Immune and virologic responses to Truvada or Combivir as a first-line therapy of HIV-infected, treatment-naïve patients

Methods 107 HIV-infected, ARV-naive patients were prospectively enrolled and treated with TVD (300 mg TDF + 200 mg FTC QD) or CBV (300 mg AZT + 150 mg 3TC BID) in combination with EFV (600 mg QD) or a PI (LPV/r, ATV/ r, fAPV/r and SQV/r). Twenty-seven patients received TVD-EFV, 33 received TVD-PI, 24 received CBV-EFV, and 23 received CBV-PI. Fifty-one of these patients have, so far, reached 12 months of therapy. Clinical, immunological and virologic parameters at baseline and after 12 months of therapy are presented

Fully Immunocompetent CD8+ T Lymphocytes Are Present in Autologous Haematopoietic Stem Cell Transplantation Recipients Despite an Ineffectual T-Helper Response

BACKGROUND: Reduced CD4 T lymphocytes counts can be observed in HIV infection and in patients undergoing autologous haematopoietic stem cell transplantation (ASCT). Nevertheless, whereas opportunistic infections (OI) are frequent in HIV-infected individuals with low cell counts, OI are uncommon in ASCT patients. METHODOLOGY/PRINCIPAL FINDINGS: To verify whether this observation could be secondary to intrinsic HIV-correlated T cell defects, we performed in-depth immunologic analyses in 10 patients with comparable CD4 counts in whom lymphopenia was secondary either to HIV-infection or ASCT-associated immunosuppressive therapy and compared them to age-matched healthy subjects. Results showed the presence of profound alterations in CD4+ T lymphocytes in both groups of patients with respect to healthy controls. Thus, a low percentage of CCR7+ CD4+ T cells and a compensative expansion of CD45RA-CCR7- CD4+ T cells, a reduced IL-2/IFN-gamma cytokine production and impaired recall antigens-specific proliferative responses were detected both in ASCT and HIV patients. In stark contrast, profound differences were detected in CD8+ T-cells between the two groups of patients. Thus, mature CD8+ T cell prevailed in ASCT patients in whom significantly lower CD45RA-CCR7- cells, higher CD45RA+CCR7- CD8+ cells, and an expansion of CCR7+CD8+ cells was detected; this resulted in higher IFN-gamma +/TNFalpha production and granzyme CD8+ expression. The presence of strong CD8 T cells mediated immune responses justifies the more favorable clinical outcome of ASCT compared to HIV patients. CONCLUSION/SIGNIFICANCE: These results indicate that CD8 T cells maturation and functions can be observed even in the face of a profound impairment of CD4+ T lymphocytes in ASCT but not in HIV patients. Primary HIV-associated CD8 defects or an imprinting by an intact CD4 T cell system in ASCT could justify these results

Modeling small area estimation problems with latent spatial processes: a proposal for business surveys

This work proposes a class of latent process models which extend the customary hierarchical Bayesian (HB) small areal-level models in order to address typical prob-lems arising in small area estimation (SAE). Our approach envisions, for the entire re-gion under study, an underlying intensity surface which is block-averaged to the areal units relevant to the study. This framework encompasses all the main instances of pa-rameters being considered in SAE studies. E.g., we can think of an incidence surface when the characteristics of interest are area counts or totals, a probability surface when they are percentages, a proper intensity surface when they are continuous vari-ates. Such intensities are commonly used for explaining spatial point patterns and are generally modeled as realizations of (functions) of latent Gaussian processes. The proposed class of models allows for integrating multiple sources of potentially relevant information, even if available on a spatial scale different from that of small areas. These supplementary sources may consist either in auxiliary data or in survey data collected on planned or major domains. Moreover, in the proposed class bench-marking to large area estimates is automatically satisfied. To illustrate our approach we consider the problem of estimating parameters re-lated to firms\u2019 activity and performance (such as the turnover or value added, which typically have a skewed distribution) as well as indicators of innovation efforts under-taken by enterprises (such as the percentage of firms investing in innovation) at Local Labour Market level. The parameters of interest are thus non-continuous or, if con-tinuous, non-symmetrical, as business statistics frequently are. Our proposal will then consider opportune specifications of unmatched models where the sampling error is non-normally distributed as standardly is in SAE problems. We carried out a simulation to compare the performance of our proposed model to that of customary small area models. The simulation is based on the sampling de-sign adopted in business surveys which typically is one-stage stratified. Predictive error of the Bayesian models under comparison is evaluated in terms of standardly used frequentist properties

Estimation of poverty indicators at sub-national level using multivariate small area models

