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

HIV specific CD4+ and CD8+ T cell functionality is reduced in HIV infected individuals co-infected with latent Mycobacterium tuberculosis infection (LTBI) and active Tuberculosis (TB) disease.

<p><b>(A)</b> Representative flow cytometry plots showing cytokine responses for HIV (gag), control (no antigen) for HIV mono-infected subjects, and subjects co-infected with latent MTB infection (LTBI) and active tuberculosis (TB) <b>(B)</b> HIV-specific CD4+ release of IFNγ (p<0.001), TNFα (p<0.01) and IL-2 (p<0.01) were significantly different between all groups (Kruskal-Wallis). <b>(C)</b> HIV-specific CD8+ release of IFNγ (p<0.01) and TNFα (p<0.001) was significantly lower from HIV mono-infected subjects, to those co-infected with active TB. We additionally assessed the polyfunctionality profile of HIV specific CD4+ and CD8+ T cells in all patient groups. The polyfunctionality profiles between groups differed significantly for both CD4+ (p = 0.04) and CD8+ (p<0.001).<b>(D)</b> HIV-specific CD4+ T cells from HIV mono-infected subjects displayed a polyfunctional CD4+ T cell profile with a maximum of four functions being present (IFN⁺IL-2⁺IL-17⁺TNFα (2%)).<b>(E)</b> HIV-specific four function CD4+ T cells were not present in subjects co-infected with LTBI <b>(F)</b> Further decreases in HIV-specific CD4+ T cell polyfunctionality were observed in HIV positive subjects co-infected with TB, being replaced by a largely mono-functional profile with a decreased amount of triple cytokine cells (5% as compared to 13% in HIV/LTBI and 15% in HIV mono-infection). Additionally, single positive TNF-α cells dominated the profile (48%). <b>(G)</b> HIV-specific CD8+ T cells in HIV mono-infected subjects displayed a polyfunctional profile with a maximum of 2 functions being present (IFN⁺ TNFα (2%). <b>(H)</b> A maximum of 2 functions (IFN⁺TNFα⁺ (28%)) were present in HIV-specific CD8+ cells from subjects co-infected with LTBI. <b>(I)</b> 87% mono-functional cells were present in the HIV-specific CD8+T cell profile from subjects co-infected with TB, suggesting a complete loss of polyfunctionality.</p

Clinical characteristics of HCV-infected individuals.

<p>*p.i. =  post infection; Risk factor for HCV acquisition; GT =  HCV genotype; ND = not determined. # normal range of ALT = 7–56 IU/ml, AST = 5–40 IU/ml.</p

Immunophenotypic profiles of blood and liver-resident NK cell subsets.

<p>Immunophenotyping of liver and blood NK cell subsets in groups of HCV-infected and –uninfected individuals was performed by flow cytometry, and both tissue-specific differences (A) and disease-specific differences (B) were analyzed. Data is presented as a heatmap, with values displayed as relative within each row. Statistical significance was accepted at p<0.05 and is indicated by * (p<0.05), ** (p<0.01), *** (p<0.001) and **** (p<0.0001).</p

NK cell subsets and distribution in liver and blood.

<p>NK cells were identified in the blood and liver of groups of HCV-infected and -uninfected individuals by flow cytometry using a robust gating strategy (A). The size of the NK and T cell populations as a percentage of the total lymphocyte population, as well as the T:NK cell ratio was calculated in the liver and blood in HCV-infected and -uninfected individuals (B), as was the contribution of the CD56^bright and CD56^dim NK cell subsets to the total NK cell population (C). Statistical significance was accepted at p<0.05 and is indicated by * (p<0.05), ** (p<0.01) and *** (p<0.001).</p

Incidence of mitochondrial toxicity, death and loss to follow-up by initial treatment.

1<p>Primary endpoint: 37 lactic acidosis, 43 hyperlactatemia.</p>2<p>As indicated by clinician report in the medical record.</p

Unique liver and blood NK phenotypes associate with markers of disease progression.

<p>Correlative analysis of NK cell immunophenotype and function in the liver and blood with clinical measures of HCV infection such as ISHAK score, ALT, AST, serum bilirubin, HCV RNA and INR were performed. The significant associations of liver NK cell receptors with clinical markers are displayed (A) along with correlations between the frequency of CD161+, (B) and perforin expression on blood CD56^bright NK cells (C) with clinical markers and the expression of other NK cell receptors. Correlations were done using Spearman's rank test and statistical significance was accepted at p<0.05 and is indicated by * (p<0.05), ** (p<0.01) and *** (p<0.001).</p

Reasons for liver surgery in non-HCV infected individuals.

<p>Reasons for liver surgery in non-HCV infected individuals.</p

Patient characteristics at study entry by treatment arm, limited to women with BMI≥25 kg/m².

1<p>T-test for continuous where mean and standard deviation reported, and Wilcoxon rank sum where median and IQR reported.</p