Red cell distribution width and mortality in acute heart failure patients with preserved and reduced ejection fraction.

Elevated red blood cell distribution width (RDW) is a valid predictor of outcome in acute heart failure (AHF). It is unknown whether elevated RDW remains predictive in AHF patients with either preserved left ventricular ejection fraction (LVEF) ≥50% or reduced LVEF (<50%). Prospective local registry including 402 consecutive hospitalized AHF patients without acute coronary syndrome or need of intensive care. The primary outcome was all-cause mortality (ACM) at 1 year after admission. Demographic and clinical data derive from admission, echocardiographic examinations (n = 269; 67%) from hospitalization. The Cox proportional hazard model including all patients (P < 0.001) was adjusted for age, gender, and RDW quartiles. Independent predictors of 1-year ACM were cardiogenic shock (HR 2.86; CI: 1.3-6.4), male sex (HR 1.9; CI: 1.2-2.9), high RDW quartile (HR 1.66; CI: 1.02-2.8), chronic HF (HR 1.61; CI: 1.05-2.5), valvular heart disease (HR 1.61; CI: 1.09-2.4), increased diastolic blood pressure (HR 1.02 per mmHg; CI: 1.01-1.03), increasing age (HR 1.04 by year; CI: 1.02-1.07), platelet count (HR 1.002 per G/l; CI: 1.0-1.004), systolic blood pressure (HR 0.99 per mmHg; CI: 0.98-0.99), and weight (HR 0.98 per kg; CI: 0.97-0.99). A total of 114 patients (28.4%) died within the first year; ACM of all patients increased with quartiles of rising RDW (χ(2) 18; P < 0.001). ACM was not different between RDW quartiles of patients with reduced LVEF (n = 153; χ(2) 6.6; P = 0.084). In AHF with LVEF ≥50% the probability of ACM increased with rising RDW (n = 116; χ(2) 9.9; P = 0.0195). High RDW is associated with increased ACM in AHF patients with preserved but not with reduced LVEF in this study population

Decreasing Proportion of Recent Infections among Newly Diagnosed HIV-1 Cases in Switzerland, 2008 to 2013 Based on Line-Immunoassay-Based Algorithms.

BACKGROUND: HIV surveillance requires monitoring of new HIV diagnoses and differentiation of incident and older infections. In 2008, Switzerland implemented a system for monitoring incident HIV infections based on the results of a line immunoassay (Inno-Lia) mandatorily conducted for HIV confirmation and type differentiation (HIV-1, HIV-2) of all newly diagnosed patients. Based on this system, we assessed the proportion of incident HIV infection among newly diagnosed cases in Switzerland during 2008-2013. METHODS AND RESULTS: Inno-Lia antibody reaction patterns recorded in anonymous HIV notifications to the federal health authority were classified by 10 published algorithms into incident (up to 12 months) or older infections. Utilizing these data, annual incident infection estimates were obtained in two ways, (i) based on the diagnostic performance of the algorithms and utilizing the relationship 'incident = true incident + false incident', (ii) based on the window-periods of the algorithms and utilizing the relationship 'Prevalence = Incidence x Duration'. From 2008-2013, 3'851 HIV notifications were received. Adult HIV-1 infections amounted to 3'809 cases, and 3'636 of them (95.5%) contained Inno-Lia data. Incident infection totals calculated were similar for the performance- and window-based methods, amounting on average to 1'755 (95% confidence interval, 1588-1923) and 1'790 cases (95% CI, 1679-1900), respectively. More than half of these were among men who had sex with men. Both methods showed a continuous decline of annual incident infections 2008-2013, totaling -59.5% and -50.2%, respectively. The decline of incident infections continued even in 2012, when a 15% increase in HIV notifications had been observed. This increase was entirely due to older infections. Overall declines 2008-2013 were of similar extent among the major transmission groups. CONCLUSIONS: Inno-Lia based incident HIV-1 infection surveillance proved useful and reliable. It represents a free, additional public health benefit of the use of this relatively costly test for HIV confirmation and type differentiation

Generation of a Recombinant Gag Virus-Like-Particle Panel for the Evaluation of p24 Antigen Detection by Diagnostic HIV Tests.

