HIV-Infected Individuals with Low CD4/CD8 Ratio despite Effective Antiretroviral Therapy Exhibit Altered T Cell Subsets, Heightened CD8+ T Cell Activation, and Increased Risk of Non-AIDS Morbidity and Mortality
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{"title"=>"HIV-Infected Individuals with Low CD4/CD8 Ratio despite Effective Antiretroviral Therapy Exhibit Altered T Cell Subsets, Heightened CD8+ T Cell Activation, and Increased Risk of Non-AIDS Morbidity and Mortality", "type"=>"journal", "authors"=>[{"first_name"=>"Sergio", "last_name"=>"Serrano-Villar", "scopus_author_id"=>"26321959900"}, {"first_name"=>"Talia", "last_name"=>"Sainz", "scopus_author_id"=>"54384199300"}, {"first_name"=>"Sulggi A.", "last_name"=>"Lee", "scopus_author_id"=>"56071466300"}, {"first_name"=>"Peter W.", "last_name"=>"Hunt", "scopus_author_id"=>"7202324398"}, {"first_name"=>"Elizabeth", "last_name"=>"Sinclair", "scopus_author_id"=>"7006061259"}, {"first_name"=>"Barbara L.", "last_name"=>"Shacklett", "scopus_author_id"=>"6701589733"}, {"first_name"=>"April L.", "last_name"=>"Ferre", "scopus_author_id"=>"24280976900"}, {"first_name"=>"Timothy L.", "last_name"=>"Hayes", "scopus_author_id"=>"7201527350"}, {"first_name"=>"Ma", "last_name"=>"Somsouk", "scopus_author_id"=>"24339287200"}, {"first_name"=>"Priscilla Y.", "last_name"=>"Hsue", "scopus_author_id"=>"6603378734"}, {"first_name"=>"Mark L.", "last_name"=>"Van Natta", "scopus_author_id"=>"6701567913"}, {"first_name"=>"Curtis L.", "last_name"=>"Meinert", "scopus_author_id"=>"7006458362"}, {"first_name"=>"Michael M.", "last_name"=>"Lederman", "scopus_author_id"=>"35227594000"}, {"first_name"=>"Hiroyu", "last_name"=>"Hatano", "scopus_author_id"=>"15055866200"}, {"first_name"=>"Vivek", "last_name"=>"Jain", "scopus_author_id"=>"57109798100"}, {"first_name"=>"Yong", "last_name"=>"Huang", "scopus_author_id"=>"56185757900"}, {"first_name"=>"Frederick M.", "last_name"=>"Hecht", "scopus_author_id"=>"7103064306"}, {"first_name"=>"Jeffrey N.", "last_name"=>"Martin", "scopus_author_id"=>"7501562043"}, {"first_name"=>"Joseph M.", "last_name"=>"McCune", "scopus_author_id"=>"7006305218"}, {"first_name"=>"Santiago", "last_name"=>"Moreno", "scopus_author_id"=>"7203036595"}, {"first_name"=>"Steven G.", "last_name"=>"Deeks", "scopus_author_id"=>"7006700221"}], "year"=>2014, "source"=>"PLoS Pathogens", "identifiers"=>{"pmid"=>"24831517", "doi"=>"10.1371/journal.ppat.1004078", "sgr"=>"84901686066", "isbn"=>"1553-7374 (Electronic)\\r1553-7366 (Linking)", "scopus"=>"2-s2.0-84901686066", "issn"=>"15537374", "pui"=>"373203693"}, "id"=>"ac2b4e3e-4c48-3621-a8d9-7850d4a4b97f", "abstract"=>"A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined. Using data from four distinct clinical cohorts and three clinical trials, we show that a low CD4/CD8 ratio in HIV-infected adults during otherwise effective ART (after CD4 count recovery above 500 cells/mm3) is associated with a number of immunological abnormalities, including a skewed T cell phenotype from naïve toward terminally differentiated CD8+ T cells, higher levels of CD8+ T cell activation (HLADR+CD38+) and senescence (CD28- and CD57+CD28-), and higher kynurenine/tryptophan ratio. Changes in the peripheral CD4/CD8 ratio are also reflective of changes in gut mucosa, but not in lymph nodes. In a longitudinal study, individuals who initiated ART within six months of infection had greater CD4/CD8 ratio increase compared to later initiators (>2 years). After controlling for age, gender, ART duration, nadir and CD4 count, the CD4/CD8 ratio predicted increased risk of morbidity and mortality. Hence, a persistently low CD4/CD8 ratio during otherwise effective ART is associated with increased innate and adaptive immune activation, an immunosenescent phenotype, and higher risk of morbidity/mortality. This ratio may prove useful in monitoring response to ART and could identify a unique subset of individuals needed of novel therapeutic