Phylodynamic evolution of HIV-1 A6 sub-subtype epidemics in Poland.

The human immunodeficiency virus type 1 (HIV-1) A6 sub-subtype is highly prevalent in Eastern Europe. Over the past decade, the dissemination of the A6 lineage has been expanding in Poland. The recent Russian invasion of Ukraine may further escalate the spread of this sub-subtype. While evolutionary studies using viral sequences have been instrumental in identifying the HIV epidemic patterns, the origins, and dynamics of the A6 sub-subtype in Poland remain to be explored. We analyzed 1185 HIV-1 A6 pol sequences from Poland, along with 8318 publicly available sequences from other countries. For analyses, phylogenetic tree construction, population dynamics inference, Bayesian analysis, and discrete phylogeographic modeling were employed. Of the introduction events to Poland, 69.94% originated from Ukraine, followed by 29.17% from Russia. Most A6 sequences in Poland (53.16%) formed four large clades, with their introductions spanning 1993-2008. Central and Southern Polish regions significantly influenced migration events. Transmissions among men who have sex with men (MSM) emerged as the dominant risk group for virus circulation, representing 72.92% of migration events. Sequences from migrants were found primarily outside the large clades. Past migration from Ukraine has fueled the spread of the A6 sub-subtype and the current influx of war-displaced people maintains the growing national epidemic.

Circulation of Human Immunodeficiency Virus 1 A6 Variant in the Eastern Border of the European Union-Dynamics of the Virus Transmissions Between Poland and Ukraine.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The Polish outbreak of the A6 epidemic was fueled by complex viral migration patterns across the country, together with cross-border transmissions from Ukraine. 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.

Clinical Perspective on Human Immunodeficiency Virus Care of Ukrainian War Refugees in Poland.

BACKGROUND: The Russian invasion of Ukraine forced migration for safety, protection, and assistance. Poland is the primary sheltering country for Ukrainian refugees, providing support including medical care, which resulted in the rapid ∼15% increase in the number of followed-up people with human immunodeficiency virus (HIV) (PWH) in the country. Here, we present the national experience on HIV care provided for refugees from Ukraine. METHODS: Clinical, antiretroviral, immunological, and virologic data from 955 Ukrainian PWH entering care in Poland since February 2022 were analyzed. The dataset included both antiretroviral-treated (n = 851) and newly diagnosed (n = 104) patients. In 76 cases, protease/reverse transcriptase/integrase sequencing was performed to identify drug resistance and subtype. RESULTS: Most (70.05%) of the patients were female, with a predominance of heterosexual (70.3%) transmissions. Anti-hepatitis C antibody and hepatitis B antigen were present in 28.7% and 2.9% of the patients, respectively. A history of tuberculosis was reported in 10.1% of cases. Among previously treated patients, the viral suppression rate was 89.6%; 77.3% of newly HIV diagnosed cases were diagnosed late (with lymphocyte CD4 count <350 cells/µL or AIDS). The A6 variant was observed in 89.0% of sequences. Transmitted mutations in the reverse transcriptase were found in 15.4% treatment-naive cases. Two patients with treatment failure exhibited multiclass drug resistance. CONCLUSIONS: Migration from Ukraine influences the characteristics of HIV epidemics in Europe, with an increase in the proportion of women and hepatitis C coinfected patients. Antiretroviral treatment efficacy among previously treated refugees was high, with new HIV cases frequently diagnosed late. The A6 subtype was the most common variant.

Non-HIV-related comorbidities and uncontrolled HIV replication are independent factors increasing the odds of hospitalization due to COVID-19 among HIV-positive patients in Poland.

