SARS-CoV-2 vaccination in inflammatory bowel disease (IBD) patients - does treatment for IBD negatively affect SARS-CoV-2 antibodies? A single-centre, prospective study.

Introduction: Inflammatory bowel disease (IBD) patients use a wide variety of immunosuppressive drugs, including biologics, but their effect on SARS-CoV-2 vaccine antibody levels remains a mystery. Aim: We analysed whether the drugs used in the treatment of IBD patients could affect the concentration of SARS-CoV-2 antibodies. Material and methods: This is a prospective, single-centre evaluation of the persistence of SARS-CoV-2 antibodies after vaccination at various time points: every 2 months throughout the 6th month after the first dose. Results: We included a total of 346 vaccinated IBD patients in the study. A negative correlation between antibody level and time from full vaccination was confirmed for the following types of therapy: infliximab (rho = -0.32, p < 0.001), adalimumab (rho = -0.35, p = 0.025), and vedolizumab (rho = -0.50, p < 0.001). In the case of other, long-term drug administration, a negative correlation between antibody level and time from full vaccination was confirmed for mesalazine (rho = -0.35, p < 0.001), budesonide (rho = -0.58, p = 0.004), systemic glucocorticoids (rho = -0.58, p < 0.001), and azathioprine (rho = -0.44, p < 0.001). Conclusions: Due to the immunosuppressive and biological treatment, IBD patients are exposed to a shorter persistence of SARS-CoV-2 antibodies and require booster doses. The role of gastroenterologists in educating patients about the need to continue SARS-CoV-2 vaccination remains crucial.

Assessment of the activity of the immune system in patients with inflammatory bowel diseases and asymptomatic COVID-19.

Introduction: Although the phenomenon of cytokine storm is well described in patients with severe COVID-19, little is known about the role of the immune system in asymptomatic patients, especially in the group with autoimmune diseases, such as inflammatory bowel disease (IBD). Aim: To assess the stimulation of the immune system expressed through the production of cytokines in IBD patients with asymptomatic COVID-19. Material and methods: This is a multi-centre, prospective study in which the concentration of many cytokines (IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL- 15, IL-17, IL-23, IFN-γ, TNF-α, TNF-ß) was assessed in patients with IBD and asymptomatic SARS-CoV-2 infection diagnosed by serological tests. Results: In the group of patients with a recent SARS-CoV-2 infection, defined as positive antibodies in the IgA + IgM class, a higher percentage of patients with the presence of interleukin (IL) 2 (IL-2) was found. No association with other cytokines or effects of IBD activity or treatment was found. However, the effect of the applied treatment on the concentration of some cytokines was found: a negative association of infliximab, vedolizumab, and prednisone with IL-2, a positive correlation of steroids, thiopurines with IL-10, and in the case of tumor necrosis factor-α (TNF-α), negative with infliximab, and positive with vedolizumab. Conclusions: The increased concentration of IL-2 may result from its regulatory role in inhibiting excessive activation of the immune system; however, considering the studies of patients with severe COVID-19, its role in the initial phase of SARS-CoV-2 infection requires further research.

Autoimmune Pancreatitis in Patients with Inflammatory Bowel Disease: A Real-World Multicentre Collaborative ECCO CONFER Study.

BACKGROUND: Autoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP-IBD and predictors of complicated AIP course have rarely been reported. METHODS: An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collected cases of AIP diagnosed in patients with IBD. Complicated AIP was defined as a composite of endocrine and/or exocrine pancreatic insufficiency, and/or pancreatic cancer. We explored factors associated with complicated AIP in IBD. RESULTS: We included 96 patients [53% males, 79% ulcerative colitis, 72% type 2 AIP, age at AIP diagnosis 35 ±â€…16 years]. The majority of Crohn's disease [CD] cases [78%] had colonic/ileocolonic involvement. In 59%, IBD preceded AIP diagnosis, whereas 18% were diagnosed simultaneously. Advanced therapy to control IBD was used in 61% and 17% underwent IBD-related surgery. In total, 82% of patients were treated with steroids for AIP, the majority of whom [91%] responded to a single course of treatment. During a mean follow-up of 7 years, AIP complications occurred in 25/96 [26%] individuals. In a multivariate model, older age at AIP diagnosis was associated with a complicated AIP course (odds ratio [OR] = 1.05, p = 0.008), whereas family history of IBD [OR = 0.1, p = 0.03], and CD diagnosis [OR = 0.2, p = 0.04] decreased the risk of AIP complications. No IBD- or AIP-related deaths occurred. CONCLUSIONS: In this large international cohort of patients with concomitant AIP-IBD, most patients have type 2 AIP and colonic IBD. AIP course is relatively benign and long-term outcomes are favourable, but one-quarter develop pancreatic complications. Age, familial history of IBD, and CD may predict uncomplicated AIP course.

