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

Background: In many Sub-Saharan African countries, first-line therapy for HIV may include a nucleoside reverse transcriptase inhibitor (NRTI). Longterm NRTI use is associated with symptomatic hyperlactataemia due to inhibition of mitochondrialDNApolymerase 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 ≥10 mmol/L (p = 0.003), pH <7.2 (p = 0.002), creatinine ≥200 mmol/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.