One-year mortality of HIV-positive patients treated for rifampicin- and isoniazid- susceptible tuberculosis in Eastern Europe, Western Europe and Latin America

OBJECTIVES: The high mortality among HIV/tuberculosis (TB) coinfected patients in Eastern Europe is partly explained by the high prevalence of drug-resistant TB. It remains unclear whether outcomes of HIV/TB patients with rifampicin/isoniazid-susceptible TB in Eastern Europe differ from those in Western Europe or Latin America. METHODS: One-year mortality of HIV-positive patients with rifampicin/isoniazid-susceptible TB in Eastern Europe, Western Europe, and Latin America was analysed and compared in a prospective observational cohort study. Factors associated with death were analysed using Cox regression modelsRESULTS:: Three hundred and forty-one patients were included (Eastern Europe 127, Western Europe 165, Latin America 49). Proportions of patients with disseminated TB (50, 58, 59%) and initiating rifampicin + isoniazid + pyrazinamide-based treatment (93, 94, 94%) were similar in Eastern Europe, Western Europe, and Latin America respectively, whereas receipt of antiretroviral therapy at baseline and after 12 months was lower in Eastern Europe (17, 39, 39%, and 69, 94, 89%). The 1-year probability of death was 16% (95% confidence interval 11-24%) in Eastern Europe, vs. 4% (2-9%) in Western Europe and 9% (3-21%) in Latin America; P < 0.0001. After adjustment for IDU, CD4 cell count and receipt of antiretroviral therapy, those residing in Eastern Europe were at nearly 3-fold increased risk of death compared with those in Western Europe/Latin America (aHR 2.79 (1.15-6.76); P = 0.023). CONCLUSIONS: Despite comparable use of recommended anti-TB treatment, mortality of patients with rifampicin/isoniazid-susceptible TB remained higher in Eastern Europe when compared with Western Europe/Latin America. The high mortality in Eastern Europe was only partially explained by IDU, use of ART and CD4 cell count. These results call for improvement of care for TB/HIV patients in Eastern Europe

Enterococcus faecalis bacteremia: please do the echo

Infective endocarditis (IE) caused by Enterococcus faecalis (E. faecalis) is a disease of the elderly with an increasing incidence, often health-care associated and with in-hospital mortality rates around 10-20%. E. faecalis IE is notoriously challenging to diagnose due to unspecific symptoms, often presenting with a complex clinical picture with low-grade fever and only moderately elevated infectious parameters. In a newly published prospective multicenter study using echocardiography to screen E. faecalis bacteremia patients, we found an IE prevalence as high as 26%. The 344 included patients with E. faecalis bacteremia had a mean age of 74 (±12) years confirming that it is indeed a disease of the elderly. The key feature of the study was that echocardiography was performed in all patients including transesophageal echocardiography (TEE) in 74%. Transthoracic echocardiography (TTE) missed vegetations in half of the cases where TEE demonstrated vegetations, underlining the importance of TEE

Baseline genotype testing to assess drug resistance before beginning HIV treatment

To the Edito

Comparative effectiveness of immediate antiretroviral therapy versus CD4-based initiation in HIV-positive individuals in high-income countries:observational cohort study