BACKGROUND: Detection of HIV-1 p24 antigen permits early identification of primary HIV infection and timely intervention to limit further spread of the infection. Principally, HIV screening should equally detect all viral variants, but reagents for a standardised test evaluation are limited. Therefore, we aimed to create an inexhaustible panel of diverse HIV-1 p24 antigens. METHODS: We generated a panel of 43 recombinantly expressed virus-like particles (VLPs), containing the structural Gag proteins of HIV-1 subtypes A-H and circulating recombinant forms (CRF) CRF01_AE, CRF02_AG, CRF12_BF, CRF20_BG and group O. Eleven 4th generation antigen/antibody tests and five antigen-only tests were evaluated for their ability to detect VLPs diluted in human plasma to p24 concentrations equivalent to 50, 10 and 2 IU/ml of the WHO p24 standard. Three tests were also evaluated for their ability to detect p24 after heat-denaturation for immune-complex disruption, a pre-requisite for ultrasensitive p24 detection. RESULTS: Our VLP panel exhibited an average intra-clade p24 diversity of 6.7%. Among the 4th generation tests, the Abbott Architect and Siemens Enzygnost Integral 4 had the highest sensitivity of 97.7% and 93%, respectively. Alere Determine Combo and BioRad Access were least sensitive with 10.1% and 40.3%, respectively. Antigen-only tests were slightly more sensitive than combination tests. Almost all tests detected the WHO HIV-1 p24 standard at a concentration of 2 IU/ml, but their ability to detect this input for different subtypes varied greatly. Heat-treatment lowered overall detectability of HIV-1 p24 in two of the three tests, but only few VLPs had a more than 3-fold loss in p24 detection. CONCLUSIONS: The HIV-1 Gag subtype panel has a broad diversity and proved useful for a standardised evaluation of the detection limit and breadth of subtype detection of p24 antigen-detecting tests. Several tests exhibited problems, particularly with non-B subtypes

The Role of Migration and Domestic Transmission in the Spread of HIV-1 Non-B Subtypes in Switzerland

Background. By analyzing human immunodeficiency virus type 1 (HIV-1) pol sequences from the Swiss HIV Cohort Study (SHCS), we explored whether the prevalence of non-B subtypes reflects domestic transmission or migration patterns. Methods. Swiss non-B sequences and sequences collected abroad were pooled to construct maximum likelihood trees, which were analyzed for Swiss-specific subepidemics, (subtrees including ≥80% Swiss sequences, bootstrap >70%; macroscale analysis) or evidence for domestic transmission (sequence pairs with genetic distance <1.5%, bootstrap ≥98%; microscale analysis). Results. Of 8287 SHCS participants, 1732 (21%) were infected with non-B subtypes, of which A (n = 328), C (n = 272), CRF01_AE (n = 258), and CRF02_AG (n = 285) were studied further. The macroscale analysis revealed that 21% (A), 16% (C), 24% (CRF01_AE), and 28% (CRF02_AG) belonged to Swiss-specific subepidemics. The microscale analysis identified 26 possible transmission pairs: 3 (12%) including only homosexual Swiss men of white ethnicity; 3 (12%) including homosexual white men from Switzerland and partners from foreign countries; and 10 (38%) involving heterosexual white Swiss men and females of different nationality and predominantly nonwhite ethnicity. Conclusions. Of all non-B infections diagnosed in Switzerland, <25% could be prevented by domestic interventions. Awareness should be raised among immigrants and Swiss individuals with partners from high prevalence countries to contain the spread of non-B subtype

Molecular Epidemiology Reveals Long-Term Changes in HIV Type 1 Subtype B Transmission in Switzerland

Background. Sequence data from resistance testing offer unique opportunities to characterize the structure of human immunodeficiency virus (HIV) infection epidemics. Methods. We analyzed a representative set of HIV type 1 (HIV-1) subtype B pol sequences from 5700 patients enrolled in the Swiss HIV Cohort Study. We pooled these sequences with the same number of sequences from foreign epidemics, inferred a phylogeny, and identified Swiss transmission clusters as clades having a minimal size of 10 and containing ⩾80% Swiss sequences. Results. More than one-half of Swiss patients were included within 60 transmission clusters. Most transmission clusters were significantly dominated by specific transmission routes, which were used to identify the following patient groups: men having sex with men (MSM) (38 transmission clusters; average cluster size, 29 patients) or patients acquiring HIV through heterosexual contact (HETs) and injection drug users (IDUs) (12 transmission clusters; average cluster size, 144 patients). Interestingly, there were no transmission clusters dominated by sequences from HETs only. Although 44% of all HETs who were infected between 1983 and 1986 clustered with injection drug users, this percentage decreased to 18% for 2003-2006 (P < .001), indicating a diminishing role of injection drug users in transmission among HETs over time. Conclusions. Our analysis suggests (1) the absence of a self-sustaining epidemic of HIV-1 subtype B in HETs in Switzerland and (2) a temporally decreasing clustering of HIV infections in HETs and IDU

Clustering of HCV coinfections on HIV phylogeny indicates domestic and sexual transmission of HCV