PURPOSE: Immunocompromised patients are postulated to be at elevated risk of unfavorable outcomes of COVID-19. The exact effect of HIV infection on the course of COVID-19 remains to be elucidated. The aim of the study was to describe the epidemiological and clinical aspects of SARS-CoV-2 infection in HIV-infected individuals. METHODS: The HIV-positive patients who were diagnosed with SARS-CoV-2 infection were identified through thirteen specialist HIV clinics routinely following them due to HIV treatment. The data were collected between November 2020 and May 2021 through an on-line electronical case report form (SurveyMonkey®). The collected information included demographics, lifestyle, comorbidities, HIV care history, COVID-19 clinical course and treatment. Logistic regression models were used to identify factors associated with the odds of death or hospitalization due to COVID-19. RESULTS: One hundred and seventy-three patients with HIV-SARS-CoV-2 coinfection were included in the analysis. One hundred and sixty-one (93.1%) subjects had a symptomatic course of the disease. Thirty-nine (23.1%) of them were hospitalized, 23 (13.3%) necessitated oxygen therapy. Three (1.8%) patients required admission to the intensive care unit and 6 (3.5%) patients died. The presence of comorbidities and an HIV viral load of more than 50 copies/mL were linked to the increased odds of hospitalization (OR 3.24 [95% CI 1.27-8.28]) and OR 5.12 [95% CI 1.35-19.6], respectively). CONCLUSIONS: As depicted by our analyses, HIV-positive patients with comorbidities and/or uncontrolled HIV replication who are diagnosed with SARS-CoV-2 infection should be considered of high risk of poor COVID-19 outcome and followed up carefully.

Delayed HIV diagnosis during the COVID-19 pandemic in Poland: A call for targeted HIV testing for those under suspicion of SARS-CoV-2.

OBJECTIVES: The aim of this study was to analyse patients newly diagnosed with HIV who were originally admitted to hospitals with suspicion of COVID-19. METHODS: This was a retrospective case series undertaken at four sites. Only adults with new HIV diagnosis and COVID-19 exclusion hospitalized in 2020-2021 were included. Demographic, clinical and laboratory data were collected from medical records. RESULTS: Twenty-five patients were included in the analysis: 19 men (76%), 11 of Ukrainian origin (44%). The median age was 38.5 years (range 25-59). The mode of HIV transmission was heterosexual for 11 (44%) patients, eight (32%) were men who have sex with men and three (12%) were people who inject drugs. The median duration of symptoms prior to hospital presentation was 20.6 days (range 3-90). The median number of SARS-CoV-2 tests per patient was 2.62 (range 1-7). All SARS-CoV-2 tests were negative. Screening for HIV was performed on average on the 18th day of hospitalization (range 1-36 days). Twenty-three patients (92%) were late presenters, 22 (88%) had advanced disease, and 19 (76%) were in the AIDS stage. The median CD4 T-cell count was 72 cells/µL (range 3-382). The rate of positive HIV testing at the two sites where it was available for people with suspected COVID-19 was 0.13% (7/5458 during the study period). CONCLUSIONS: We strongly recommend introducing the HIV screening test in the diagnostic algorithm for every patient suspected of having COVID-19, presenting with clinical and/or radiological pulmonary symptoms.

Simvastatin Coadministration Modulates the Electrostatically Driven Incorporation of Doxorubicin into Model Lipid and Cell Membranes.

Understanding the interactions between drugs and lipid membranes is a prerequisite for finding the optimal way to deliver drugs into cells. Coadministration of statins and anticancer agents has been reported to have a positive effect on anticancer therapy. In this study, we elucidate the mechanism by which simvastatin (SIM) improves the efficiency of biological membrane penetration by the chemotherapeutic agent doxorubicin (DOX) in neutral and slightly acidic solutions. The incorporation of DOX, SIM, or a combination of them (DOX:SIM) into selected single-component lipid membranes, zwitterionic unsaturated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), neutral cholesterol, and negatively charged 1,2-dimyristoyl-sn-glycero-3-phospho-l-serine (DMPS) was assessed using the Langmuir method. The penetration of neutral lipid monolayers by the codelivery of SIM and DOX was clearly facilitated at pH 5.5, which resembles the pH conditions of the environment of cancer cells. This effect was ascribed to partial neutralization of the DOX positive charge as the result of intermolecular interactions between DOX and SIM. On the other hand, the penetration of the negatively charged DMPS monolayer was most efficient in the case of the positively charged DOX. The efficiency of the drug delivery to the cell membranes was evaluated under in vitro conditions using a panel of cancer-derived cell lines (A172, T98G, and HeLa). MTS and trypan blue exclusion assays were performed, followed by confocal microscopy and spheroid culture tests. Cells were exposed to either free drugs or drugs encapsulated in lipid carriers termed cubosomes. We demonstrated that the viability of cancer cells exposed to DOX was significantly impaired in the presence of SIM, and this phenomenon was greatly magnified when DOX and SIM were coencapsulated in cubosomes. Overall, our results confirmed the utility of the DOX:SIM combination delivery, which enhances the interactions between neutral components of cell membranes and positively charged chemotherapeutic agents.