Awareness and Compliance with the Recommendations of Primary and Secondary Prevention of Cancer in Patients with Inflammatory Bowel Disease.

INTRODUCTION: Patients with Inflammatory Bowel Disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are at high risk of developing malignancies, so prevention and adherence to cancer screening may improve detection. The aim of this study was to assess compliance with medical recommendations, especially primary and secondary prevention of cancer. METHODS: This one-center cross-sectional study was carried out between June and December 2021 amongst patients at the Department of Internal Medicine and Gastroenterology, IBD Division, National Medical Institute of Ministry of Interior Affairs and Administrations, or the outpatient clinic. Patients with IBD were asked to complete an anonymous questionnaire, which included 42 questions concerning lifestyle, cancer risk factors, cancer history, and checkups. STATISTICAL METHODS: The results of the qualitative variables were expressed as frequencies and percentages. We used Fisher's exact test and the Chi-squared test. A value of p < 0.05 was considered significant. Statistical analyses were performed with the SPSS statistical package. RESULTS: A total of 313 patients were enrolled in the study: 145 women and 168 men. In the group, 182 had Crohn's disease (CD), 120 had ulcerative colitis (UC), and 11 with IBDU (unclassified IBD). Most participants had a disease duration of over 8 years and received biological treatment, corticoids, and/or immunosuppressive therapy. Amongst respondents, 17% (31) of patients with CD and 25.8% (31) with UC were overweight, and 10.5% (19) with CD and 15.8% (19) with UC were obese (p = 0.017). We found that 16.3% of all respondents were smokers (79.6% (144) with CD, 90.8% (109) with UC, and 72.7% (8) with IBDU; p = 0.053), and 33.9% declared that they consumed alcohol (39.4% (71) with CD, 26.9% (32) with UC, and 18.2% (2) with IBDU; p = 0.045). A total of 25.4% of patients were exposed to UV radiation, but only 18.8% used sunblock. In addition, 58.8% (67) of patients with CD and 35.8% (19) with UC receiving immunosuppressants had regular laboratory tests (p = 0.02). Furthermore, 41.4% (46) of patients with UC, 27.1% (49) of patients with CD, and 70.0% (7) of patients with IBDU declared not to perform any dermatological control (p = 0.013). A total of 77% of patients had abdominal ultrasound. Out of 52.9% of patients for whom colonoscopy was recommended, only 27.3% had it performed (16.9% (30) with CD vs. 43.1% (50) with UC p < 0.001). Most examinations were ordered by gastroenterologists. Female patients had regular breast control (CD, 78.6% (66); UC, 91.2% (52); IBDU, 50% (2); p = 0.034), and 93.8% (76) had gynecological examinations. Additionally, 80.2% of patients knew about HPV, but most declared not to be vaccinated. A total of 17.9% of patients had urological control, but most had no important pathology detected. CONCLUSIONS: According to our study, many patients are still exposed to risk factors, such as obesity, smoking, and low physical activity, that are modifiable. Laboratory tests in patients with immunosuppressive treatment should be performed regularly. Systematic control, especially dermatological checkups, should be recommended. Additionally, not only gastrologists but also other specialists and GPs should remind patients about regular checkups. Primary prevention, such as HPV vaccinations, should be recommended to all patients.

A Prospective Questionnaire-Based Study to Evaluate Factors Affecting the Decision to Receive COVID-19 Vaccination in 267 Patients with Inflammatory Bowel Disease in Poland.

