Apostolia Margariti

Time trends and correlates of late presentation for HIV care in Northern Greece during the decade 2000 to 2010

The aim of our study was to assess the extent of late presentation for HIV care in Northern Greece during the period 2000 to 2010 and to explore correlations aiming to provide guidance for future interventions.

High rates of transmitted drug resistance among newly-diagnosed antiretroviral naïve HIV patients in Northern Greece, data from 2009–2011

We conducted a retrospective study on the prevalence and correlates of transmitted drug resistance among newly-diagnosed antiretroviral naive human immunodeficiency virus (HIV) patients in Northern Greece, during the period 2009-11. Transmitted drug resistance was documented in 21.8% of patients enrolled, affecting approximately 40% of subtype A HIV-1-infected individuals. Overcoming challenges due to the ongoing financial crisis, effective preventive measures should be implemented to control further dissemination of resistant HIV strains.

The role of Visfatin in atherosclerotic peripheral arterial obstructive disease

ABSTRACT Visfatin is an adipokine molecule acting as an essential coenzyme in multiple cellular redox reactions. The increased serum levels of Visfatin have been correlated with metabolic syndrome and endothelial homeostasis. In this study we investigate the possible relationship of Visfatin serum levels with the severity and location of atherosclerotic peripheral arterial occlusive disease (PAOD). Study protocol included 45 consecutive PAOD and 20 Control patients with age >55 years old. Definition of PAOD was based in Rutherords classification (RC). End‐stage PAOD patients (RC‐V & ‐VI) were excluded from study. Data were collected prospectively and included age, gender, atherosclerotic risk factors and the body mass index (BMI). In PAOD patients recorded the PAODs clinical stage and the presence of carotid stenosis >50%. PAOD patients divided in two subgroups, those with mild (RC‐I & ‐II) and moderate disease (RC‐III & ‐IV). In all serum samples Visfatin was measured, blindly, twice by anosoenzymatic technique. Statistical analysis was performed by non‐parametric Mann‐Whitney U test, Pearsons chi‐square, One Way Anova and Kruskall‐Wallis tests, as appropriate. The mean Visfatin value in PAOD and Control groups were 38.5 ± 16.0 and 13.9 ± 3.8 ng/ml respectively (p < 0.0005). In‐PAOD subgroup of patients the visfatin values were not affected by demographics, BMI and atherosclerotic risk factors (p > 0.05). Univariate analysis showed that severity of PAOD (mild vs severe), presence of carotid stenosis >50% and multilevel disease significantly affected outcomes (p = 0.018, p = 0.010 and p = 0.006 respectively). In multivariate regression analysis severity of PAOD was the solely factor with strong correlation with high visfatin values (p = 0.001). High Visfatin levels seem to be strongly correlated with the presence and severity of PAOD. Further and in depth investigation is needed to define the possible role of Visfatin in atherosclerosis and its value as a potential prognostic biomarker of PAOD.

Comparing Abbott m2000 RealTime HIV test and Roche COBAS Ampliprep/COBAS Taqman HIV test, v2.0 in treated HIV-1 B and non-B subjects with low viraemia.

Viral load testing is a valuable tool in HIV clinical care and research. Discrepancies among diverse viral load assays, especially with regard to non‐B HIV‐1 subtypes have been reported. Our study aimed to explore the impact of HIV subtype (B versus non‐B) on the agreement between CAP/CTM, v2.0 and m2000 RealTime in treated HIV patients, focusing on low viral loads (<200 copies/ml). Our findings indicate that there is a significant difference in the performance of the compared assays in the low‐viremic range and non–B subtypes, suggesting that a single assay should be used for follow‐up. J. Med. Virol. 88:724–727, 2016.

The controversial impact of B cells subsets on immune response to pneumococcal vaccine in HIV-1 patients.

