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Drug Saf. 2011 Jun 1;34(6):521-7. doi: 10.2165/11588240-000000000-00000.

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.

Author information

1
Department of Emergency Medicine, Mt Sinai School of Medicine, New York, New York 10029, USA. liza.leung@mssm.edu

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.

PMID:
21488705
PMCID:
PMC4959600
DOI:
10.2165/11588240-000000000-00000
[Indexed for MEDLINE]
Free PMC Article
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