BACKGROUND The aim of the study was to assess the rate of COVID-19 vaccination and the attitudes toward receiving COVID-19 vaccination among patients with inflammatory bowel disease (IBD) in Poland. An important aim of the study was to determine why some people get vaccinated and others refuse to do so. MATERIAL AND METHODS This was a single-center, prospective survey. The study included 267 IBD patients who agreed to complete an anonymous questionnaire comprising 31 questions. RESULTS We found that 71.2% of the IBD patients had been vaccinated. The history of COVID-19 was associated with a lower vaccination rate (16.9% vs 36.8%; P=0.001), regardless of IBD severity. In the vaccinated group, there were more vaccinated people among household members (90.4% vs 43.4%; p<0.001) and friends (52.9% vs 22.4%; P<0.001). Family safety (71.1%), the desire to avoid COVID-19 (67.9%), social responsibility (60.5%), the desire to return to normal life (51.6%), and faith in vaccination as such (43.2%) were the most common reasons for vaccination. The most common cause of non-vaccination was concern about adverse effects (50.0%), including long-term adverse effects (36.8%), and about the possible exacerbation of gastroenterological disease (34.2%). CONCLUSIONS IBD patients are more likely to be vaccinated against SARS-CoV-2 than the rest of the population in Poland. Young age, low socioeconomic status, low education, and living in the countryside were factors associated with lower vaccination rates. Family and friends had the greatest influence on the decision to vaccinate, but the influence of the mass media was very small.

Inflammatory and thrombotic parameters associated with the COVID-19 course in Poland (SARSTer study).

PURPOSE: The aim of the study was to assess the coagulation and inflammatory markers connected with severe course of COVID-19 and no clinical improvement. MATERIAL AND METHODS: The study population included 2590 adult patients, diagnosed with COVID-19, selected from the SARSTer national database - an ongoing project led by the Polish Association of Epidemiologists and Infectiologists and supported by the Medical Research Agency. Clinical and laboratory parameters, such as C-reactive protein (CRP), white blood cells (WBCs), neutrophil and lymphocyte count, procalcitonin, ferritin, interleukin-6 (IL-6), D-dimer concentration and platelet (PLT) count were analyzed before and after treatment (remdesivir, tocilizumab, dexamethasone, anticoagulants). RESULTS: Significant differences between patients with mild and severe course of the disease were observed in all examined parameters before treatment (p â€‹< â€‹0.05). After treatment only ferritin concentration did not differ significantly. In patients with pulmonary embolism, CRP concentration, neutrophil count, D-dimer and IL-6 concentration were significantly higher than in patients without embolism (p â€‹< â€‹0.05). The significant differences between the groups with and without fatal outcome were observed within all analyzed parameters. Significant differences in all examined parameters before treatment were observed between patients with and without clinical improvement (p â€‹< â€‹0.05). Multivariate logistic regression showed that no clinical improvement was associated with: IL-6>100 â€‹pg/ml (OR-2.14), D-dimer concentration over 1000 â€‹ng/ml (OR-1.62) and PLT count below 150,000/µl (OR-1.57). CONCLUSIONS: Severe course of the disease is associated with lower PLT and lymphocyte count, higher D-dimer, CRP, neutrophil count and IL-6 concentration. The best predictors of no clinical improvement in COVID-19 are: IL-6>100 â€‹pg/ml, D-dimer>1000 â€‹ng/ml and PLT<150,000/µl.

Social Distancing during COVID-19 Pandemic among Inflammatory Bowel Disease Patients.

(1) Background: Social distancing rules have been widely introduced in the fight against the coronavirus disease 2019 (COVID-19) pandemic. So far, the effectiveness of these methods has not been assessed in the group of inflammatory bowel disease (IBD) patients. (2) Methods: The study included 473 patients with IBD who made 1180 hospital visits from 1 May to 30 September 2020. During each visit, the patients completed a five-step, progressive scale that was developed to assess the degree of social isolation. In parallel, other demographic data were collected and the concentrations of anti-severe acute respiratory coronavirus 2 (SARS-CoV-2) IgG and IgM+IgA antibodies were measured using the ELISA method. (3) Results: The study found a significant correlation between the degree of social distancing and the presence of anti-SARS-CoV-2 antibodies in the groups with the lowest degree of isolation (3 to 5). (4) Conclusions: Maintaining social distancing is an effective method for reducing the spread of SARS-CoV-2 virus among IBD patients.

Inflammatory bowel disease is associated with higher seroprevalence rates of antibodies against SARS-CoV-2.

