Risk factors for fatality in HIV-infected patients with dideoxynucleoside-induced severe hyperlactataemia or lactic acidosis

Alejandro Arenas-Pinto; Alison Grant; Krishnan Bhaskaran; Andrew Copas; Andrew Carr; Signe W Worm; Esteban Martinez; Peter Reiss; David Dunn; Rainer Weber; Jennifer Hoy; Ian Weller; Lactic Acidosis International Study Group

doi:10.3851/IMP1732

Risk factors for fatality in HIV-infected patients with dideoxynucleoside-induced severe hyperlactataemia or lactic acidosis

Alejandro Arenas-Pinto, Alison Grant, Krishnan Bhaskaran, Andrew Copas, Andrew Carr, Signe W Worm, Esteban Martinez, Peter Reiss, David Dunn, Rainer Weber, Jennifer Hoy, Ian Weller, Lactic Acidosis International Study Group

8 Citations (Scopus)

Abstract

Background: Lactic acidosis (LA) and severe hyperlactataemia (HL) are infrequent but serious complications of antiretroviral therapy that have been associated with a high fatality rate. Methods: In a multinational retrospective cohort study, LA was defined as arterial blood pH<7.35, bicarbonate <20 mmol/l and lactate above normal, and HL as confirmed blood lactate >5 mmol/l. Logistic regression was used to identify factors associated with fatality. Sensitivity and specificity of different case definitions as predictors of death were compared. Results: The overall case-fatality rate was 19/110 (17.3%), but among acidotic patients it was 33% (16/49 cases). There were 10 asymptomatic patients and none of them died as a consequence of the event. The median lactate for fatal, non-fatal and all patients was 8.3 mmol/l (IQR 7.2-13.1), 6.4 mmol/l (IQR 5.4-7.8) and 6.7 mmol/l (IQR 5.5-8.1), respectively. After adjusting for age and current CD4⁺ T-cell count, lactate >7 mmol/l (OR 6.27, 95% CI 1.13-34.93), blood bicarbonate <12 mmol/l (OR 10.02 relative to >18 mmol/l, 95% CI 1.33-75.65) and concurrent opportunistic infections (OR 8.69, 95% CI 1.45-52.22) were independently associated with case fatality. Blood lactate >7 mmol/l showed a sensitivity of 84% for fatality with a specificity of 60%, whereas bicarbonate <12 mmol/l showed a better specificity (85%) but a poorer sensitivity (42%). Bicarbonate <18 mmol/l appears to be as good as lactate <7 mmol/l at predicting death (sensitivity 90% and specificity 54%). Conclusions: Our data suggest that blood lactate >7 mmol/l and blood bicarbonate <18 mmol/l appear to predict death and might help clinicians in selecting patients who may benefit from more intense monitoring.

Original language	English
Journal	Antiviral Therapy
Volume	16
Issue number	2
Pages (from-to)	219-26
Number of pages	8
ISSN	1359-6535
DOIs	https://doi.org/10.3851/IMP1732
Publication status	Published - 1 Jan 2011

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Arenas-Pinto, A., Grant, A., Bhaskaran, K., Copas, A., Carr, A., Worm, S. W., Martinez, E., Reiss, P., Dunn, D., Weber, R., Hoy, J., Weller, I., & Lactic Acidosis International Study Group (2011). Risk factors for fatality in HIV-infected patients with dideoxynucleoside-induced severe hyperlactataemia or lactic acidosis. Antiviral Therapy, 16(2), 219-26. https://doi.org/10.3851/IMP1732

Arenas-Pinto, A, Grant, A, Bhaskaran, K, Copas, A, Carr, A, Worm, SW, Martinez, E, Reiss, P, Dunn, D, Weber, R, Hoy, J, Weller, I & Lactic Acidosis International Study Group 2011, 'Risk factors for fatality in HIV-infected patients with dideoxynucleoside-induced severe hyperlactataemia or lactic acidosis', Antiviral Therapy, vol. 16, no. 2, pp. 219-26. https://doi.org/10.3851/IMP1732

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title = "Risk factors for fatality in HIV-infected patients with dideoxynucleoside-induced severe hyperlactataemia or lactic acidosis",

abstract = "Background: Lactic acidosis (LA) and severe hyperlactataemia (HL) are infrequent but serious complications of antiretroviral therapy that have been associated with a high fatality rate. Methods: In a multinational retrospective cohort study, LA was defined as arterial blood pH<7.35, bicarbonate <20 mmol/l and lactate above normal, and HL as confirmed blood lactate >5 mmol/l. Logistic regression was used to identify factors associated with fatality. Sensitivity and specificity of different case definitions as predictors of death were compared. Results: The overall case-fatality rate was 19/110 (17.3%), but among acidotic patients it was 33% (16/49 cases). There were 10 asymptomatic patients and none of them died as a consequence of the event. The median lactate for fatal, non-fatal and all patients was 8.3 mmol/l (IQR 7.2-13.1), 6.4 mmol/l (IQR 5.4-7.8) and 6.7 mmol/l (IQR 5.5-8.1), respectively. After adjusting for age and current CD4+ T-cell count, lactate >7 mmol/l (OR 6.27, 95% CI 1.13-34.93), blood bicarbonate <12 mmol/l (OR 10.02 relative to >18 mmol/l, 95% CI 1.33-75.65) and concurrent opportunistic infections (OR 8.69, 95% CI 1.45-52.22) were independently associated with case fatality. Blood lactate >7 mmol/l showed a sensitivity of 84% for fatality with a specificity of 60%, whereas bicarbonate <12 mmol/l showed a better specificity (85%) but a poorer sensitivity (42%). Bicarbonate <18 mmol/l appears to be as good as lactate <7 mmol/l at predicting death (sensitivity 90% and specificity 54%). Conclusions: Our data suggest that blood lactate >7 mmol/l and blood bicarbonate <18 mmol/l appear to predict death and might help clinicians in selecting patients who may benefit from more intense monitoring.",

