Mihaela Rădulescu

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).

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.

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.

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 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.

Antiretroviral therapy adherence monitoring and its impact on immuno-virological outcome

One of the most important factors in achieving a good outcome is treatment adherence. Poor adherence to antiretroviral therapy (ART) leads to less viral suppression, permanent treatment resistance and increased costs. There are multiple causes of poor adherence: regimen complexity, side effects etc. Aim: to analyze ART adherence, risk factors for poor adherence and their impact on the outcome. We performed a one year survey (from January to December 2013) of HIV infected patients monitored in the Third Department of the National Institute for Infectious Diseases “Prof. Dr. Matei Bals”. The data (number of days covered by ART) was collected from patients’ files. We correlated the adherence with gender, regimen rank and complexity. Statistical analysis was made using EPI INFO 6. We retrospectively analyzed 111 patients who came in to our clinic monthly to pick-up their ART, 52 women (46.84%) and 59 men (53.16%) with a mean age of 43.5 years old. The adherence to ART was: 23 (20.62%) – 100% adherence, 36 (32.43%) – more than 96.7% adherence (less than 12 days without medication), 38 (34.23%) – 91.8% to 96.7% adherence (13-30 days without medication), 10 (9%) – 83.6% to 91.8% adherence (30-60 days without medication) and 4 (3.6%) with less than 83.6% adherence (more than 60 days without medication). The level of adherence was correlated with therapeutic failure: for 100% adherence – two failures (8.69%), for more than 96.7% adherence – no failure, for more than 91.8% adherence – 4 failures (11.1%), for more than 83.6% adherence – 2 failures (20%) and for less than 80% adherence – 3 failures (75%). Adherence below 91.8% was correlated with treatment failure: RR 5.65 (CI95% 1.99; 16.09, p=0.0007). We analyzed some possible risk factors for poor adherence: gender, regimen rank and complexity. Although 51.95% from the non-adherence group were women, the adherence wasn’t correlated with gender: RR 1.23 (CI95% 0.93; 1.62, p=0.16). A regimen rank higher than 1 was correlated with low adherence – 45.76% vs. 28.84% in the adherence vs. non-adherence group: RR 1.5 (CI95% 0.95; 2.38, p=0.07). The regimen containing protease inhibitors wasn’t correlated with low adherence: 33.9% vs. 30.8%, RR 1.08 (CI95% 0.71; 1.67, p=0.73). We emphasize the impact of therapy adherence on the outcome. A level of adherence below 91% was correlated with therapeutic failure. ART adherence wasn’t correlated with gender, PI regimen and rank regimen.