12 research outputs found
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The social context of tuberculosis treatment in urban risk groups in the United Kingdom: a qualitative interview study
Objectives: There is scant qualitative research into the experiences of tuberculosis treatment in urban risk groups with complex health and social needs in the UK. This study aimed to describe the social context of adherence to treatment in marginalised groups attending a major tuberculosis centre in London.
Methods: Qualitative cross-sectional study using semi-structured interviews with patients receiving treatment for tuberculosis. Analytical frameworks aimed to reflect the role of broader social structures in shaping individual health actions.
Results: Seventeen participants, the majority were homeless and had complex medical and social needs including, drug and alcohol use or immigration problems affecting entitlement to social welfare. Participants rarely actively chose not to take their medication but described a number of social and institutional barriers to adherence and their need for practical support. Many struggled with the physical aspects of taking medication and the side effects. Participants receiving DOT reported both positive and negative experiences reflecting type of DOT provider and culture of the organisation.
Conclusions: There is a need for integrated care across drug, alcohol, HIV and homeless services in order to address complex clinical co-morbidities and social need which impact on patients’ ability to sustain a course of treatment
Immune Activation and CD8(+) T-Cell Differentiation towards Senescence in HIV-1 Infection
Progress in the fight against the HIV/AIDS epidemic is hindered by our failure to elucidate the precise reasons for the onset of immunodeficiency in HIV-1 infection. Increasing evidence suggests that elevated immune activation is associated with poor outcome in HIV-1 pathogenesis. However, the basis of this association remains unclear. Through ex vivo analysis of virus-specific CD8(+) T-cells and the use of an in vitro model of naïve CD8(+) T-cell priming, we show that the activation level and the differentiation state of T-cells are closely related. Acute HIV-1 infection induces massive activation of CD8(+) T-cells, affecting many cell populations, not only those specific for HIV-1, which results in further differentiation of these cells. HIV disease progression correlates with increased proportions of highly differentiated CD8(+) T-cells, which exhibit characteristics of replicative senescence and probably indicate a decline in T-cell competence of the infected person. The differentiation of CD8(+) and CD4(+) T-cells towards a state of replicative senescence is a natural process. It can be driven by excessive levels of immune stimulation. This may be part of the mechanism through which HIV-1-mediated immune activation exhausts the capacity of the immune system
Health outcomes and the transition experience of HIV-infected adolescents after transfer to adult care in Québec, Canada
Understanding Gender Inequality in Poverty and Social Exclusion through a Psychological Lens:Scarcities, Stereotypes and Suggestions
CD8<sup>+</sup> T-Cell Differentiation and HIV-1 Disease Progression
<div><p>(A) Distribution of the CD8<sup>+</sup> T-cell population in differentiated subsets (CD28<sup>+</sup>/CD27<sup>+</sup> early, CD28<sup>−</sup>/CD27<sup>+</sup> intermediate, and CD28<sup>−</sup>/CD27<sup>−</sup> late) through the course of HIV-1 infection. Abbreviations: H, healthy (<i>n</i> = 15); A, acute HIV infection (<i>n</i> = 11); C, chronic HIV infection nonprogressor (no ART; <i>n</i> = 14); P, chronic HIV infection with signs of disease progression (no ART; <i>n</i> = 10). Statistics: * <i>p</i> < 0.0001 with the ANOVA test and <i>p</i> < 0.005 between each group.</p>
<p>(B) Percentages of CD27<sup>−</sup> CD8<sup>+</sup> T-cells that are specific for HLA-B8 HIV (nef) or HLA-A2 CMV in HIV-1-infected individuals at different stages of infection. Statistics: ** <i>p</i> < 0.005 with the nonparametric Mann–Whitney test.</p>
