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.

Polymorphisms in the genes encoding RLR and TLR3 and CMV DNAemia in subjects coinfected with human immunodeficiency virus and cytomegalovirus.

Cytomegalovirus (CMV) is a pathogen that is common worldwide and is often present in individuals infected with human immunodeficiency virus (HIV). Pattern recognition receptors (PRRs) are host sensors that activate the immune response against infectious agents. However, it is unclear whether PRR single-nucleotide polymorphisms (SNPs) are associated with the occurrence of CMV DNAemia in subjects coinfected with HIV and CMV. HIV/CMV-coinfected patients with and without CMV DNAemia were recruited for this study. The DDX58 rs10813831 and IFIH1 (rs3747517 and rs1990760) polymorphisms were genotyped using the TaqMan Allelic Discrimination Assay, whereas the DDX58 rs12006123 and TLR3 (rs3775291 and rs3775296) SNPs were analyzed using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. A mutation present in at least one allele of the DDX58 rs12006123 SNP occurred at least two times more frequently in HIV/CMV-coinfected patients with CMV DNAemia than in coinfected subjects without CMV DNAemia (OR, 2.50; 95% CI, 1.33-4.68; p = 0.004, in the dominant model). A higher level of CMV DNAemia was observed in subjects who had the heterozygous (GA) or homozygous recessive (AA) genotype for the DDX58 rs12006123 SNP compared with those who had the wild-type (GG) genotype (p = 0.0003). Moreover, in subjects with a mutation detected in at least one allele of the DDX58 rs12006123 SNP, a lower serum IFN-ß concentration was found compared with those who had a wild-type (GG) genotype for this polymorphism (p = 0.024). The DDX58 rs12006123 SNP is associated with CMV DNAemia in HIV/CMV-coinfected patients.

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.

The high incidence of late presenters for HIV/AIDS infection in the Lodz province, Poland in the years 2009-2016: we are still far from the UNAIDS 90% target.

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.

Efficacy and safety of nucleoside-sparing regimen based on raltegravir and ritonavir-boosted darunavir in HIV-1-infected treatment-experienced patients.

AIM: To assess the efficacy and tolerability of dual therapy containing raltegravir (RAL) and ritonavir boosted darunavir (DRV/r) in HIV-1-infected treatment-experienced patients. METHOD: Retrospective analysis of 81 HIV-1-infected treatment-experienced patients (56 male and 25 female, 5 Polish centers) who switched to RAL/DRV/r. RESULTS: The main reasons for the introduction of dual therapy were renal dysfunction (16/81 patients-19.8%) and virologic failure on previous regimens (15/81 patients-18.5%). At 48 weeks the treatment was continued in 58/81 (71.6% of patients). In three patients the therapy was discontinued because of virologic failure. However, no mutations to DRV or integrase inhibitors (InI) were detected. At 48 weeks of treatment CD4+ lymphocyte count increased statistically significantly (median 121 cells/µL) P < 0.005. The main reasons for the discontinuation of therapy were treatment simplification (11/23-47.8% patients), adverse events (7/23 patients 30.4%), virologic failure (3/23 patients 13.0%). All patients who switched to RAL/DRV/r therapy because of prior renal impairment were maintained on the treatment for 48 weeks. In this group, before the introduction of dual therapy eGFR (estimated glomerular filtration rate) <60 mL/min/1.72 m2 was reported in nine patients and after 48 weeks in four patients (56.3% vs 25%) (P > 0.05). We found a statistically significant decrease in the prevalence of proteinuria or eGFR <60 mL/min/1.72 m2 (93.8% vs 37.5%; P = 0.004 before and after the introduction of dual therapy, respectively). CONCLUSIONS: Dual therapy was effective and safe for the vast majority of antiretroviral-experienced subjects. Such therapy can be recommended especially for patients with renal impairment or NRTIs intolerance.

Prevalence of Transmitted Drug-Resistance Mutations and Polymorphisms in HIV-1 Reverse Transcriptase, Protease, and gp41 Sequences Among Recent Seroconverters in Southern Poland.