interventions.", "link"=>"http://www.mendeley.com/research/hivinfected-individuals-low-cd4cd8-ratio-despite-effective-antiretroviral-therapy-exhibit-altered-t", "reader_count"=>150, "reader_count_by_academic_status"=>{"Unspecified"=>5, "Professor > Associate Professor"=>6, "Researcher"=>31, "Student > Doctoral Student"=>14, "Student > Ph. D. Student"=>28, "Student > Postgraduate"=>8, "Student > Master"=>19, "Other"=>8, "Student > Bachelor"=>22, "Lecturer"=>3, "Lecturer > Senior Lecturer"=>4, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>5, "Professor > Associate Professor"=>6, "Researcher"=>31, "Student > Doctoral Student"=>14, "Student > Ph. D. Student"=>28, "Student > Postgraduate"=>8, "Student > Master"=>19, "Other"=>8, "Student > Bachelor"=>22, "Lecturer"=>3, "Lecturer > Senior Lecturer"=>4, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>13, "Agricultural and Biological Sciences"=>35, "Arts and Humanities"=>1, "Business, Management and Accounting"=>1, "Engineering"=>2, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>6, "Nursing and Health Professions"=>3, "Mathematics"=>1, "Medicine and Dentistry"=>69, "Neuroscience"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>2, "Social Sciences"=>2, "Immunology and Microbiology"=>11}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>69}, "Social Sciences"=>{"Social Sciences"=>2}, "Psychology"=>{"Psychology"=>2}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>13}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}, "Engineering"=>{"Engineering"=>2}, "Neuroscience"=>{"Neuroscience"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>11}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>35}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}}, "reader_count_by_country"=>{"Canada"=>1, "Brazil"=>1, "United Kingdom"=>1, "Italy"=>1, "South Africa"=>2}, "group_count"=>5}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1498977"], "description"=>"<p>The CD4/CD8 ratio was compared between HIV-uninfected individuals (blue) and HIV-infected individuals initiating ART “early,” ≤6 months of infection (green), or “later,” ≥2 years after initial infection (red), at acute HIV diagnosis and after 1 year of ART. Median CD4/CD8 ratio was significantly higher after one year in early ART initiators compared to later initiators. (<b>A</b>). Early ART initiators experienced higher CD4+ T cell increase (<b>B</b>) than later initiators (<b>C</b>) after one year of ART (221 cells/mm<sup>3</sup> vs. 130, respectively, P<0.001). No differences were observed in CD8+ T cell counts between early (<b>D</b>) and later ART initiators (<b>E</b>) after one year of ART (−212 cells/mm<sup>3</sup> vs. −114, respectively, P = 0.098) but CD8+ T cells were significantly different between groups beyond one year of ART (−309 cells/mm<sup>3</sup> vs. −114, respectively, P = 0.014). Changes in the CD4/CD8 ratio among recently HIV-infected individuals initiating ART early (<b>F</b>) and later (<b>G</b>) were also assessed over time. Early ART initiators experienced a higher increase at one year of ART than later initiators (+0.43 vs. +0.25, P<0.001). Individual participant trajectories shown with red lines, estimated mean values over time from linear mixed models adjusted by age, sex, baseline CD4+ T cells shown in thick black lines.</p>", "links"=>[], "tags"=>["anatomy", "Lymphatic system", "Lymphoid organs", "cell biology", "Cellular types", "Animal cells", "Blood cells", "White blood cells", "t cells", "Immune cells", "immunology", "Clinical immunology", "HIV immunopathogenesis", "Immune response", "inflammation", "Immune system", "Acquired immune system", "Innate immune system", "immunity", "Immune activation", "microbiology", "Medical microbiology", "Microbial pathogens", "Viral pathogens", "Immunodeficiency viruses", "hiv", "Diagnostic medicine", "HIV clinical manifestations", "HIV diagnosis and management", "Infectious diseases", "Viral diseases", "initiation", "peripheral", "counts", "options"], "article_id"=>1027821, "categories"=>["Biological Sciences"], "users"=>["Sergio Serrano-Villar", "Talia