Control of HBV infection in HIV/HBV co-infected patients treated with antiretroviral therapy - experience of Lodz Centre.

Aim of the study: To analyse the impact of combined antiretroviral therapy (cART) on selected markers of hepatitis B virus (HBV) infection, as well as assessment of the degree of fibrosis in antiretroviral patients who had HIV/HBV co-infection. Material and methods: Analysis of HBs antigen (HBsAg), anti-HBs, HBsAg levels, anti-HDV, anti-HCV, as well as assessment of HBV DNA viraemia and liver fibrosis by elastography in people with HIV/HBV co-infection. Results: Among 515 people under the care of the Lodz Centre at the time of treatment initiation 28 people (5.4%) HBsAg was detected. In HIV/HBV coinfected patients 14 people (50%) had anti-HCV and 6 (21.6%) had anti-HDV. In the group of 23 people treated with antiretroviral therapy for more than 12 months, all but one patient achieved HBV viraemia below the detection threshold. Six (26.1%) eliminated HBsAg, 3 (13%) produced anti-HBs. In the group we examined, four patients has fibrosis at level F4 on the Metavir scale - 3 patients were treated for more than 12 months and one patient was treated for less than 12 months. Conclusions: Antiretroviral treatment of patients co-infected with HIV/HBV based on tenofovir (in the form of disoproxil or alafenamide) with emtricitabine or lamivudine leads to virological control of HBV infection.

Hypersensitivity reactions, hepatotoxicity, and other discontinuations in persons receiving integrase strand transfer inhibitors: results from the EuroSIDA study.

Background: Hypersensitivity reaction (HSR) and hepatotoxicity are rare, but potentially serious side-effects of antiretroviral use.Objective: To investigate discontinuations due to HSR, hepatotoxicity or other reasons among users of dolutegravir (DTG) vs. raltegravir (RAL) or elvitegravir (EVG) in the EuroSIDA cohort.Methods: We compared individuals ≥18 years and starting combination antiretroviral therapy (ART, ≥3 drugs) with DTG vs. RAL or EVG, with or without abacavir (ABC), between January 16, 2014 and January 23, 2019. Discontinuations due to serious adverse events (SAEs) were independently reviewed.Results: Altogether 4366 individuals started 5116 ART regimens including DTG, RAL, or EVG, contributing 9180 person-years of follow-up (PYFU), with median follow-up 1.6 (interquartile range 0.7-2.8) years per treatment episode. Of these, 3074 (60.1%) used DTG (1738 with ABC, 1336 without) and 2042 (39.9%) RAL or EVG (286 with ABC, 1756 without). 1261 (24.6%) INSTI episodes were discontinued, 649 of the DTG-containing regimens (discontinuation rate 115, 95% CI 106-124/1000 PYFU) and 612 RAL or EVG-containing regimens (173, CI 160-188/1000 PYFU). After independent review, there were five HSR discontinuations, two for DTG (one with and one without ABC, discontinuation rate 0.35, CI 0.04-1.28/1000 PYFU), and three for RAL or EVG without ABC (0.85, CI 0.18-2.48/1000 PYFU). There was one hepatotoxicity discontinuation on DTG with ABC (discontinuation rate 0.18, CI 0.00-0.99/1000 PYFU).Conclusion: During 5 years of observations in the EuroSIDA cohort independently reviewed discontinuations due to HSR or hepatotoxicity were very rare, indicating a low rate of SAEs.