BACKGROUND Chronic HIV infection leads to severe perturbations of the B cell populations and hypo-responsiveness to vaccines. The associations between circulating B cell subpopulations and the antibody response to pneumococcal polysaccharide vaccine in antiretroviral-naïve and treated patients were studied. METHODS Sixty-six HIV-infected adults were grouped according to antiretroviral therapy (ART) and CD4+ cell count; 31 were ART-naïve and 35 were ART-treated, and they were matched for age, CD4 cell count, and duration of HIV infection. All subjects were immunized with the 23-valent polysaccharide vaccine against Streptococcus pneumoniae. Pre- and post-vaccination B cell subpopulations were assessed by flow cytometry. Serum IgG concentrations for vaccine serotypes were quantified by ELISA at baseline and at 4 and 48 weeks post-vaccination. RESULTS Patients under highly active antiretroviral therapy (HAART) had significantly higher antibody levels against pneumococcal vaccine antigens, while an adequate number of patients responded to vaccination. Memory B cells were diminished over time, although treated patients maintained higher levels of all subsets studied, with the exception of activated memory and isotype-switched memory B cells. CONCLUSIONS Low concentrations of total B cells and exhausted memory B cells was the strongest independent predictor of poor pneumococcal vaccine responsiveness, emphasizing that B cell subset disturbances are associated with a poor vaccine response among HIV-infected patients.

Deficient Phagocytosis Among HIV-1 Infected Adults Over Time Even in HAART Setting

BACKGROUND Phagocytosis is regarded to be impaired in HIV-1 infected adults, leading to high frequency and severity of several infections in this population. Data is contradictory with regards to individual facets in HIV infection. OBJECTIVE Aim of this study was to assess the phagocytic activity during the natural course of HIV infection. METHOD It is a longitudinal study assessing natural course and impairment of neutrophil and monocyte phagocytosis in both naïve and HAART treated patients. RESULTS A lower neutrophil phagocytic activity was recorded in naïve patients compared to treated patients. Interestingly, a downward trend of neutrophil phagocytic activity was recorded in both groups, irrespectively of HAART intake, within 48 weeks of observation. CONCLUSION Defects of innate immunity appear to be present in HIV infected patients regarding phagocytic activity of monocytes and of neutrophils which seems to decline over time. These deficiencies are influenced by the levels of CD4 cell counts and viral load.

Evaluation of blood T-lymphocyte subpopulations involved in host cellular immunity in dogs with mammary cancer

Cancer-bearing patients are often immunosuppressed. In dogs with mammary or other cancers, various alterations in blood cell populations involved in host cellular immunity have been reported; among these cell populations some T-lymphocyte subsets play an important role against cancer. The purpose of the present study was to investigate any alterations in circulating T-lymphocyte subpopulations involved in cellular immunity in bitches with mammary cancer, in comparison to age-matched healthy intact bitches. Twenty eight dogs with mammary cancer and 14 control dogs were included in this study. Twelve out of the 28 bitches had mammary cancer of clinical stage II and 16/28 of stage III. Histological examination revealed that 23/28 animals had carcinomas, 3/28 sarcomas and 2/28 carcinosarcomas. White blood cell, neutrophil and lymphocyte absolute numbers were measured by complete blood count. Furthermore, blood T-lymphocyte population (CD3+) and the subpopulations CD4+, CD8+ and CD5low+ were assessed by flow cytometry. White blood cell and neutrophil but not lymphocyte absolute numbers were higher (P=0.003 and P=0.001, respectively) in cancer patients than controls. Flow cytometric analysis revealed that the relative percentage of T-lymphocytes (CD3+) and of CD4+, CD8+ subpopulations was lower (the CD4+/CD8+ ratio was higher), whereas the percentage of CD5low+ T-cells was higher, in dogs with cancer compared to controls; however, a statistically significant difference was found only in the case of CD8+ T-cells (P=0.014), whereas in the case of the CD4+/CD8+ ratio the difference almost reached statistical significance (P=0.059). Based on these findings, it can be suggested that, although the absolute number of blood lymphocytes is unchanged, the relative percentages of T-lymphocyte subpopulations involved in host cell-mediated immunity are altered, but only cytotoxic CD8+ T-cells are significantly suppressed, in dogs with mammary cancer of clinical stage II or III compared to age-matched healthy controls.