Sainz", "Sulggi A. Lee", "Peter W. Hunt", "Elizabeth Sinclair", "Barbara L. Shacklett", "April L. Ferre", "Timothy L. Hayes", "Ma Somsouk", "Priscilla Y. Hsue", "Mark L. Van Natta", "Curtis L. Meinert", "Michael M. Lederman", "Hiroyu Hatano", "Vivek Jain", "Yong Huang", "Frederick M. Hecht", "Jeffrey N. Martin", "Joseph M. McCune", "Santiago Moreno", "Steven G. Deeks"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004078.g005", "stats"=>{"downloads"=>3, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impact_of_early_or_later_ART_initiation_in_peripheral_CD4_T_cell_counts_CD8_T_cell_counts_and_CD4_CD8_ratio_in_the_OPTIONS_cohort_/1027821", "title"=>"Impact of early or later ART initiation in peripheral CD4+ T cell counts, CD8+ T cell counts and CD4/CD8 ratio in the OPTIONS cohort.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-15 02:59:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1498976"], "description"=>"<p>While no association with the CD4/CD8 ratio in lymph nodes was detected (<b>A</b>), it correlated positively with the ratio in GALT (<b>B</b>). The red line represents a linear prediction.</p>", "links"=>[], "tags"=>["anatomy", "Lymphatic system", "Lymphoid organs", "cell biology", "Cellular types", "Animal cells", "Blood cells", "White blood cells", "t cells", "Immune cells", "immunology", "Clinical immunology", "HIV immunopathogenesis", "Immune response", "inflammation", "Immune system", "Acquired immune system", "Innate immune system", "immunity", "Immune activation", "microbiology", "Medical microbiology", "Microbial pathogens", "Viral pathogens", "Immunodeficiency viruses", "hiv", "Diagnostic medicine", "HIV clinical manifestations", "HIV diagnosis and management", "Infectious diseases", "Viral diseases", "lymph", "nodes"], "article_id"=>1027820, "categories"=>["Biological Sciences"], "users"=>["Sergio Serrano-Villar", "Talia Sainz", "Sulggi A. Lee", "Peter W. Hunt", "Elizabeth Sinclair", "Barbara L. Shacklett", "April L. Ferre", "Timothy L. Hayes", "Ma Somsouk", "Priscilla Y. Hsue", "Mark L. Van Natta", "Curtis L. Meinert", "Michael M. Lederman", "Hiroyu Hatano", "Vivek Jain", "Yong Huang", "Frederick M. Hecht", "Jeffrey N. Martin", "Joseph M. McCune", "Santiago Moreno", "Steven G. Deeks"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004078.g004", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_between_the_CD4_CD8_ratio_in_blood_and_in_lymph_nodes_or_in_GALT_/1027820", "title"=>"Association between the CD4/CD8 ratio in blood and in lymph nodes or in GALT.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-15 02:59:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1498973"], "description"=>"<p>HIV-infected individuals with low CD4/CD8 ratio had lower percentages of T<sub>N</sub>, T<sub>CM</sub>, and T<sub>TR</sub> CD8+ cells, higher T<sub>EM</sub> and T<sub>EMRA</sub> (<b>A</b>), and higher absolute counts (<b>B</b>) of all subsets compared to those with higher CD4/CD8 ratio and with healthy controls.</p>", "links"=>[], "tags"=>["anatomy", "Lymphatic system", "Lymphoid organs", "cell biology", "Cellular types", "Animal cells", "Blood cells", "White blood cells", "t cells", "Immune cells", "immunology", "Clinical immunology", "HIV immunopathogenesis", "Immune response", "inflammation", "Immune system", "Acquired immune system", "Innate immune system", "immunity", "Immune activation", "microbiology", "Medical microbiology", "Microbial pathogens", "Viral pathogens", "Immunodeficiency viruses", "hiv", "Diagnostic medicine", "HIV clinical manifestations", "HIV diagnosis and management", "Infectious diseases", "Viral diseases", "counts", "maturation", "subsets", "individuals", "art-suppressed", "hiv-infected", "patients", "cd4", "stratified"], "article_id"=>1027817, "categories"=>["Biological Sciences"], "users"=>["Sergio Serrano-Villar", "Talia Sainz", "Sulggi A. Lee", "Peter W. Hunt", "Elizabeth Sinclair", "Barbara L. Shacklett", "April L. Ferre", "Timothy L. Hayes", "Ma Somsouk", "Priscilla Y. Hsue", "Mark