Comparison between patients who interrupted ART and those with late HIV diagnosis.

Early diagnosis of human immunodeficiency virus (HIV) and retention in care are cornerstones of better prognosis of people living with HIV (PLWH). The purpose of this study was to compare patients who discontinued antiretroviral treatment (ART) with those who were diagnosed late with HIV. In this retrospective analysis of PLWH under the care of one of the Infectious Diseases Clinics in Poland between 2020 and 2021, two sub-analyses were carried out. One comparing patients who relinked to care after treatment interruption ("Group A") with those who had late HIV diagnosis ("Group B"), another comparing group A to those who were adherent to ART ("Group C"). 215 patients were included in this study (Group A = 47, Group B = 53, Group C = 115). Those who discontinued ART more often used actively drugs (p = 0.001) in comparison to those with late HIV diagnosis. In both bivariate and multivariable analysis migrants were more often diagnosed late with HIV than interrupted ART (p = 0.004 and 0.015, respectively). In the second analysis, in the multivariable analysis female sex was not associated with treatment interruption, whereas active drug usage was. People using drugs have a higher risk of ART interruption. Migrants are more at risk of late HIV diagnosis. Adequate interventions should be made towards both groups.

Adenovirus 36 Infection in People Living with HIV-An Epidemiological Study of Seroprevalence and Associations with Cardiovascular Risk Factors.

Background. With the life expectancy of people living with HIV (PLHIV) rapidly approaching that of the general population, cardiovascular health in this group is as relevant as ever. Adenovirus 36 (Adv36) is one of the few viruses suspected to be a causative factor in promoting obesity in humans, yet there is a lack of data on this infection in PLHIV. Methods. PLHIV on stable suppressive antiretroviral therapy were included in the study, with assessment of anthropometric measures, blood pressure, serum lipid levels, fasting serum glucose and insulin, non-classical serum cardiovascular risk markers related to inflammation (hsCRP, resistin, calprotectin), and anti-Adv36 antibodies during a routine check-up. Results. 91 participants were recruited, of which 26.4% were Adv36-seropositive (Adv36(+)). Compared to Adv36-seronegative (Adv36(−)) controls, Adv36(+) individuals had a lower waist circumference (Adv36(+) 89.6 ± 7.7 cm, Adv36(−) 95.5 ± 11.7 cm, p = 0.024) and a lower waist-to-hip ratio (Adv36(+) 0.88 ± 0.06, Adv36(−) 0.92 ± 0.09, p = 0.014), but this did not reach statistical significance in the multivariate analysis (p > 0.05). Adv36(+) participants were less likely to be on lipid-lowering treatment (Adv36(+) 12.5%, Adv36(−) 34.3%, p = 0.042), even after adjustment for relevant baseline characteristics (OR = 0.23, 95%CI = 0.04−0.91), but no differences in cholesterol or triglyceride levels were found. No other statistically significant associations were observed. Conclusions. We found no evidence to support the claim that past Adv36-infection is associated with an increased prevalence of cardiovascular risk factors or with elevated inflammatory markers in PLHIV. More research is needed to replicate these findings in other samples of PLHIV and to compare them with the HIV-negative population.

VCAM-1 as a Biomarker of Endothelial Function among HIV-Infected Patients Receiving and Not Receiving Antiretroviral Therapy.

The Human Immunodeficiency Virus and retroviral therapy are both known risk factors for cardiovascular disease. It remains an open question whether HIV or ARV leads to increased arterial inflammation. The objective of this study was to investigate the changes in endothelial activation by measuring VCAM-1 levels among HIV-infected patients who were and were not treated with antiretroviral therapy. It is a retrospective study that included 68 HIV-infected patients, 23 of whom were never antiretroviral-treated, 15 who were ART-treated for no longer than a year, and 30 who were ART-treated for longer than a year. Blood samples were collected for biochemical analysis of the concentration of VCAM-1. The results show a statistically lower VCAM-1 level (p = 0.007) in patients treated with ART longer than a year (1442 ng/mL) in comparison to treatment-naïve patients (2392 ng/mL). The average VCAM-1 level in patients treated no longer than a year (1552 ng/mL) was also lower than in treatment-naïve patients, but with no statistical significance (p = 0.096). Long-term antiretroviral therapy was associated with the decline of VCAM-1 concentration. That may suggest the lowering of endothelial activation and the decreased risk of the development of cardiovascular disease among ARV-treated patients. However, VCAM-1 may not be a sufficient factor itself to assess this, since simultaneously there are a lot of well-known cardiovascular-adverse effects of ART.

Significance of Vascular Cell Adhesion Molecule-1 and Tumor Necrosis Factor-Alpha in HIV-Infected Patients.

