there is a marked increase in endogenous lactate production, even in patients who have very moderate increase in lactatemia. Evaluation of the lactate turnover in patients with symptoms of NRTI toxicity reveals an increase in endogenous production an a respect of lactate clearance. These abnormalities are reversible after NRTI discontinuation. With this test (ELCT), we are able to measure lactate endogenous production. It is a tool easy to realize and so to repeat, allowing a monitoring of energetic metabolism in patients under HAART when a mitochondrial dysfunction is suspected.

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