The TLR9 2848C/T Polymorphism Is Associated with the CMV DNAemia among HIV/CMV Co-Infected Patients.

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and are essential components of the host's innate immune response. The aim of this study was to determine the TLR9 genotype frequency and investigate the association between TLR9 polymorphisms and cytomegalovirus (CMV) DNAemia in human immunodeficiency virus (HIV)/CMV co-infected patients. A total of 205 HIV/CMV co-infected adults were screened for the presence of the four TLR9 polymorphisms (-1237T/C, -1486T/C, 1174G/A, and 2848C/T) by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Mutation presented in at least one allele of the TLR9 2848C/T single nucleotide polymorphism (SNP) was associated with the occurrence of CMV DNAemia among HIV-infected patients with CMV co-infection (p = 0.004). The level of CMV DNA was higher in patients who were homozygous recessive or heterozygous for the 2848C/T polymorphism compared with those who had a wild-type genotype for this polymorphism (p = 0.005). Mutation detected in at least one allele of this SNP was also associated with a lower interferon type ß (IFN-ß) concentration (p = 0.048), while no relationships between TLR9 -1237T/C, -1486T/C, and 1174G/A SNPs and CMV DNAemia were observed. Our findings suggest that the mutation present in at least one allele of the TLR9 2848C/T SNP may be associated with the active CMV infection in HIV/CMV co-infected subjects.

Molecular epidemiology and HIV-1 variant evolution in Poland between 2015 and 2019.

The occurrence of HIV-1 subtypes differs worldwide and within Europe, with non-B variants mainly found across different exposure groups. In this study, we investigated the distribution and temporal trends in HIV-1 subtype variability across Poland between 2015 and 2019. Sequences of the pol gene fragment from 2518 individuals were used for the analysis of subtype prevalence. Subtype B was dominant (n = 2163, 85.90%). The proportion of subtype B-infected individuals decreased significantly, from 89.3% in 2015 to 80.3% in 2019. This was related to the increasing number of subtype A infections. In 355 (14.10%) sequences, non-B variants were identified. In 65 (2.58%) samples, recombinant forms (RFs) were noted. Unique recombinant forms (URFs) were found in 30 (1.19%) sequences. Three A/B recombinant clusters were identified of which two were A6/B mosaic viruses not previously described. Non-B clades were significantly more common among females (n = 81, 22.8%, p = 0.001) and heterosexually infected individuals (n = 45, 32.4%, p = 0.0031). The predominance of subtype B is evident, but the variability of HIV-1 in Poland is notable. Almost half of RFs (n = 65, 2.58%) was comprised of URFs (n = 30, 1.19%); thus those forms were common in the analyzed population. Hence, molecular surveillance of identified variants ensures recognition of HIV-1 evolution in Poland.

Gut Microbiota Diversity in HIV-Infected Patients on Successful Antiretroviral Treatment is Linked to Sexual Preferences but not CD4 Nadir.

The effects of HIV infection and antiretroviral therapy (ART) on the gut microbiome are poorly understood and the literature data are inconsistent. The aim of this study was to assess the alpha and beta diversity of the fecal microbiota in HIV-infected patients on successful antiretroviral therapy with regard to sexual preferences and CD4 nadir. Thirty-six HIV-infected ART-treated patients with HIV viremia below 20 copies/ml and CD4 > 500 cells/µl were divided into two subgroups based on CD4 nadir. The composition of the intestinal microbiota was assessed by 16SrRNA sequencing (MiSeq Illumina). The alpha and beta diversity were analyzed according to CD4 nadir count and sexual preference. Several alpha diversity indexes were significantly higher in the MSM group than in heterosexual patients. The alpha diversity did not differ significantly between patients with CD4 nadir > 500 cells/µl and CD4 nadir < 200 cells/µl. Beta diversity was also associated with sexual preference. A significant difference in Weighted Unifrac was observed between all MSM and all non-MSM participants (p = 0.001). The MSM group was more diverse and demonstrated greater distances in Weighted Unifrac than the non-MSM group. The relative abundance of the Prevotella enterotype was higher in the MSM than the non-MSM group. Sexual preferences demonstrated a stronger influence on alpha and beta diversity in HIV-infected patients following successful antiretroviral treatment than HIV infection itself. The observed lack of association between CD4 nadir and alpha and beta diversity may be caused by the restoration of the faecal microbiota following antiretroviral treatment.