BACKGROUND Monitoring of drug resistance-related mutations among patients with recent HIV-1 infection offers an opportunity to describe current patterns of transmitted drug resistance (TDR) mutations. MATERIAL AND METHODS Of 298 individuals newly diagnosed from March 2008 to February 2014 in southern Poland, 47 were deemed to have recent HIV-1 infection by the limiting antigen avidity immunoassay. Proviral DNA was amplified and sequenced in the reverse transcriptase, protease, and gp41 coding regions. Mutations were interpreted according to the Stanford Database algorithm and/or the International Antiviral Society USA guidelines. TDR mutations were defined according to the WHO surveillance list. RESULTS Among 47 patients with recent HIV-1 infection only 1 (2%) had evidence of TDR mutation. No major resistance mutations were found, but the frequency of strains with ≥1 accessory resistance-associated mutations was high, at 98%. Accessory mutations were present in 11% of reverse transcriptase, 96% of protease, and 27% of gp41 sequences. Mean number of accessory resistance mutations in the reverse transcriptase and protease sequences was higher in viruses with no compensatory mutations in the gp41 HR2 domain than in strains with such mutations (p=0.031). CONCLUSIONS Despite the low prevalence of strains with TDR mutations, the frequency of accessory mutations was considerable, which may reflect the history of drug pressure among transmitters or natural viral genetic diversity, and may be relevant for future clinical outcomes. The accumulation of the accessory resistance mutations within the pol gene may restrict the occurrence of compensatory mutations related to enfuvirtide resistance or vice versa.

Trends in Incidences and Risk Factors for Hepatocellular Carcinoma and Other Liver Events in HIV and Hepatitis C Virus-coinfected Individuals From 2001 to 2014: A Multicohort Study.

BACKGROUND: While liver-related deaths in human immunodeficiency virus (HIV) and hepatitis C virus (HCV)-coinfected individuals have declined over the last decade, hepatocellular carcinoma (HCC) may have increased. We describe the epidemiology of HCC and other liver events in a multicohort collaboration of HIV/HCV-coinfected individuals. METHODS: We studied HCV antibody-positive adults with HIV in the EuroSIDA study, the Southern Alberta Clinic Cohort, the Canadian Co-infection Cohort, and the Swiss HIV Cohort study from 2001 to 2014. We calculated the incidence of HCC and other liver events (defined as liver-related deaths or decompensations, excluding HCC) and used Poisson regression to estimate incidence rate ratios. RESULTS: Our study comprised 7229 HIV/HCV-coinfected individuals (68% male, 90% white). During follow-up, 72 cases of HCC and 375 other liver events occurred, yielding incidence rates of 1.6 (95% confidence interval [CI], 1.3, 2.0) and 8.6 (95% CI, 7.8, 9.5) cases per 1000 person-years of follow-up, respectively. The rate of HCC increased 11% per calendar year (95% CI, 4%, 19%) and decreased 4% for other liver events (95% CI, 2%, 7%), but only the latter remained statistically significant after adjustment for potential confounders. Older age, cirrhosis, and low current CD4 cell count were associated with a higher incidence of both HCC and other liver events. CONCLUSIONS: In HIV/HCV-coinfected individuals, the crude incidence of HCC increased from 2001 to 2014, while other liver events declined. Individuals with cirrhosis or low current CD4 cell count are at highest risk of developing HCC or other liver events.

Interactions of Lipidic Cubic Phase Nanoparticles with Lipid Membranes.

The interactions of liquid-crystalline monoolein (GMO) cubic phase nanoparticles with various model lipid membranes spread at the air-solution interface by the Langmuir technique were investigated. Cubosomes have attracted attention as potential biocompatible drug delivery systems, and thus understanding their mode of interaction with membranes is of special interest. Cubosomes spreading at the air-water interface as well as interactions with a monolayer of 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) compressed to different surface pressures were studied by monitoring surface pressure-time dependencies at constant area. Progressive incorporation of the nanoparticles was shown to lead to mixed monolayer formation. The concentration of cubosomes influenced the mechanism of incorporation, as well as the fluidity and permeability of the resulting lipid membranes. Brewster angle microscopy images reflected the dependence of the monolayer structure on the cubosomes presence in the subphase. A parameter Csat was introduced to indicate the point of saturation of the lipid membrane with the cubosomal material. This parameter was found to depend on the surface pressure showing that the cubosomes disintegrate in prolonged contact with the membrane, filling available voids in the lipid membrane. At highest surface pressures when the layer is most compact, the penetration of cubosomal material is not possible and only some exchange with the membrane lipid becomes the route of including GMO into the layer. Finally, comparative studies of the interactions between lipids with various headgroup charges with cubosomes suggest that at high surface pressure an exchange of lipid component between the monolayer and the cubosome in its intact form may occur.

Adherence to antiviral therapy in HIV or HBV-infected patients.

