Randomized, crossover, double-blind, placebo-controlled trial to assess the lipid lowering effect of co-formulated TDF/FTC

Abstract INTRODUCTION: Previous studies have described improvements on lipid parameters when switching from other antiretroviral drugs to tenofovir (TDF) and impairments in lipid profile when discontinuing TDF. [1-3] It is unknown, however, if TDF has an intrinsic lipid-lowering effect or such findings are due to the addition or removal of other offending agents or other reasons. MATERIALS AND METHODS: RESULTS: 46 subjects with a median age of 43 (40-48) years were enrolled in the study: 70% were male, 56% received DRV/r and 44% LPV/r. One subject withdrew the study voluntarily at week 4 and another one interrupted due to diarrhoea at week 24. Treatment with TDF/FTC decreased total, LDL and HDL-cholesterol from 235.9 to 204.9 (p<0.001), 154.7 to 127.6 (p<0.001) and 50.3 to 44.5 mg/dL (p<0.001), respectively. In comparison, total, LDL and HDL-cholesterol levels remained stable during placebo exposure. Week 12 total cholesterol (p<0.001), LDL-cholesterol (p<0.001) and HDL-cholesterol (p=0.011) levels were significantly lower in TDF/FTC versus placebo. Treatment with TDF/FTC reduced the fraction of subjects with abnormal fasting total-cholesterol (≥200 mg/dL) from 86.7% to 56.8% (p=0.001) and LDL-cholesterol (≥130 mg/dL) from 87.8% to 43.9% (p<0.001), which was not observed with placebo. There were no virological failures, and CD4 and triglyceride levels remained stable regardless of exposure. CONCLUSION: Coformulated TDF/FTC has an intrinsic lipid-lowering effect, likely attributable to TDF.

Different Plasma Markers of Inflammation Are Influenced by Immune Recovery and cART Composition or Intensification in Treated HIV Infected Individuals

Abstract Background HIV-1 infection increases plasma levels of inflammatory markers. Combination antiretroviral therapy (cART) does not restore inflammatory markers to normal levels. Since intensification of cART with raltegravir reduced CD8 T-cell activation in the Discor-Ral and IntegRal studies, we have evaluated the effect of raltegravir intensification on several soluble inflammation markers in these studies. Methods Longitudinal plasma samples (0–48 weeks) from the IntegRal (n = 67, 22 control and 45 intensified individuals) and the Discor-Ral studies (44 individuals with CD4 T-cell counts<350 cells/µl, 14 control and 30 intensified) were assayed for 25 markers. Mann-Whitney, Wilcoxon, Spearman test and linear mixed models were used for analysis. Results At baseline, different inflammatory markers were strongly associated with HCV co-infection, lower CD4 counts and with cART regimens (being higher in PI-treated individuals), but poorly correlated with detection of markers of residual viral replication. Although raltegravir intensification reduced inflammation in individuals with lower CD4 T-cell counts, no effect of intensification was observed on plasma markers of inflammation in a global analysis. An association was found, however, between reductions in immune activation and plasma levels of the coagulation marker D-dimer, which exclusively decreased in intensified patients on protease inhibitor (PI)-based cART regimens (P = 0.040). Conclusions The inflammatory profile in treated HIV-infected individuals showed a complex association with HCV co-infection, the levels of CD4 T cells and the cART regimen. Raltegravir intensification specifically reduced D-dimer levels in PI-treated patients, highlighting the link between cART composition and residual viral replication; however, raltegravir had little effect on other inflammatory markers.

Exposición bibliográfica americanista: selección de los fondos de la Biblioteca Universitaria de Barcelona

La presente exposición no pretende ofrecer un conjunto, como colección de rarezas ni un material que cubra bibliograficamente un tema o período; se limita o presentar una simple muestra de los fondos americanistas antiguos que posee uno biblioteca universitaria, en este caso la de nuestra Universidad de Barcelona. La labor desarrollada por los focultativos de esta biblioteca, Sras. Rubio y Torroja, al seleccionar el material, según las pautas dadas por su director y la osesoría de lo Cátedra de Historio de América, cumplen el propósito que señalamos.