L. Van Natta", "Curtis L. Meinert", "Michael M. Lederman", "Hiroyu Hatano", "Vivek Jain", "Yong Huang", "Frederick M. Hecht", "Jeffrey N. Martin", "Joseph M. McCune", "Santiago Moreno", "Steven G. Deeks"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004078.g001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Percentages_and_absolute_counts_of_CD8_T_cell_maturation_subsets_among_HIV_CMV_individuals_and_ART_suppressed_HIV_infected_patients_with_CD4_counts_500_cells_mm_3_stratified_by_a_normal_4th_quartile_8805_1_or_low_1st_quartile_8804_0_4_CD4_CD8_ratio_/1027817", "title"=>"Percentages and absolute counts of CD8+ T cell maturation subsets among HIV-/CMV+ individuals and ART-suppressed HIV-infected patients with CD4 counts >500 cells/mm<sup>3</sup> stratified by a normal (4th quartile, ≥1) or low (1st quartile, ≤0.4) CD4/CD8 ratio.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-15 02:59:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1498981"], "description"=>"<p>*N = 47.</p><p>Because of colinearity, we fitted one model to calculate the coefficients of CD4+ and CD8+ T cells, and a different model for the CD4/CD8 ratio.</p><p>Variables CD4+ and CD8+ T cells, and the CD4/CD8 ratio were log transformed.</p><p>Coefficients are adjusted by age, gender, nadir CD4+ T cell count and duration of viral suppression.</p><p>To interpret the logarithmically transformed coefficients, we applied the following formula: <i>Beta*log(1.10)</i>, resulting in the % of change in the odds of the outcome predicted by each 10% increase in the independent variable.</p>", "links"=>[], "tags"=>["anatomy", "Lymphatic system", "Lymphoid organs", "cell biology", "Cellular types", "Animal cells", "Blood cells", "White blood cells", "t cells", "Immune cells", "immunology", "Clinical immunology", "HIV immunopathogenesis", "Immune response", "inflammation", "Immune system", "Acquired immune system", "Innate immune system", "immunity", "Immune activation", "microbiology", "Medical microbiology", "Microbial pathogens", "Viral pathogens", "Immunodeficiency viruses", "hiv", "Diagnostic medicine", "HIV clinical manifestations", "HIV diagnosis and management", "Infectious diseases", "Viral diseases", "logistic", "regression", "morbidity", "counts", "madrid", "cohort", "soca", "nested"], "article_id"=>1027825, "categories"=>["Biological Sciences"], "users"=>["Sergio Serrano-Villar", "Talia Sainz", "Sulggi A. Lee", "Peter W. Hunt", "Elizabeth Sinclair", "Barbara L. Shacklett", "April L. Ferre", "Timothy L. Hayes", "Ma Somsouk", "Priscilla Y. Hsue", "Mark L. Van Natta", "Curtis L. Meinert", "Michael M. Lederman", "Hiroyu Hatano", "Vivek Jain", "Yong Huang", "Frederick M. Hecht", "Jeffrey N. Martin", "Joseph M. McCune", "Santiago Moreno", "Steven G. Deeks"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004078.t005", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Conditional_logistic_regression_analysis_Predicted_morbidity_and_mortality_by_the_CD4_and_CD8_T_cell_counts_and_the_CD4_CD8_ratio_in_the_Madrid_cohort_and_SOCA_cohort_mortality_nested_studies_/1027825", "title"=>"Conditional logistic regression analysis: Predicted morbidity and mortality by the CD4+ and CD8+ T cell counts and the CD4/CD8 ratio in the Madrid cohort and SOCA cohort mortality nested studies.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-05-15 02:59:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1498979"], "description"=>"<p>Correlations with biomarkers of innate immune activation and epithelial integrity in SOCA cohort.