BACKGROUND: Antiviral therapies in HIV and chronic HBV infection are lifelong and require strict adherence to medication to ensure therapeutic success. AIMS: The aim of this study was to analyze adherence levels in HIV patients on antiretroviral regimen and in B-infected patients treated with nucleos(t)ide reverse transcriptase inhibitors. MATERIAL AND METHODS: The study group consisted of 134 HIV-infected patients and 42 with chronic hepatitis B. The self-reported Morisky 8-Item Medication Adherence Scale (MMAS-8) was used to assess the adherence to medication. We analyzed potential predictors of optimal adherence to the antiretroviral therapy. RESULTS: Mean adherence levels according to MMAS-8 in HIV-infected patients on antiretroviral therapy was 6.64 (SD+/- 1.47) and was significant lower than in patients with chronic hepatitis B 7.48 (SD+/- 1.40) (p < 0.0001). However, adherence levels in HIV-infected patients treated with One-pill-Once a-day antiretroviral regimen were similar to patients with chronic hepatitis B (p>0.05). In univariante logistic regression alcohol abstinence, sexual route of HIV transmission, once daily dosing and reduced number of pills were significantly associated with high adherence. According to multivariante logistic regression analysis, only once-daily drug regimen was independent factor of high adherence (OR=2.89, p=0.038). Higher adherence had positive impact on the effectiveness of antiretroviral therapy (p=0.04). CONCLUSIONS: The implementation of once-daily antiretroviral regimen has improved adherence that had beneficial effect on the effectiveness of antiretroviral therapy.

Transmitted HIV drug resistance in antiretroviral-treatment-naive patients from Poland differs by transmission category and subtype.

OBJECTIVES: The surveillance of HIV-transmitted drug resistance mutations (t-DRMs), including temporal trends across subtypes and exposure groups, remains a priority in the current management of the epidemic worldwide. METHODS: A cross-sectional analysis of 833 treatment-naive patients from 9 of 17 Polish HIV treatment centres. Partial pol sequences were used to analyse drug resistance with a general time reversible (GTR)-based maximum likelihood algorithm used for cluster/pair identification. Mutation frequencies and temporal trends were investigated. RESULTS: t-DRMs were observed in 9% of cases (5.8% for NRTI, 1.2% NNRTI and 2.0% PI mutations) and were more common among heterosexually infected (HET) individuals (13.4%) compared with MSM (8.3%, P = 0.03) or injection drug users (IDUs; 2.9%, P = 0.001) and in MSM compared with IDUs (P = 0.046). t-DRMs were more frequent in cases infected with the non-B variant (21.6%) compared with subtype B (6.6%, P < 0.001). With subtype B a higher mutation frequency was found in MSM compared with non-MSM cases (8.3% versus 1.8% for IDU + HET, P = 0.038), while non-B variants were associated with heterosexual exposure (30.4% for HET versus 4.8% for MSM, P = 0.019; versus 0 for IDU, P = 0.016). Trends in t-DRM frequencies were stable over time except for a decrease in NNRTI t-DRMs among MSM (P = 0.0662) and an NRTI t-DRM decrease in HET individuals (P = 0.077). With subtype B a higher frequency of sequence pairs/clusters in MSM (50.4%) was found compared with HET (P < 0.001) and IDUs (P = 0.015). CONCLUSIONS: Despite stable trends over time, patterns of t-DRMs differed notably between transmission categories and subtypes: subtype B was associated with MSM transmission and clustering while in non-B clades t-DRMs were more common and were associated with heterosexual infections.

The Spectrum of Malignancies among Adult HIV Cohort in Poland between 1995 and 2012: A Retrospective Analysis of 288 Cases.