Background Recommendations have differed nationally and internationally with respect to the best time to start antiretroviral therapy (ART). We compared effectiveness of three strategies for initiation of ART in high-income countries for HIV-positive individuals who do not have AIDS: immediate initiation, initiation at a CD4 count less than 500 cells per mu L, and initiation at a CD4 count less than 350 cells per mu L. Methods We used data from the HIV-CAUSAL Collaboration of cohort studies in Europe and the USA. We included 55 826 individuals aged 18 years or older who were diagnosed with HIV-1 infection between January, 2000, and September, 2013, had not started ART, did not have AIDS, and had CD4 count and HIV-RNA viral load measurements within 6 months of HIV diagnosis. We estimated relative risks of death and of death or AIDS-defining illness, mean survival time, the proportion of individuals in need of ART, and the proportion of individuals with HIV-RNA viral load less than 50 copies per mL, as would have been recorded under each ART initiation strategy after 7 years of HIV diagnosis. We used the parametric g-formula to adjust for baseline and time-varying confounders. Findings Median CD4 count at diagnosis of HIV infection was 376 cells per mu L (IQR 222-551). Compared with immediate initiation, the estimated relative risk of death was 1.02 (95% CI 1.01-1.02) when ART was started at a CD4 count less than 500 cells per mu L, and 1.06 (1.04-1.08) with initiation at a CD4 count less than 350 cells per mu L. Corresponding estimates for death or AIDS-defining illness were 1.06 (1.06-1.07) and 1.20 (1.17-1.23), respectively. Compared with immediate initiation, the mean survival time at 7 years with a strategy of initiation at a CD4 count less than 500 cells per mu L was 2 days shorter (95% CI 1-2) and at a CD4 count less than 350 cells per mu L was 5 days shorter (4-6). 7 years after diagnosis of HIV, 100%, 98.7% (95% CI 98.6-98.7), and 92.6% (92.2-92.9) of individuals would have been in need of ART with immediate initiation, initiation at a CD4 count less than 500 cells per mu L, and initiation at a CD4 count less than 350 cells per mu L, respectively. Corresponding proportions of individuals with HIV-RNA viral load less than 50 copies per mL at 7 years were 87.3% (87.3-88.6), 87.4% (87.4-88.6), and 83.8% (83.6-84.9). Interpretation The benefits of immediate initiation of ART, such as prolonged survival and AIDS-free survival and increased virological suppression, were small in this high-income setting with relatively low CD4 count at HIV diagnosis. The estimated beneficial effect on AIDS is less than in recently reported randomised trials. Increasing rates of HIV testing might be as important as a policy of early initiation of ART

Infeccions bacterianes i fungiques en adictes a drogues per via parenteral

L'addicció a drogues per via parenteral i les seves complicacions mèdiques constitueixen en el nostre país un problema real i greu. Avui dia no sorprén a ningú que els mitjans de difusio social i les revistes mèdiques nacionals es facin ressó, quasi cada dia, d'algun deis múltiples problemes relacionats amb la drogaaddicció, com poden ser la mort d'heroínomans per sobredosi o la descripció de complicacions infeccioses greus. Hi han alguns hospitals urbans els addictes a drogues per via parenteral (ADVP) representen un percentatge important del total de consultes en els Serveis d'Urgències i del total d'ingresos, sobretot en determinades Àrees Mèdiques com Unitats de Cures Intensives o Serveis d'Infeccions. El motiu de la consulta van des de la recerca d'un tractament per a la seva dependència física o psíquica fins a l'aparició de complicacions infeccioses greus o Taturada cardio-respiratòria per sobredosi. Quasi sense haver-nos-en adonat ens trobem davant d'una vertadera 'epidèmia', de gran magnitud i que tendeix a augmentar, les conseqüéncies socials i sanitàries de la qual son difícils de preveure

Reply to Head and Keynan

We thank Keynan et al. for their interest in and comments on our work. They make several noteworthy points. Although community-acquired pneumonia (CAP) is frequently described as the most prevalent pulmonary infection in human immunodeficiency virus (HIV)-infected patients following pneumocystis and tuberculosis, it is well known that the prevalence of these 3 pulmonary infections varies with geographic region. In Spain, the geographical area of our study, Legionella pneumophila is the third most frequent cause of CAP in HIV-infected patients, requiring hospitalization after pneumococcal and viral pneumoni

Colorectal Adenomas

Carta a l'editor com a resposta al document: https://doi.org/10.1056/NEJMra1513581In his review article, Strum (March 17 issue)1 provides data on the overall prevalence of colorectal adenomas in the United States and risk factors for these lesions. It is well established that patients with Streptococcus bovis–group infective endocarditis are at high risk for colorectal cancer.2 Although a strong relationship between Enterococcus faecalis endocarditis and colorectal adenomas is suspected, robust data are lacking