Prevalence and correlates of persistent intracellular HIV transcription in individuals on efavirenz versus atazanavir-based regimens: A prospective cohort study

Objectives Despite successful virological suppression, HIV transcription frequently persists intracellularly. In this study, we hypothesize that HIV persistent transcription(HIVpt) may affect to a different extent patients on stable efavirenz(EFV) versus atazanavir(ATV)-based regimens. The role of the expression of drug efflux transporters in HIVpt was also investigated. Methods We prospectively enrolled 51 virologically suppressed patients on first-line treatment for one year with EFV or ATV combined with emtricitabine and tenofovir and followed them up for one year. Simultaneous ultrasensitive subpopulation staining/hybridization in situ(SUSHI) was performed to identify HIVpt in CD4+ T-cells and in the CD4+CD45RO+ T-cell subpopulation. The differential mRNA expression of P-glycoprotein(P-gp/ABCB1) and multidrug resistance-associated protein-1(MRP1/ABCC1) was also evaluated. Univariate logistic regression models were used to evaluate predictors of HIVpt. Results In the CD4+ T-cell population, HIVpt affected 13/30 of patients on EFV versus 10/21 on ATV. In the CD4+CD45RO+ T-cell population, HIVpt was present in 14/30 of patients on EFV versus 15/21 on ATV. A trend for association was observed between the risk of HIVpt and ATV treatment in the CD4+CD45RO+ T-cell population (OR 2.86, 95% CI 0.87–9.37, p = 0.083). HIVpt status was not associated with loss of virological suppression or CD4 evolution. We found no evidence of differential expression of the drug efflux transporters P-gp and MRP1. Conclusions Further study is required to evaluate whether the HIVpt profile in specific cell populations may differ across different antiretroviral regimens and to elucidate the potential clinical impact.

West Nile virus meningitis in a patient with human immunodeficiency virus type 1 infection

The emergence of West Nile virus lineage 2 in central Macedonia, Greece, in 2010 resulted in large outbreaks for 5 consecutive years. We report a case of viral meningitis in an individual infected with human immunodeficiency virus type 1, which preceded the recognition of the outbreak and was confirmed retrospectively as West Nile virus neuroinvasive disease.

Antiretroviral naive and treated patients: Discrepancies of B cell subsets during the natural course of human immunodeficiency virus type 1 infection

AIM To evaluate alterations of memory B cell subpopulations during a 48-wk period in human immunodeficiency virus type 1 (HIV-1) patients. METHODS Forty-one antiretroviral naïve and 41 treated HIV-1 patients matched for age and duration of HIV infection were recruited. All clinical, epidemiological and laboratory data were recorded or measured. The different B cell subsets were characterized according to their surface markers: Total B cells (CD19+), memory B cells (CD19+CD27+, BMCs), resting BMCs (CD19+CD27+CD21high, RM), exhausted BMCs (CD19+CD21lowCD27-, EM), IgM memory B (CD19+CD27+IgMhigh), isotype-switched BMCs (CD19+CD27+IgM-, ITS) and activated BMCs (CD19+CD21low+CD27+, AM) at baseline on week 4 and week 48. RESULTS Mean counts of BMCs were higher in treated patients. There was a marginal upward trend of IgM memory B cell proportions which differed significantly in the treated group (overall trend, P = 0.004). ITS BMC increased over time significantly in all patients. Naive patients had of lower levels of EM B cells compared to treated, with a downward trend, irrespectively of highly active antiretroviral therapy (HAART) intake. Severe impairment of EM B cells was recorded to both treated (P = 0.024) and naive (P = 0.023) and patients. Higher proportions of RM cells were noted in HAART group, which differed significantly on week 4th (P = 0.017) and 48th (P = 0.03). Higher levels of AM were preserved in HAART naive group during the whole study period (week 4: P = 0.018 and 48: P = 0.035). HIV-RNA viremia strongly correlated with AM B cells (r = 0.54, P = 0.01) and moderately with RM cells (r = -0.45, P = 0.026) at baseline. CONCLUSION HIV disrupts memory B cell subpopulations leading to impaired immunologic memory over time. BMC, RM, EM and ITS BMC were higher in patients under HAART. Activated BMCs (AM) were higher in patients without HAART. Viremia correlated with AM and RM. Significant depletion was recorded in EM B cells irrespectively of HAART intake. Perturbations in BMC-populations are not fully restored by antiretrovirals.