INTRODUCTION: According to the current data, there has been no increase in the incidence of COVID­19 in patients with inflammatory bowel disease (IBD). OBJECTIVES: The available data are based on symptomatic cases and do not include the asymptomatic ones. To measure the exact infection rate, we initiated a study that aimed to assess the seroprevalence of anti-SARS­CoV­2 antibodies in IBD. PATIENTS AND METHODS: A total of 864 individuals were enrolled in the study, including 432 patients with IBD (290 with Crohn disease and 142 with ulcerative colitis) and 432 controls without IBD (healthcare professionals) matched for age and sex. Serum samples were prospectively collected, and the presence of anti-SARS­CoV­2 immunoglobulin (Ig) G and IgM + IgA antibodies were measured using the enzyme­linked immunoassay method (Vircell Microbiologists). RESULTS: A significantly higher percentage of positive results for anti-SARS­CoV­2 antibodies, both in the IgG and IgM + IgA class, was found in patients with IBD (4.6% and 6%, respectively, compared with 1.6% and 1.1%, respectively, in controls; both P values <0.05). No patient had symptomatic COVID­19. There was no association among patients' age, sex, drugs used for IBD, or disease activity and the occurrence of IgG antibodies. CONCLUSION: Patients with IBD may be at higher risk of developing SARS­CoV­2 infection, defined as the presence of elevated levels of anti-SARS­CoV­2 IgG antibodies, but not of having a symptomatic and / or severe course of COVID­19 compared with healthcare professionals without IBD.

Hepatotropic Properties of SARS-CoV-2-Preliminary Results of Cross-Sectional Observational Study from the First Wave COVID-19 Pandemic.

Liver injury-expressed as elevated liver enzymes-is common in patients with COVID-19. Little is known about the potential mechanisms of liver damage by SARS-CoV-2. A direct cytopathic effect on hepatocytes as well as injury related to hypoxia or hepatotoxicity are being considered. The aim of the study was to compare the clinical characteristic of COVID-19 disease in patients with normal and abnormal liver enzymes activity. A group of 150 patients with COVID-19, hospitalized in our center, was analyzed. Patients with the known liver comorbidities were excluded (n = 15). Clinical features and laboratory parameters were compared between patients with normal and abnormal aminotransferase values. Liver injury expressed as any alanine aminotransferase (ALT) elevation was noted in 45.6% of patients hospitalized due to COVID-19. The frequencies of aspartate aminotransferase (AST) elevation were lower. It was noted that elevated ALT/AST unfavorably affected other parameters related to liver function such as albumin level; gamma-glutamyl transpeptidase (GGTP); and partly, ALP activity and influenced inflammation-related parameters. The most probable cause of mild hepatitis during COVID-19 was anoxia and immune-mediated damage due to the inflammatory response following SARS-CoV-2 infection. A direct cytopathic effect of SARS-CoV-2 on hepatocytes, albeit less probable, can be considered as well. The use of potentially hepatotoxic drugs may contribute to liver damage.

Characterization of atmospheric PM2.5 sources at a Central European urban background site.

For the purposes of this work, a first in Poland, full-year collection of daily PM2.5 (particulate matter with aerodynamic diameter smaller than 2.5 µm) samples was chemically analyzed to determine the contents of elemental and organic carbon, water-soluble inorganic ions and 21 minor and trace elements in PM in an urban background site in Warsaw. Annual mean PM2.5 concentration reached 18.8 µg/m3, with the lowest levels in summer (11.5 µg/m3 on average) and the highest in winter (27.5 µg/m3), with several episodes reaching over 80 µg/m3. Strong seasonal differences were observed mainly for the contents of nitrate and secondary organic carbon (SOC), while sulphate showed the least variability. Secondary species constituted on average 45% of PM2.5 mass, suggesting large influence of regional and long-range transport of pollutants. Source apportionment with the use of positive matrix factorization (PMF) method, supported by the analysis of enrichment factors, led to identification of six main sources of PM2.5 origin: residential combustion (fresh & aged aerosol) (46% of PM2.5 mass), traffic exhaust (21%) and non-exhaust (10%) emissions, mineral dust/construction works (12%), high-temperature processes (8%) and steel processing (3%). Including primary organic carbon (POC) and SOC as two separate constituents helped to distinguish between the primary and secondary sources of the aerosol. The identification of sources was also supported by investigating their yearly and weekly profiles, as well as the correlation of PM constituents with meteorological conditions, which are one of the main drivers of heat generation activities. We found that the most distinctive markers of PM sources in Warsaw are SOC, Cl- and As for residential combustion, NH4+, Sb and POC for road transport, Ca and Mg for construction works and SO42- for long-range transport of PM.

Aging and the evolution of comorbidities among HIV-positive individuals in a European cohort.

