Ana Maria Tudor

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

Chatting online – is this good for you?

Methods We analyze different aspects of a project developed by nongovernmental organizations for people affected by HIV, namely the Romanian Anti-AIDS Association (ARAS), the National Union of Organizations of People Affected by HIV/AIDS (UNOPA) along with the Romanian HIV/AIDS Center and the National Institute for Infectious Diseases “Prof. Dr. Matei Bals”. Medical, psychological and social support was given by Matei Bals personnel. The conferences offered direct connection between AIDS care specialists and patients. The IT logistics was provided by Data Center Solutions.

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.

Birth defects in HIV vertically exposed children

Objective: to identify types of birth defects in HIV vertically exposed children and to determine the rate of congenital disorders counted in children born to HIV infected mothers. We analyzed the data recorded for HIV perinatally exposed children followed up in the National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest, the Pediatric Department from January 1st 2006 to December 31st 2012. Of 203 children with data on clinical, imagistic and virologic aspects, 20% were diagnosed with HIV infection and more than 33% had at least one congenital condition. The birth defects identified in studied children were: congenital heart defects 63%, musculoskeletal defects 23%, renal malformations 10%, neurologic defects 10%, digestive tract malformations 5%, metabolic and storage disorders 2% and genetic disorders 2%. 9% from studied children with birth defects had more than one organ involvement. Among HIV infected children the most frequent congenital disease was heart malformation, followed by renal and neurologic malformations. In total less than 30% from HIV vertical infected children and more than 33% HIV exposed but negative children had congenital diseases. The difference is not statistically significant (p=0.38). Comparing the group of children born by treated mothers to those from untreated mothers we have noticed that the use of antiretrovirals during or before pregnancy is not associated with malformations (p=0.45). In the same time the risk of congenital diseases in our patients is associated with mothers being part of Romanian cohort (p=0.05). The relative risk to have malformations in the second generation of Romanian cohort is 1.49 higher comparing with children born by more recently infected mothers. We also found very rare congenital diseases: chromosomal hermaphroditism, gangliosidosis and Niemann Pick syndrome (less than 1/100,000 live births). The rate of malformations is relatively high among HIV exposed children compared with general population in Romania and it was associated with long history of HIV disease (Romanian cohort).

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.

Antiretroviral treatment and association with prematurity in perinatal HIV-exposed children

Results From 206 children with complete 18 months follow up, 21% (43 cases) were diagnosed with HIV infection and more than 33% had at least one congenital condition. We found birth defects in various organs in studied children: heart (130 cases), musculoskeletal system (47 cases), kidney (20 cases), nervous system (20 cases), digestive tract (10 cases) and metabolic and genetic disorders (2 cases each). 26 from the 163 HIV-exposed children and 6 from the 43 HIV-infected cases were born before 37 weeks of gestation, 4 HIV-exposed and 4 HIV-infected children were small for gestational age. We found low birth weight (<2500 g) in 18 HIV-exposed children and 3 HIV infected children and extremely low birth weight (1000) in one HIV-exposed child. We found congenital malformation in 11 preterm HIV-exposed children and 2 preterm HIV-infected children, but also in 38 HIV-exposed children and 19 HIV-infected babies with normal gestation period. The difference between the rate of congenital malformation and prematurity was not statistically significant (p=0.08) in any of studied groups and HIV diagnosis was not associated with a higher risk of preterm birth (p=0.93). Mother being part of the Romanian cohort was not statistically associated with higher risk of prematurity. We found a significant association between antiretroviral treatment during pregnancy and prematurity (p=0.003). The most used drugs to treat mothers were boosted protease inhibitors (99% cases).

Evaluation of adipose tissue changes with bioimpedance and dual-energy X-ray absorptiometry in treatment of multi-experienced HIV-infected patients

Multi-experienced HIV-infected patients bear the burden of treatment-related toxicities over the years. This study evaluated the correlation between bioimpedance- and DXA-quantified changes of adipose tissue with duration of infection and duration of combined antiretroviral therapy (cART) in HIV-seropositive patients. A cross-sectional study, belonging to prospective grant PNCDI2 no.62077/2008, was conducted in a national reference hospital in 2011-2012. DXA whole-body adipose tissue analysis and bioimpedance analysis revealed fat and lean tissue (% and grams), android/gynoid distribution, arm+legs/trunk ratio and waist/hip ratio (WHR). There were 78 patients enrolled, including the control seronegative group. HIV-seropositive patients had equal sex distribution, median age of 33 years with mode of 20 years and body mass index of 23.6 kg/sqm [21;25.7]. Duration of diagnosed infection, duration of cART and number of previous therapeutic regimens had medians of 69 months [36;113], 57 months [27;111] and 2 [1;3], respectively. Among all variables, WHR correlated with duration of infection (rho= -0.36, p=0.05), duration of cART (rho= -0.36, p=0.05) and duration of number of therapeutic regimens (rho= -0.48, p=0,007). Also fat and lean tissue, as grams, correlated with duration of cART - rho= -0.26, p=0.048 for both. In this young treatment-experienced HIV-infected population undergoing antiretroviral therapy, the waist/hip ratio correlated best with the number of previous therapeutic regimens, inversely proportional. Adipose changes, measured by bioimpedance and DXA, were rather correlated with treatment duration than with time from diagnosis. Patients experiencing the history of antiretrovirals still present adverse effects on long term, which could influence their adherence to antiretrovirals.

