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Four Cases of Fatal Lactic Acidosis Due to Mitochondrial Toxicity of NRTI Treatment: Analysis of Clinical Features and Risk Factors H. TER HOFSTEDE1, S. DE MARIE2, N. FOUDRAINE3, S. DANNER3, and K. BRINKMAN*1‚4.
1Univ. Hosp. Nijmegen; 2Univ. Med. Ctr. Rotterdam; 3Academic Med. Ctr., Univ. of Amsterdam; and 4Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands Objective: To describe clinical features and predisposing factors attributed to lactic acidosis in 4 HIV-infected patients on long-term NRTI therapy.
Results: All patients had received at least 6-20 months of NRTI containing antiretroviral therapy: all used d4T, in one combined with 3TC, in the other three with ddI; in one hydroxyurea was added. In all, the initial symptoms were gastrointestinal (nausea and vomiting), followed by tachypnoea preceding the lactic acidosis; death followed 6-22 days after admission (liver failure and uncontrollable arrhythmias). Treatment with riboflavin was unsuccessful in one patient. The only definite risk factor in all cases was NRTI induced mitochondrial toxicity; one patient was concomitantly treated for Kaposi sarcoma (with bleomycin and vinblastine), and one just recovered from pneumococcal sepsis. None of the patients had a history of chronic HBV or HCV infection. In all patients, some sort of toxicity to other previously used NRTIs had occurred earlier.
Conclusions: Lactic acidosis occurred after months of NRTI therapy in patients who had already suffered other forms of NRTI toxicity. Concomitant diseases or co-medication might have aggravated the mitochondrial toxicity of the NRTIs. Screening methods to detect mitochondrial toxicity are necessary, since lactic acidosis occurs rather unexpectedly, with a rapid, fatal course.
Key Words: lactic acidosis, mitochondrial toxicity, risk factors
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