THE AIM OF THE STUDY: The aim of the study was to evaluate the spectrum of AIDS-defining malignancies (ADMs) and non-AIDS-defining malignancies (NADMs) in HIV-infected patients in Poland. MATERIAL AND METHODS: A retrospective observational study was conducted among HIV-infected adult patients who developed a malignancy between 1995 and 2012 in a Polish cohort. Malignancies were divided into ADMs and NADMs. Non-AIDS-defining malignancies were further categorised as virus-related (NADMs-VR) and unrelated (NADMs-VUR). Epidemiological data was analysed according to demographic data, medical history, and HIV-related information. Results were analysed by OR, EPITools package parameters and Fisher's exact test. RESULTS: In this study 288 malignancies were discovered. The mean age at diagnosis was 41.25 years (IQR20-81); for ADMs 38.05 years, and for NADMs-VURs 46.42 years; 72.22% were male, 40.28% were co-infected with HCV. The risk behaviours were: 37.85% IDU, 33.33% MSM, and 24.31% heterosexual. Mean CD4+ at the diagnosis was 282 cells/mm(3) (for ADMs 232 and for NADMs-VUR 395). Average duration of HIV infection at diagnosis was 5.69 years. There were 159 (55.2%) ADMs and 129 (44.8%) NADMs, among whom 58 (44.96%) NADMs-VR and 71 (55.04%) NADMs-VUR. The most frequent malignancies were: NHL (n = 76; 26.39%), KS (n = 49; 17.01%), ICC (n = 34; 11.81%), HD (n = 23; 7.99%), lung cancer (n = 18; 6.25%) and HCC (n = 14; 4.86%). The amount of NADMs, NADMs-VURs in particular, is increasing at present. Male gender (OR = 1.889; 95% CI: 1.104-3.233; p = 0.024), advanced age: 50-60 years (OR = 3.022; 95% CI: 1.359-6.720; p = 0.01) and ≥ 60 years (OR = 15.111; 95% CI: 3.122-73.151; p < 0.001), longer duration of HIV-infection and successful HAART (OR = 2.769; 95% CI: 1.675-4.577; p = 0) were independent predictors of NADMs overall, respectively. CONCLUSIONS: In a Polish cohort NHL was the most frequent malignancy among ADMs, whereas HD was the most frequent among NADMs. Increased incidence of NADMs appearing in elderly men with longer duration of HIV-infection and with better virological and immunological control was confirmed. As HIV-infected individuals live longer, better screening strategies, especially for NADMs-VUR, are needed. The spectrum of cancer diagnoses in Poland currently does not appear dissimilar to that observed in other European populations.

Dependence of interfacial film organization on lipid molecular structure.

Combination of surface analytical techniques was employed to investigate the interfacial behavior of the two designed lipids-N-stearoylglycine (1) and its bulky neutral headgroup-containing derivative N-stearoylvaline ethyl ester (2)-at the air-solution interface and as transferred layers on different substrates. Formation of monolayers at the air-water interface was monitored on pure water and on aqueous solutions of different pH. Crystallization effects were visualized at pure water by recording the hystereses in the Langmuir-Blodgett (LB) isotherms and by transferring the layers onto mica, gold (111), and ITO (indium-tin oxide on glass) electrodes. Subphase pH affects the morphology and patch formation in monolayers of 1, as evidenced by BAM measurements. At pH 8.2, formation of well-ordered crystallites is observed, which upon compression elongate according to predominantly 1-D growth mechanism to form a dense layer of crystallites. This effect is not observed in monolayers of 2, whose headgroup is not protonated. The orientation of layers of 1 transferred to the solid supports is also pH dependent, and their stability can be related to formation of a hydrogen-bonded networks. AFM images of 1 exhibited platelets of multilayer phase. The IR spectra of the ITO substrates covered by 1 indicated formation of hydrogen bonds between the amide groups. The nature of the adsorption layer and its organization as a function of potential were studied in-depth by EC STM using Au(111) as the substrate. A model showing the arrangement of hydrogen bonds between adsorbed molecules is presented and related to the observed organization of the layer.

Expression of selected genes in liver biopsy specimens in relation to early virological response in patients with chronic hepatitis C with HCV mono- and HIV/HCV co-infection.

The aim of our study was to evaluate the significance of IL-28B single-nucleotide polymorphism and hepatic expression of IFI27, SOCS3 and miR-122 in order to predict early virological response (EVR) in patients infected with HCV genotype 1 or 4. The study group consisted of 65 patients: 46 with HCV mono- and 19 with HIV/HCV co-infection. Analyses of IL-28B single-nucleotide polymorphism C/T (rs12979860) in the blood and expression of SOCS3, IFI27 and miR-122 in liver biopsy samples obtained before PegIFN and ribavirin treatment were performed by the RT-PCR method. EVR was defined as a >2log decline in HCV viremia at week 12. EVR was associated with a lower expression of IFI27 and a more frequent presence of the IL28BCC genotype. IFI27 expression was lower in patients with the CC genotype, irrespective of EVR. In multivariate logistic regression, only IL28B CC genotype and age above 40 years influenced EVR (OR =5.09 and 0.29 respectively). In contrast to IFI27, expression of miR-122 and SOCS3 in patients with different IL28B genotypes was not statistically significantly different. A correlation between miR-122 and SOCS3 was found (Rho =0.495094 p< 0.0001). Analysis of IFI27, SOCS3 and miR-122 hepatic expression does not provide substantial benefits for the prognosis of EVR. The only independent prognostic factors for EVR are age and IL28B genotype. The prognostic significance of IFI27 expression for EVR is dependent on the genetic polymorphism of IL28B.

Ribavirin priming has no beneficial effects for chronic hepatitis C patients.

