Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed countries and is associated with obesity, dyslipidaemia, diabetes, and metabolic syndrome. Atherosclerosis and cardiovascular diseases are also highly prevalent in this group of patients, due to the...

The human immunodeficiency virus (HIV) type 1 A6 variant is dominating in high-prevalence Eastern European countries, with increasing prevalence over the remaining regions of Europe. The recent war in Ukraine may contribute to further introductions of this A6 lineage. Our aim was to model the transmission dynamics of the HIV-1 A6 variant between Poland and Ukraine. HIV-1 A6 partial pol sequences originating from Poland (n = 1185) and Ukraine (n = 653) were combined with publicly available sequences (n = 7675) from 37 other countries. We used maximum likelihood-based tree estimation followed by a bayesian inference strategy to characterize the putative transmission clades. Asymmetric discrete phylogeographic analysis was used to identify the best-supported virus migration events across administrative regions of Poland and Ukraine. We identified 206 clades (n = 1362 sequences) circulating in Poland or Ukraine (63 binational clades, 79 exclusively Polish, and 64 exclusively Ukrainian). Cross-border migrations were almost exclusively unidirectional (from Ukraine to Poland, 99.4%), mainly from Eastern and Southern Ukraine (Donetsk, 49.7%; Odesa, 17.6% regions) to the Central (Masovian, 67.3%; Lodz, 18.2%) and West Pomeranian (10.1%) districts of Poland. The primary sources of viral dispersal were the Eastern regions of Ukraine, long affected by armed conflict, and large population centers in Poland. The Polish outbreak of the A6 epidemic was fueled by complex viralmigration patterns across the country, together with cross-border transmissions fromUkraine. There is an urgent need to include war-displaced people in the national HIV prevention and treatment programs to reduce the further spread of transmission networks.

The present study retrospectively analyses the prevalence of late diagnosis in patients with newly-diagnosed HIV infection in Lodz, Poland from January 2009 to December 2016, and assesses the predictive factors associated with late presenters. Late presentation is defined as a diagnosis of HIV with a CD4 count<350 cells/μL, or the occurrence of an AIDS- defining event, regardless of the CD4 cell count. Two hundred and fifty-nine (62.86%) patients were late presenters, 178 of whom (68.72%) were advanced late presenters (CD4 cell count below 200 cells/μL). Multivariate factors associated with late HIV presentation included referral from physician for HIV testing (OR: 3.95, 95% CI 2.42–6.46), older age (OR: 1.81, 95% CI: 1.38–2.38) and route of HIV transmission. Heterosexual patients (OR 1.98, 95% CI: 1.01–3.90), active drug users (OR: 3.49, 95% CI: 1.63–7.48) and patients who did not report the route of transmission (OR: 4.29, 95%: CI 1.45–12.62) were more likely to present late than MSM subjects. In conclusion, the majority of HIV-infected patients are still diagnosed late. There is a need for expanded testing not only in MSM group, in which HIV prevalence is the highest, but also in intravenous drug users, or among subjects who are heterosexual or from a higher age group.

Dual therapy based on dolutegravir and ritonavir-boosted darunavir (DTG/DRV/r) is a combination of well-known drugs with a high genetic barrier to HIV resistance. A retrospective analysis of all HIV-1 infected treatment-experienced patients who switched to DTG/DRV/r from May 2014 till March 2017 in 4 Polish centres–results of a 48-week treatment. The study group consisted of 59 men and 17 women. Median baseline parameters were: age– 42.7 years, CD4 cells count– 560.5 cells/μl, CD4 cells nadir– 150 cells/μl, number of prior antiretroviral regimens– 3. The introduction of dual therapy was primarily due to virologic failure (30 patients), adverse events on previous regimens (17 patients) and therapy simplification (27 patients). At week 48 the treatment was continued in 70/76 of patients and the median CD4 cells count increased from 560.5 to 641.0 cells/μl. The therapy was discontinued in six patients (1 –virologic failure, 1 –decrease of estimated glomerular filtration rate (eGFR), 1 –myalgia, 3 –lost to follow-up). At week 48 six patients had detectable viremia, but only in one patient viremia was higher than 200 copies/ml. At week 48 the level of serum total cholesterol of the investigated subjects was statistically significantly higher than at the moment of dual therapy introduction (185.8 mg/dl vs. 174.8 mg/dl- p<0.05). However, in patients previously not treated with TDF, there were no changes in lipid parameters during therapy. Proteinuria was observed in 13.2% of patients before the switch to dual therapy and in 7.1% of patients at week 48. The investigated dual therapy was effective and safe. The observed increase in lipid parameters only concerned the patients who had used a TDF-based regimen prior to analysed dual treatment.

Damage of the mucosal barrier in HIV infection, microbial translocation, and immune activation can persist even in patients on successful antiretroviral therapy (ART) especially advanced late presenters. The aim of this study was to find factors that determine immune activation and bacterial translocation in HIV-infected advanced late presenters on suppressive ART. Forty-three late presenters (CD4 < 200 cells/µl prior to ART) on successful ART (more than 2 years of ART) with optimal and suboptimal CD4 recovery were enrolled into this study. The serum concentrations of intestinal fatty acid-binding peptide (I-FABP), zonulin-1, programmed cell death-1 protein (PCDP-1), and soluble (s)CD14 were measured using the ELISA test. We found higher serum levels of I-FABP and sCD14 in successfully antiretroviral-treated advanced late presenters compared to healthy subjects (p < 0.0001 and p = 0.0004). The serum concentration of PCDP-1 and zonulin-1 in HIV-infected patients did not differ from healthy controls. The levels of microbial translocation and immune activation markers were not associated with the degree of CD4 recovery. A serum concentration of I-FABP above 2.03 ng/ml was independently associated with a shorter ART (OR 0.78; p = 0.03). Older age was related to serum levels of sCD14 above 2.35 µg/ml (OR 1.1; p = 0.01). Higher serum levels of I-FABP and sCD14 in successfully antiretroviral-treated advanced late presenters compared to healthy subjects suggest an incomplete reconstruction of the intestinal barrier and sustained immune activation despite good CD4 recovery. It was not the CD4 level, but the length of the suppressive ART that was found to be associated with the restoration of the intestinal barrier.

Estimating the prevalence of accumulated HIV drug resistance in patients receiving antiretroviral therapy (ART) is difficult due to lack of resistance testing at all occasions of virological failure and in patients with undetectable viral load. A method to estimate this for 6498 EuroSIDA patients who were under follow-up on ART at 1 July 2008 was therefore developed by imputing data on patients with no prior resistance test results, based on the probability of detecting resistance in tested patients with similar profiles. Using all resistance test results available, predicted intermediate/high-level resistance to specific drug classes [nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs)] was derived using the Stanford algorithm v5.1.2. Logistic regression models were then employed to estimate predicted probability of resistance to each drug class for given values of current viral load, history of virological failure and previous virological suppression. Based on these predicted probabilities and patients’ covariate profiles, estimates of prevalence in 5355 patients with no prior test results were obtained. Overall prevalence of resistance was estimated by pooling these data with those observed in the remaining 1143 tested patients. Prevalence of NRTI, NNRTI and PI resistance was estimated as 43% (95% confidence interval: 39%–46%), 15% (13%–18%) and 25% (22%–28%), respectively. This method provides estimates for the proportion of treated patients in a cohort who harbour resistance on a given date, which are less likely to be affected by selection bias due to missing resistance data and will allow us to estimate prevalence of resistance to different drug classes at specific timepoints in HIV-infected populations on ART.