</p>", "links"=>[], "tags"=>["anatomy", "Lymphatic system", "Lymphoid organs", "cell biology", "Cellular types", "Animal cells", "Blood cells", "White blood cells", "t cells", "Immune cells", "immunology", "Clinical immunology", "HIV immunopathogenesis", "Immune response", "inflammation", "Immune system", "Acquired immune system", "Innate immune system", "immunity", "Immune activation", "microbiology", "Medical microbiology", "Microbial pathogens", "Viral pathogens", "Immunodeficiency viruses", "hiv", "Diagnostic medicine", "HIV clinical manifestations", "HIV diagnosis and management", "Infectious diseases", "Viral diseases", "biomarkers", "innate", "activation", "epithelial", "soca"], "article_id"=>1027823, "categories"=>["Biological Sciences"], "users"=>["Sergio Serrano-Villar", "Talia Sainz", "Sulggi A. Lee", "Peter W. Hunt", "Elizabeth Sinclair", "Barbara L. Shacklett", "April L. Ferre", "Timothy L. Hayes", "Ma Somsouk", "Priscilla Y. Hsue", "Mark L. Van Natta", "Curtis L. Meinert", "Michael M. Lederman", "Hiroyu Hatano", "Vivek Jain", "Yong Huang", "Frederick M. Hecht", "Jeffrey N. Martin", "Joseph M. McCune", "Santiago Moreno", "Steven G. Deeks"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004078.t003", "stats"=>{"downloads"=>3, "page_views"=>64, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Correlations_with_biomarkers_of_innate_immune_activation_and_epithelial_integrity_in_SOCA_cohort_/1027823", "title"=>"Correlations with biomarkers of innate immune activation and epithelial integrity in SOCA cohort.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-05-15 02:59:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1498980"], "description"=>"<p>“%CD57 of CD28−” refers to the percentage of CD28−CD8+ T cells expressing CD57.</p>", "links"=>[], "tags"=>["anatomy", "Lymphatic system", "Lymphoid organs", "cell biology", "Cellular types", "Animal cells", "Blood cells", "White blood cells", "t cells", "Immune cells", "immunology", "Clinical immunology", "HIV immunopathogenesis", "Immune response", "inflammation", "Immune system", "Acquired immune system", "Innate immune system", "immunity", "Immune activation", "microbiology", "Medical microbiology", "Microbial pathogens", "Viral pathogens", "Immunodeficiency viruses", "hiv", "Diagnostic medicine", "HIV clinical manifestations", "HIV diagnosis and management", "Infectious diseases", "Viral diseases", "biomarkers", "activation", "senescence", "soca"], "article_id"=>1027824, "categories"=>["Biological Sciences"], "users"=>["Sergio Serrano-Villar", "Talia Sainz", "Sulggi A. Lee", "Peter W. Hunt", "Elizabeth Sinclair", "Barbara L. Shacklett", "April L. Ferre", "Timothy L. Hayes", "Ma Somsouk", "Priscilla Y. Hsue", "Mark L. Van Natta", "Curtis L. Meinert", "Michael M. Lederman", "Hiroyu Hatano", "Vivek Jain", "Yong Huang", "Frederick M. Hecht", "Jeffrey N. Martin", "Joseph M. McCune", "Santiago Moreno", "Steven G. Deeks"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004078.t002", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Correlations_with_biomarkers_of_T_cell_activation_and_senescence_in_SOCA_cohort_/1027824", "title"=>"Correlations with biomarkers of T cell activation and senescence in SOCA cohort.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-05-15 02:59:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1498978"], "description"=>"<p>“%CD57 of CD28-” refers to the percentage of CD28−CD8+ T cells expressing CD57.</p>", "links"=>[], "tags"=>["anatomy", "Lymphatic system", "Lymphoid organs", "cell biology", "Cellular types", "Animal cells", "Blood cells", "White blood cells", "t cells", "Immune cells", "immunology", "Clinical immunology", "HIV immunopathogenesis", "Immune response", "inflammation", "Immune system", "Acquired immune system", "Innate immune system", "immunity", "Immune activation", "microbiology", "Medical microbiology", "Microbial pathogens", "Viral pathogens", "Immunodeficiency viruses", "hiv", "Diagnostic medicine", "HIV clinical manifestations", "HIV diagnosis and management", "Infectious diseases", "Viral diseases", "counts", "correlations", "maturation", "subsets", "activation", "phenotypes", "hiv-infected"], "article_id"=>1027822, "categories"=>["Biological Sciences"], "users"=>["Sergio Serrano-Villar", "Talia Sainz", "Sulggi A. Lee", "Peter W. Hunt", "Elizabeth Sinclair", "Barbara L. Shacklett", "April L. Ferre", "Timothy L. Hayes", "Ma Somsouk", "Priscilla Y. Hsue", "Mark L. Van Natta", "Curtis L. Meinert", "Michael