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

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 pH5 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 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 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

Risk factors for lactic acidosis and severe hyperlactataemia in HIV-1-infected adults exposed to antiretroviral therapy.

BACKGROUND: Severe hyperlactataemia and lactic acidosis are rare serious complications of antiretroviral therapy (ART). METHODS: Lactic acidosis was defined as pH 5 mmol/l. The case-control study of 110 cases and 220 controls(two randomly selected from treated patients by centre and calendar year) from centres in 10 countries included 40 (36.4%) female cases and 40 female controls (18.2%) (P < 0.001). Median age was 42.4 years [interquartile range (IQR, 36.0-52.5] for cases and 40 (IQR, 35.0-47.1) for controls (P = 0.013). More cases were nonwhite (41.9%) than controls (31.2%) (P = 0.032). Cases had a shorter duration of exposure to dideoxynucleosides. RESULTS: After adjusting for age, gender and current CD4 cell count, hyperlactataemia/lactic acidosis remained associated with exposure to didanosine in every category of exposure duration but was most strongly associated with exposure < 12 months. In a separate multivariable model, apart from exposure to stavudine, didanosine, or even more strongly both, age above 40 years [odds ratio (OR), 2.6; 95% confidence interval (CI), 1.08-6.29], female gender (OR, 5.97; 95% CI, 1.92-18.5) and advanced immunosuppression were independent associations (CD4 cell count 200-349, 100-199 and < 100 cells/mul: OR, 3.89, 7.58 and 8.11, respectively). INTERPRETATION: Hyperlactataemia/lactic acidosis was associated with exposure to dideoxynucleosides, female gender, advanced immunosuppression and possibly ethnicity. This has important consequences for choice of ART in resource-limited settings. The association with shorter duration of exposure may support the hypothesis of susceptibility in a small proportion of patients