Roxana Petre

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).

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.

Characteristics of Kaposi sarcoma in HIV-infected patients

Objective: to describe clinical and laboratory characteristics; to assess predictors for death in HIV-infected patients with Kaposi sarcoma (KS). We performed a retrospective study of HIV-infected patients diagnosed with KS in one infectious diseases hospital in Romania, between January 2008-November 2013. KS diagnosis was established on physical examination, skin biopsy, and for visceral involvement upper gastrointestinal endoscopy, bronchoscopy and computed tomography. KS was staged according to the AIDS Clinical Trials Group (ACTG) [1] and the Mitsuyasu classification system [2]. We identified 27 HIV-infected patients with KS. The median age was 42 years (IQR 34-52) and 18 (67%) were male. The median CD4 count at HIV diagnosis was 195 cells/cmm (IQR 55-313), while at KS diagnosis the median CD4 count was 101 cells/cmm (IQR 41-270). Eighteen (67%) patients had a CD4 count <200 cells/cmm. The median HIV viral load at the time of KS diagnosis was 120,000 copies/mL (IQR 316-328,522). HIV infection was diagnosed before KS in 19 patients (70%), with a median time between HIV and KS diagnosis of 7 months (IQR 0-58). The most frequent KS localization was the lower limb in 16 (59%) patients and 7 (26%) patients had disseminated KS. Oral, gastrointestinal and pulmonary involvements were seen in 10 (37%), 4 (15%) and 3 (11%) patients respectively. Concomitant opportunistic infections were diagnosed in 20 (74%), while other malignancies in 3 (12%) patients. According to the ACTG classification 16 (59%) patients had poor risk KS. Fifteen (56%), 6 (22%), 1 (4%) and 5 (18%) were in stage 1, 2, 3 and 4, respectively according to the Mitsuyasu classification. Six (22%) patients received specific KS treatment: three local radiotherapy and three systemic therapy (two with interferon; one with liposomal doxorubicin). The overall mortality was 41% with a median duration between KS diagnosis and death of 6 months (IQR 2-15). Gastrointestinal involvement (p=0.019), poor-risk KS in ACTG classification (p<0.001) and stage IV Mitsuyasu (p=0.006) were associated with death in univariate analysis. The mortality rate in this study was high, due to poor immunological status, extended KS and high incidence of opportunistic infections, but also due to the lack of specific systemic treatment.

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.

Clinical and epidemiologic features of community versus hospital-acquired Clostridium difficile infection

Methods We enrolled all CDI patients admitted to the Adults III department of the National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest, between January – July 2014. Stool culture, toxin EIA and Cepheid Gene Xpert C. difficile test were used for CDI diagnosis. The subjects were divided into two groups: CA-CDI patients (Group 1) and HA-CDI patients (Group 2). Our objective was to describe the clinical, epidemiologic features and outcome of CA-CDI compared to hospital-associated CDIs (HA-CDI) including the ATLAS bedside severity scoring system. Statistical analyses were performed using SPSS Statistics package v.17.

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.

The cost-effectiveness of treatment in chronic HBV non-cirrhotic hepatitis – finite versus long-life therapy.

Background Although the ideal end point of chronic HBV hepatitis therapy is HBsAg loss, a realistic end point is the induction of sustained virological remission. The definitions of virological responses vary according to therapeutic regimen: viral load <2000 IU/mL after interferon (IFN) regimens and undetectable HBV-DNA during nucleoside/nucleotide analogues (NNA) regimens. Objective: To compare the direct costs of medication between two therapeutic strategies: NNA versus NNA after IFN in non-cirrhotic patients without contraindications for IFN.

Treatment of chronic HBV hepatitis – between immune control and virological control

Background According to international guidelines, the treatment of HBV hepatitis can use both pegylated interferon (IFN) and nucleoside/nucleotide analogues with high genetic barrier (NNA). The main advantage of IFN based regimen is the possibility of immune control after a therapy with finite duration. The main advantage of NNA is the virological control during lifelong therapy. Objectives: To estimate the level of immune control after IFN therapy and the level of virological control during NNA.

Tuberculosis reactivation during novel, biologic therapy

Tuberculosis reactivation during novel, biologic therapy Cristina Popescu, Violeta Molagic, Cătălin Tiliscan, Ruxandra Moroti, Adriana Hristea, Mihaela Rădulescu, Raluca Mihăilescu, Daniela Munteanu, Iulia Niculescu, Raluca Năstase, Raluca Dulama, Alina Lobodan, Raluca Hriscă, Raluca Jipa, Anca-Ruxandra Negru, Irina Lăpădat, Roxana Petre, Mircea Chiotan, Cornel Camburu, Viorica Poghirc, Raluca Popescu, Victoria Aramă

Isolated tuberculous pericarditis, an unusual presentation of tuberculosis – a case report

Background Although during the past years a constant decreasing trend of extrapulmonary tuberculosis (TB) was registered in Romania, the number of reported cases of pericardial effusion TB remained steady at 40-50 cases annually, most of them in association with pleural effusion. Pericardial TB is a potentially lethal complication of TB and it is associated with high rates of morbidity and mortality.