Mihai Lazăr

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

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).

Body composition in HIV-infected patients receiving highly active antiretroviral therapy

Background: The development of combination antiretroviral therapies (cART) represents a significant advance in the treatment of (human immunodeficiency virus) HIV infection. However, several studies report that a large percentage of individuals with HIV, particularly those receiving cART, present body composition differences compared with the general population. The aim of this study was to explore body composition differences by dual-energy X-ray absorptiometry (DEXA), among HIV-positive patients receiving cART, in comparison to healthy controls. Methods: The cross-sectional study included 60 HIV-infected patients (all under 50 years old). We analyzed the association of antiretroviral medication use and different HIV-related factors, to the body composition parameters. Results: Our cohort had significantly lower fat mass and lower bone mass compared to non HIV-infected persons. Median time since HIV infection diagnosis was 5 years (interquartile range, [IQR], 2–10.25) and viral suppression was achieved in 49 (81.66%) patients. Treatment with protease inhibitors (PIs) was strongly correlated with low fat mass, reduced lean mass and loss of bone mineral density. Nucleoside reverse transcriptase inhibitors (NRTIs)-containing treatment was associated with decrease of lean tissue mass (LM). The prevalence of osteopenia was 41.67% at the lumbar spine (L1–L4) and 36.7% at the hip. We found osteoporosis in 10% of the patients at the lumbar spine. Reduced bone mass was associated, in the patient group, with the duration of PIs use and with smoking (in the males group). Conclusion: In our research, HIV-infected individuals compared to healthy controls had body composition differences, including fat mass atrophy and reduced bone mineral content.

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.

Hepato-porto-biliary changes following a high energy electrical shock

Present day increasing dependence on electricity, in both home and work environments, can lead, if the necessary precautions are not met, to a wide type of injuries, from cutaneous burns to important visceral lesions. We report the case of a 44 year-old male with cutaneous and severe visceral lesions, paresis and paresthesia of the right upper limb induced by a high energy electrical shock. No psychiatric manifestations were observed. This case followed an unusual course due to the particular evolution of the hepatic lesions, which included necrosis, abscesses, thrombosis and angiocholitis.

Jetrena osteodistrofija: globalni pre(po)gled problema

Hepatic osteodystrophy is a common and frequently untreated complication, manifested as osteoporosis or osteopenia, encountered in the evolution of chronic liver diseases. This article provides a narrative review of hepatic osteodystrophy. The aim is to revise the prevalence, pathophysiology, diagnosis and management of hepatic osteodystrophy. We searched medical literature via PubMed, Google Scholar, Wiley, Science Direct, and Springer Link using respective keywords to obtain data on low bone mineral density connected to chronic liver diseases. Many studies have reported an increased prevalence of osteoporosis/osteopenia in patients with chronic liver diseases. The pathogenesis is multifactorial, involving genetic factors, vitamin deficiencies, proinflammatory cytokines, hypogonadism, hyperbilirubinemia, antiviral therapy, corticosteroid drugs, and lifestyle factors. The management of patients should include individualized assessment for fracture risk factors and bone mineral density. Vitamin D and calcium supplementation should be recommended in all patients with chronic liver diseases and osteoporosis. Bisphosphonates are the most efficient drugs used in the treatment of hepatic osteodystrophy. In the future, it is necessary to define better the management and specific treatment of hepatic osteodystrophy for prevention of fragility fractures and to improve the patient quality of life.

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.

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.

Whole-body DXA evaluation in HIV patients

Background After the introduction of highly active antiretroviral therapy for the treatment of HIV infection, metabolic abnormalities were increasingly observed, associated with both protease inhibitors and nucleoside reverse transcriptase inhibitors, characterized by abnormal fat distribution in the body (lipoatrophy, lipohypertrophy or both), hyperglycemia and lean tissue mass wasting. However such metabolic changes are not always treatment related, having a multifactorial etiology. Dual-energy X-ray absorptiometry (DXA) evaluates the quantity of body fat and lean tissue and their distribution, allowing the diagnosis of both quantitative and qualitative changes.