Searching for consensus in ahp-group decision making. A bayesian perspective

This paper sets out to identify the initial positions of the different decisionmakers who intervene in a group decision making process with a reducednumber of actors, and to establish possible consensus paths between theseactors. As a methodological support, it employs one of the most widely-knownmulticriteria decision techniques, namely, the Analytic Hierarchy Process(AHP). Assuming that the judgements elicited by the decision makers follow theso-called multiplicative model (Crawford and Williams, 1985; Altuzarra et al.,1997; Laininen and Hämäläinen, 2003) with log-normal errors and unknownvariance, a Bayesian approach is used in the estimation of the relative prioritiesof the alternatives being compared. These priorities, estimated by way of themedian of the posterior distribution and normalised in a distributive manner(priorities add up to one), are a clear example of compositional data that will beused in the search for consensus between the actors involved in the resolution ofthe problem through the use of Multidimensional Scaling tools

Compositional data analysis of vote shares in the 2001 Australian Federal election

First application of compositional data analysis techniques to Australian election data

Group preference structures in AHP–group decision making

This paper presents a procedure that allows us to determine the preference structures(PS) associated to each of the different groups of actors that can be identified in a groupdecision making problem with a large number of individuals. To that end, it makesuse of the Analytic Hierarchy Process (AHP) (Saaty, 1980) as the technique to solvediscrete multicriteria decision making problems. This technique permits the resolutionof multicriteria, multienvironment and multiactor problems in which subjective aspectsand uncertainty have been incorporated into the model, constructing ratio scales correspondingto the priorities relative to the elements being compared, normalised in adistributive manner (wi = 1). On the basis of the individuals’ priorities we identifydifferent clusters for the decision makers and, for each of these, the associated preferencestructure using, to that end, tools analogous to those of Multidimensional Scaling.The resulting PS will be employed to extract knowledge for the subsequent negotiationprocesses and, should it be necessary, to determine the relative importance of thealternatives being compared using anyone of the existing procedures

Regression analysis of compositional data when both the dependent variable and independent variable are components

It is well known that regression analyses involving compositional data need special attention because the data are not of full rank. For a regression analysis where both the dependent and independent variable are components we propose a transformation of the components emphasizing their role as dependent and independent variables. A simple linear regression can be performed on the transformed components. The regression line can be depicted in a ternary diagram facilitating the interpretation of the analysis in terms of components. An exemple with time-budgets illustrates the method and the graphical features

The single principle of compositional data analysis, continuing fallacies, confusionsand misunderstandings and some suggested remedies

In any discipline, where uncertainty and variability are present, it is important to haveprinciples which are accepted as inviolate and which should therefore drive statisticalmodelling, statistical analysis of data and any inferences from such an analysis.Despite the fact that two such principles have existed over the last two decades andfrom these a sensible, meaningful methodology has been developed for the statisticalanalysis of compositional data, the application of inappropriate and/or meaninglessmethods persists in many areas of application. This paper identifies at least tencommon fallacies and confusions in compositional data analysis with illustrativeexamples and provides readers with necessary, and hopefully sufficient, arguments topersuade the culprits why and how they should amend their ways

Proyecto DIL-D: Grado de Desarrollo de políticas y estrategias de Integración Laboral de las personas con Discapacidad en las organizaciones que operan en territorio nacional. Informe de investigación Resultados del primer año

El presente informe expone los principales resultados alcanzados en el primer año de andadura de la Cátedra UB – Fundación Adecco para la Integración Laboral de Personas con Discapacidad (http://www.ub.edu/catedrainlab/). Esta Cátedra parte de la necesidad de analizar y evaluar el impacto que tiene en las empresas una estrategia de Responsabilidad Social Corporativa (RSC)1 orientada a la integración laboral de las personas con discapacidad, en la calidad de vida laboral y en los niveles de efectividad organizacional.

