Cătălin Tilişcan

Correlation between inflammatory biomarkers and metabolic disorders in HIV infected patients undergoing antiretroviral therapy

Correlation between inflammatory biomarkers and metabolic disorders in HIV infected patients undergoing antiretroviral therapy Raluca Mihăilescu, Victoria Aramă, Cătălin Tiliscan, Daniela Munteanu, Viorica Leoveanu, Mihaela Rădulescu, Adriana Hristea, Cristina Popescu, Ruxandra Moroti, Violeta Molagic, Raluca Năstase, Loredana Benea, Ana Maria Tudor, Mihai Lazăr, Anca-Ruxandra Negru, Irina Lăpădat, Ligia Ionescu, Mirela Cernat, Georgeta Jugănaru, Doina Cristea, Adriana Manea, Adrian Streinu-Cercel, Daniela Adriana Ion, Sorin Ștefan Aramă

Serum adipokines and HIV viral replication in patients undergoing antiretroviral therapy.

INTRODUCTION Several studies have reported that cytokines secreted by adipose tissue (adipokines) may be linked to HIV replication. The aim of the study was to evaluate the relationship between HIV replication and serum levels of adipokines, in a Caucasian HIV-infected population of men and women undergoing complex antiretroviral therapy. METHODS A cross-sectional study was conducted in an unselected sample of 77 HIV-1-positive patients. Serum adipokines levels were measured including circulating adiponectin, leptin, resistin, tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Patients were divided into two groups: Group 1 - with undetectable viral load and Group 2 - with persistent HIV viral replication. Differences between groups ? were tested using independent-sample t-test for Gaussian variables and Mann-Whitney-Wilcoxon test for non-parametric variables. Pearsons chi-squared test was used for correlation analysis. RESULTS A total of 77 patients (age range: 17-65, mean: 32.5 years) including 44 men (57.1% men, age range: 17-63 years, mean: 34.1 years) and 33 women (42.9% women age range: 19-65 years, mean: 30.3 years) were included in the study. TNF-alpha had significantly higher serum levels in patients with detectable viral load (16.89 vs. 9.35 pg/mL), (p=0.043), but correlation analysis lacked statistical significance. Adiponectin had median serum levels of 9.22 ìg/mL in Group 1 vs. 16.50 ìg/mL in Group 2 but the results lacked statistical significance (p=0.059). Higher leptin, IL-6 and resistin serum levels were noted in patients with undetectable HIV viral load, without statistical significance. CONCLUSIONS The present study reported higher TNF-alpha serum levels in patients with persistent HIV viral load. We found no statistically significant correlations between adiponectin, leptin, resistin and IL-6 and HIV viral load in our Caucasian HIV-positive study population, undergoing antiretroviral therapy.

Tumor necrosis factor alpha – an useful biomarker in a combined predictive model for liver fibrosis staging in patients with chronic HCV infection

Background Staging liver fibrosis in chronic HCV infection represents an important step for an individualized management. In the last decade the liver biopsy was less used for fibrosis staging due to its invasive nature and risk of complications. Multiple non-invasive methods were developed for the evaluation of liver fibrosis, none of these being an ideal one. The aim of this study was to evaluate the diagnostic accuracy of a new non-invasive method designed to differentiate patients with significant liver fibrosis from those without. (F2-F4 vs. F0-F1).

In the era of broad spectrum antibiotics, is ampicillin still an option?

Background In the era of broad spectrum antibiotics it is sometimes difficult to choose the best antimicrobial regimens. Because of misuse and abuse of antimicrobial usage, the level of resistance is increasing and sometimes we do not have treatment options. Infectious diseases specialists traditionally have the leadership role in optimal use of antimicrobials. Antimicrobial stewardship represents a worldwide accepted concept in order to preserve currently available antibiotics.

Leptin expression in HIV-infected patients during antiretroviral therapy.

BACKGROUND Leptin is an adipokine with complex metabolic, neuroendocrine and immune functions. Our objective was to evaluate leptin serum levels in a cohort of Romanian HIV-infected patients undergoing antiretroviral therapy in relation to their immune-virological status, lipid and glucose metabolic abnormalities and the presence of metabolic syndrome (MS). METHODS We enrolled consecutive non-diabetic HIV-infected patients aged 18 and over on stable cART for at least 6 months. Blood samples were tested for: leptin, CD4 T cells count, HIV viral load and lipid panel. RESULTS A total of 90 HIV-infected patients were included in the study: 50 males (55.6%) with a mean age of 33.3 years and 40 females with a mean age of 30.4 years. Most patients (74.4%) had HIV viral load below the limit of detection and the median CD4 count for the cohort was 476 (410) cells/cmm. More than one third of the patients (41.1%) had hypoleptinemia. The prevalence of MS was 13.3%. Hypoleptinemia was significantly more frequent in men. In a subset of patients with undetectable HIV viral load, the median leptin value was 0.6 (6.07) ng/mL in patients with poor immune recovery (CD4 count ≤ 200/cmm) compared to 2 (3.07) ng/mL for those with better immune response (CD4 count > 200/cmm), without statistical significance. The median values of leptin were similar for persons with and without MS criteria. HDL-cholesterol values were positively correlated to leptin values in a linear regression model. CONCLUSION A significant proportion of patients in our study presented low levels of leptin; this finding was not associated with immune and virological parameters or the presence of MS. Hypoleptinemia was significantly correlated with lower levels of HDL-cholesterol, a key cardiovascular risk factor.