Prevalence and outcomes of pregnancies in women with HIV over a 20-year period.

OBJECTIVE: To evaluate time trends in pregnancies and pregnancy outcomes among women with HIV in Europe. DESIGN: European multicentre prospective cohort study. METHODS: EuroSIDA has collected annual cross-sectional audits of pregnancies between 1996 and 2015. Pregnancy data were extracted and described. Odds of pregnancy were modelled, adjusting for potential confounders using logistic regression with generalized estimating equations. RESULTS: Of 5535 women aged 16 to <50 years, 4217 (76.2%) had pregnancy information available, and 912 (21.6%) reported 1315 pregnancies. The proportions with at least one pregnancy were 28.1% (321/1143) in East, 24.5% (146/596) in North, 19.8% (140/706) in West/Central, 19.3% (110/569) in Central East and 16.2% (195/1203) in South Europe. Overall 319 pregnancies (24.3%) occurred in 1996-2002, 576 (43.8%) in 2003-2009 and 420 (31.9%) in 2010-2015. After adjustment, the odds of pregnancy were lower in 1996-2002, in South, Central East and East compared to West/Central Europe, in older women, those with low CD4+ cell count or with prior AIDS, and higher in those with a previous pregnancy or who were hepatitis C virus positive.Outcomes were reported for 999 pregnancies in 1996-2014, with 690 live births (69.1%), seven stillbirths (0.7%), 103 spontaneous (10.3%) and 199 medical abortions (19.9%). CONCLUSIONS: Around 20% of women in EuroSIDA reported a pregnancy, with most pregnancies after 2002, when more effective antiretroviral therapy became available. Substantial differences were seen between European regions. Further surveillance of pregnancies and outcomes among women living with HIV is warranted to ensure equal access to care.

Prevalence and Outcomes for Heavily Treatment-Experienced Individuals Living With Human Immunodeficiency Virus in a European Cohort.

BACKGROUND: Although antiretroviral treatments have improved survival of persons living with HIV, their long-term use may limit available drug options. We estimated the prevalence of heavily treatment-experienced (HTE) status and the potential clinical consequences of becoming HTE. SETTING: EuroSIDA, a European multicenter prospective cohort study. METHODS: A composite definition for HTE was developed, based on estimates of antiretroviral resistance and prior exposure to specific antiretroviral regimens. Risks of progressing to clinical outcomes were assessed by Poisson regression, comparing every HTE individual with 3 randomly selected controls who never became HTE. RESULTS: Of 15,570 individuals under follow-up in 2010-2016, 1617 (10.4%, 95% CI: 9.9% to 10.9%) were classified as HTE. 1093 individuals became HTE during prospective follow-up (HTE incidence rate 1.76, CI: 1.66 to 1.87 per 100 person-years of follow-up). The number of HTE individuals was highest in West/Central Europe (636/4019 persons, 15.7%) and lowest in East Europe (26/2279 persons, 1.1%). Although most HTE individuals maintained controlled viral loads (<400 copies/mL), many had low CD4 counts (≤350 cells/µL). After controlling for age, immunological parameters and pre-existing comorbidities, HTE status was not associated with the risk of new AIDS (adjusted incidence rate ratio, aIRR 1.44, CI: 0.86 to 2.40, P = 0.16) or non-AIDS clinical events (aIRR 0.96, CI: 0.74 to 1.25, P = 0.77). CONCLUSIONS: HTE prevalence increased with time. After adjusting for key confounding factors, there was no evidence for an increased risk of new AIDS or non-AIDS clinical events in HTE. Additional therapeutic options and effective management of comorbidities remain important to reduce clinical complications in HTE individuals.