<p>(C) Inverse correlation between CD4<sup>+</sup> T-cell counts and percentage of highly differentiated CD27<sup>−</sup> cells in the whole CD8<sup>+</sup> T-cell population of HIV-1-infected donors during chronic infection (untreated nonprogressors and progressors). The <i>p</i> value was obtained using the nonparametric Spearman rank correlation test.</p></div
CD8<sup>+</sup> T-Cell Activation during Acute HIV-1 Infection
<div><p>(A) Percentages of activated CD38<sup>+</sup> cells (gated on whole CD8<sup>+</sup> T-cells, HIV tetramer-positive CD8<sup>+</sup> T-cells, or whole CD4<sup>+</sup> T-cells) in donors during acute HIV-1 infection and later postacute on ART (<i>n</i> = 12); healthy donors (<i>n</i> = 11) and untreated donors with nonprogressing chronic infection (<i>n</i> = 12) are also shown.</p>
<p>(B and C) CD38 and Ki67 expression on CD8<sup>+</sup> T-cell subsets defined by CD45RA/CD62L (B) or CD28/CD27 (C) expression, shown in one single donor from acute to postacute (on ART) HIV-1 infection. Percentages of positive cells are shown. Means (± SEM) of CD38<sup>+</sup> and Ki67<sup>+</sup> CD8<sup>+</sup> T-cells for ten patients are also shown; statistics concern CD38 expression.</p>
<p>(D) Staining for the activation marker CD38 on CMV-, EBV-, or influenza A virus-specific CD8<sup>+</sup> T-cells during acute and postacute (on ART) HIV-1 infection in a single donor. Percentages of CD38<sup>+</sup> tetramer-positive CD8<sup>+</sup> T-cells are shown. Data on all donors (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020020#pbio-0020020-t001" target="_blank">Table 1</a>) are also shown.</p>
<p>(E) Activation (CD38 and Ki67 staining) of CMV-specific CD8<sup>+</sup> T-cells or whole CD8<sup>+</sup> T-cell population during acute and postacute (on ART) HIV-1 infection in a single donor. Percentages of cells present in quadrants are shown.</p>
<p>Statistics: * <i>p</i> < 0.002, ** <i>p</i> < 0.01, NS = nonsignificant, with the nonparametric Mann–Whitney test.</p></div
CD8<sup>+</sup> T-Cell Differentiation and Senescence
<div><p>(A) Expression of the replicative senescence-associated marker CD57 on antigen-experienced CD8<sup>+</sup> T-cell subsets. The percentage and mean fluorescence intensity for the CD57<sup>+</sup> cells are shown for one single donor. Data on several donors (HIV-1-infected or healthy) are also shown (<i>n</i> = 24).</p>
<p>(B) Expression of CD57 on CD8<sup>+</sup> T-cells (whole population or antigen-specific) from acute to postacute (on ART) HIV-1 infection.</p>
<p>(C) CD69 expression and CFSE proliferation profile for CD8<sup>+</sup> T-cell subsets gated on the basis of CD57 and CD27 expression following stimulation with anti-CD3 antibodies. PBMCs were analysed for CD69 expression after 18 h and CFSE labeling after 6 d. Percentages of proliferating cells (with background subtracted) are indicated. Representative results from three experiments (one HIV-infected and two healthy donors) are shown.</p>
<p>(D) Telomere length measurement by flow FISH on naïve and antigen-experienced CD8<sup>+</sup> T-cell subsets FACS-sorted on the basis of CD57, CD27, CCR7, and CD45RA expression. The average length of telomeres was obtained by substracting the mean fluorescence of the background control (no probe; open histogram) from the mean fluorescence obtained from cells hybridised with the FITC-labeled telomere probe (gray histogram). Representative results from two experiments (on healthy donors) are shown.</p>
<p>(E) CD57 and perforin expression in the CD8<sup>+</sup> T-cell population dissected into naïve (CD27<sup>+high</sup>, perforin-negative), antigen-experienced CD27<sup>+</sup> (perforin<sup>low</sup>), and antigen-experienced CD27<sup>−</sup> perforin<sup>low</sup> or perforin<sup>high</sup> subsets. The percentage and mean fluorescence intensity for the CD57<sup>+</sup> cells are indicated.</p>
<p>(F) Representative staining for perforin and CD57 in CD8<sup>+</sup> T-cells from a HIV-1-infected or a healthy donor. Percentages of cells present in the top quadrants are shown.</p>
<p>(G) Representative staining for perforin and CD57 in CD4<sup>+</sup> T-cells from an HIV-1-infected or a healthy donor. Percentages of cells present in the top quadrants are shown.</p></div