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

Background: Lactic acidosis (LA) and severe hyperlactataemia (HL) are infrequent but serious complications of antiretroviral therapy which 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 predictor 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 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 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%; specificity 54%). Conclusions: Our data suggest that a 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.