M. Lederman", "Hiroyu Hatano", "Vivek Jain", "Yong Huang", "Frederick M. Hecht", "Jeffrey N. Martin", "Joseph M. McCune", "Santiago Moreno", "Steven G. Deeks"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004078.t001", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CD4_T_cell_counts_CD8_T_cell_counts_and_CD4_CD8_ratio_correlations_with_the_percentage_of_T_cell_maturation_subsets_and_T_cell_activation_phenotypes_in_HIV_infected_participants_in_SCOPE_cohort_/1027822", "title"=>"CD4+ T cell counts, CD8+ T cell counts and CD4/CD8 ratio correlations with the percentage of T cell maturation subsets and T cell activation phenotypes in HIV-infected participants in SCOPE cohort.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-05-15 02:59:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1498975"], "description"=>"<p>The KT ratio significantly correlated with the CD4/CD8 ratio and the % of CD28+CD8+ T cells. The between the CD4/CD8 ratio and the KT ratio was confirmed in a linear regression analysis adjusted by age, gender and cumulative ART exposure (Beta = −0.72, P = 0.009). The red line represents a linear prediction.</p>", "links"=>[], "tags"=>["anatomy", "Lymphatic system", "Lymphoid organs", "cell biology", "Cellular types", "Animal cells", "Blood cells", "White blood cells", "t cells", "Immune cells", "immunology", "Clinical immunology", "HIV immunopathogenesis", "Immune response", "inflammation", "Immune system", "Acquired immune system", "Innate immune system", "immunity", "Immune activation", "microbiology", "Medical microbiology", "Microbial pathogens", "Viral pathogens", "Immunodeficiency viruses", "hiv", "Diagnostic medicine", "HIV clinical manifestations", "HIV diagnosis and management", "Infectious diseases", "Viral diseases", "cells", "indoleamine", "soca", "cohort", "500"], "article_id"=>1027819, "categories"=>["Biological Sciences"], "users"=>["Sergio Serrano-Villar", "Talia Sainz", "Sulggi A. Lee", "Peter W. Hunt", "Elizabeth Sinclair", "Barbara L. Shacklett", "April L. Ferre", "Timothy L. Hayes", "Ma Somsouk", "Priscilla Y. Hsue", "Mark L. Van Natta", "Curtis L. Meinert", "Michael M. Lederman", "Hiroyu Hatano", "Vivek Jain", "Yong Huang", "Frederick M. Hecht", "Jeffrey N. Martin", "Joseph M. McCune", "Santiago Moreno", "Steven G. Deeks"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004078.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_between_the_CD4_CD8_ratio_and_the_of_CD28_CD8_T_cells_with_indoleamine_2_3_dioxygenase_1_IDO_1_activity_kinurenine_tryptophan_ratio_among_participants_in_the_SOCA_cohort_with_500_CD4_T_cells_mm_3_/1027819", "title"=>"Association between the CD4/CD8 ratio and the % of CD28−CD8+ T cells with indoleamine 2,3-dioxygenase-1 (IDO-1) activity (kinurenine/tryptophan ratio) among participants in the SOCA cohort with 500 CD4+ T cells/mm<sup>3</sup>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-15 02:59:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1498974"], "description"=>"<p>Subjects with low CD4/CD8 ratio showed higher percentages (<b>A</b>) and absolute counts (<b>B</b>) of HLADR+, CD28− and CD28−CD57+, and higher absolute counts of PD1+ cells (<b>B</b>). There were no differences in HIV-infected individuals in the proportion of CD28−CD8+ T cells expressing CD57, being significantly lower in both groups compared to HIV-/CMV+ controls.</p>", "links"=>[], "tags"=>["anatomy", "Lymphatic system", "Lymphoid organs", "cell biology", "Cellular types", "Animal cells", "Blood cells", "White blood cells", "t cells", "Immune cells", "immunology", "Clinical immunology", "HIV immunopathogenesis", "Immune response", "inflammation", "Immune system", "Acquired immune system", "Innate immune system", "immunity", "Immune activation", "microbiology", "Medical microbiology", "Microbial pathogens", "Viral pathogens", "Immunodeficiency viruses", "hiv", "Diagnostic medicine", "HIV clinical manifestations", "HIV diagnosis and management", "Infectious diseases", "Viral