Estimating Trends in the Proportion of Transmitted and Acquired HIV Drug Resistance in a Long Term Observational Cohort in Germany

Objective: We assessed trends in the proportion of transmitted (TDR) and acquired (ADR) HIV drug resistance and associated mutations between 2001 and 2011 in the German ClinSurv-HIV Drug Resistance Study. Method: The German ClinSurv-HIV Drug Resistance Study is a subset of the German ClinSurv-HIV Cohort. For the ClinSurv-HIV Drug Resistance Study all available sequences isolated from patients in five study centres of the long term observational ClinSurv-HIV Cohort were included. TDR was estimated using the first viral sequence of antiretroviral treatment (ART) naive patients. One HIV sequence/patient/year of ART experienced patients was considered to estimate the proportion of ADR. Trends in the proportion of HIV drug resistance were calculated by logistic regression. Results: 9,528 patients were included into the analysis. HIV-sequences of antiretroviral naive and treatment experienced patients were available from 34% (3,267/9,528) of patients. The proportion of TDR over time was stable at 10.4% (95% CI 9.1-11.8; p (for trend)=0.6; 2001-2011). The proportion of ADR among all treated patients was 16%, whereas it was high among those with available HIV genotypic resistance test (64%; 1,310/2,049 sequences; 95% CI 62-66) but declined significantly over time (OR 0.8; 95% CI 0.77-0.83; p (for trend)<0.001; 2001-2011). Viral load monitoring subsequent to resistance testing was performed in the majority of treated patients (96%) and most of them (67%) were treated successfully. Conclusions: The proportion of TDR was stable in this study population. ADR declined significantly over time. This decline might have been influenced by broader resistance testing, resistance test guided therapy and the availability of more therapeutic options and not by a decline in the proportion of TDR within the study population

an evaluation of data sources to determine the number of people living with HIV who are receiving antiretroviral therapy in Germany

Background This study aimed to determine the number of people living with HIV receiving antiretroviral therapy (ART) between 2006 and 2013 in Germany by using the available numbers of antiretroviral drug prescriptions and treatment data from the ClinSurv HIV cohort (CSH). Methods The CSH is a multi-centre, open, long-term observational cohort study with an average number of 10.400 patients in the study period 2006–2013. ART has been documented on average for 86% of those CSH patients and medication history is well documented in the CSH. The antiretroviral prescription data (APD) are reported by billing centres for pharmacies covering >99% of nationwide pharmacy sales of all individuals with statutory health insurance (SHI) in Germany (~85%). Exactly one thiacytidine-containing medication (TCM) with either emtricitabine or lamivudine is present in all antiretroviral fixed-dose combinations (FDCs). Thus, each daily dose of TCM documented in the APD is presumed to be representative of one person per day receiving ART. The proportion of non-TCM regimen days in the CSH was used to determine the corresponding number of individuals in the APD. Results The proportion of CSH patients receiving TCMs increased continuously over time (from 85% to 93%; 2006–2013). In contrast, treatment interruptions declined remarkably (from 11% to 2%; 2006–2013). The total number of HIV-infected people with ART experience in Germany increased from 31,500 (95% CI 31,000-32,000) individuals to 54,000 (95% CI 53,000-55,500) over the observation period (including 16.3% without SHI and persons who had interrupted ART). An average increase of approximately 2,900 persons receiving ART was observed annually in Germany. Conclusions A substantial increase in the number of people receiving ART was observed from 2006 to 2013 in Germany. Currently, the majority (93%) of antiretroviral regimens in the CSH included TCMs with ongoing use of FDCs. Based on these results, the future number of people receiving ART could be estimated by exclusively using TCM prescriptions, assuming that treatment guidelines will not change with respect to TCM use in ART regimens

Calculation of Direct Antiretroviral Treatment Costs and Potential Cost Savings by Using Generics in the German HIV ClinSurv Cohort

