Phase 2 (community based clinical setting) sensitivity, specificity, and predictive values for the 3 point-of-care tests to detect or exclude anemia.

<p>Phase 2 (community based clinical setting) sensitivity, specificity, and predictive values for the 3 point-of-care tests to detect or exclude anemia.</p

Diagnostic Accuracy of the HemoCue Hb 301, STAT-Site M^Hgb and URIT-12 Point-of-Care Hemoglobin Meters in a Central Laboratory and a Community Based Clinic in Durban, South Africa

<div><p>In South Africa, various point-of-care hemoglobin meters are used. However, the regulatory framework for approval, implementation and oversight of use of point-of-care hemoglobin meters is suboptimal. We assessed the diagnostic accuracy of the HemoCue Hb 301, STAT-Site M^Hgb and URIT-12 point-of-care hemoglobin meters, compared to a central laboratory based reference assay, in a central laboratory and a community based clinic in Durban, South Africa. Differences in performance of the point-of-care assays, compared to the reference assay, were more pronounced in the community based clinic. Results were reasonable for the HemoCue Hb 301, but poor for the STAT-Site M^Hgb and the URIT-12. Poor test performance of point-of-care hemoglobin meters, and inadequate evaluations and oversight in South Africa, leads to suboptimal clinical care and clinical research, and increased costs. There is a need for proper evaluation and quality assurance of point-of-care tests, the results of which should be made widely available to key stakeholders.</p></div

Correlation of the 3 point-of-care assays with values within the dynamic range of the reference Hemoglobin meter in 60 samples in a central laboratory (phase 1), and 100 samples in a community based clinical setting (phase 2).

<p>In phase 1 of the study the STAT-Site had a high failure rate. It seems that this was related to uneven migration of the sample through the sample strip, resulting in the sample migration time exceeding the maximum time specified by the manufacturer.</p

Bland-Altman plots comparing the reference laboratory test with the 3 point-of-care assays in phase 1 (left column) and phase 2 (right column).

<p>In phase 1 of the study the STAT-Site had a high failure rate. It seems that this was related to uneven migration of the sample through the sample strip, resulting in the sample migration time exceeding the maximum time specified by the manufacturer.</p

Correlation of the 3 point-of-care assays with values within the dynamic range of the reference hemoglobin meter in 100 samples in a community based clinical setting in phase 2 of the study.

<p>Dots in the blue quadrant indicate that the point-of-care assay missed anemia, i.e., misclassified a finger prick sample as non-anemic where the venous blood sample was classified as anemic according to the reference assay in a central laboratory. Dots in the red quadrant indicate that the point-of-care assay misclassified as anemic a sample that was non-anemic according to the reference assay.</p

Gating strategy for the different substrate uptake by the different leukocytes.

Gating strategy for the different substrate uptake by the different leukocytes.</p

Study participant characteristics.

BackgroundFor optimal functionality, immune cells require a robust and adaptable metabolic program that is fueled by dynamic mitochondrial activity. In this study, we investigate the metabolic alterations occurring in immune cells during HIV infection and antiretroviral therapy by analyzing the uptake of metabolic substrates and mitochondrial phenotypes. By delineating changes in immune cell metabolic programming during HIV, we may identify novel potential therapeutic targets to improve anti-viral immune responses.MethodsAfter consent and voluntary participation was confirmed, whole blood was drawn from HIV uninfected women and women with chronic HIV infection on long-term combination antiretroviral therapy (HIV/cART). Peripheral blood mononuclear cells-derived immune cells were directly incubated with different fluorescently tagged metabolites and markers of mitochondrial activity: FITC-2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose), FITC-BODIPY (4,4-Difluoro-5,7-Dimethyl-4-Bora-3a,4a-Diaza-s-Indacene-3-Hexadecanoic Acid), FITC-MitoTracker Green and APC-MitoTracker Deep Red. The uptake of glucose and fats and the mitochondrial mass and potential were measured using flow cytometry. All values are reported quantitatively as geometric means of fluorescence intensity.ResultsDuring chronic HIV infection, cellular uptake of glucose increases in HIV+ dendritic cells in particular. CD4+ T cells had the lowest uptake of glucose and fats compared to all other cells regardless of HIV status, while CD8+ T cells took up more fatty acids. Interestingly, despite the lower utilization of glucose and fats in CD4+ T cells, mitochondrial mass increased in HIV+ CD4+ T cells compared to HIV negative CD4+ T-cells. HIV+ CD4+ T cells also had the highest mitochondrial potential.ConclusionsSignificant disparities in the utilization of substrates by leukocytes during chronic HIV/cART exist. Innate immune cells increased utilization of sugars and fats while adaptive immune cells displayed lower glucose and fat utilization despite having a higher mitochondrial activity. Our findings suggest that cART treated HIV-infected CD4+ T cells be dysfunctional or may prefer alternative fuel sources not included in these studies. This underscores the importance of understanding the metabolic effects of HIV treatment on immune function.</div

Gating strategy for the different leukocyte populations.

Gating strategy for the different leukocyte populations.</p

Gating strategy for the different leukocyte populations.

Gating strategy for the different leukocyte populations.</p

HIV-1 viral loads in plasma and cerebrospinal fluid (CSF).

<p>(A) Plasma viral loads are significantly higher than CSF viral loads in ART-naïve participants. (B) For ART-experienced participants with meningitis, there was no significant difference in HIV-1 viral load levels when comparing plasma versus CSF. (C) HIV-1 viral loads in the CSF versus plasma of ART-naïve patients with tuberculous meningitis (TBM), showing no significant differences between the two compartments. (D) ART-naïve non-TBM patients had significantly higher plasma compared to CSF viral loads. (E) Plasma viral loads of ART-naïve patients with TBM versus other meningitides are not significantly different. (F) Significantly higher HIV-1 viral loads in CSF of ART-naïve TBM patients compared to those with other meningitides. P-values are shown for each comparison and are bolded if the differences are statistically significant.</p