Regional differences in AIDS and non-AIDS related mortality in HIV-positive individuals across Europe and Argentina: the EuroSIDA study

BACKGROUND Differences in access to care and treatment have been reported in Eastern Europe, a region with one of the fastest growing HIV epidemics, compared to the rest of Europe. This analysis aimed to establish whether there are regional differences in the mortality rate of HIV-positive individuals across Europe, and Argentina. METHODS 13,310 individuals under follow-up were included in the analysis. Poisson regression investigated factors associated with the risk of death. FINDINGS During 82,212 person years of follow-up (PYFU) 1,147 individuals died (mortality rate 14.0 per 1,000 PYFU (95% confidence interval [CI] 13.1-14.8). Significant differences between regions were seen in the rate of all-cause, AIDS and non-AIDS related mortality (global p<0.0001 for all three endpoints). Compared to South Europe, after adjusting for baseline demographics, laboratory measurements and treatment, a higher rate of AIDS related mortality was observed in East Europe (IRR 2.90, 95%CI 1.97-4.28, p<.0001), and a higher rate of non-AIDS related mortality in North Europe (IRR 1.51, 95%CI 1.24-1.82, p<.0001). The differences observed in North Europe decreased over calendar-time, in 2009-2011, the higher rate of non-AIDS related mortality was no longer significantly different to South Europe (IRR 1.07, 95%CI 0.66-1.75, p = 0.77). However, in 2009-2011, there remained a higher rate of AIDS-related mortality (IRR 2.41, 95%CI 1.11-5.25, p = 0.02) in East Europe compared to South Europe in adjusted analysis. INTERPRETATIONS There are significant differences in the rate of all-cause mortality among HIV-positive individuals across different regions of Europe and Argentina. Individuals in Eastern Europe had an increased risk of mortality from AIDS related causes and individuals in North Europe had the highest rate of non-AIDS related mortality. These findings are important for understanding and reviewing HIV treatment strategies and policies across the European region

Comparison of the design and methodology of Phase 3 clinical trials of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and dolutegravir-based dual therapy (DTG) in HIV: a systematic review of the literature

Introduction: Current recommended antiretroviral regimens include a combination of two (dual; DT) or three (triple; TT) antiretroviral drugs. This study aims to determine whether the quality of evidence from clinical trials of dolutegravir (dolutegravir/lamivudine [DTG/3TC] or dolutegravir/rilpivirine [DTG/RPV]) is methodologically comparable to that of clinical trials conducted with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Areas covered: A systematic review of the medical literature was carried out in PubMed without date or language restrictions, following the PRISMA guidelines. All aspects of the methodological design of phase 3 randomized clinical trials (RCTs) of DT and TT, evaluated by the European Medicines Agency (registration trials), were reviewed. The quality of clinical trials was assessed using the Jadad scale. Expert opinion: The search identified 5, 3 and 2 phase 3 RCTs with BIC/FTC/TAF, DTG/3TC and DTG/RPV, respectively, that met the inclusion criteria. The designs would not be comparable due to differences in pre-randomization losses, blinding, patient recruitment, as well as differences in methodological quality, with the average score of the RCTs conducted with BIC/FTC/TAF, DTG/3TC and DTG/RPV being 4.2 (high quality), 3.0 (medium quality) and 3.0 (medium quality), respectively. Due to methodological differences between the BIC/FTC/TAF, DTG/3TC and DTG/RPV RCTs, the results of these are not comparable

Incidence and predictors of immune reconstitution inflammatory syndrome in a rural area of Mozambique.

There is limited data on the epidemiology of Immune Reconstitution Inflammatory Syndrome (IRIS) in rural sub-Saharan Africa. A prospective observational cohort study was conducted to assess the incidence, clinical characteristics, outcome and predictors of IRIS in rural Mozambique