Interferon-Gamma Release Assays for the Diagnosis of Active Tuberculosis in HIV-Infected Patients: A Systematic Review and Meta-Analysis

BACKGROUND: Interferon-gamma release assays (IGRAs) have provided a new method for the diagnosis of Mycobacterium tuberculosis infection. However, the role of IGRAs for the diagnosis of active tuberculosis (TB), especially in HIV-infected patients remains unclear. METHODS: We searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001-July 2011 that evaluated the evidence of using QuantiFERON-TB Gold in-tube (QFT-GIT) and T-SPOT.TB (T-SPOT) on blood for the diagnosis of active TB in HIV-infected patients. RESULTS: The search identified 16 eligible studies that included 2801 HIV-infected individuals (637 culture confirmed TB cases). The pooled sensitivity for the diagnosis of active TB was 76.7% (95%CI, 71.6-80.5%) and 77.4% (95%CI, 71.4-82.6%) for QFT-GIT and T-SPOT, respectively, while the specificity was 76.1% (95%CI, 74.0-78.0%) and 63.1% (95%CI, 57.6-68.3%) after excluding the indeterminate results. Studies conducted in low/middle income countries showed slightly lower sensitivity and specificity when compared to that in high-income countries. The proportion of indeterminate results was as high as 10% (95%CI, 8.8-11.3%) and 13.2% (95%CI, 10.6-16.0%) for QFT-GIT and T-SPOT, respectively. CONCLUSION: IGRAs in their current formulations have limited accuracy in diagnosing active TB in HIV-infected patients, and should not be used alone to rule out or rule in active TB cases in HIV-infected patients. Further modification is needed to improve their accuracy

Proteomic analysis of PBMCs: characterization of potential HIV-associated proteins

<p>Abstract</p> <p>Background</p> <p>The human immunodeficiency virus type 1 (HIV-1) pandemic has continued unabated for nearly 30 years. To better understand the influence of virus on host cells, we performed the differential proteome research of peripheral blood mononuclear cells (PBMCs) from HIV-positive patients and healthy controls.</p> <p>Results</p> <p>26 protein spots with more than 1.5-fold difference were detected in two dimensional electrophoresis (2DE) gels. 12 unique up-regulated and one down-regulated proteins were identified in HIV-positive patients compared with healthy donors. The mRNA expression of 10 genes was analyzed by real time RT-PCR. It shows that the mRNA expression of talin-1, vinculin and coronin-1C were up-regulated in HIV positive patients and consistent with protein expression. Western blotting analysis confirmed the induction of fragments of vinculin, talin-1 and filamin-A in pooled and most part of individual HIV-positive clinical samples. Bioinformatic analysis showed that a wide host protein network was disrupted in HIV-positive patients.</p> <p>Conclusions</p> <p>Together, this work provided useful information to facilitate further investigation of the underlying mechanism of HIV and host cell protein interactions, and discovered novel potential biomarkers such as fragment of vinculin, filamin-A and talin-1 for anti-HIV research.</p

Clinical features and prognosis of AIDS complicated by drug-induced liver injury: an analysis of 119 cases

ObjectiveTo investigate the clinical features and prognosis of AIDS patients complicated by drug-induced liver injury (DILI). MethodsA total of 119 patients who were diagnosed with AIDS in First Department of Infectious Diseases in Shanghai Public Health Clinical Center from January 2014 to December 2015 and met the diagnostic criteria for DILI were enrolled. The clinical data including medications, CD4+ T lymphocyte count, clinical manifestations, liver biochemical parameters, therapies, duration of liver injury, and prognosis were analyzed, and DILI type and classification were determined for all patients. The influence of DILI caused by different drugs on liver biochemical parameters was analyzed. The Wilcoxon rank sum test was used for comparison of continuous data between two groups and the Kruskal-Wallis H test was used for comparison between multiple groups; the chi-square test was used for comparison of categorical data between groups. ResultsThe 58 patients who received highly active antiretroviral treatment (HAART) had significantly higher grade of liver injury (χ2=15.756, P＜0.001) and levels of total bilirubin (TBil) (Z=-3.466, P=0.010) and albumin (Alb) (Z=-1.968, P=0.049) than the 61 patients who did not. Among the patients who had a clear cause of DILI, 8 had DILI caused by antifungal drugs, 41 had DILI caused by antibacterial drugs, 18 had DILI caused by antitubercular agents, and 24 had DILI caused by antiviral drugs; the patients with DILI caused by antitubercular agents had a significantly higher level of TBil than those with DILI caused by other three types of drugs (H=12.804, P＜0.05), the patients with DILI caused by antibacterial drugs and antitubercular agents had a significantly lower level of Alb than those with DILI caused by the other two types of drugs (H=14.236, P＜0.05), and the patients with DILI caused by antitubercular agents and antiviral drugs had a significantly higher grade of liver injury than those with DILI caused by the other two types of drugs (χ2=16.373, P＜0.05). The hepatocellular injury-type patients had a shorter length of hospital stay (χ2=8.046, P=0.045). A high level of alkaline phosphatase and a low level of alanine aminotransferase indicated a longer length of hospital stay (Z=-2.943 and -2.592, both P＜0.05). ConclusionAIDS patients are given various drugs and have a high incidence rate of DILI. HARRT can aggravate liver injury, but it does not significantly affect patients' prognosis. Liver function examination should be performed regularly during clinical medication to know the state of liver inflammation and reduce the incidence rate of DILI in AIDS patients

Reasons and Risk Factors for the Initial Regimen Modification in Chinese Treatment-Naïve Patients with HIV Infection: A Retrospective Cohort Analysis.