HIV-associated Burkitt lymphoma with bone marrow and cerebral invasion in a patient with history of Plasmodium falciparum infection

HIV infected patients are more likely to develop non-Hodgkin lymphoma (NHL). Burkitt lymphoma (BL) is a highly aggressive NHL, associated with immunosuppression, especially with HIV. According to WHO classification there are three clinical types of BL: endemic, sporadic and immunosuppression-associated. Sporadic lymphoma was described especially in children (40% of child lymphomas in USA and EU). Two cofactors seem to be associated with BL: Ebstein Barr virus (EBV) and Plasmodium falciparum (PF) infection. PF and EBV are well-known co-factors in the pathogenesis of BL, but the mechanisms of interaction remain unclear. We present a 51 year-old male, who developed lymphadenopathy, prolonged fever, weight loss, splenomegaly and seizure. The patient was admitted to a Hematology University Hospital. After lymph node biopsy he was diagnosed with BL. A specimen of bone marrow from the right iliac crest showed gross invasion by Burkitt tumor cells. The patient tested positive for HIV and he was referred to the National Institute of Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest. According to CDC Classification System for HIV Infection the patient had AIDS (C3 stage with a CD4 count of 39/cmm) and a high HIV viral load (500,262 copies/mL). The patient’s medical history revealed Plasmodium falciparum malaria 4 years ago, while he was living in South America. Epidemiological data revealed more than 200 sexual partners in the last two years. At admission to our hospital he had pancytopenia: white blood cells 1400/cmm, with 600 neutrophils and 600 lymphocytes, hemoglobin 9.6 g/dL and platelet count 25,000/cmm. The patient was tested for EBV infection and high titer of anti-VCA antibodies was found. ART was initiated with TDF-FTC-lopinavir/r with good virological outcome (after 6 weeks of therapy the viral load was 383 copies/mL). Cerebral MRI showed diffuse lymphomatous invasion. After 3 weeks of ART the patient was referred to Hematology Hospital where chemotherapy was started. Post-chemotherapy the pancytopenia was more severe: white blood cells – 200/cmm with CD4 count – 10/cmm, platelets – 15,000/cmm and hemoglobin – 7.9 g/dL. The BL response after chemotherapy was poor and the patient died two months after the diagnosis, despite the good virological outcome. We present a rare case of NHL in a HIV-infected patient, with multiple co-factors for BL: HIV infection, EBV infection and Plasmodium falciparum infection. The prognostic in AIDS depends on the comorbidities’ outcome.

Metabolic syndrome, insulin resistance and the risk of cardiovascular disease in HIV patients undergoing antiretroviral therapy

We enrolled 103 patients, including 60 males (58.3%) and 43 females (41.7%). The mean age was 32.3±13.3 years (range: 13-65 years). The median Framingham score was 1.2% (IQR=5.8%). Most patients (81.63%) had a low CVR (below 10%) and 18.37% had Framingham score values above 10%. MS and IR prevalences were 16.9% and 61.2%, respectively. CVR in the general population is primarily dependent on age. This observation was valid for our group: the median age was 24 years in people with low CVR, compared with 50 years for those with Framingham score above 10% (p=0.000). None of the antiretroviral drug classes significantly influenced CVR.

The Importance of Haemogram Parameters in the Diagnosis and Prognosis of Septic Patients

Abstract Sepsis represents a severe pathology that requires both rapid and precise positive and differential diagnosis to identify patients who need immediate antimicrobial therapy. Monitoring septic patients′ outcome leads to prolonged hospitalisation and antibacterial therapy, often accompanied by substantial side effects, complications and a high mortality risk. Septic patients present with complex pathophysiological and immunological disorders and with a predominance of pro-inflammatory or anti-inflammatory mediators which are heterogeneous with respect to the infectious focus, the aetiology of sepsis or patients′ immune status or comorbidities. Previous studies performed have analysed inflammatory biomarkers, but a test or combinations of tests that can quickly and precisely establish a diagnosis or prognosis of septic patients has yet to be discovered. Recent research has focused on re-analysing older accessible parameters found in the complete blood count to determine the sensitivity, specificity, positive and negative predictive values for the diagnosis and prognosis of sepsis. The neutrophil/lymphocyte count ratio (NLCR), mean platelet volume (MPV) and red blood cells distribution width (RDW) are haemogram indicators which have been evaluated and which are of proven use in septic patients′ management.