Lipid membranes exposed to dispersions of phytantriol and monoolein cubosomes: Langmuir monolayer and HeLa cell membrane studies.

The interactions of liquid-crystalline nanoparticles based on lipid-like surfactants, glyceryl monooleate, monoolein (GMO) and 1,2,3-trihydroxy-3,7,11,15-tetramethylhexadecane, phytantriol (PT) with selected model lipid membranes prepared by Langmuir technique were compared. Monolayers of DPPC, DMPS and their mixture DPPC:DMPS 87:13 mol% were used as simple models of one leaflet of a cell membrane. The incorporation of cubosomes into the lipid layers spread at the air-water interface was followed by surface-pressure measurements and Brewster angle microscopy. The cubosome - membrane interactions lead to the fluidization of the model membranes but this effect depended on the composition of the model membrane and on the type of cubosomes. The interactions of PT cubosomes with lipid layers, especially DMPS-based monolayer were stronger compared with those of GMO-based nanoparticles. The kinetics of incorporation of cubosomal material into the lipid layer was influenced by the extent of hydration of the polar headgroups of the lipid: faster in the case of smaller, less hydrated polar groups of DMPS than for strongly hydrated uncharged choline of DPPC. The membrane disrupting effect of cubosomes increased at longer times of the lipid membrane exposure to the cubosome solution and at larger carrier concentrations. Langmuir monolayer observations correspond well to results of studies of HeLa cells exposed to cubosomes. The larger toxicity of PT cubosomes was confirmed by MTS. Their ability to disrupt lipid membranes was imaged by confocal microscopy. On the other hand, PT cubosomes easily penetrated cellular membranes and released cargo into various cellular compartments more effectively than GMO-based nanocarriers. Therefore, at low concentrations, they may be further investigated as a promising drug delivery tool.

Effectiveness and Safety of Interferon-Free Direct-Acting Antiviral Hepatitis C Virus Therapy in HIV/Hepatitis C Virus Coinfected Individuals: Results From a Pan-European Study.

OBJECTIVES: To investigate the effectiveness, safety, and reasons for premature discontinuation of direct-acting antivirals (DAAs) in a diverse population of HIV/hepatitis C virus (HCV) coinfected individuals in Europe. METHODS: All HIV/HCV coinfected individuals in the EuroSIDA study that started interferon free DAA treatment between January 6, 2014, and January 3, 2018, with ≥12 weeks of follow-up after treatment stop were included in this analysis. Sustained virological response (SVR) was defined as a negative HCV-RNA result ≥12 weeks after stopping treatment (SVR12). Logistic regression was used to explore factors associated with SVR12. RESULTS: 1042 individuals started interferon-free DAA treatment after 1/6/2014 and were included, 862 (82.2%) had a known response to treatment, and 789 [91.5%, 95% confidence interval (CI): 89.7 to 93.4] of which achieved SVR12. There were no differences in SVR12 across regions of Europe (P = 0.84). After adjustment, the odds of achieving SVR12 was lower in individuals that received sofosbuvir/simeprevir ± ribavirin (RBV) [adjusted odds ratio 0.21 (95% CI: 0.08 to 0.53)] or ombitasvir/paritaprevir/dasabuvir ± RBV [adjusted odds ratio 0.46 (95% CI: 0.22 to 1.00)] compared with sofosbuvir/ledipasvir ± RBV. Forty-three (4.6%) individuals had one or more components of their HCV regimen stopped early, most commonly because of toxicity (n = 14); of these 14, 11 were treated with ribavirin. Increased bilirubin was the most common grade 3 or 4 laboratory adverse event (n = 15.3%) and was related to treatment with atazanavir and ribavirin. CONCLUSIONS: Our findings from real-world data on HIV/HCV coinfected individuals across Europe show DAA treatment is well tolerated and that high rates of SVR12 can be achieved in all regions of Europe.