To investigate the reasons and risk factors for modification of the first combined antiretroviral therapy (cART) currently used for HIV infected patients who were treatment naïve in Shanghai China.Making a retrospective observational research on treatment naïve patients with HIV infection who initiated cART during the period of September 1st 2005---December 1st 2013. The demographic and clinical data were collected from the first visit to the time of the first regimen modification or the last visit in December 1st, 2014. The reasons of treatment modification were recorded. Survival analysis of modification was made by Kaplan-Meier curves analysis and log rank test, and a Cox multiple regression model was constructed to identify related factors of modification.A total number of the eligible participants were 3372 and 871(25.8%) patients changed their first cART regimen. The median follow up was 22 months [interquartile range (IQR) 14-39]. Among patients who modified the original regimen, drug toxicity occurred in 805(92.4%) participants and 44(5.1%) experienced treatment failure. In multiple regression analysis regimen modification was associated with patients' age more than 40 years old (aHR 1.224, 95%CI 1.051-1.426, P = 0.010), CD4 less than 200(aHR 1.218, 95%CI 1.044-1.421, P = 0.012) and the initial regimen they received. Compared with the regimen of TDF+3TC+EFV, patients with regimen of d4T+3TC+NVP, d4T+3TC+EFV, AZT+3TC+NVP or AZT+3TC+EFV were 10.4, 8.2, 6.4, 2.5 times more likely to modify their initial regimen, respectively.The main reason for the regimen switch was drug toxicity and main risk factors for regimen modification were age older than 40 years, CD4 cell counts less than 200 at baseline and regimen they received. Among the 2NRTI plus 1NNRTI regimens, the co-formulation of d4T+3TC+NVP had the highest risk for modification while the regimen of TDF+3TC+EFV was the most tolerable treatment regimen in first years' follow up

Anti-retroviral therapy decreases but does not normalize indoleamine 2,3-dioxygenase activity in HIV-infected patients.

Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, catabolizes tryptophan to kynurenine and other downstream catabolites. It is known to be an immune mediator in HIV pathogenesis. The impact of anti-retroviral therapy on its activity has not been well established.We measured systemic IDO activity (the ratio of plasma kynurenine to tryptophan) in HIV-infected patients before and after highly active antiretroviral therapy (HAART) and its association with a microbial translocation marker, soluble CD14 (sCD14).Among 76 participants, higher baseline IDO activity was associated with lower CD4+ T cell counts (P<0.05) and higher plasma sCD14 levels (P<0.001). After 1 year of HAART, IDO activity decreased significantly (P<0.01), but was still higher than in healthy controls (P<0.05). The baseline IDO activity did not predict CD4+ T cell recovery after 1 year of therapy. The percentages of myeloid and plasmacytoid dendritic cells were not correlated with IDO activity.IDO activity is elevated in HIV-infected patients, which is partially associated with microbial translocation. HAART reduced, but did not normalize the activity of IDO

Anti-Retroviral Therapy Decreases but Does Not Normalize Indoleamine 2,3-Dioxygenase Activity in HIV-Infected Patients

<div><p>Background</p><p>Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, catabolizes tryptophan to kynurenine and other downstream catabolites. It is known to be an immune mediator in HIV pathogenesis. The impact of anti-retroviral therapy on its activity has not been well established.</p><p>Methods</p><p>We measured systemic IDO activity (the ratio of plasma kynurenine to tryptophan) in HIV-infected patients before and after highly active antiretroviral therapy (HAART) and its association with a microbial translocation marker, soluble CD14 (sCD14).</p><p>Results</p><p>Among 76 participants, higher baseline IDO activity was associated with lower CD4⁺ T cell counts (<i>P</i><0.05) and higher plasma sCD14 levels (<i>P</i><0.001). After 1 year of HAART, IDO activity decreased significantly (<i>P</i><0.01), but was still higher than in healthy controls (<i>P</i><0.05). The baseline IDO activity did not predict CD4⁺ T cell recovery after 1 year of therapy. The percentages of myeloid and plasmacytoid dendritic cells were not correlated with IDO activity.</p><p>Conclusions</p><p>IDO activity is elevated in HIV-infected patients, which is partially associated with microbial translocation. HAART reduced, but did not normalize the activity of IDO.</p></div

Adipose-derived stem cells show hepatic differentiation potential and therapeutic effect in rats with acute liver failure

Hepatocyte transplantation contributes to the repair of liver damage, but hepatocyte resources are limited, making it difficult for this to become a routine treatment. Previous studies have confirmed that mesenchymal stem cells (MSCs) can be induced to differentiate into hepatocyte-like cells (HLCs) by adding different cytokine combinations in vitro, and they then play some roles of hepatocytes. Our previous studies found that the differentiation ability of stem cells is closely related to the origin of the tissue. To identify the mesenchymal stem cells that are most suitable for hepatic differentiation and the treatment of liver failure, we use a three-phase induction process in which human adipose-derived stem cells (hADSCs) and umbilical cord mesenchymal stem cells (hUCMSCs) are induced to differentiate towards HLCs in vitro, and rats with acute liver failure (ALF) induced by D-gal are cured by MSCs and MSC-derived HLCs (MSCs-HLC), respectively. We find that hADSCs are stronger than hUCMSCs in hepatic differentiation ability, and they have a better curative effect when using hADSCs-HLC or jointly using hADSCs and hADSCs-HLC, which has positive significance for hepatocyte regeneration, recovery of liver function and reduction of systemic inflammatory reaction, finally improving the survival rate of rats with acute liver failure