Incidence of tuberculosis among HIV-infected patients receiving highly active antiretroviral therapy in Europe and North America

Background. We obtained estimates of the incidence of tuberculosis (TB) among patients receiving HAART and identified determinants of the incidence. Methods. We analyzed the incidence of TB during the first 3 years after initiation of HAART among 17,142 treatment-naive, AIDS- free persons starting HAART who were enrolled in 12 cohorts from Europe and North America. We used univariable and multivariable Poisson regression models to identify factors associated with the incidence. Results. During the first 3 years (36,906 person-years), 173 patients developed TB (incidence, 4.69 cases per 1000 person-years). In multivariable analysis, the incidence rate was lower for men who have sex with men, compared with injection drug users (relative rate, 2.46; 95% confidence interval [CI], 1.51-4.01), heterosexuals (relative rate, 2.42; 95% CI, 1.64-3.59), those with other suspected modes of transmission (relative rate, 1.66; 95% CI, 0.91-3.06), and those with a higher CD4(+) count at the time of HAART initiation (relative rate per log(2) cells/mL, 0.87; 95% CI, 0.84-0.91). During 28,846 person-years of follow-up after the first 6 months of HAART, 88 patients developed TB (incidence, 3.1 cases per 1000 person-years of follow-up). In multivariable analyses, a low baseline CD4(+) count (relative rate per log(2) cells/mL, 0.89; 95% CI, 0.83-0.96), 6-month CD4(+) count (relative rate per log(2) cells/mL, 0.90; 95% CI, 0.81-0.99), and a 6-month HIV RNA level 1400 copies/mL (relative rate, 2.21; 95% CI, 1.33-3.67) were significantly associated with the risk of acquiring TB after 6 months of HAART. Conclusion. The level of immunodeficiency at which HAART is initiated and the response to HAART are important determinants of the risk of TB. However, this risk remains appreciable even among those with a good response to HAART, suggesting that other interventions may be needed to control the TB epidemic in the HIV-infected population

Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal.

Abstract Background—The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)–defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. Methods—We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of anti-retroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together to form a “rare ADEs” category. Results—During a median follow-up period of 43 months (interquartile range, 19–70 months), 2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non- Hodgkin’s lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84–22.35) and progressive multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70–14.92). Three groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped confidence intervals: severe (non-Hodgkin’s lymphoma and progressive multifocal leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55–9.48]), moderate (cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76–3.13]), and mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08–2.00]). Conclusions—In the combination antiretroviral therapy era, mortality rates subsequent to an ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in clinical end point trials, prognostic studies, and patient management

Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy: not all AIDS-defining conditions are created equal

Abstract Background—The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)–defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. Methods—We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of anti-retroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together to form a “rare ADEs” category. Results—During a median follow-up period of 43 months (interquartile range, 19–70 months), 2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non- Hodgkin’s lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84–22.35) and progressive multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70–14.92). Three groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped confidence intervals: severe (non-Hodgkin’s lymphoma and progressive multifocal leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55–9.48]), moderate (cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76–3.13]), and mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08–2.00]). Conclusions—In the combination antiretroviral therapy era, mortality rates subsequent to an ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in clinical end point trials, prognostic studies, and patient management

Mortality after surgery in Europe: a 7 day cohort study

Background: Clinical outcomes after major surgery are poorly described at the national level. Evidence of heterogeneity between hospitals and health-care systems suggests potential to improve care for patients but this potential remains unconfirmed. The European Surgical Outcomes Study was an international study designed to assess outcomes after non-cardiac surgery in Europe.Methods: We did this 7 day cohort study between April 4 and April 11, 2011. We collected data describing consecutive patients aged 16 years and older undergoing inpatient non-cardiac surgery in 498 hospitals across 28 European nations. Patients were followed up for a maximum of 60 days. The primary endpoint was in-hospital mortality. Secondary outcome measures were duration of hospital stay and admission to critical care. We used χ² and Fisher’s exact tests to compare categorical variables and the t test or the Mann-Whitney U test to compare continuous variables. Significance was set at p&lt;0·05. We constructed multilevel logistic regression models to adjust for the differences in mortality rates between countries.Findings: We included 46 539 patients, of whom 1855 (4%) died before hospital discharge. 3599 (8%) patients were admitted to critical care after surgery with a median length of stay of 1·2 days (IQR 0·9–3·6). 1358 (73%) patients who died were not admitted to critical care at any stage after surgery. Crude mortality rates varied widely between countries (from 1·2% [95% CI 0·0–3·0] for Iceland to 21·5% [16·9–26·2] for Latvia). After adjustment for confounding variables, important differences remained between countries when compared with the UK, the country with the largest dataset (OR range from 0·44 [95% CI 0·19 1·05; p=0·06] for Finland to 6·92 [2·37–20·27; p=0·0004] for Poland).Interpretation: The mortality rate for patients undergoing inpatient non-cardiac surgery was higher than anticipated. Variations in mortality between countries suggest the need for national and international strategies to improve care for this group of patients.Funding: European Society of Intensive Care Medicine, European Society of Anaesthesiology