Background: HCV coinfection remains a major cause of morbidity and mortality among HIV-infected individuals and its incidence has increased dramatically in HIV-infected men who have sex with men(MSM). Methods: Hepatitis C virus (HCV) coinfection in the Swiss HIV Cohort Study(SHCS) was studied by combining clinical data with HIV-1 pol-sequences from the SHCS Drug Resistance Database(DRDB). We inferred maximum-likelihood phylogenetic trees, determined Swiss HIV-transmission pairs as monophyletic patient pairs, and then considered the distribution of HCV on those pairs. Results: Among the 9748 patients in the SHCS-DRDB with known HCV status, 2768(28%) were HCV-positive. Focusing on subtype B(7644 patients), we identified 1555 potential HIV-1 transmission pairs. There, we found that, even after controlling for transmission group, calendar year, age and sex, the odds for an HCV coinfection were increased by an odds ratio (OR) of 3.2 [95% confidence interval (CI) 2.2, 4.7) if a patient clustered with another HCV-positive case. This strong association persisted if transmission groups of intravenous drug users (IDUs), MSMs and heterosexuals (HETs) were considered separately(in all cases OR >2). Finally we found that HCV incidence was increased by a hazard ratio of 2.1 (1.1, 3.8) for individuals paired with an HCV-positive partner. Conclusions: Patients whose HIV virus is closely related to the HIV virus of HIV/HCV-coinfected patients have a higher risk for carrying or acquiring HCV themselves. This indicates the occurrence of domestic and sexual HCV transmission and allows the identification of patients with a high HCV-infection ris

Increased HIV Incidence in Men Who Have Sex with Men Despite High Levels of ART-Induced Viral Suppression: Analysis of an Extensively Documented Epidemic

Background: There is interest in expanding ART to prevent HIV transmission, but in the group with the highest levels of ART use, men-who-have-sex-with-men (MSM), numbers of new infections diagnosed each year have not decreased as ART coverage has increased for reasons which remain unclear. Methods: We analysed data on the HIV-epidemic in MSM in the UK from a range of sources using an individual-based simulation model. Model runs using parameter sets found to result in good model fit were used to infer changes in HIV-incidence and risk behaviour. Results: HIV-incidence has increased (estimated mean incidence 0.30/100 person-years 1990–1997, 0.45/100 py 1998–2010), associated with a modest (26%) rise in condomless sex. We also explored counter-factual scenarios: had ART not been introduced, but the rise in condomless sex had still occurred, then incidence 2006–2010 was 68% higher; a policy of ART initiation in all diagnosed with HIV from 2001 resulted in 32% lower incidence; had levels of HIV testing been higher (68% tested/year instead of 25%) incidence was 25% lower; a combination of higher testing and ART at diagnosis resulted in 62% lower incidence; cessation of all condom use in 2000 resulted in a 424% increase in incidence. In 2010, we estimate that undiagnosed men, the majority in primary infection, accounted for 82% of new infections. Conclusion: A rise in HIV-incidence has occurred in MSM in the UK despite an only modest increase in levels of condomless sex and high coverage of ART. ART has almost certainly exerted a limiting effect on incidence. Much higher rates of HIV testing combined with initiation of ART at diagnosis would be likely to lead to substantial reductions in HIV incidence. Increased condom use should be promoted to avoid the erosion of the benefits of ART and to prevent other serious sexually transmitted infections

Comparative Evaluation of Three Automated Systems for DNA Extraction in Conjunction with Three Commercially Available Real-Time PCR Assays for Quantitation of Plasma Cytomegalovirus DNAemia in Allogeneic Stem Cell Transplant Recipients▿

Limited data are available on the performance of different automated extraction platforms and commercially available quantitative real-time PCR (QRT-PCR) methods for the quantitation of cytomegalovirus (CMV) DNA in plasma. We compared the performance characteristics of the Abbott mSample preparation system DNA kit on the m24 SP instrument (Abbott), the High Pure viral nucleic acid kit on the COBAS AmpliPrep system (Roche), and the EZ1 Virus 2.0 kit on the BioRobot EZ1 extraction platform (Qiagen) coupled with the Abbott CMV PCR kit, the LightCycler CMV Quant kit (Roche), and the Q-CMV complete kit (Nanogen), for both plasma specimens from allogeneic stem cell transplant (Allo-SCT) recipients (n = 42) and the OptiQuant CMV DNA panel (AcroMetrix). The EZ1 system displayed the highest extraction efficiency over a wide range of CMV plasma DNA loads, followed by the m24 and the AmpliPrep methods. The Nanogen PCR assay yielded higher mean CMV plasma DNA values than the Abbott and the Roche PCR assays, regardless of the platform used for DNA extraction. Overall, the effects of the extraction method and the QRT-PCR used on CMV plasma DNA load measurements were less pronounced for specimens with high CMV DNA content (>10,000 copies/ml). The performance characteristics of the extraction methods and QRT-PCR assays evaluated herein for clinical samples were extensible at cell-based standards from AcroMetrix. In conclusion, different automated systems are not equally efficient for CMV DNA extraction from plasma specimens, and the plasma CMV DNA loads measured by commercially available QRT-PCRs can differ significantly. The above findings should be taken into consideration for the establishment of cutoff values for the initiation or cessation of preemptive antiviral therapies and for the interpretation of data from clinical studies in the Allo-SCT setting