BACKGROUND/AIM OF THE STUDY: The study aimed to determine the cost impacts of antiretroviral drugs by analysing a long-term follow-up of direct costs for combined antiretroviral therapy, cART, -regimens in the nationwide long-term observational multi-centre German HIV ClinSurv Cohort. The second aim was to develop potential cost saving strategies by modelling different treatment scenarios. Antiretroviral regimens (ART) from 10,190 HIV-infected patients from 11 participating ClinSurv study centres have been investigated since 1996. Biannual data cART-initiation, cART-changes, surrogate markers, clinical events and the Centre of Disease Control- (CDC)-stage of HIV disease are reported. Treatment duration was calculated on a daily basis via the documented dates for the beginning and end of each antiretroviral drug treatment. Prices were calculated for each individual regimen based on actual office sales prices of the branded pharmaceuticals distributed by the license holder including German taxes. During the 13-year follow-up period, 21,387,427 treatment days were covered. Cumulative direct costs for antiretroviral drugs of €812,877,356 were determined according to an average of €42.08 per day (€7.52 to € 217.70). Since cART is widely used in Germany, the costs for an entire regimen increased by 13.5%. Regimens are more expensive in the advanced stages of HIV disease. The potential for cost savings was calculated using non-nucleotide-reverse-transcriptase-inhibitor, NNRTI, more frequently instead of ritonavir-boosted protease inhibitor, PI/r, in first line therapy. This calculation revealed cumulative savings of 10.9% to 19.8% of daily treatment costs (50% and 90% substitution of PI/r, respectively). Substituting certain branded drugs by generic drugs showed potential cost savings of between 1.6% and 31.8%. Analysis of the data of this nationwide study reflects disease-specific health services research and will give insights into the cost impacts of antiretroviral therapy, and might allow a more rational allocation of resources within the German health care system

Money: A Market Microstructure Approach

The current discussion about the future of the financial system draws heavily on a set of theories known as the ‘New Monetary Economics’. The New Monetary Economics predicts that deregulation and financial innovation will lead to a moneyless world. This paper uses a market microstructure approach to show that a common medium of exchange that serves as unit of account will remain a necessary instrument to reduce transaction costs. This finding is supported by empirical evidence from foreign exchange markets

Transverse-Momentum Dependence of the J/psi Nuclear Modification in d+Au Collisions at sqrt(s_NN)=200 GeV

We present measured J/psi production rates in d+Au collisions at sqrt(s_NN) = 200 GeV over a broad range of transverse momentum (p_T=0-14 GeV/c) and rapidity (-2.2<y<2.2). We construct the nuclear-modification factor R_dAu for these kinematics and as a function of collision centrality (related to impact parameter for the R_dAu collision). We find that the modification is largest for collisions with small impact parameters, and observe a suppression (R_dAu<1) for p_T<4 GeV/c at positive rapidities. At negative rapidity we observe a suppression for p_T1) for p_T>2 GeV/c. The observed enhancement at negative rapidity has implications for the observed modification in heavy-ion collisions at high p_T.Comment: 384 authors, 24 pages, 19 figures, 13 tables. Submitted to Phys. Rev. C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are publicly available at http://www.phenix.bnl.gov/phenix/WWW/info/data/ppg123_data.htm

Cold Nuclear Matter Effects on J/psi Yields as a Function of Rapidity and Nuclear Geometry in Deuteron-Gold Collisions at sqrt(s_NN) = 200 GeV

We present measurements of J/psi yields in d+Au collisions at sqrt(s_NN) = 200 GeV recorded by the PHENIX experiment and compare with yields in p+p collisions at the same energy per nucleon-nucleon collision. The measurements cover a large kinematic range in J/psi rapidity (-2.2 < y < 2.4) with high statistical precision and are compared with two theoretical models: one with nuclear shadowing combined with final state breakup and one with coherent gluon saturation effects. To remove model dependent systematic uncertainties we also compare the data to a simple geometric model. We find that calculations where the nuclear modification is linear or exponential in the density weighted longitudinal thickness are difficult to reconcile with the forward rapidity data.Comment: 449 authors from 66 institutions, 6 pages, 3 figures. Submitted to Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Cross-realm assessment of climate change impacts on species' abundance trends