diseases", "counts", "activation", "phenotypes", "individuals", "art-suppressed", "hiv-infected", "patients", "cd4", "stratified"], "article_id"=>1027818, "categories"=>["Biological Sciences"], "users"=>["Sergio Serrano-Villar", "Talia Sainz", "Sulggi A. Lee", "Peter W. Hunt", "Elizabeth Sinclair", "Barbara L. Shacklett", "April L. Ferre", "Timothy L. Hayes", "Ma Somsouk", "Priscilla Y. Hsue", "Mark L. Van Natta", "Curtis L. Meinert", "Michael M. Lederman", "Hiroyu Hatano", "Vivek Jain", "Yong Huang", "Frederick M. Hecht", "Jeffrey N. Martin", "Joseph M. McCune", "Santiago Moreno", "Steven G. Deeks"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004078.g002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Percentages_and_absolute_counts_of_CD8_activation_phenotypes_among_HIV_CMV_individuals_and_ART_suppressed_HIV_infected_patients_with_CD4_counts_500_cells_mm_3_stratified_by_a_normal_4th_quartile_8805_1_in_green_or_low_1st_quartile_8804_0_4_in_red_CD4_CD8/1027818", "title"=>"Percentages and absolute counts of CD8+ activation phenotypes among HIV-/CMV+ individuals and ART-suppressed HIV-infected patients with CD4 counts >500 cells/mm<sup>3</sup> stratified by a normal (4th quartile, ≥1, in green) or low (1st quartile, ≤0.4, in red) CD4/CD8 ratio.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-15 02:59:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1498983", "https://ndownloader.figshare.com/files/1498984", "https://ndownloader.figshare.com/files/1498985", "https://ndownloader.figshare.com/files/1498986", "https://ndownloader.figshare.com/files/1498988", "https://ndownloader.figshare.com/files/1498989", "https://ndownloader.figshare.com/files/1498990", "https://ndownloader.figshare.com/files/1498992", "https://ndownloader.figshare.com/files/1498993", "https://ndownloader.figshare.com/files/1498994", "https://ndownloader.figshare.com/files/1498996"], "description"=>"<div><p>A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined. Using data from four distinct clinical cohorts and three clinical trials, we show that a low CD4/CD8 ratio in HIV-infected adults during otherwise effective ART (after CD4 count recovery above 500 cells/mm<sup>3</sup>) is associated with a number of immunological abnormalities, including a skewed T cell phenotype from naïve toward terminally differentiated CD8+ T cells, higher levels of CD8+ T cell activation (HLADR+CD38+) and senescence (CD28− and CD57+CD28−), and higher kynurenine/tryptophan ratio. Changes in the peripheral CD4/CD8 ratio are also reflective of changes in gut mucosa, but not in lymph nodes. In a longitudinal study, individuals who initiated ART within six months of infection had greater CD4/CD8 ratio increase compared to later initiators (>2 years). After controlling for age, gender, ART duration, nadir and CD4 count, the CD4/CD8 ratio predicted increased risk of morbidity and mortality. Hence, a persistently low CD4/CD8 ratio during otherwise effective ART is associated with increased innate and adaptive immune activation, an immunosenescent phenotype, and higher risk of morbidity/mortality. This ratio may prove useful in monitoring response to ART and could identify a unique subset of individuals needed of novel therapeutic interventions.</p></div>", "links"=>[], "tags"=>["anatomy", "Lymphatic system", "Lymphoid organs", "cell biology", "Cellular types", "Animal cells", "Blood cells", "White blood cells", "t cells", "Immune cells", "immunology", "Clinical immunology", "HIV immunopathogenesis", "Immune response", "inflammation", "Immune system", "Acquired immune system", "Innate immune system", "immunity", "Immune activation", "microbiology", "Medical microbiology", "Microbial pathogens", "Viral pathogens", "Immunodeficiency viruses", "hiv", "Diagnostic medicine", "HIV clinical manifestations", "HIV diagnosis and management", "Infectious diseases", "Viral diseases", "individuals", "antiretroviral", "altered", "heightened", "non-aids", "morbidity"], "article_id"=>1027827, "categories"=>["Biological Sciences"], "users"=>["Sergio