OBJECTIVES: To describe changes in the prevalence of comorbidities and risk factors among HIV-positive individuals in the EuroSIDA study. DESIGN: Comparison of two cross-sectional cohorts of HIV-positive adults under active follow-up in 2006 and 2014. METHODS: Baseline demographics and prevalence of comorbidities were described. Factors associated with the prevalence of chronic kidney disease (CKD) and cardiovascular disease (CVD) were assessed by logistic regression modelling using generalized estimating equations. RESULTS: Nine thousand, seven hundred and ninety-eight individuals were under active follow-up in EuroSIDA during 2006 and 12 882 during 2014. Compared with study participants in 2006, those in 2014 were older [median age 48.6 years (IQR 40.3-55.1) vs. 43.1 years (37.2-50.0) in 2006] and had higher prevalence of hypertension (59.6 vs. 47% in 2006), diabetes (6.3 vs. 5.4%), CKD (6.9 vs. 4.1%) and CVD (5.0 vs. 3.7%). Individuals in the 2014 cohort had higher odds for CKD (unadjusted OR 2.62, 95% CI 2.30-2.99, P < 0.0001) and CVD (OR 1.88, CI 1.68-2.10, P < 0.0001), but after multivariable adjustment for age group, comorbidities and other factors, year of cohort was no longer significantly associated with the odds of CKD [adjusted OR (aOR) 0.97, CI 0.52-1.82, P = 0.92) or of CVD (aOR 0.94, CI 0.54-1.63, P = 0.82). CONCLUSION: Between 2006 and 2014, the population aged and experienced an overall higher prevalence of non-AIDS comorbidities, including CKD and CVD. The increase in CVD could be explained by the aging population, and the increase in CKD by aging and changes in other factors. Treatment strategies balancing HIV outcomes with long-term management of comorbidities remain a priority.

Hepatitis C coinfection adversely affects the life expectancy of people living with HIV in northwestern Poland.

INTRODUCTION: Hepatitis C (HCV) infection adversely affects survival among people living with HIV, increasing mortality risk due to liver-related causes. In Poland HCV is found among ~30% of HIV infected individuals, with only a small percentage successfully treated for this coinfection. This study aimed to analyze the HCV-associated influence on the life expectancy among HIV/HCV coinfected patients from northwestern Poland. MATERIAL AND METHODS: Longitudinal data of 701 (368 HIV monoinfected and 368 HIV/HCV coinfected) patients were investigated to assess the life expectancy and survival after HIV diagnosis. Kaplan-Meier and Cox analyses were used to assess the mortality risk in both unadjusted and multivariate models. Effect plots indicate the adjusted hazard ratio for HCV-associated survival. RESULTS: Overall mortality was significantly higher among HCV coinfected (22.52%) compared to HIV monoinfected (10.32%) cases (p < 0.001, OR = 2.52 (95% CI: 1.65-3.85)), with shorter life expectancy among HIV/HCV infected patients (median: 55.4 (IQR: 42.8-59.1) years) compared to HIV monoinfection (median 72.7 (IQR: 60.4-76.8) years, univariate HR = 4.15 (95% CI: 2.7-6.38), p < 0.0001, adjusted HR = 2.32 (95% CI: 1.47-3.65), p < 0.0001). After HIV diagnosis, HCV adversely influenced the survival after 15 years of follow-up, with a strengthened impact in the subsequent 5 years (univariate HR = 1.57 (95% CI: 1.05-2.34) p = 0.026 for the 20-year survival time point, adjusted HR = 2.21 (95% CI: 1.18-4.13), p = 0.013). CONCLUSIONS: Among patients living with HIV, HCV coinfection is associated with a median life expectancy decrease of 17.3 years and low probability of surviving until the age of 65 years. In the era of directly acting anti-HCV drugs, treatment scale-up and immediacy of treatment are advisable in this cohort.

The transparency of published health technology assessment-based recommendations on pharmaceutical reimbursement in Poland.

BACKGROUND: The appropriate access to public information is very important for healthcare system stakeholders. The goal of this study was to examine how the execution of the formally existing right to public information on the HTA-based recommendations on reimbursement of new health technologies from public funds has been changing in Poland. METHODS: All recommendations published within two predefined equal periods of time between 2013 and 2015 were analyzed. The gathered data was subjected to statistical analysis. RESULTS: The frequency and intensity of censoring the published HTA-based recommendations on the pharmaceutical reimbursement has diminished. The text readability and clarity of message has improved, although the degree of decisiveness of the recommendations has dropped. CONCLUSION: The positive changes in the public communication policy should be continued. The transparency of the HTA-based recommendations should be increased further in some areas in the future.

