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.

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.

Preliminary report on the provision of HIV care to war refugees with HIV who are migrating from Ukraine: data from the ECEE Network Group.

The ECEE Network Group investigated early provision of HIV care to war refugees migrating from Ukraine in Central and Eastern Europe (CEE) through an online survey. Fourteen countries admitting war refugees from Ukraine on March 31, 2022, completed the survey. Most centers (86%) organized provision of same day antiretroviral therapy (ART) for at least 30 days (77%), but indicated that it may affect the local HIV care. CEE countries put effective emergency mechanisms, which need continuation with international support.

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.

Gender as a factor affecting NK cell activity in patients successfully treated for chronic hepatitis C with direct-acting antivirals.

Chronic hepatitis C (CHC) affects the activity of natural killer (NK) cells, but successful interferon- free treatment partially restores it. The goal of this study was to assess whether gender influences NK functionality. We examined 21 post-menopausal women and 24 men with CHC who were treated with direct-acting antivirals (DAA) and 33 healthy volunteers. Using flow cytometry, we analysed KIR2DS4, NKG2D, NKp30, KIR2DL2/DL3, NKG2A and TRAIL on the surface of NK cells. Intracellular granzyme B was also assessed and serum CXCL10 was quantified via ELISA. Overall, patients with CHC had higher expression of KIR2DS4, NKG2A, and NKp30 relative to the control group. Further, CHC patients had a lower percentage of NK cells among lymphocytes relative to the control group. After treatment, KIR2DS4, KIR2DL2/DL, NKG2A, TRAIL and NKp30 on NK cells were decreased whilst the percentage of NK cells and the expression of granzyme B and NKG2D increased. Prior to treatment, serum CXCL10 was elevated, but it was inhibited post-treatment. We observed gender-specific differences in the expression of KIR2DL2/DL3 (higher in women) and NKp30 (elevated in men) compared to CHC/control groups. After treatment, KIR2DL2/DL3, NKp30 and CXCL10 dropped only in the female group while granzyme B increased in the male group. In conclusion, the response of NK cells among men and women of post-menopausal ages with CHC differs. Our research may lead to more studies on the different nature of female and male immune systems in the context of HCV infection and treatment.

Correlates of inconsistent condom use and drug use among men having sex with men in Poland: a cross-sectional study.

The number of new human immunodeficiency virus (HIV) diagnoses is rising in many parts of Europe. We sought to evaluate the rising prevalence of new HIV diagnoses in Poland, where the majority of newly-diagnosed HIV cases are men having sex with men (MSM). This study aims to measure the prevalence of condom use and drug use and to identify risk factors for contracting sexually transmitted infections (STIs) among MSM in Poland by distributing an anonymous online survey aimed toward MSM. Among the 1438 participants who completed valid surveys, those with low education level and greater than 100 prior sexual partners showed the highest odds for inconsistent condom use (adjusted odds ratio [aOR] 3.027, 2.044, respectively). Participants who identified themselves as heterosexuals, with multiple sexual partners and living in big cities showed the highest odds for drug use (aOR 4.869, 3.305, 1.720, respectively). This study identifies groups at the highest risk of HIV/STIs and provides valuable information for public health experts to develop targeted STI prevention campaigns.

Influence of Hepatitis C Coinfection and Treatment on Risk of Diabetes Mellitus in HIV-Positive Persons.

BACKGROUND: The role of hepatitis C virus (HCV) coinfection and HCV-RNA in the development of diabetes mellitus (DM) in HIV-positive persons remains unclear. METHODS: Poisson regression was used to compare incidence rates of DM (blood glucose >11.1 mmol/L, HbA1C >6.5% or >48 mmol/mol, starting antidiabetic medicine or physician reported date of DM onset) between current HIV/HCV groups (anti-HCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, HCV-RNA-positive after HCV treatment). RESULTS: A total of 16 099 persons were included; at baseline 10 091 (62.7%) were HCV-Ab-negative, 722 (4.5%) were spontaneous clearers, 3614 (22.4%) were chronically infected, 912 (5.7%) had been successfully treated, and 760 (4.7%) were HCV-RNA-positive after treatment. During 136 084 person-years of follow-up (PYFU; median [interquartile range], 6.9 [3.6-13.2]), 1108 (6.9%) developed DM (crude incidence rate, 8.1/1000 PYFU; 95% CI, 7.7-8.6). After adjustment, there was no difference between the 5 HCV strata in incidence of DM (global P = .33). Hypertension (22.2%; 95% CI, 17.5%-26.2%) and body mass index >25 (22.0%; 95% CI, 10.4%-29.7%) had the largest population-attributable fractions for DM. CONCLUSIONS: HCV coinfection and HCV cure were not associated with DM in this large study. The biggest modifiable risk factors were hypertension and obesity, and continued efforts to manage such comorbidities should be prioritized.

Efficacy of HCV treatment in Poland at the turn of the interferon era - the EpiTer study.

THE AIM OF THE STUDY: Was to analyze the efficacy achieved with regimens available for chronic hepatitis C (CHC) in Poland between 2013 and 2016. MATERIAL AND METHODS: Data were collected from 29 centers and included 6786 patients with available sustained virologic response (SVR) data between 1 January 2013 and 31 March 2016. RESULTS: The sustained virologic response rate for genotypes (G) 1a, 1b, 2, 3 and 4 was 62%, 56%, 92%, 67% and 56% respectively; 71% patients (n = 4832) were treated with pegylated interferon α (Peg-IFNα) and ribavirin (RBV), with SVR rates of 58%, 49%, 92%, 67% and 55% respectively. The sustained virologic response among 5646 G1 infected patients was the lowest with natural interferon α (7%, n = 70) or PegIFN (50%, n = 3779) with RBV, and improved in those receiving triple regimens of Peg-IFN + RBV combined with boceprevir (47%, n = 485), telaprevir (64%, n = 805), simeprevir (73%, n = 132) or sofosbuvir (70%, n = 23). The sustained virologic response with interferon-free regimens of sofosbuvir and RBV (n = 7), sofosbuvir and simeprevir (n = 53), and ledipasvir and sofosbuvir (n = 64) achieved 86%, 89% and 94% respectively. The highest SVR of 98% was observed with ombitasvir/paritaprevir combined with dasabuvir (n = 227). Patients infected with G3 (n = 896) and G4 (n = 220) received mostly Peg-IFN + RBV with SVR of 67% and 56% respectively. Interferon-free regimens were administered in 18 G3/G4 patients and all achieved an SVR. Sofosbuvir combined with Peg-IFN and RBV was administered to 33 patients with an SVR rate of 94%, and a similar rate was achieved among 13 G2 patients treated with interferon and RBV. CONCLUSIONS: We observed significant differences in efficacy of HCV regimens available in Poland at the turn of the interferon era. The data will be useful as a comparison for therapeutic options expected in the next few years.

Prevalence of HCV genotypes in Poland - the EpiTer study.

THE AIM OF THE STUDY: Was to assess current prevalence of hepatitis C virus (HCV) genotypes in Poland, including their geographic distribution and changes in a given period of time. MATERIAL AND METHODS: Data were collected with questionnaires from 29 Polish centers and included data of patients diagnosed with HCV infection between 1 January 2013 and 31 March 2016. RESULTS: In total, data of 9800 patients were reported. The highest prevalence was estimated for genotype 1b (81.7%), followed by 3 (11.3%), 4 (3.5%), 1a (3.2%) and 2 (0.2%). Genotype 5 or 6 was reported in 6 patients only (0.1%). The highest prevalence of genotype 1 was observed in central (lódzkie, mazowieckie, swietokrzyskie), eastern (lubelskie) and southern (malopolskie, slaskie) Poland. The highest rate for genotype 3 was observed in south-western (dolnoslaskie, lubuskie) and eastern (podlaskie, warminsko-mazurskie and podkarpackie) Poland. Compared to historical data, we observed an increasing tendency of G1 prevalence from 72.0% in 2003 to 87.5% in 2016, which was accompanied by a decrease of G3 (17.9% vs. 9.1%) and G4 (9.0% vs. 3.1%). CONCLUSIONS: Almost 85% of patients with HCV in Poland are infected with genotype 1 (almost exclusively subgenotype 1b), and its prevalence shows an increasing tendency, accompanied by a decrease of genotypes 3 and 4.

Genetic (KIR, HLA-C) and Some Clinical Parameters Influencing the Level of Liver Enzymes and Early Virologic Response in Patients with Chronic Hepatitis C.

Natural killer cells play an important role as effectors of innate immunity and regulators of adaptive immunity. They are important elements of the innate response to viral infections, which they detect using human leukocyte antigen (HLA) class I-binding receptors. Most polymorphic of these are killer cell immunoglobulin-like receptors (KIRs) which exist as two basic isotypes, activating or inhibitory receptors and are encoded by genes distributed differently in unrelated individuals. We searched for links between selected clinical data (including HCV viremia, liver enzymes level and liver histology parameters) and the presence of genes encoding these receptors and their ligands in hepatitis C virus-infected individuals subjected to pegylated interferon-α and ribavirin therapy. Genomic DNA samples from two hundred and ninety-two chronically infected patients were typed by polymerase chain reaction for the presence or absence of genes for KIRs and their ligands, class I HLA molecules, and clinical data of the patients were collected. Our results suggest an importance of clinical parameters and the contribution of KIR and HLA genes to the course of hepatitis C virus infection and the response to therapy. The study revealed that levels of liver enzymes before therapy were about 30% higher in patients who possessed a variant KIR2DS4 gene with 22-base pair deletion. Decrease of ALT activity after treatment was higher in HLA-C C2-positive than negative individuals. Beside it, patients demonstrated early virologic response to the therapy if the time lag before treatment was short, particularly in women.