BACKGROUND: The aim of this study was the evaluation of the correlation between VCAM-1 and TNF-alpha serum concentrations and various clinical and laboratory parameters in HIV-infected patients. METHODS: All included subjects were patients of the Department of Infectious and Tropical Diseases and Hepatology of the Medical University of Warsaw in Poland in the years 2014-2016. The inclusion criteria were: confirmed HIV infection, Caucasian origin, and age > 18 years old. PCT, CRP, serum HIV-1 RNA, CD4/CD8 T cell count, PCR HCV RNA, HBsAg, VCAM-1, and TNF-alpha were measured. The VCAM-1 and TNF-alpha serum levels were evaluated by ELISA. RESULTS: Seventy-two HIV-infected patients were included (16 women and 56 men: mean age 38.7 years, 66.6% cigarette smokers, 34.7% HCV co-infected HCV, and 27.8% ART-naïve). VCAM-1 concentrations were significantly higher in HIV/HCV co-infected patients than in HIV mono-infected patients (125.6 ± 85.4 vs. 78.4 ± 58.6 ng/mL, p = 0.011) and ART-naïve in comparison to patients on cART (121.9 ± 76.5 vs. 69.4 ± 57.1 ng/mL, p = 0.003). The significant positive correlation between HCV-infection and VCAM-1 and negative correlation between cART use and VCAM-1 was confirmed in multivariate analyses. The only variable associated significantly with TNF-alpha concentration was lymphocytes T CD8+ cell count (p = 0.026, estimate = 0.033). CONCLUSIONS: Successful cART and HCV eradication seemed to play an important role in the reduction of endothelial dysfunction and persistent inflammation in HIV-infected patients. CD8 T cell count seemed to be one of the markers of the pro-inflammatory state in HIV-infection patients.

Impact of Combined Antiretroviral Therapy on Metabolic Syndrome Components in Adult People Living with HIV: A Literature Review.

The development of metabolic derangements as a result of HIV treatment has been an important area of research since the introduction of zidovudine in the 1980's. Antiretroviral therapy has intensely evolved in the last three decades, with new drugs gradually incorporated into everyday clinical practice. With the life expectancy of people living with HIV rapidly approaching that of their HIV-negative counterparts, the influence of these antiretrovirals on the development of the components of the metabolic syndrome remains of major interest to clinicians and their patients. In this review, we aimed to discuss the impact of cART on components of the metabolic syndrome, i.e., weight, plasma lipid levels, plasma glucose levels, and blood pressure, describing the influence of cART classes and of individual antiretrovirals. We also aimed to outline the limitations of the research conducted to date and the remaining knowledge gaps in this area.

Change in γ-glutamyl transpeptidase activity as a useful tool in identifying a group of patients with elevated risk of hepatocellular carcinoma development after DAA treatment of chronic hepatitis C.

AIM OF THE STUDY: Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) incidence will be diminishing due to use of direct acting antiviral agents (DAA), but there is still constant risk for HCC development. Elevated serum g-glutamyl transpeptidase (GGT) activity is associated with increased risk of liver cancer. In our study we tried to determine whether change in GGT activity may be useful in identifying patients with elevated risk of HCC development after DAA treatment. MATERIAL AND METHODS: The study population consisted of 111 patients with chronic hepatitis C (CHC) treated with DAA. Laboratory tests [alanine aminotransferase (ALT), GGT, a-fetoprotein (AFP)] and liver stiffness measurement (using FibroScan) were performed at the beginning and at the end of therapy. RESULTS: Pre-treatment ALT activity, GGT activity and AFP concentration in patients with CHC were directly associated with the stage of liver fibrosis. Elimination of HCV after DAA treatment caused significant reduction in serum GGT activity and was not associated with pre-treatment liver fibrosis. AFP concentration was significantly lower after treatment. It was observed regardless of pre-treatment AFP concentration, but the largest reduction was demonstrated in the group of patients with advanced fibrosis. In multivariate analysis there was no significant difference in GGT activity after treatment only in patients with pre-treatment normal AFP concentration and advanced liver fibrosis. CONCLUSIONS: Patients who after achieving a sustained virological response (SVR) did not lower both AFP concentration and GGT activity may have higher risk of HCC development. Special monitoring may be required in patients with advanced liver fibrosis and normal AFP concentration before treatment.

Risk Factors of Hypovitaminosis D in HIV-Infected Patients on Suppressive Antiretroviral Therapy.