Cardiovascular risk and response to lipid lowering therapy in patients with HIV infection according to different recommendations.

BACKGROUND: HIV patients are at increased cardiovascular risk while available European cardiovascular recommendations are ambiguous. METHODS: Retrospective analysis of 389 HIV-patients was conducted. Cardiovascular risk was determined by D:A:D, Framingham and SCORE scales. Patients were divided into risk groups as recommended by EACS 2019, PTN AIDS 2019 and ESC/EAS 2019 Guidelines and hypolipemic treatment was evaluated. RESULTS: In total, 389 HIV-positive patients took part in the study, most of whom were men (n = 312, 80.4%), mean age 41.69±10years. Mean lipid levels among all HIV patients: Tch:177.2±36mg/dl, HDL:48.9±18mg/dl, LDL:103.8±31mg/dl, TG:143.3±81mg/dl, AIP:0.45±0.3, non-HDL:129.2±36 mg/dl. Most of the participants (n = 360, 92.5%) were assigned to the high cardiovascular risk group according to ESC/EAS and PTN AIDS guidelines. The achievement of therapeutic LDLs according to ESC/EAS was 10.3% for those at very high cardiovascular risk (8.7% on lipid lowering treatment vs. 16.7% without hypolipemic drugs) and 12.0% (5.8% treated vs. 13.6% untreated) at high cardiovascular risk; according to PTN AIDS,17.2% achievement was noted by the very high-risk group (13% treated vs. 33.3% untreated), and 45.9% for the high-risk group (37.7% treated vs. 48.0% untreated); according to EACS Guidelines, 2.5% achievement in secondary prevention (3.8% treatedvs. 0% untreated) and 24.7% in primary prevention (22.2% treated vs. 26.1% untreated). Mean doses of statins were 8.75mg±6mg (Rosuvastatin) and 22.35±19mg (Atorvastatin). CONCLUSIONS: The achievement of therapeutic LDLs by all recommendations is unsatisfactory, and generally worse in patients on lipid lowering therapy. Hypolipemic treatment of our HIV patients is based on low doses of statins, even in secondary prevention.

How do lipid nanocarriers - Cubosomes affect electrochemical properties of DMPC bilayers deposited on gold (111) electrodes?

Cubosome nanocarriers are promising biomimetic drug delivery systems used in particular for highly toxic drugs in cases where decreasing unwanted side effects is especially important. The properties of electrode supported lipid bilayer prepared by the combined Langmuir-Blodgett and Langmuir-Schaefer techniques were studied using electrochemical techniques following exposure of the film - covered electrode to a solution containing phytantriol - based cubosomes. The inclusion of the carrier in the model membrane under different experimental conditions was probed and the modifications induced in the lipid organization were for the first time inferred by quantitative analysis of the responses of cyclic voltammetry (CV), AC voltammetry and Electrochemical Impedance Spectroscopy (EIS) as well as blocking assays using a redox probe in the solution. Exposure of a preformed DMPC bilayer to cubosome solution resulted in the improved barrier properties of the film reflecting disintegration of cubosomes and formation of additional phytantriol/Pluronic F-108 polymer layer on the top of the DMPC bilayer. On the other hand, formation of the layer in the presence of cubosomes in the subphase lead to an increased capacitance of the film since penetration of the lipid layers by the cubosomal phytantriol increased the porosity of the film.

Hepatic Expression of Phosphorylated Kinase Akt and Glycogen Synthase Kinase-3 Isoforms in Patients with Chronic Hepatitis C.

