Victoria Aramă

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

The role of sonication in the microbiological diagnosis of implant-associated infections – the experience of the National Institute for Infectious Diseases “Prof. Dr. Matei Balş”, Bucharest

The role of sonication in the microbiological diagnosis of implant-associated infections – the experience of the National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest Raluca Mihăilescu, Daniela Tălăpan, Olga Dorobăț, Alexandru Rafila, Emilia Capraru, Daniela Munteanu, Anca Streinu-Cercel, Oana Streinu-Cercel, Vlad Predescu, Florian Purghel, Cătălin Cârstoiu, Razvan Ene, Dana Mihaela Jianu, Cristina Popescu, Victoria Aramă, Adrian Streinu-Cercel

Toxoplasmosis: a rare cause of IRIS in HIV infected patients. Case series

Results Three patients, one male and 2 women, aged 55 years old, respectively 41 and 42 year-old, all 3 diagnosed concomitantly with HIV infection (as very late presenters) and cerebral toxoplasmosis, with a CD4 count of 6, 6 and 7/cmm respectively, viral loads (VL) of 254,000, 57,000 and 156,000 copies/mL respectively, and CSF viral load below the plasmatic VL in all 3 cases. We recorded minimal abnormalities of CSF analysis regarding the number of cells and biochemical exams; all had positive PCR for Toxoplasma gondii in the CSF and positive serology (IgG). All 3 had intracerebral lesions (abscesses) and all were biopsied at the neurosurgery department for diagnostic purpose before knowing their HIV-positive status. They received high doses of oral trimethoprim/sulfamethoxazole (T/S) for toxoplasmosis and antiretroviral therapy in the first 2 weeks after the diagnosis. They repeated cerebral imagery (MRI) after 3 weeks of T/S and had no regression of the size of lesions (although with the decreasing of perilesional edema) and new lesions, in two cases without having corresponding symptoms; in all 3 cases the CD4 count increased in the first month more than 100%. The search for another cause for the augmentation of their brain lesions was negative. Maintaining the same medication, the next imagery exams showed improvement in 2 out of 3 cases, in which the outcome was favorable with almost complete neurological recovery. In the remaining case the evolution was unfavorable (death).

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.

Molecular determinants of resistance in Escherichia coli-ST131 isolated blood stream infections

Background During the past years an E coli clonal lineage ST131 has emerged explosively, causing predominantly communityonset antimicrobial resistant infections. E coli ST131 has been shown to harbor a number of virulence and resistance genes and is now recognized for its ability to cause potentially severe infections in many parts of the developing world, implying public health measures in attempt to control infection.

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.

Avascular osteonecrosis mechanism – between osteoporosis and antiphospholipid syndrome

HIV infected patients receiving antiretroviral therapy (ART) can develop avascular osteonecrosis, 45 times greater than the general population. Avascular osteonecrosis increased in the last few years in patients with HIV infection. The most important mechanisms for avascular osteonecrosis in HIV-infected patients are: changes in bone metabolism, especially osteoporosis correlated with protease inhibitors and coagulopathy and antiphospholipid syndrome, frequently described in HIV infection. Aim: to describe different mechanisms of avascular osteonecrosis We present two HIV-infected patients under antiretroviral therapy who developed avascular osteonecrosis. First patient, male, 38 year-old, with AIDS-C3, with good immuno-virological outcome under AZT-3TC and lopinavir/ritonavir, developed severe osteoporosis after 5 years of ART, diagnosed by DXA test with a T-score <-2,5. The patient had: C4-C5-C6 severe osteoporosis with high fracture risk, with segmental instrumentation applied at those levels, and then bilateral avascular necrosis of femoral head (ANFH) with bilateral hip arthroplasty. ART regimen was changed and the patient received 3TC-ABC and Nevirapine. The patient didn’t have other risk factors for avascular osteonecrosis or osteoporosis: nonsmoker, normal CD4, undetectable viral load, without dyslipidemia. Despite ART changes, the patient developed bilateral osteonecrosis of the right knee and of both humeral heads. The second patient, male, 23 year-old with HIV-B3, was treated in 2007 with AZT-3TC and lopinavir/ritonavir. After 9 months of ART the patient had normal CD4 count and undetectable viral load but developed right ANFH stage II, diagnosed by MRI, without surgery recommendation. DXA didn’t show signs of osteoporosis or osteopenia. The ART regimen was changed and the patient received 3TC-ABC and raltegravir with good ANFH outcome. After one year the patient discontinued the ART. One year later symptoms related with avascular osteonecrosis reappeared and bilateral ANFH was diagnosed by MRI. The patient had low CD4 count (<200/cmm), high HIV viral load and positive antiphospholipid antibodies. The patient had risk factors for coagulopathies: smoker, recreational drug user, alcohol consumer, uncontrolled HIV infection with low CD4. We restarted the same regimen with 3TC-ABC and raltegravir with a good outcome for bone affliction. When HIV infection was well-controlled, the antiphospholipid antibodies became negative and bone affliction was improved. We emphasize the importance of metabolic disturbances in HIV-infected patients, among them avascular osteonecrosis with different mechanisms. Both, ART and uncontrolled HIV infection can affect bone metabolism and vascularization.

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.