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

Management of Patients with Chronic Hepatitis B Before and After Liver Transplantation: An Update

The use of newer and more potent antiviral agents against hepatitis B virus (HBV) results in greater viral suppression; however, liver transplantation is still required for complications of HBV infection. Post-transplant outcomes for HBV-related disorders are currently comparable to or slightly better than for other indications for liver transplantation in adults in the United States. In the absence of prophylactic antiviral therapy, recurrent HBV infection occurs invariably in patients with detectable serum HBV-deoxyribonucleic acid (DNA) at the time of transplantation, leading to poorer outcomes with severe graft injury, reduced patient and allograft survival. Therefore, anti-HBV therapy is indicated in all patients with detectable serum HBV-DNA pre-transplantation and prophylactic therapy to prevent recurrent HBV infection is standard-of-care. This review summarizes available evidence for the use of different antiviral agents before liver transplantation, the effectiveness of prophylactic agents in preventing recurrent HBV infection post-liver transplantation, and the efficacy of several regimens for treating recurrent HBV infection post-liver transplantation