Some patients with chronic hepatitis C also demonstrate liver steatosis, but the mechanism remains elusive. To analyze the hepatic expression of phosphorylated kinase Akt at Thr 308 and phosphorylated GSK-3 (Glycogen synthase kinase-3) isoforms, GSK3α at Ser 21 and GSK3ß at Ser 9, in chronic hepatitis C patients with normal body weight, glucose, and lipid profiles depending on homeostasis model assessment of insulin resistance (HOMA-IR) levels and histological parameters. The study group consisted of 31 patients with chronic hepatitis C. The hepatic expression of kinase Akt (Thr308), GSK3ß (Ser9), and GSK3α (Ser21) was measured using Western blot assay. Liver steatosis was observed in 41.93% of patients with HCV infection, in those with increased HOMA-IR index (p = 0.02). However, the hepatic expression of Akt (Thr308), GSK3ß (Ser9), and GSK3α (Ser21) was not related to progression of liver steatosis, inflammation, and fibrosis. There was no significant difference in the hepatic expression of kinase Akt (Thr308), GSK3ß (Ser9), and GSK3α (Ser21) in relation to HOMA-IR. Liver steatosis was found to be positively associated with HOMA-IR levels in patients with chronic hepatitis C without metabolic disorders. However, the hepatic expression of Akt (Thr308), GSK3ß (Ser9), and GSK3α (Ser21) did not correspond to progression of liver disease.

NFE2L2 is associated with NQO1 expression and low stage of hepatic fibrosis in patients with chronic hepatitis C.

BACKGROUND: Oxidative stress is extremely important in the pathogenesis of chronic hepatitis C virus (HCV). In response to oxidative stress, adaptive antioxidant defenses are upregulated in the liver. The balance between antioxidant response and oxidative stress plays a key role in hepatic injury in HCV infection. OBJECTIVES: The objective of this study was to assess the hepatic expression of the antioxidant genes GFER (growth factor erv1-like) and NQO1 (NAD(P)H:quinone oxidoreductase-1) and the regulatory gene NFE2L2 (nuclear factor erythroid 2-related factor-2) in liver biopsy specimens obtained from chronic HCV patients with regard to selected clinical parameters and histology, and to determine whether GFER and NQO1 expression is dependent on NFE2L2. MATERIAL AND METHODS: The study group consisted of 42 patients with chronic HCV. Reverse transcription polymerase chain reaction (RT-PCR) was used to analyze the expression of antioxidant and regulatory genes in liver biopsy samples. RESULTS: Positive correlation was observed between the hepatic expression of NFE2L2 and NQO1 in the chronic HCV patients (p < 0.0001). The hepatic expression of NFE2L2 was significantly lower in patients with advanced liver fibrosis (p = 0.05). However, there was no significant difference in the hepatic expression of GFER and NQO1 in relation to the progression of liver steatosis, inflammation and fibrosis. CONCLUSIONS: The hepatic expression of NFE2L2 is associated with NQO1 and low stage of hepatic fibrosis in patients infected with HCV.

Transmission patterns of HIV-1 non-R5 strains in Poland.

HIV-1 env sequencing enables predictions of viral coreceptor tropism and phylogenetic investigations of transmission events. The aim of the study was to estimate the contribution of non-R5 strains to the viral spread in Poland. Partial proviral env sequences were retrieved from baseline blood samples of patients with newly diagnosed HIV-1 infection between 2008-2014, including 46 patients with recent HIV-1 infection (RHI), and 246 individuals with long-term infection (LTHI). These sequences were subjected to the genotypic coreceptor tropism predictions and phylogenetic analyses to identify transmission clusters. Overall, 27 clusters with 57 sequences (19.5%) were detected, including 15 sequences (26.3%) from patients with RHI. The proportion of non-R5 strains among all study participants was 23.3% (68/292), and was comparable between patients with RHI and LTHI (11/46, 23.9% vs 57/246, 23.2%; p = 1.000). All 11 patients with non-R5 strains and RHI were men having sex with men (MSM). Among these patients, 4 had viral sequences grouped within phylogenetic cluster with another sequence of non-R5 strain obtained from patient with LTHI, indicating potential acquisition of non-R5 HIV-1 for at least 4/46 (8.7%) patients with RHI. We were unable to confirm the contribution of patients with RHI to the forward transmission of non-R5 strains, but a relatively high proportion of non-R5 strains among them deserves attention due to the limited susceptibility to CCR5 antagonists.