The multiple faces of tuberculosis in HIV infected patients – a continuous challenge

Tuberculosis (TB)/HIV co-infection represents a major problem in many regions of the world, including Romania. TB is a leading cause of death among people infected with HIV and HIV infection is the most important risk factor for progression from latent to active TB. TB can occur at any stage of HIV disease and its manifestations depend on the severity of immunosuppression. The proportion of extra-pulmonary tuberculosis in HIV infected patients has increased. Aim: to analyze the cases of pulmonary and extrapulmonary TB in HIV-seropositive patients monitored in Third Department of the “Matei Bals” Institute. We performed a retrospective analysis of all HIV infected patients monitored in our clinic from 2000 to 2014 in order to establish the location of TB, the diagnosis methods, the correlation with the immune status and the outcome. 122 patients were retrospectively analyzed; from them, 18 patients were diagnosed with certain, probable or possible TB infection (14.75%). Sex ratio in TB group was M:F=1.57:1 and mean age was 39.7 years old at the moment of TB diagnosis. TB occurs at a variable level of immunosuppression (CD4 count from 6 to 460/cmm) - 4 patients (22.2%) in stage 2 - CD4=200-500/cmm and 14 patients (77.8%) in stage 3 - CD4<200/cmm. Mean CD4 count in TB group was 113.23/cmm vs. 218.33 mean nadir CD4 count in non-TB group. Pleuro-pulmonary TB accounted for only 27.7% of all cases - one pleural effusion and 4 pulmonary TB. In most of cases, TB infection was extrapulmonary (72.3%): 5 cases of meningoencephalitis (27.7%), 3 cases of disseminated TB (16.66%), 2 cases of lymph node TB (11.11%) and 3 cases with unknown location (16.66%). TB was microbiologically confirmed in only 6 cases – 33.33%, 3 by blood culture, 2 by PCR (one from CSF and one from pleural effusion) and 1 by histopathologic exam (lymph node biopsy). In 9 cases TB was probable but without bacteriologic confirmation and in 3 cases TB was possible – prolonged fever with a good outcome under anti-TB medication. Quantiferon TB was performed in only 8 cases – in 6 cases was positive, in one case was negative and in one case was undetermined. Three patients died: one patient because of disseminated TB and two patients because of other HIV-related comorbidities. HIV infected patients developed especially extra-pulmonary TB infection. TB can occur in any stage of HIV infection. Microbiological diagnosis in TB is positive in a small number of cases.

Variation in CD4 cell count among IDUs versus sexually-infected HIV-positive naïve patients in Romania

Since 2011 Romania is experiencing a dramatic increase of newly diagnosed HIV infections among injecting drug users (IDUs), mainly linked to the introduction of new psychoactive substances (NPS) on the Romanian market, their use being related to higher levels of risk behavior compared to opioid abuse. There is no sufficient data showing the natural course of HIV in subjects infected through IDU – the majority are ART-naive due to recently acquired infection (many are asymptomatic and have a CD4 cell count over 350 cells/cmm) and poor adherence. Our objective was to determine if IDUs have a faster decline in CD4 cells than sexually-infected patients. We performed a retrospective study, including ART-naive HIV-positive patients diagnosed between January 2011 and June 2013 at the National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, who had 2 subsequent CD4 cell count determinations over a timespan of 6-24 months and a baseline CD4 count higher than 350 cells/cmm. Among 1,248 newly diagnosed patients, 234 met these inclusion criteria. The data were statistically analyzed using SPSS version 17 (independent sample t-test, Mann-Whitney test, linear regression; the significance level was set at 0.05). The majority (80%, 187/234) were men and the median age was 29 years (15-76). More than half of the patients (138; 59%) were former or active IDUs, with low socioeconomic status, most of them injecting both opioids and NPS and 55 (40%) of them were in detention at the moment of HIV diagnosis. Among them, 98% were coinfected with HCV, as opposed to only 21% of the sexually-infected patients. Subtype analysis was performed for 64 patients and revealed the following subtypes and circulating recombinant forms (CRF): 50 F1, 3 B, 10 CRF14_BG and 1 CRF14_F. There was no significant difference of CD4 cell count between the two groups at baseline (p=0.55). The median variation of CD4 cells in IDUs was 150 and 42 in the non IDUs group. IDUs had a statistically significant CD4 cell decline (p=0.01). HCV coinfection was also correlated with a faster decline in CD4 cells (p <0.001). The more rapid decline of CD4 cells among IDUs could be explained by direct effect of drugs, differences in the virulence of the HIV strains circulating among IDUs and HCV coinfection. These data highlight the importance of carefully monitoring IDUs with HIV infection and of initiating ART earlier in this risk group.