CD4 count outcomes at 12 and 30 months based on patient demographic and pre-HAART characteristics.

<p>CD4 count outcomes at 12 and 30 months based on patient demographic and pre-HAART characteristics.</p

CD4+ T-cell count trajectories and baseline characteristics predicting failure of CD4 cell count recovery.

<p><b>A</b>. CD4+ T-cell count trajectories for all 442 subjects over the course of 30 months. The red line reflects the median±SEM. <b>B</b>. OR and 95% confidence intervals (CI) for not achieving CD4 counts above 200 cells/mm³ at 12 months (grey) and 500 cells/mm³ at 30 months (black) depending on baseline characteristics. Shown are only factors with significant or close to significant effect in the multivariate model.</p

Clinical and immunological characteristics of viremic non-progressors and putative progressors.

<p>(<b>A</b>) Estimated duration of HIV diagnosis based on first HIV+ test. (<b>B</b>) Plasma HIV RNA in VNPs and PPs as measured by RT-PCR. (<b>C</b>) The fraction of CD4+ T cells in VNPs and PPs measured by flow cytometry. (<b>D</b>) Absolute CD4+ T cell count in blood from VNPs and PPs based on CD4+ T cell fraction and lymphocyte count by CBC. <i>p</i> values from Mann Whitney T test. Line reflects median. Circles, VNPs; Squares, PPs.</p

Transcriptomic signatures between HIV-infected putative progressors and viremic non-progressors.

<p>Gene expression profiles from whole blood were assayed by microarray analysis. (<b>A</b>) Prinicipal components analysis was used to assess the divergence of the entire transcriptomic profile of the patient classes. (<b>B</b>) Volcano plot showing the distribution of fold-changes and significance level between the PP and VNP phenotypes and the <i>p</i>-value assessed by two-sample t-test. Red data points indicate genes upregulated in PP patient samples, defined as >1.5-fold greater than the VNP samples, and a <i>p</i>-value of <0.05. Blue data points indicate genes >1.5-fold in VNPs with 0.05 p-value. The y-axis is plotted as the log of the inverse of the p-value. (<b>C</b>) Pathway analysis of genes differentially expressed between VNPs and PPs was performed using the Gene Ontology database. Fisher's exact test was used to estimate the significance of enrichment an annotations of probesets on the arrays were used as a background. The forest plot shows genes identified by GO as have immune function and divides them into GO subcategories. (<b>D</b>) Heat map showing the overall concordance amongst patients in each class. The top 50 most highly expressed genes were median-normalized and organized by hierarchical clustering using Pearson's dissimilarity metric and average linkage. (<b>E</b>) Forest plot of 52 genes defined in the GO category “Immune Process” in panel C. Branches indicate subcategories, the number of genes with higher expression in each phenotype are indicated by the scale on the x-axis, and the magnitude of the fold-change is indicated by the color scale. (<b>F</b>) Relative expression of ISGs between phenotypes. (<b>G</b>) Forest plots of individual genes contained with GO categories and unincorporated immune genes. *probeset is predicted to hybridize to multiple genes. (<b>H & I</b>) Gene Set Enrichment plots of ISGs and IL6 signaling genes. GSEA performed using geneset permutation, and array data ranked by signal-to-noise ratio. Vertical dotted lines indicate the margin between gene upregulated in VNPs (left) and PPs (right) of all non-redundant, annotated genes on the array. Data points in red indicate leading edge genes contributing to the majority of the enrichment score.</p

CD4+ T cell memory subset numbers are associated with differential preservation mechanisms.

<p>CD4+ T_CM cells (<b>A–B</b>): Correlation between frequency of CD4+Ki67+ memory cells and absolute number of CD4+ T_CM cells in VNPs (<b>A</b>) and PPs (<b>B</b>). CD4+ T_SCM cells (<b>C–D</b>) Correlation between frequency of CD4+Ki67+ memory cells and absolute number of CD4+ T_SCM cells in VNPs (<b>C</b>) and PPs (<b>D</b>). (<b>E</b>) Correlation between HIV DNA infection per 100 CD4+ T_SCM cells and absolute number of CD4+ T_SCM cells. CD4+ T_EM cells (<b>F–H</b>): Correlation between frequency of CD4+Ki67+ memory cells and absolute number of CD4+ T_EM cells in VNPs (<b>F</b>) and PPs (<b>G</b>). (<b>H</b>) Correlation between frequency of CD4+CD38+HLA-DR+ memory T cells and absolute number of CD4+ T_EM cells. <i>p</i> and r values from spearman correlations, with linear regression shown as line. Box around significant (<i>p</i><0.05) values. Circles, VNPs; Squares, PPs.</p

Patient characteristics.

<p>Patient characteristics.</p

T cell proliferation and activation in VNPs and PPs.

<p>(<b>A–B</b>) The frequency of activated CD38+HLA-DR+ T cells in VNPs and PPs by flow cytometry: (<b>A</b>) total CD4+ CD38+HLA-DR+ T cells and (<b>B</b>) CD8+ CD38+HLA-DR+ T cells. (<b>C–D</b>) The frequency of proliferating (Ki67+) VNPs and PPs by flow cytometry: (<b>C</b>) total CD4+Ki67+ T cells and (<b>D</b>) total CD8+Ki67+ T cells. (<b>E–G</b>) The absolute count of Ki67+CD4+ T cell memory subsets measured by flow cytometry and lymphocyte count by CBC for: (<b>E</b>) CD4+Ki67+ T_EM cells; (<b>F</b>) CD4+Ki67+ T_CM cells; (<b>G</b>) and CD4+Ki67+ T_SCM cells. <i>p</i> values from Mann Whitney T test. Line reflects median. Circles, VNPs; Squares, PPs.</p

VNPs have decreased HIV infection of central memory and stem cell memory T cells.

<p>CD4+ T_EM cells (left), T_CM (center), and T_SCM (right) from VNPs and PPs were sorted by flow cytometry and quantitaive real-time PCR was used to determine the HIV infection frequency in each subset. Infection frequency was determined by copies of <i>gag</i> DNA/100 infected cells. <i>p</i> values from Mann Whitney T test (VNPs vs PPs) or paired T test (T_CM vs T_EM within PP cohort). Line reflects median. Circles, VNPs; Squares, PPs.</p