title: Fatal toxicity from symptomatic hyperlactataemia: a retrospective cohort study of factors implicated with long-term nucleoside reverse transcriptase inhibitor use in a South African hospital.
abstract: BACKGROUND
  In many Sub-Saharan African countries, first-line therapy for HIV may include a nucleoside reverse transcriptase inhibitor (NRTI). Long-term NRTI use is associated with symptomatic hyperlactataemia due to inhibition of mitochondrial DNA polymerase γ, a potentially fatal complication.
  
  
  OBJECTIVE
  The purpose of the study was to evaluate the factors associated with inhospital fatality for HIV inpatients prescribed NRTIs long term who presented with symptomatic hyperlactataemia.
  
  
  METHODS
  We performed a retrospective cohort study at a 900-bed university hospital in South Africa over 4 years (2005-2008). We included HIV inpatients prescribed NRTIs long term who presented with symptomatic hyperlactataemia (long-term NRTI use; lactate >4.0 mmol/L; absence of infectious source; symptoms requiring admission). Data included demographics, medical history, NRTI duration, blood pressure, symptom duration and relevant laboratory data.
  
  
  RESULTS
  Of 79 patients who met inclusion criteria (mean age 38.2 ± 10.5 years, 97% female) there were 46 fatalities (58%). Factors significantly associated with fatality were presence of diabetes mellitus (p = 0.04), lactate ≥10 mmol/L (p = 0.003), pH <7.2 (p = 0.002), creatinine ≥200 μmol/L (p = 0.03) and altered mental status (p = 0.03).
  
  
  CONCLUSIONS
  In this study, NRTI-related symptomatic hyperlactataemia occurred predominantly in females. Mortality was associated with severely elevated lactate (≥10 mmol/L), the degree of acidosis, elevated creatinine, history of diabetes and altered mental status on presentation.
authors.affiliation: Department of Emergency Medicine, Mt Sinai School of Medicine, New York, New York 10029, USA. liza.leung@mssm.edu
authors.forename: Liza
authors.initials: L
authors.lastname: Leung
authors.forename: Douglas
authors.initials: D
authors.lastname: Wilson
authors.forename: Alex F
authors.initials: AF
authors.lastname: Manini
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy; D017052:Hospital Mortality; D006801:Humans; D019344:Lactic Acid / Q000097:blood*; D008134:Long-Term Care; D008297:Male; D009705:Nucleosides / Q000008:administration & dosage; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D012307:Risk Factors; D013019:South Africa
chemical_list: D019380:Anti-HIV Agents; D009705:Nucleosides; D018894:Reverse Transcriptase Inhibitors; D019344:Lactic Acid