Low serum vitamin D levels are very common in human immunodeficiency virus (HIV)-infected patients. In our cross-sectional study, we investigated the association between 25-hydroxyvitamin D (25(OH)D) levels and serum inflammation markers [C-reactive protein (CRP), white blood cells (WBC), D-dimers, platelet count (PLT)] in 148 HIV-infected patients on combined antiretroviral therapy [28 on tenofovir alafenamide (TAF)] and 40 healthy controls. The controls were significantly older (56.6 ± 19.1 years for HIV(-) vs. 45.1 ± 11.8 years for HIV(+); p = .001) and more females were observed in this group (65% for HIV(-) vs. 16.7% for HIV(+); p = .001). The vitamin D serum level was comparable in the two studied groups (74.2 ± 35.9 nmol/L for HIV(+) vs. 78.0 ± 27.6 nnmol/L for HIV(-), p = .545). In HIV-infected group, a significant positive correlation between CD4+ cell percentage and vitamin D level was observed (r = 0.17; p = .036). Furthermore, the significant negative correlation between vitamin D level and CD8+ cell percentage, PLT, CRP, and D-dimers was seen. In univariate analysis, only TAF use and AIDS status was associated with vitamin D level deficiency. No other antiretroviral (ARV) drug nor gender or smoking had influence on vitamin D serum level. In multivariate analysis, only AIDS status and CRP level were correlated with vitamin D level (slope estimate = 11.6 and p = .032 and slope estimate = -0.83 and p = .002; respectively). In summary, we report that low vitamin D level may be associated with high CRP level in HIV-infected patients on suppressive antiretroviral therapy, especially in AIDS phase. More larger studies are required to assess our observation concerning TAF use and vitamin D level in HIV-positive patients.

In Search of Risk Factors for Recurrent Erysipelas and Cellulitis of the Lower Limb: A Cross-Sectional Study of Epidemiological Characteristics of Patients Hospitalized due to Skin and Soft-Tissue Infections.

BACKGROUND: Erysipelas and cellulitis are common, acute, bacterial infections of the skin and subcutaneous tissue. The incidence of these infections is growing, and the recurrence rate is high. Effective antibiotic prophylaxis is available, but insufficient data exist on the risks factors for recurrent infection. PURPOSE: To compare comorbidities and laboratory findings in patients with single-episode and recurrent erysipelas/cellulitis in order to identify risk factors for recurrent erysipelas/cellulitis. METHODS: A cross-sectional study, which included patients hospitalized in the Department of Infectious and Tropical Diseases and Hepatology of the Medical University of Warsaw due to erysipelas and cellulitis during 3 consecutive years (July 2016-June 2019). RESULTS: The study included 163 patients, of which 98 had a first episode of erysipelas/cellulitis and 65 had a recurrence. The recurrent infection was significantly associated with a history of lymphedema (12.3% in the recurrent group vs. 2.0% in the first-episode group, p=0.015), a higher BMI (35.4 vs. 31.2, respectively, p=0.002), chronic obstructive pulmonary disease (10.8% vs. 2.0%, p=0.030), and a shorter history of symptoms prior to hospitalization (6.0 days vs. 11.8 days, p=0.004). Patients with the first episode of infection were more likely to have had minor local trauma directly preceding the symptoms of infection (20.4% in the first-episode group vs. 1.5% in the recurrent group, p=0.001). CONCLUSIONS: Patients with lymphedema and obesity should be viewed at high risk of developing recurrence of erysipelas and thus should be considered as candidates for antibiotic prophylaxis and other prevention methods. Minor local trauma directly preceding the skin infection does not by itself confer a higher risk for erysipelas recurrence. More research is needed to assess the association of recurrent skin and soft-tissue infection to preceding minor local trauma, individual components of the metabolic syndrome, and COPD.

Significance of Heparin-Binding Protein and D-dimers in the Early Diagnosis of Spontaneous Bacterial Peritonitis.