AIM: The aim of this study is to assess the efficacy of an initial dose of ribavirin administered before a 48-week course of treatment with peg-IFN + ribavirin in treatment-naïve patients and in patients after previous failure of CHC treatment. MATERIAL AND METHODS: A total of 103 patients with chronic hepatitis C infected with genotype 1 HCV were qualified to the study. Study patients were randomised to receive one of two treatments: A- RBV for 4 weeks followed by combined therapy with peg-IFN alpha-2a +RBV for 48 weeks (n = 73), or B- combined therapy with peg-IFN alpha-2a +RBV for 48 weeks (n = 30). RESULTS: SVR 24 was observed in 44% patients in group A and in group 40% patients in group B (40%), p > 0.05. Comparing subgroups of the naive patients, it was found that the SVR24 value was higher in group A than group B (57% vs. 47%, p > 0.05). In the re-therapy subgroups, higher treatment response rates in patients not responding earlier was found in group A than group B (39% vs. 16%, p > 0.05). CONCLUSION: No significant advantage was found in the use of a priming method over a standard regimen. However, it could be recommended in patients with a total lack of response to peg-IFN and ribavirin when no other therapeutic options are available.

Has COVID-19 Changed the Incidence and Profile of Late Presenters for HIV Infection in Lodz, Polish Reference Centre, Poland?

Objectives: The aim of this study was to compare the prevalence and characteristics of HIV late presenters (LPs) and advanced LPs (aLPs) registered in the Lodz HIV centre during the COVID-19 pandemic (2020-2021) with those of the pre-pandemic period (2017-2019). Methods: A retrospective analysis was performed of the predictive factors associated with HIV LPs and aLPs based on multivariable logistic regression. The patient entry into specialist HIV care after diagnosis during the pandemic was analysed. Results: Of 121 newly diagnosed HIV infections during the pandemic, 49.6% had late presentation and 36.4% had advanced HIV disease (AHD). In the pre-pandemic period, out of 154 newly diagnosed patients, 58.4% were LPs and 38.3% were aLPs. Independent risk factors for HIV late presentation were older age (OR: 1.04, 95% CI: 1.01-1.076; p = 0.008), diagnosis in hospital (OR: 5.63, 95% CI: 2.87-11.05; p < 0.001) and negative VDRL as compared to positive VDRL (OR: 2.48, 95% CI: 1.19-5.15; p = 0.015). The same predictive factors were associated with aLPs: older age (OR: 1.07, 95% Cl 1.04-1.11; p < 0.001), HIV diagnosis in hospital (OR: 4.25, 95% CI 2.17-8.29; p < 0.001) and negative VDRL as compared to positive VDRL (OR: 4.95, 95% CI 1.87-13.10; p = 0.001). HIV diagnosis during the pandemic was not a risk factor for late presentation nor for advanced late presentation. However, the time between HIV diagnosis and the first visit to an HIV centre was statistically lower in the pre-pandemic period (p = 0.0048); the median lengths of time between the date of HIV testing, the first visit to the centre and the initiation of ART did not differ between these two periods in LPs and aLPs (p > 0.05). Conclusions: The COVID-19 pandemic did not change the prevalence or characteristics of late presentation and aLPs among newly diagnosed patients, nor did it extend the time to enrolment in HIV care or ART introduction in these groups.

Molecular epidemiology of recent HIV-1 infections in southern Poland.

The genetic diversity of human immunodeficiency virus type 1 (HIV-1) offers an opportunity to track the development of the epidemic across different populations. Viral pol gene fragments from 55 individuals of Polish origin with recent HIV-1 infection identified in 2008-2010 in four Polish cities were analyzed. Viral sequences were compared with sequences from 100 individuals (reference group) infected before 2004. Viral spread among groups with different HIV transmission categories was compared using a phylogenetic approach. The majority of sequences from individuals with recent infection were subtype B (93%) within which four transmission clusters (18% of samples) were detected. Samples from men infected through sex between men and from persons infected through injecting drugs were broadly separated (P < 0.0001), while samples from individuals infected by heterosexual contacts were dispersed uniformly within phylogenetic tree (P = 0.244) inferred from viral sequences derived from individuals infected recently and the reference group. The percentage of samples from persons infected by heterosexual contacts which clustered with samples from men infected through sex between men was not significantly higher for those with recent infection (47%), compared to the reference group (36%). In conclusion, men infected by sex between men and individuals infected through injecting drugs appear to form separate HIV transmission networks in Poland. The recent spread of HIV-1 among persons infected with subtype B by heterosexual contacts appears to be linked to both these groups.

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.