Proyecto EFO+CVL: Influencia del desarrollo de políticas y estrategias de integración laboral de las personas con discapacidad en la efectividad organizativa (EfO) y la calidad de vida laboral (CVL). Informe de investigación Resultados del segundo año

El presente informe tiene por objeto exponer los resultados correspondientes al segundo año de andadura de la Cátedra UB – Fundación Adecco para la Integración Laboral de Personas con Discapacidad (http://www.ub.edu/catedrainlab/).

A human immune data-informed vaccine concept elicits strong and broad T-cell specificities associated with HIV-1 control in mice and macaques

Background: None of the HIV T-cell vaccine candidates that have reached advanced clinical testing have been able to induce protective T cell immunity. A major reason for these failures may have been suboptimal T cell immunogen designs. Methods: To overcome this problem, we used a novel immunogen design approach that is based on functional T cell response data from more than 1,000 HIV-1 clade B and C infected individuals and which aims to direct the T cell response to the most vulnerable sites of HIV-1. Results: Our approach identified 16 regions in Gag, Pol, Vif and Nef that were relatively conserved and predominantly targeted by individuals with reduced viral loads. These regions formed the basis of the HIVACAT T-cell Immunogen (HTI) sequence which is 529 amino acids in length, includes more than 50 optimally defined CD4+ and CD8+ T-cell epitopes restricted by a wide range of HLA class I and II molecules and covers viral sites where mutations led to a dramatic reduction in viral replicative fitness. In both, C57BL/6 mice and Indian rhesus macaques immunized with an HTI-expressing DNA plasmid (DNA.HTI) induced broad and balanced T-cell responses to several segments within Gag, Pol, and Vif. DNA.HTI induced robust CD4+ and CD8+ T cell responses that were increased by a booster vaccination using modified virus Ankara (MVA.HTI), expanding the DNA.HTI induced response to up to 3.2% IFN-γ T-cells in macaques. HTI-specific T cells showed a central and effector memory phenotype with a significant fraction of the IFN-γ+ CD8+ T cells being Granzyme B+ and able to degranulate (CD107a+). Conclusions: These data demonstrate the immunogenicity of a novel HIV-1 T cell vaccine concept that induced broadly balanced responses to vulnerable sites of HIV-1 while avoiding the induction of responses to potential decoy targets that may divert effective T-cell responses towards variable and less protective viral determinants.

Gp120/CD4 blocking antibodies are frequently elicited in ART-naïve chronically HIV-1 infected individuals

Antibodies with the ability to block the interaction of HIV-1 envelope glycoprotein (Env) gp120 with CD4, including those overlapping the CD4 binding site (CD4bs antibodies), can protect from infection by HIV-1, and their elicitation may be an interesting goal for any vaccination strategy. To identify gp120/CD4 blocking antibodies in plasma samples from HIV-1 infected individuals we have developed a competitive flow cytometry-based functional assay. In a cohort of treatment-naïve chronically infected patients, we showed that gp120/ CD4 blocking antibodies were frequently elicited (detected in 97% plasma samples) and correlated with binding to trimeric HIV-1 envelope glycoproteins. However, no correlation was observed between functional CD4 binding blockade data and titer of CD4bs antibodies determined by ELISA using resurfaced gp120 proteins. Consistently, plasma samples lacking CD4bs antibodies were able to block the interaction between gp120 and its receptor, indicating that antibodies recognizing other epitopes, such as PGT126 and PG16, can also play the same role. Antibodies blocking CD4 binding increased over time and correlated positively with the capacity of plasma samples to neutralize the laboratory-adapted NL4.3 and BaL virus isolates, suggesting their potential contribution to the neutralizing workforce of plasma in vivo. Determining whether this response can be boosted to achieve broadly neutralizing antibodies may provide valuable information for the design of new strategies aimed to improve the anti-HIV-1 humoral response and to develop a successful HIV- 1 vaccine.