Disparities in HIV clinic care across Europe: findings from the EuroSIDA clinic survey.

BACKGROUND: Although advances in HIV medicine have yielded increasingly better treatment outcomes in recent years, HIV-positive people with access to antiretroviral therapy (ART) still face complex health challenges. The EuroSIDA Study Group surveyed its clinics to explore regional differences in clinic services. METHODS: The EuroSIDA study is a prospective observational cohort study that began enrolling patients in 1994. In early 2014, we conducted a 59-item survey of the 98 then-active EuroSIDA clinics. The survey covered HIV clinical care and other aspects of patient care. The EuroSIDA East Europe study region (Belarus, Estonia, Lithuania, the Russian Federation and Ukraine) was compared to a "non-East Europe" study region comprised of all other EuroSIDA countries. RESULTS: A larger proportion of clinics in the East Europe group reported deferring ART in asymptomatic patients until the CD4 cell count dropped below 350 cells/mm(3) (75 % versus 25 %, p = 0.0032). Considerably smaller proportions of East Europe clinics reported that resistance testing was provided before ART initiation (17 % versus 86 %, p < 0.0001) and that it was provided upon treatment failure (58 % versus 90 %, p = 0.0040). Only 33 % of East Europe clinics reported providing hepatitis B vaccination, compared to 88 % of other clinics (p < 0.0001). Only 50 % of East Europe clinics reported having access to direct-acting antivirals for hepatitis C treatment, compared to 89 % of other clinics (p = 0.0036). There was significantly less tuberculosis/HIV treatment integration in the East Europe group (27 % versus 84 % p < 0.0001) as well as significantly less screening for cardiovascular disease (58 % versus 90 %, p = 0.014); tobacco use (50 % versus 93 %, p < 0.0001); alcohol consumption (50 % versus 93 %, p < 0.0001); and drug use (58 % versus 87 %, p = 0.029). CONCLUSIONS: Study findings demonstrate how specific features of HIV clinics differ across Europe. Significantly more East Europe clinics deferred ART in asymptomatic patients for longer, and significantly fewer East Europe clinics provided resistance testing before initiating ART or upon ART failure. The East Europe group of clinics also differed in regard to hepatitis B vaccination, direct-acting antiviral access, tuberculosis/HIV treatment integration and screening for other health issues. There is a need for further research to guide setting-specific decision-making regarding the optimal array of services at HIV clinics in Europe and worldwide.

The temporal increase in HIV-1 non-R5 tropism frequency among newly diagnosed patients from northern Poland is associated with clustered transmissions.

INTRODUCTION: CCR5 (R5) tropic viruses are associated with early stages of infection, whereas CXCR4 (X4) HIV-1 tropism has been associated with severe immunodeficiency. We investigated the temporal changes in the genotype-predicted tropism frequency and the phylogenetic relationships between the R5 and non-R5 clades. METHODS: A cohort of 194 patients with a newly diagnosed HIV infection that was linked to their care from 2007 to 2014 was analyzed. Baseline plasma samples were used to assess the HIV-1 genotypic tropism with triplicate V3-loop sequencing. The non-R5 tropism prediction thresholds were assigned using a false positive rate (FPR) of 10 and 5.75% and associated with clinical and laboratory data. The transmission clusters were analyzed using pol sequences with a maximum likelihood and Bayesian inference. RESULTS: The overall non-R5 tropism frequency for 5.75% FPR was 15.5% (n=30) and 27.8% (n=54) for 10% FPR. The frequency of the non-R5 tropism that was predicted using 5.75% FPR increased significantly from 2007 (0%) to 2014 (n=5/17, 29.4%) (p=0.004, rough slope +3.73%/year) and from 0% (2007) to 35.3% (2014, n=6/17) (p=0.071, rough slope +2.9%/year) using 10% FPR. Increase in the asymptomatic diagnoses over time was noted (p=0.05, rough slope +3.53%/year) along with a tendency to increase the lymphocyte CD4 nadir (p=0.069). Thirty-two clusters were identified, and non-R5 tropic viruses were found for 26 (30.95%) sequences contained within 14 (43.8%) clusters. Non-R5 tropism was associated with subtype D variants (p=0.0001) and the presence of CCR5 Δ32/wt genotype (p=0.052). CONCLUSIONS: R5 tropism predominates among the treatment of naive individuals, but the increases in the frequency of non-R5 tropic variants may limit the clinical efficacy of the co-receptor inhibitors. The rising prevalence of non-R5 HIV-1 may indicate transmission of X4 clades.