Resistin, insulin sensitivity and markers of inflammation in a cohort of Romanian patients under combined antiretroviral therapy

Methods We performed a transversal study that used the following inclusion criteria: non-diabetic patients with documented HIV infection, undergoing stable cART for at least 6 months. Clinical, metabolic, inflammatory and immuno-virological patterns were assessed (age, sex, body mass index, HIV load, actual and nadir CD4, duration of HIV infection and antiretroviral therapy, lipid panel, C-reactive protein CRP). Resistin levels were evaluated using KAPME Biosource EASIA. In order to test the sensitivity to insulin we used the QUICKI index, the best surrogate marker after glucose clamp index. Parametric and non-parametric variables were described using means (±Standard Deviation SD) and medians (Interquartile Ratio IQR), respectively.

Tuberculosis in children perinatally exposed to HIV in the current epidemiological TB context

Method During 01.01.2011 -01.07.2014 in the Immunocompromised Children Department from the National Institute for Infectious Diseases “Prof. Dr. Matei Bals” we analyzed the dynamical evolution of 214 perinatally HIV exposed children, aged 0-4 years. Lack of vaccination due to prematurity and the degree of immunosuppression in maternity contributed considerably to the increased incidence of TB in the family’s epidemiological context (at least one family member is diagnosed with tuberculosis). A troubling aspect is that these children come from families with resistant forms of tuberculosis (TB MDR) due to their parents’ poor adherence to treatment, mainly those pertaining to the 1989-1993 HIV cohort in Romania.

Leptin dysfunction and the risk of dyslipidemia and metabolic syndrome in Romanian HIV-infected patients undergoing antiretroviral therapy

Leptin is a hormone secreted by the adipose tissue that may be associated in the general population with components of the metabolic syndrome (MS). Our objective was to test the association between dyslipidemia, MS presence and circulating leptin dysfunction in a cohort of HIV-infected non-diabetic patients undergoing combinant antiretroviral therapy (cART). We included HIV-infected non-diabetic consecutive patients undergoing cART, admitted to the National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, between 2008-2011. The diagnosis of MS was made using the International Diabetes and American Heart Association harmonized criteria from 2009. Circulating levels of leptin (BioSource EASIA) were measured. We enrolled 95 patients: 53 (55.8%) males (mean age=33.1±13.4 years) and 42 (44.2%) females (mean age=30.5±13.6 years). Most patients (72.5%) had undetectable HIV viral load; median CD4 count was 493.5 (IQR=422)/cmm. The median time from HIV diagnosis was 60 (IQR=73) months. The median time on cART was 58.5 (IQR=70) months, 53.8% of patients had experienced more than one cART regimen. The prevalence of MS was 17.1%. Elevated blood pressure, elevated waist circumference and abnormal fasting glucose prevalences were 30.3%, 17.1% and 6.5%, respectively. Median serum leptin was 1.89 (IQR=3.57) ng/mL. Circulating leptin dysfunction was present in almost half of patients, hypoleptinemia being more frequent (42.%) than hyperleptinemia (8.5%). Hypoleptinemia was more frequent in men (62.3%) comparative to women (17.1%), p=0.000. The prevalence of MS in patients with hypoleptinemia was 25.8% vs 10.8% in persons with normal leptin values (p=0.261). Hypoleptinemia was associated with elevated waist circumference (p=0.004) and abnormal fasting glucose (p=0.05) in women. More than half (65.6%) of men with hypoleptinemia had reduced HDL-cholesterol levels vs 29.4% in men with normal levels of leptin. As expected, hyperleptinemia was associated with the increase of body mass index, both in men (p=0.000) and women (p=0.05). In our cohort of young cART multiexperienced HIV patients leptin dysfunction was not significantly associated with MS presence. Leptin was correlated with several MS components (HDL-dyslipidemia, elevated circumference, abnormal fasting glucose) with significant gender differences, that suggests that leptin may play different roles in the regulation of glucose and lipid metabolism according to the sex.