OBJECTIVES: Ascites and spontaneous bacterial peritonitis (SBP) are among the most important complications of decompensated liver cirrhosis. In clinical practice, new inflammation biomarkers are needed for the early diagnosis of SBP, as well-known biomarkers, such as C-reactive protein (CRP), procalcitonin (PCT), or peripheral blood white blood cell (WBC) count, lack the required specificity and sensitivity. The aim of the study was to evaluate the significance of heparin-binding protein (HBP) in comparison to CRP, PCT, WBC, and D-dimers in the diagnosis of SBP. DESIGN: Cross-sectional descriptive single-center study. SETTING: Department of Infectious and Tropical Diseases and Hepatology, Medical University of Warsaw, Poland. PATIENTS: All patients admitted to the aforementioned department with decompensated liver cirrhosis and ascites between February 1, 2016, and June 30, 2017. INTERVENTION: Several markers (HBP, CRP, PCT, WBC, and D-dimers) were analysed in blood serum in regard to their potential use in the diagnosis of SBP in patients with decompensated liver cirrhosis and ascites. We correlated the levels of the aforementioned markers with an ascitic fluid polymorphonuclear count using simple linear regression and multiple linear regression. Sensitivities, specificities, and positive and negative predictive values for SBP were calculated for the aforementioned makers of inflammation. MEASUREMENTS AND MAIN RESULTS: A total of 63 patients with decompensated liver cirrhosis and ascites participated in the study. The etiology of liver cirrhosis was varied (HCV: n = 40, HBV: n = 13, HCV/HBV: n = 4, AIH: n = 3, PBC: n = 2, and haemochromatosis: n = 1). After the peritoneal tap, 31 patients were determined to have SBP (defined as an ascitic fluid polymorphonuclear count > 250 cells/µL) and 32 patients had no evidence of SBP on peritoneal tap. A very weak, but statistically significant, correlation of HBP, WBC, and D-dimer levels with the peritoneal fluid polymorphonuclear (PMN) count was observed in the simple regression model, but multivariable analysis using the multiple regression model showed that only D-dimers correlated with peritoneal fluid PMNs independently from other inflammation biomarkers. A D-dimer cutoff value of 1500 ng/mL was determined optimal for ruling out SBP due to high sensitivity (96.8%) and a high negative predictive value (92.9%), although predictably, this marker was not useful for confirming SBP due to low specificity (40.6%) and a low positive predictive value (61.2%). The usefulness of D-dimers was limited by the fact that only 22.2% of the studied patients had D-dimer levels below 1500 ng/mL. HBP and WBC showed little to no predictive value in this study. CONCLUSIONS: D-dimers < 1500 ng/mL make the diagnosis of SBP unlikely, although the peritoneal tap is still the reference method in such situations. In the studied group, the determination of HBP was of no diagnostic benefit in the diagnosis of SBP.

Serum ADAMTS-13 Levels as an Indicator of Portal Vein Thrombosis.

BACKGROUND: Coagulation disorders in patients with liver cirrhosis are a common clinical problem. Cirrhosis should be considered a state of impaired blood clotting or an imbalance of the whole coagulation system. Cirrhosis-induced coagulopathy encompasses disturbances in both the procoagulant and anticoagulant systems. This mechanism may promote the development of thrombosis with portal vein thrombosis (PVT), which is considered an obstacle to orthotopic liver transplantation (OLT). We assessed serum ADAMTS-13 levels in patients with decompensated liver cirrhosis, with and without PVT. MATERIAL AND METHODS: Serum ADAMTS-13 levels, age, platelet count (PLT), and INR (international normalized ratio) were evaluated in (n = 64) patients with liver cirrhosis either with PVT (group 1, n = 31) or without PVT (group 2, n = 33). The results were compared with those from healthy volunteers (group 3, n = 37). Liver cirrhosis was based on Desmet's classification of chronic hepatitis in liver biopsy stage ≥ 3 or liver elastography F-score ≥ 3. Serum ADAMTS-13 levels were measured with Quantikine® ELISA Human ADAMTS13 Immunoassay, R&D Systems Inc. We used Welch's F-test, Games-Howell, one-way ANOVA, Bonferroni test, and logistic regression to determine whether ADAMTS-13 levels were a predictor that was independent of MELD and Child-Pugh scores. All results (P < 0.05) were considered statistically significant. RESULTS: The mean serum ADAMTS-13 level in patients with PVT was significantly lower than that in patients without PVT (P = 0.001) and controls (P = 0.001). The mean serum ADAMTS-13 level in patients without PVT was significantly lower than that in controls (P = 0.001). ADAMTS-13 levels were significantly associated with PVT accounting for the Child-Pugh or MELD score in the logistic regression model. CONCLUSIONS: Low serum ADAMTS-13 levels can be a useful indicator of portal thrombosis in patients with decompensated liver cirrhosis irrespective of Child-Pugh or MELD scores. Further research is needed to determine whether ADAMTS-13 levels will find use in everyday clinical practice.

Effects of ionization on stability of 1-methylcytosine - DFT and PCM studies.

Consequences of ionization were studied by quantum-chemical methods (DFT and PCM) for 1-methylcytosine (MC)-a model of the nucleobase cytosine (C) connected with sugar in DNA. For calculations, three prototropic tautomers (one amino and two imino forms) and two imino zwitterions were considered, including conformational or configurational isomerism of exo heterogroups. Ionization and interactions between neighboring groups affect intramolecular proton-transfers, geometric and thermodynamic parameters, and electron delocalization for individual isomers. We discovered that an imino isomer is present in the isomeric mixture in the highest amount for positively ionized MC. Its contribution in neutral and negatively ionized MC is considerably smaller. Acid-base parameters for selected radical ions were estimated in the gas phase and compared to those of neutral MC. Gas-phase acidity of radical cations is close to that of the conjugate acid of MC, and gas-phase basicity of radical anions is close to that of the conjugate base of MC. Various routes of amino-imino conversion between neutral and ionized isomers were considered. Energetic-barrier for intramolecular proton-transfer in MC is close to that in the parent system-formamidine.