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.

Temporal increase in HIV-1 non-R5 tropism frequency among antiretroviral-naive patients from northern Poland.

INTRODUCTION: Sequencing of the third hypervariable loop allows to identify genotype-based HIV tropism. R5-tropic viruses associated with early stages of infection are preferentially transmitted, while non-R5 HIV-1 tropism has been associated with severe immunodeficiency and lower lymphocyte CD4 nadir and may reflect delayed HIV diagnosis. In this study, we investigate the changes in tropism frequency from 2007 to 2013. MATERIALS AND METHODS: Study included 194 patients with confirmed HIV infection linked to care in 2007-2013. Baseline plasma samples from treatment naive patients were used for HIV-1 genotypic tropism assessment based on triplicate V3 loop sequencing. Non-R5 tropism prediction thresholds were assigned using a false positive rate (FPR) of 10% and 5.75% FPR and associated with clinical and laboratory data (age, gender, date of HIV diagnosis, route of transmission, CDC clinical category at diagnosis, pretreatment HIV viral load, baseline and nadir lymphocyte CD4 counts). For statistics, chi-square and Mann-Whitney U tests were used, time trends were examined using logistic regression (R statistical platform, v. 3.1.0) for binary variables and linear regression for continuous ones. RESULTS: Overall non-R5 tropism frequency for the 5.75% FPR was 15.5% and 27.8% for 10% FPR. Frequency of the non-R5 tropism predicted using 5.75% FPR increased significantly from 2007 (0%) to 2013 (25%) [OR: 1.44 (95% CI 1.14-1.86), p=0.003, rough slope +3.89%/year] (Figure 1a). With 10% FPR, the frequency changed from 7% (2007) to 33% (2013) [OR: 1.17 (95% CI 0.99-1.39), p=0.054, rough slope +3.0%/year] (Figure 1b). Baseline lymphocyte CD4 count and nadir, as well as pretreatment HIV-1 viral loads were stable over time of observation (r=0.014, p=0.84; r=0.13, p=0.085; r=0.016, p=0.83 for CD4 baseline, nadir and HIV load, respectively). Frequency of AIDS at HIV diagnosis increased from 21.4% in 2007 to 38.0% in 2013, however trend over time was insignificant [OR: 1.1 (95% CI 0.95-1.31), p=0.19]. Temporal trends for HIV transmission route, gender, non-B variant frequencies also were not significant. CONCLUSIONS: R5 tropism predominates among the treatment naive individuals but increase in the frequency of non-R5 tropic variants may limit clinical efficacy of the coreceptor inhibitors. Increased prevalence of non-R5 HIV-1 may be related to late care entry and higher number of AIDS diagnoses in the recent years.

Time trends in HIV-1 transmitted drug resistance mutation frequency in Poland.

INTRODUCTION: In Poland, the HIV epidemic has shifted recently from being predominantly related to injection drug use (IDU) to being driven by transmissions among men-who-have-sex-with-men (MSM). The number of new HIV cases has increased in the recent years, while no current data on the transmitted drug resistance associated mutations (tDRM) frequency trend over time are available from 2010. In this study, we analyze the temporal trends in the spread of tDRM from 2008 to 2013. MATERIALS AND METHODS: Partial pol sequences from 833 antiretroviral treatment-naive individuals of European descent (Polish origin) linked to care in 9 of 17 Polish HIV treatment centres were analyzed. Drug resistance interpretation was performed according to WHO surveillance recommendations, subtyping with REGA genotyping 2.0 tool. Time trends were examined for the frequency of t-DRM across subtypes and transmission groups using logistic regression (R statistical platform, v. 3.1.0). RESULTS: Frequency of tDRM proved stable over time, with mutation frequency change from 11.3% in 2008 to 8.3% in 2013 [OR: 0.91 (95% CI 0.80-1,05), p=0.202] (Figure 1a). Also, no significant differences over time were noted for the subtype B (decrease from 8.4% 2008 to 6.2% in 2013 [OR: 0.94 (95% CI 0.79-1.11), p=0.45] and across non-B variants [change from 22.6% 2008 to 23.1% in 2013, OR: 0.94 (95% CI 0.75-1.19), p=0.62]. When patient groups were stratified according to transmission route, in MSM there was a trend for a NNRTI t-DRM decrease (from 6.8% 2008 to 1% in 2013, OR: 0.61 (95% CI 0.34-1.02), p=0.0655, slope -0.74%/year) (Figure 1b), related to the subtype B infected MSM (decrease from 7% 2008 to 1% in 2013, OR: 0.61 (95% CI 0.34-1.03), p=0.0662, slope -0.75%/year). Overall tDRM frequency decrease was also noted for the heterosexually infected patients [from 17.6% 2008 to 10.3% in 2013, OR: 0.83 (95% CI 0.67-1.02, p=0.077, slope -2.041%/year)] but did not associate with drug class (Figure 1c). In IDUs, the trends in t-DRM frequency were not significant over time (change from 1.9% in 2008 to 0 in 2013 [OR:1.24 (95% CI 0.73-2.26), p=0.4)]. CONCLUSIONS: The frequency of t-DRM in Poland is generally stable over time. Decrease in the overall tDRM frequency in heterosexual infected cases and NNRTI resistance in subtype B infected MSM may be related to the higher treatment efficacy of current cART.