author = "Alejandro Arenas-Pinto and Alison Grant and Krishnan Bhaskaran and Andrew Copas and Andrew Carr and Worm, {Signe W} and Esteban Martinez and Peter Reiss and David Dunn and Rainer Weber and Jennifer Hoy and Ian Weller and {Lactic Acidosis International Study Group}",

year = "2011",

month = jan,

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doi = "10.3851/IMP1732",

language = "English",

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journal = "Antiviral Therapy",

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TY - JOUR

T1 - Risk factors for fatality in HIV-infected patients with dideoxynucleoside-induced severe hyperlactataemia or lactic acidosis

AU - Arenas-Pinto, Alejandro

AU - Grant, Alison

AU - Bhaskaran, Krishnan

AU - Copas, Andrew

AU - Carr, Andrew

AU - Worm, Signe W

AU - Martinez, Esteban

AU - Reiss, Peter

AU - Dunn, David

AU - Weber, Rainer

AU - Hoy, Jennifer

AU - Weller, Ian

AU - Lactic Acidosis International Study Group

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Background: Lactic acidosis (LA) and severe hyperlactataemia (HL) are infrequent but serious complications of antiretroviral therapy that have been associated with a high fatality rate. Methods: In a multinational retrospective cohort study, LA was defined as arterial blood pH<7.35, bicarbonate <20 mmol/l and lactate above normal, and HL as confirmed blood lactate >5 mmol/l. Logistic regression was used to identify factors associated with fatality. Sensitivity and specificity of different case definitions as predictors of death were compared. Results: The overall case-fatality rate was 19/110 (17.3%), but among acidotic patients it was 33% (16/49 cases). There were 10 asymptomatic patients and none of them died as a consequence of the event. The median lactate for fatal, non-fatal and all patients was 8.3 mmol/l (IQR 7.2-13.1), 6.4 mmol/l (IQR 5.4-7.8) and 6.7 mmol/l (IQR 5.5-8.1), respectively. After adjusting for age and current CD4+ T-cell count, lactate >7 mmol/l (OR 6.27, 95% CI 1.13-34.93), blood bicarbonate <12 mmol/l (OR 10.02 relative to >18 mmol/l, 95% CI 1.33-75.65) and concurrent opportunistic infections (OR 8.69, 95% CI 1.45-52.22) were independently associated with case fatality. Blood lactate >7 mmol/l showed a sensitivity of 84% for fatality with a specificity of 60%, whereas bicarbonate <12 mmol/l showed a better specificity (85%) but a poorer sensitivity (42%). Bicarbonate <18 mmol/l appears to be as good as lactate <7 mmol/l at predicting death (sensitivity 90% and specificity 54%). Conclusions: Our data suggest that blood lactate >7 mmol/l and blood bicarbonate <18 mmol/l appear to predict death and might help clinicians in selecting patients who may benefit from more intense monitoring.

AB - Background: Lactic acidosis (LA) and severe hyperlactataemia (HL) are infrequent but serious complications of antiretroviral therapy that have been associated with a high fatality rate. Methods: In a multinational retrospective cohort study, LA was defined as arterial blood pH<7.35, bicarbonate <20 mmol/l and lactate above normal, and HL as confirmed blood lactate >5 mmol/l. Logistic regression was used to identify factors associated with fatality. Sensitivity and specificity of different case definitions as predictors of death were compared. Results: The overall case-fatality rate was 19/110 (17.3%), but among acidotic patients it was 33% (16/49 cases). There were 10 asymptomatic patients and none of them died as a consequence of the event. The median lactate for fatal, non-fatal and all patients was 8.3 mmol/l (IQR 7.2-13.1), 6.4 mmol/l (IQR 5.4-7.8) and 6.7 mmol/l (IQR 5.5-8.1), respectively. After adjusting for age and current CD4+ T-cell count, lactate >7 mmol/l (OR 6.27, 95% CI 1.13-34.93), blood bicarbonate <12 mmol/l (OR 10.02 relative to >18 mmol/l, 95% CI 1.33-75.65) and concurrent opportunistic infections (OR 8.69, 95% CI 1.45-52.22) were independently associated with case fatality. Blood lactate >7 mmol/l showed a sensitivity of 84% for fatality with a specificity of 60%, whereas bicarbonate <12 mmol/l showed a better specificity (85%) but a poorer sensitivity (42%). Bicarbonate <18 mmol/l appears to be as good as lactate <7 mmol/l at predicting death (sensitivity 90% and specificity 54%). Conclusions: Our data suggest that blood lactate >7 mmol/l and blood bicarbonate <18 mmol/l appear to predict death and might help clinicians in selecting patients who may benefit from more intense monitoring.

U2 - 10.3851/IMP1732

DO - 10.3851/IMP1732

M3 - Journal article

C2 - 21447871

SN - 1359-6535

VL - 16

SP - 219

EP - 226

JO - Antiviral Therapy

JF - Antiviral Therapy

IS - 2

ER -

Risk factors for fatality in HIV-infected patients with dideoxynucleoside-induced severe hyperlactataemia or lactic acidosis

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