Climate change, land-use change, pollution and exploitation are among the main drivers of species' population trends; however, their relative importance is much debated. We used a unique collection of over 1,000 local population time series in 22 communities across terrestrial, freshwater and marine realms within central Europe to compare the impacts of long-term temperature change and other environmental drivers from 1980 onwards. To disentangle different drivers, we related species' population trends to species- and driver-specific attributes, such as temperature and habitat preference or pollution tolerance. We found a consistent impact of temperature change on the local abundances of terrestrial species. Populations of warm-dwelling species increased more than those of cold-dwelling species. In contrast, impacts of temperature change on aquatic species' abundances were variable. Effects of temperature preference were more consistent in terrestrial communities than effects of habitat preference, suggesting that the impacts of temperature change have become widespread for recent changes in abundance within many terrestrial communities of central Europe.Additionally, we appreciate the open access marine data provided by the International Council for the Exploration of the Sea. We thank the following scientists for taxonomic or technical advice: C. Brendel, T. Caprano, R. Claus, K. Desender, A. Flakus, P. R. Flakus, S. Fritz, E.-M. Gerstner, J.-P. Maelfait, E.-L. Neuschulz, S. Pauls, C. Printzen, I. Schmitt and H. Turin, and I. Bartomeus for comments on a previous version of the manuscript. R.A. was supported by the EUproject LIMNOTIP funded under the seventh European Commission Framework Programme (FP7) ERA-Net Scheme (Biodiversa, 01LC1207A) and the long-term ecological research program at the Leibniz-Institute of Freshwater Ecology and Inland Fisheries (IGB). R.W.B. was supported by the Scottish Government Rural and Environment Science and Analytical Services Division (RESAS) through Theme 3 of their Strategic Research Programme. S.D. acknowledges support of the German Research Foundation DFG (grant DO 1880/1-1). S.S. acknowledges the support from the FP7 project EU BON (grant no. 308454). S.K., I.Kü. and O.S. acknowledge funding thorough the Helmholtz Association’s Programme Oriented Funding, Topic ‘Land use, biodiversity, and ecosystem services: Sustaining human livelihoods’. O.S. also acknowledges the support from FP7 via the Integrated Project STEP (grant no. 244090). D.E.B. was funded by a Landes–Offensive zur Entwicklung Wissenschaftlich–ökonomischer Exzellenz (LOEWE) excellence initiative of the Hessian Ministry for Science and the Arts and the German Research Foundation (DFG: Grant no. BO 1221/23-1).Peer Reviewe

Genome-wide linkage screen for testicular germ cell tumour susceptibility loci

A family history of disease is a strong risk factor for testicular germ cell tumour (TGCT). In order to identify the location of putative TGCT susceptibility gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an average inter-marker distance of 10 cM. An additional 58 pedigrees were used to more intensively investigate several genomic regions of interest. Genetic linkage analysis was performed with the ALLEGRO software using two model-based parametric analyses and a non-parametric analysis. Six genomic regions on chromosomes 2p23, 3p12, 3q26, 12p13-q21, 18q21-q23 and Xq27 showed heterogeneity LOD (HLOD) scores of greater than 1, with a maximum HLOD of 1.94 at 3q26. Genome-wide simulation studies indicate that the observed number of HLOD peaks greater than one does not differ significantly from that expected by chance. A TGCT locus at Xq27 has been previously reported. Of the 237 pedigrees examined in this study, 66 were previously unstudied at Xq27, no evidence for linkage to this region was observed in this new pedigree set. Overall, the results indicate that no single major locus can account for the majority of the familial aggregation of TGCT, and suggests that multiple susceptibility loci with weak effects contribute to the diseas