Serrano-Villar", "Talia Sainz", "Sulggi A. Lee", "Peter W. Hunt", "Elizabeth Sinclair", "Barbara L. Shacklett", "April L. Ferre", "Timothy L. Hayes", "Ma Somsouk", "Priscilla Y. Hsue", "Mark L. Van Natta", "Curtis L. Meinert", "Michael M. Lederman", "Hiroyu Hatano", "Vivek Jain", "Yong Huang", "Frederick M. Hecht", "Jeffrey N. Martin", "Joseph M. McCune", "Santiago Moreno", "Steven G. Deeks"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1004078.s001", "https://dx.doi.org/10.1371/journal.ppat.1004078.s002", "https://dx.doi.org/10.1371/journal.ppat.1004078.s003", "https://dx.doi.org/10.1371/journal.ppat.1004078.s004", "https://dx.doi.org/10.1371/journal.ppat.1004078.s005", "https://dx.doi.org/10.1371/journal.ppat.1004078.s006", "https://dx.doi.org/10.1371/journal.ppat.1004078.s007", "https://dx.doi.org/10.1371/journal.ppat.1004078.s008", "https://dx.doi.org/10.1371/journal.ppat.1004078.s009", "https://dx.doi.org/10.1371/journal.ppat.1004078.s010", "https://dx.doi.org/10.1371/journal.ppat.1004078.s011"], "stats"=>{"downloads"=>43, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HIV_Infected_Individuals_with_Low_CD4_CD8_Ratio_despite_Effective_Antiretroviral_Therapy_Exhibit_Altered_T_Cell_Subsets_Heightened_CD8_T_Cell_Activation_and_Increased_Risk_of_Non_AIDS_Morbidity_and_Mortality_/1027827", "title"=>"HIV-Infected Individuals with Low CD4/CD8 Ratio despite Effective Antiretroviral Therapy Exhibit Altered T Cell Subsets, Heightened CD8+ T Cell Activation, and Increased Risk of Non-AIDS Morbidity and Mortality", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-05-15 02:59:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/1498982"], "description"=>"<p>Because of colinearity, we fitted one model to calculate the coefficients of CD4+ and CD8+ T cells, and a different model for the CD4/CD8 ratio.</p><p>Variables CD4+ and CD8+ T cells, and the CD4/CD8 ratio were log transformed.</p><p>Coefficients are adjusted by age, gender, nadir CD4+ T cell count and duration of viral suppression.</p><p>To interpret the logarithmically transformed coefficients, we applied the following formula: <i>Beta*log(1.10)</i>, resulting in the % of change in the odds of the outcome predicted by each 10% increase in the independent variable.</p>", "links"=>[], "tags"=>["anatomy", "Lymphatic system", "Lymphoid organs", "cell biology", "Cellular types", "Animal cells", "Blood cells", "White blood cells", "t cells", "Immune cells", "immunology", "Clinical immunology", "HIV immunopathogenesis", "Immune response", "inflammation", "Immune system", "Acquired immune system", "Innate immune system", "immunity", "Immune activation", "microbiology", "Medical microbiology", "Microbial pathogens", "Viral pathogens", "Immunodeficiency viruses", "hiv", "Diagnostic medicine", "HIV clinical manifestations", "HIV diagnosis and management", "Infectious diseases", "Viral diseases", "linear", "regression", "associations", "kt", "soca"], "article_id"=>1027826, "categories"=>["Biological Sciences"], "users"=>["Sergio Serrano-Villar", "Talia Sainz", "Sulggi A. Lee", "Peter W. Hunt", "Elizabeth Sinclair", "Barbara L. Shacklett", "April L. Ferre", "Timothy L. Hayes", "Ma Somsouk", "Priscilla Y. Hsue", "Mark L. Van Natta", "Curtis L. Meinert", "Michael M. Lederman", "Hiroyu Hatano", "Vivek Jain", "Yong Huang", "Frederick M. Hecht", "Jeffrey N. Martin", "Joseph M. McCune", "Santiago Moreno", "Steven G. Deeks"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1004078.t004", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Multivariate_linear_regression_analysis_Associations_of_the_KT_ratio_dependent_variable_with_CD4_and_CD8_T_cells_and_the_CD4_CD8_ratio_independent_variables_in_SOCA_cohort_/1027826", "title"=>"Multivariate linear regression analysis: Associations of the KT ratio (dependent variable) with CD4+ and CD8+ T cells, and the CD4/CD8 ratio (independent variables) in SOCA cohort.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-05-15 02:59:35"}

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