Drug Safety

, Volume 34, Issue 6, pp 521–527

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
  • Liza Leung
  • Douglas Wilson
  • Alex F. Manini
Original Research Article

DOI: 10.2165/11588240-000000000-00000

Cite this article as:
Leung, L., Wilson, D. & Manini, A.F. Drug-Safety (2011) 34: 521. doi:10.2165/11588240-000000000-00000


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 g, 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 ≥10mmol/L (p = 0.003), pH <7.2 (p = 0.002), creatinine ≥200mmol/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 (≥10mmol/L), the degree of acidosis, elevated creatinine, history of diabetes and altered mental status on presentation.

Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  • Liza Leung
    • 1
  • Douglas Wilson
    • 2
  • Alex F. Manini
    • 3
  1. 1.Department of Emergency MedicineMt Sinai School of MedicineNew YorkUSA
  2. 2.Department of Infectious DiseasesEdendale HospitalPietermaritzburgSouth Africa
  3. 3.Division of Medical Toxicology, Department of Emergency MedicineMount Sinai School of MedicineNew YorkUSA