title: Clinical features and risk factors of lactic acidosis following long-term antiretroviral therapy: 4 fatal cases.
abstract: Our objective was to describe clinical features and predisposing factors attributed to lactic acidosis in 4 HIV-infected patients on long-term nucleoside reverse transcriptase inhibitor (NRTI) therapy. All patients had received at least 6-20 months of NRTI-containing antiretroviral therapy: all used stavudine (d4T), in one combined with lamivudine (3TC), in the other 3 with didanosine (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's sarcoma (with bleomycin and vinblastine) and one just recovered from pneumococcal sepsis. None of the patients had a history of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. In all patients, some sort of toxicity to other previously used NRTIs had occurred earlier. Lactic acidosis occurred after months of NRTI therapy in patients who had already suffered other forms of NRTI toxicity. Concomitant diseases or comedication 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.
authors.affiliation: Department of Internal Medicine, University Hospital Nijmegen, The Netherlands. H.terHofstede@aig.azn.nl
authors.forename: H J
authors.initials: HJ
authors.lastname: ter Hofstede
authors.forename: S
authors.initials: S
authors.lastname: de Marie
authors.forename: N A
authors.initials: NA
authors.lastname: Foudraine
authors.forename: S A
authors.initials: SA
authors.lastname: Danner
authors.forename: K
authors.initials: K
authors.lastname: Brinkman
mesh_terms: D000140:Acidosis, Lactic / Q000139:chemically induced* / Q000175:diagnosis; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D017809:Fatal Outcome; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D012307:Risk Factors
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors