Changes in Primary HIV-1 Drug Resistance Due to War Migration from Eastern Europe.

In recent years, especially as a result of war in Ukraine, enormous movements of migration to Poland from eastern European countries have been reported, including people living with Human Immunodeficiency Virus (HIV). We have conducted multi-center, prospective study, which aimed to establish HIV-1 subtype and assess the presence of primary drug resistance mutations to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors in antiretroviral treatment naïve patients. The clinical trial recruited 117 individuals during 2 years period (2020-2022). The prevalence of HIV-1 subtype A was statistically significantly more frequent in Ukrainian, and HIV-1 subtype B in Polish patients (p < 0.05). Drug resistance mutations were detected in 44% of all cases and the comparison of presence of mutations in the analyzed groups, as well as in the subgroups of subtype A and B HIV-1 has not revealed any significant differences (p > 0.05), nevertheless Polish patients had multidrug resistance mutations more frequent (p < 0.05). The results from our trial show no increased risk of transmission of multidrug resistant HIV strains in our cohort of Ukrainian migrants.Clinical trials. Gov number NCT04636736; date of registration: November 19, 2020.

The Clinical Course and Outcomes of Patients Hospitalized Due to COVID-19 during Three Pandemic Waves in Poland: A Single Center Observational Study.

Background: The first case of coronavirus disease 2019 (COVID-19) in Poland was reported on 4 March 2020. We aim to compare the clinical course and outcomes of patients hospitalized in the Hospital for Infectious Diseases in Warsaw due to COVID-19 during three pandemic waves. Materials and methods: The medical data were collected for all patients diagnosed with COVID-19 hospitalized in our hospital from 6 March 2020 till 30 November 2021. COVID-19 diagnosis was confirmed by nasopharyngeal swabs using real-time polymerase chain reaction assay (RT-PCR) or SARS-CoV-2 antigen test. COVID-19 waves were defined based on the number and dynamics of cases. Results: Altogether, 2138 patient medical records were analyzed. The majority of the cohort was male (1235/2138, 57.8%), and the median age was 65 years [IQR: 50−74 years]. Patients hospitalized during the third wave had lower oxygen saturation on admission (p < 0.001) and were more likely to receive oxygen supplementation (p < 0.001). Serious complications, including pneumothorax (p < 0.001) and thromboembolic complications (p < 0.001), intensive care unit admission (p = 0.034), and death (p = 0.003), occurred more often in patients of the third wave. Conclusions: During the third wave, patients in our cohort experienced a more severe course of the disease and poorer outcomes.

Evaluation of Clinical Biomarkers Related to CD4 Recovery in HIV-Infected Patients-5-Year Observation.

Human Immunodeficiency Virus infection leads to the impairment of immune system function. Even long-term antiretroviral therapy uncommonly leads to the normalization of CD4 count and CD4:CD8 ratio. The aim of this study was to evaluate possible clinical biomarkers which may be related to CD4 and CD4:CD8 ratio recovery among HIV-infected patients with long-term antiretroviral therapy. The study included 68 HIV-infected patients undergoing sustained antiretroviral treatment for a minimum of 5 years. Clinical biomarkers such as age, gender, advancement of HIV infection, coinfections, comorbidities and applied ART regimens were analyzed in relation to the rates of CD4 and CD4:CD8 increase and normalization rates. The results showed that higher rates of CD4 normalization are associated with younger age (p = 0.034), higher CD4 count (p = 0.034) and starting the therapy during acute HIV infection (p = 0.012). Higher rates of CD4:CD8 ratio normalization are correlated with higher CD4 cell count (p = 0.022), high HIV viral load (p = 0.006) and acute HIV infection (p = 0.013). We did not observe statistically significant differences in CD4 recovery depending on gender, HCV/HBV coinfections, comorbidities and opportunistic infections. The obtained results advocate for current recommendations of introducing antiretroviral therapy as soon as possible, preferably during acute HIV infection, since it increases the chances of sufficient immune reconstruction.

Study of the first clinical cases on monkeypox in Poland.

Monkeypox is a viral, zoonotic, emerging infectious disease that has become the most significant orthopoxviral infection among humans since the eradication of smallpox. It is endemic in Central and West Africa, and since May 2022 it has caused a multi-country outbreak in six continents. So far, no clinical cases of this disease have been observed in Poland. Monkeypox can be transmitted by any person, regardless of gender identity or sexual preferences, through direct contact with the secretion from skin lesions or through fomites contaminated with infectious material. Therefore, people infected with the monkeypox virus require isolation until the skin lesions heal completely and the scabs fall off, which is equivalent to the end of their infectivity. The paper presents a study of the first nine clinical cases of monkeypox in Poland, along with photographic documentation. All patients were young men, the vast majority of whom had contact with multiple sexual partners, and presented a higher prevalence of human immunodeficiency virus (HIV) infection than in the general population. The course of the disease was self-limited and no specific antiviral treatment was required by any of the patients. Nonetheless, there was a change in the route of transmission of the infection to sexual contact and an atypical clinical course of the disease, which resulted both in skin lesions initially appearing in the anogenital area, skin lesions occurring at various stages of development, and the appearance of skin lesions before the onset of general symptoms. In one of the patients, skin changes were not observed at all.

How to follow-up a patient who received tocilizumab in severe COVID-19: a case report.

BACKGROUND: COVID-19 is characterized by fast deterioration in the mechanism of cytokine storm. Therefore, treatment with immunomodulating agents should be initiated as soon as hyperinflammation is established. Evidence for the use of tocilizumab (TCZ) in COVID-19 is emerging, but the drug in this setting is used "off label" with limited data on both effectiveness and safety. Therefore, Hospital for Infectious Diseases in Warsaw established a Standard Operating Procedure (SOP) for the use of TCZ in severe COVID-19 cases. CASE PRESENTATION: Here, we present a case of 27-year-old, otherwise healthy man, who was successfully treated with chloroquine, azithromycin, tocilizumab and a standard of care. Initially the magnitude of lung devastation, clinical deterioration and the need for mechanical ventilation suggested unfavorable prognosis. However, we observed complete regression in radiological changes and rapid clinical improvement. Irrespective of this, patient's serum interleukin 6 and aminotransferases remained elevated even after a month from treatment. CONCLUSIONS: An overlapping effect of hyperinflammation, hypoxic organ injury and drug-related toxicity warrants a long-term follow-up for COVID-19 survivors. In addition, residual IL-6 receptors blockage may mask new infections. A standardized approach to follow-up for COVID-19 survivors is urgently needed. Current and future research should also investigate the impact of experimental therapies on lung tissue healing and regeneration, as well as long-term treatment toxicities.

Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe.

BACKGROUND: HBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe. METHODS: This study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence. The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence. RESULTS: At least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32-3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by analysing drug-naïve patients (29.5% vs 21.2%, P = 0.032). Strong correlation was observed between sP120T and rtM204I/V (P < 0.001), and their co-presence determined an increased HBV-DNA. At least one NA-induced immune-escape mutation occurred in 28.6% of patients, and their selection correlated with genotype-A (OR[95%CI]:2.03[1.32-3.10],P = 0.001). Finally, stop-codons are present in 8.4% of patients also at HBsAg-positions 172 and 182, described to enhance viral oncogenic-properties. CONCLUSIONS: Immune-escape mutations and stop-codons develop in a large fraction of NA-exposed patients from Europe. This may represent a potential threat for horizontal and vertical HBV transmission also to vaccinated persons, and fuel drug-resistance emergence.

Combined Analysis of the Prevalence of Drug-Resistant Hepatitis B Virus in Antiviral Therapy-Experienced Patients in Europe (CAPRE).

BACKGROUND: European guidelines recommend treatment of chronic hepatitis B virus infection (CHB) with the nucleos(t)ide analogs (NAs) entecavir or tenofovir. However, many European CHB patients have been exposed to other NAs, which are associated with therapy failure and resistance. The CAPRE study was performed to gain insight in prevalence and characteristics of NA resistance in Europe. METHODS: A survey was performed on genotypic resistance testing results acquired during routine monitoring of CHB patients with detectable serum hepatitis B virus DNA in European tertiary referral centers. RESULTS: Data from 1568 patients were included. The majority (73.8%) were exposed to lamivudine monotherapy. Drug-resistant strains were detected in 52.7%. The most frequently encountered primary mutation was M204V/I (48.7%), followed by A181T/V (3.8%) and N236T (2.6%). In patients exposed to entecavir (n = 102), full resistance was present in 35.3%. Independent risk factors for resistance were age, viral load, and lamivudine exposure (P < .001). CONCLUSIONS: These findings support resistance testing in cases of apparent NA therapy failure. This survey highlights the impact of exposure to lamivudine and adefovir on development of drug resistance and cross-resistance. Continued use of these NAs needs to be reconsidered at a pan-European level.

Prevalence of hepatitis C virus mutants resistant to protease inhibitors among Polish HCV genotype 1-infected patients.

AIM: The aim of this study was to evaluate prevalence of hepatitis C virus (HCV) harbouring mutations associated with decreased susceptibility to protease inhibitors (Boceprevir/Telaprevir) among Polish untreated patients infected with HCV genotype 1. MATERIAL AND METHOD: Population sequencing was used, sequencing data were interpreted by web based geno2pheno algorithm. A total of 91 serum samples were obtained from patients infected with HCV genotype 1, admitting Outpatient Clinics of Hospital of Infectious Diseases, Warsaw. RESULTS: Sequencing analysis of the NS3 protease catalytic domain was successful in 85 out of 91 subjects. In seventy three (85.9%) out of 85 samples wild-type HCV was detected; in 12 (14.1%) samples mutations associated with clinically observed Boceprevir/Telaprevir-decreased susceptibility were detected. SUMMARY AND CONCLUSIONS: Obtained results document the presence of HCV strains harbouring protease inhibitors (PIs) resistance-associated mutations among Polish therapy-naïve patients. The determined prevalence of drug resistant HCV variants is 14.1%. Further and continuous surveillance is necessary to estimate how preexisting and emerging drug resistance mutations influence clinical outcome in triple-therapy experienced patients.

Evolving patterns of HIV-1 transmitted drug resistance in Poland in the years 2000-2008.

The aim of the study was to determine the rate of transmission of drug resistant human immunodeficiency virus-1 (HIV-1) variants among therapy-naïve HIV positive patients in Poland in the year 2008, to compare the data with the results from the years 2000 to 2007 and to monitor patterns of HIV-1 subtypes present in Polish population and their evolution. Complete protease and part of reverse transcriptase regions were sequenced from the sera of patients directed to the laboratory for drug resistance testing. The Stanford's HIVdb program was used for the interpretation of results and subtyping. The variants scoring at least "intermediate resistance" for at least one drug were considered as resistant. The results obtained were compared to those obtained in the years 2000-2007. A total of 95 patients were enrolled in the 2008 study. Homosexual transmission of infection was documented in more than 55% of all cases. The overall prevalence of transmitted drug resistance (TDR) was 5.3% (3.9% in 2007, 5.8% in 2006, and 14.1% in the years 2002-2005). The study from the years 2000 to 2001 revealed 28.7% prevalence. Preliminary analysis of the first half of 2009 shows the ratio of 7.8%. In four (4.2%) cases drug resistance was associated with protease inhibitors class, in one case (1.1%) with resistance to non-nucleoside reverse transcriptase inhibitors class. In four cases (4.2%) non-B subtype was identified (C, G, CRF01_AE, CRF02_AG). An increase of percentage of drug resistant mutants-from 3.9% (2007) to 5.3% (2008)-was recognized. In this study, TDR was limited to single classes of antiretroviral drugs. HIV-1 subtype B prevails in Poland.

Better outcome of HBe Ag (-) than HBe Ag (+) lamivudine treatment of HBV chronically infected patients.

From May 2006 to December 2007 in Warsaw Hospital for Infectious Diseases one hundred and eight patients chronically infected HBV were treated with lamivudine. Among them 46 (42.5%) were HBeAg (+) and 62 (57.5%) HBeAg (-). HBV DNA levels were analysed in weeks 24, 48 and 72 of therapy using Real Time HBV PCR (Abbott) with a limit of detection of 28 copies/ml. Complete response for treatment was defined as HBV VL of less than 10(2) copies/ml (group A). Partial response was defined as HBV VL ranging from 10(2) to 10(5) copies/ml (group B), and treatment failure was determined by HBV VL above 10(5) copies/ml (group C). Presented results confirmed better response to lamivudine treatment in patients HBeAg (-) than HBeAg (+).