Phylogeographic analysis on the travel-related introduction of HIV-1 non-B subtypes to Northern Poland.

Phylodynamic, sequence data based reconstructions for the surveillance of the geographic spatial spread are a powerful tool in molecular epidemiology. In this study region of origin for the set of 57 partial pol sequences derived from the patients the history of travel-related HIV transmission was analyzed using phylogeographic approach. Maximum likelihood trees based on the sets of country-annotated reference sequences were inferred for identified non-B variants. Region of sequence import was assigned using on the highest approximate likelihood ratios. Import of the A1 clades was traced to the Eastern Europe and associated with immigration from this region. Subtype C infections clustered most frequently with sequences of the South African origin while majority of subtype Ds were similar to the European clades. Subtype G sequences clustered with Portuguese lineage, CRF01_AE with Eastern or South-Eastern Asian. Eastern European, Middle African or Western African lineage was assigned for the CFR02_AG. Rare circulating recombinants originated either from Central Africa (CRF11_cpx - Democratic Republic of Congo, CRF13_cpx - Central African Republic, CRF37_cpx - Cameroon) or South America (CRF28_BF and CRF46_BF - Brazil). Import of the HIV-1 non-B variants, including recombinant forms previously rarely found in Poland and Europe is frequent among travelers. Observed founder events result in the heterosexually-driven introduction of the novel HIV-1 variants into the population.

Transmitted drug resistance to rilpivirine among antiretroviral-naïve patients living with HIV from northern Poland.

INTRODUCTION: Rilpivirine (RPV) is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) that was recently approved for the treatment of antiretroviral-naïve individuals with HIV-1 viral load of <100,000 copies/ml. As transmission of the drug resistance mutations to this NNRTI may affect treatment outcomes, the frequency of primary, RPV-associated drug resistance mutations was assessed in this study. METHODS: For the study, 244 viral genome sequences from antiretroviral-naïve individuals were obtained by bulk sequencing. RPV-associated mutations were divided into RPV resistance mutations (K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L) according to the International AIDS Society-USA (IAS-USA) mutation list and variants potentially affecting RPV susceptibility (L100I, K101H/T, E138S, V179F/D/G/T, G190A/E/S, F227L and M230V) based on the in vitro and in vivo data. RESULTS: IAS-USA RPV drug resistance mutations were found in 5.3% sequences, with E138A and E138G being the most common (3.7 and 0.8%, respectively), followed by K101E (0.4%) and Y181C (0.4%), with no significant differences in the frequency between subtype B and non-B clades. Mutations potentially reducing RPV susceptibility were found in 2.5% of sequences, and they included V179D (1.6%) and G190A (0.8%), with equal distribution among non-B (n=2, 2.5%) and subtype B (n=4, 2.5%) clades. Clustering of RPV mutations was infrequent. CONCLUSIONS: Prevalence of RPV-associated drug resistance mutations was low in the analysed sample and did not vary across the subtypes. The frequency of variants with potential influence on RPV susceptibility was similar among non-B variants if compared to B clades. Transmitted drug resistance to RPV is uncommon, which makes this a good option for the treatment of ARV-naïve patients; however, genotype resistance testing should remain compulsory before starting an RPV-based regimen.