In recent years, the measure of regional disparities on poverty and social exclusion has received increasing attention by policy makers and this has produced a growing demand of sub-national statistical information on income parameters. Taking into account the multidimensionality of this phenomenon, in the Laeken European Council (Eurostat, 2003) a set of financial poverty indicators were suggested to monitor the progress in fighting inequality. In the European Union regional statistical information on income can be obtained from the European Community Household Panel, a survey designed to provide reliable estimates for large regions in the countries. The aim of this work is to estimate at sub-national level some of the income indicators suggested in the Laeken council. We propose Bayesian small area estimators based on multivariate area level models exploiting the correlation between different indicators. The tendency of model based estimates to over-shrink towards the synthetic component can be a draw-back for policy makers interested in capturing regional disparities in financial poverty. To preserve the relationship between different indicators and disparities over areas, we adopt a multivariate constrained Bayes estimator. The comparison between results based on different models allows us to select the estimator realizing the best compromise between gain in efficiency and reduction of the over-shrinkage

Small Area Estimation of Average Household Income based on Unit Level Models for Panel Data \u201cSurvey Methodology\u201d, 33, 2, pp.187-198, 2007.

The European Community Household Panel (ECHP) is a panel survey covering a wide range of topics regarding economic, social and living conditions. In particular, it makes it possible to calculate disposable equivalized household income, which is a key variable in the study of economic inequity and poverty. To obtain reliable estimates of the average of this variable for regions within countries it is necessary to have recourse to small area estimation methods. In this paper, we focus on empirical best linear predictors of the average equivalized income based on \u201cunit level models\u201d borrowing strength across both areas and times. Using a simulation study based on ECHP data, we compare the suggested estimators with crosssectional modelbased and designbased estimators. In the case of these empirical predictors, we also compare three different MSE estimators. Results show that those estimators connected to models that take units\u2019 autocorrelation into account lead to a significant gain in efficiency, even when there are no covariates available whose population mean is known

Low interleukin-10 production is associated with diabetes in HIV-infected patients undergoing antiviral therapy

Reduced interleukin-10 (IL-10) production is associated with type 2 diabetes in elderly individuals. Antiviral therapy (ARV)-induced immune modulation results in diminished IL-10 production, and diabetes can be observed in ARV-treated human immunodeficiency virus (HIV)-infected individuals. We analyzed, in a cross-sectional pilot study, HIV-antigen-stimulated IL-10 and tumor necrosis factor alpha (TNFalpha) production, and intracellular concentration (ICC), as well as B7-H1 expression, a marker preferentially presented by IL-10-producing cells, in 20 ARV-treated individuals in whom diabetes did (n=10; diabetes mellitus, DM) or did not (n=10; controls) develop. Pre-ARV glucose, cholesterol, and triglycerides levels, duration of HIV infection and of therapy, exposure to protease inhibitors (PI), HIV plasma viremia, CD4 counts, and nadir were similar in DM and control patients. Results showed that: (1) IL-10 production was lower; (2) IL-10 ICC was reduced; (3) B7-H1-expressing CD19(+) cells were diminished; and (4) TNFalpha production and ICC by CD4(+) T cells was augmented in DM patients. Development of diabetes in HIV infected, ARV-treated individuals could be a response to therapy. Similar to what is observed in elderly individuals, low IL-10 production is associated with diabetes in antiviral-treated HIV infection. Further studies will be necessary to clarify whether low IL-10 is a risk factor for, or a consequence of, diabetes

Costimulatory pathways in multiple sclerosis : distinctive expression of PD-1 and PD-L1 in patients with different patterns of disease

T lymphocytes costimulatory molecules, including CD80, CD86, CD28, CTLA4, PD-1, PD-L1, and B7-H3, are associated with the preferential production of pro- or anti-inflammatory cytokines. We analyzed the expression of these molecules and myelin basic protein (MBP)-specific IL-10 and IFN-gamma production in patients with multiple sclerosis (MS) with relapsing-remitting acute (AMS, n = 40) or stable (SMS, n = 38). Twenty-two patients successfully undergoing therapy with glatimer acetate (n = 12) or IFNbeta (n = 10) were also analyzed. MBP-specific and PD-1-expressing T lymphocytes, PD-L1-expressing CD19(+) cells, and PD-L1(+)/IL-10(+)/CD14(+) and CD19(+) cells were significantly augmented in SMS patients. Additionally, MBP-specific and annexin V-expressing CD4(+) and CD8(+) (apoptotic) T lymphocytes were augmented and pAkt-positive (proliferating) cells were decreased in SMS compared with AMS patients. PD-1 ligation resulted in the increase of pAkt(+) lymphocytes in AMS patients alone. B7-H3 expression and IFN-gamma production were comparable in all individuals but the PD-L1(+)/IL-10(+) over B7-H3(+)/IFN-gamma(+) ratio was significantly lower in AMS compared with SMS patients. Finally, PD-L1 expression on immune cells was reduced in treated patients, suggesting that therapy-induced disease remission is not associated with the modulation of the expression of this molecule. The PD-1/PD-L1 pathway plays an important role in modulating immune functions in MS patients; monitoring and targeting these proteins could offer diagnostic and therapeutic advantages