Ewa Firląg-Burkacka

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 Stanfords 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. J. Med. Virol. 82:1291–1294, 2010.

Changes in the trends of the HIV/AIDS epidemic, based on surveillance data of Warsaw cohort

Summary HIV infection remains one of the major public health concern, with evidence of increasing, even in several developed countries. The article provides an overview of HIV surveillance data of patients from outpatient clinic in Warsaw. In Poland the first HIV infection was detected in 1985, and the first case of AIDS one year later. In the period between 1990–2000y among HIV infected patients approximately 70% were intravenous drug users. In the next decade the shift of predominant mode of transmission for HIV infection is observed. From 2001 onward, the increasing number of persons infected through sexual contacts, without the past history of intravenous drug using has been noticed. Since 2005, among newly reported HIV infected adolescents the sexual contact between men followed by heterosexual contact has been the main route of transmission. The significant increase of this mode of transmission was noticed in 2008. The deaths rate remains relatively low, even decreases.

Poor Linkage to Care Despite Significant Improvement in Access to Early cART in Central Poland – Data from Test and Keep in Care (TAK) Project

Background The main objective of the TAK project is investigating barriers in accessing HIV care after HIV-diagnosis at the CBVCTs of central Poland. Here we describe factors associated with and changes over time in linkage to care and access to cART. Method Data collected in 2010–2013 in CBVCTs were linked with HIV clinics records using unique identifiers. Individuals were followed from the day of CBVCTs visit until first clinical visit or 4/06/2014. Cox-proportional hazard models were used to identify factors associated with being linked to care and starting cART. Results In total 232 persons were diagnosed HIV-positive and 144 (62.1% 95%CI: 55.5–68.3) persons were linked to care. There was no change over time in linkage to care (p = 0.48), while time to starting cART decreased (p = 0.02). Multivariate factors associated with a lower rate of linkage to care were hetero/bisexual sexual orientation, lower education, not having an HIV-positive partner and not using condoms in a stable relationship. Multivariate factors associated with starting cART were lower education, recent year of linked to care, and first HIV RNA and CD4 cell count. Conclusions Benefits of linkage to care, measured by access to early treatment, steadily improved in recent years. However at least 1 in 3 persons aware of their HIV status in central Poland remained outside professional healthcare. Persons at higher risk of remaining outside care, thus target population for future interventions, are bi/heterosexuals and those with lower levels of education.

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 Fishers 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/mm3 (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.

Age and HIV effects on resting state of the brain in relationship to neurocognitive functioning

HighlightsHIV reduces resting state functional connectivity (FC) within Occipital Network.Age‐HIV interaction affects FC within Motor Network (MN).HIV strengthens relationship between FC within‐MN values and cognitive performance.In healthy aging, FC values have decreasing power in explaining cognitive functions.In HIV, age does not moderate relationships between RS‐FC and cognitive functions. ABSTRACT This study examined the effects of age and HIV infection on the resting state (RS) functional connectivity (FC) of the brain and cognitive functioning. The objective was to evaluate the moderating role of age and HIV on the relationship between RS‐FC and cognition. To examine RS‐FC we implemented the Independent Component Analysis (ICA) and Regional Homogeneity (ReHo). Neurocognition was evaluated with comprehensive battery of standardized neuropsychological tests. Age and HIV were entered as the independent variables. The independent effects of age, HIV, and interaction effects of age‐HIV on RS‐fMRI measures (ICA, ReHo) were tested in 108 participants (age M = 42). RS‐FC indices that exhibited age‐HIV interactions were entered into further analysis. Bivariate correlation analysis was performed between the retained RS‐FC indices and T‐scores of neurocognitive domains (Attention, Executive, Memory, Psychomotor, Semantic Skills). Multivariate regression modeling determined the impact of age and HIV on these relationships. We found that in the ICA measures, HIV‐seropositivity was decreasing RS‐FC in the left middle occipital gyrus (p < .001). Age‐HIV interaction was observed in the left superior frontal gyrus (LSupFrontG), where FC was decreasing with age in HIV+ (p < .001) and increasing in HIV− (p = .031). ReHo indices did not reveal significant effects. HIV strengthened the relationship between RS‐FC in LSupFrontG, Memory and Psychomotor Factor scores. Aging weakened those relationships only in control group. In sum, age‐HIV interaction effects are prominent rather in remote than local RS‐FC. Seroconversion strengthens relationships between intrinsic brain activity and neurocognition, but no acceleration with years of age was noted in HIV+ individuals.

Genetic detection of HLA-B*5701 allele for prediction of Abacavir hypersensitivity among HIV-positive patients in Polish population

Summary Abacavir (ABC) is a potent nucleoside reverse transcriptase inhibitor used in combined antiretroviral therapy (cART) of HIV-positive patients. However, 5 to 8% of patients manifest hypersensitivity reaction to ABC (ABC HSR) during first 6 weeks after therapy initiation. ABC HSR can be fatal if therapy with ABC is continued or ABC is restarted. There is an association between ABC HSR occurrence and a carriage of the Major Histocompatibility Complex class I allele HLA-B*5701. Genetic screening, before ABC initiation, significantly reduces a risk of developing ABC HSR. In accordance with European AIDS Clinical Societys guidelines Molecular Diagnostics Laboratory has been testing towards HLA-B*5701 since 2008.

Study comparing lipid metabolism disorders and effectiveness of treatment in HIV infected patients on long-term treatment with various thymidine analogues

Summary Disorders in lipid metabolism exist in most patients treated for the long time. In our study were included 186 patients on antiretroviral treatment lasting 96 weeks treated either with AZT/3TC or with D4T/3TC. Performed studies have shown that both d4T/3TC and AZT/3TC regimens are effective as backbone of CART. Similar immunological values are achieved using above mentioned regimens. Elevation of TG and TC level during antiretroviral therapy is much more frequent in persons treated with d4T/3TC and is not dependent on type of the third drug used.

HIV infection across aging: Synergistic effects on intrinsic functional connectivity of the brain.

Abstract The objective of the study was to examine additive and synergistic effects of age and HIV infection on resting state (RS) intra‐ and inter‐network functional connectivity (FC) of the brain. We also aimed to assess relationships with neurocognition and determine clinical‐, treatment‐, and health‐related factors moderating intrinsic brain activity in aging HIV‐positive (HIV+) individuals. The current report presents data on 54 HIV+ individuals (age M = 41, SD = 12 years) stabilized on cART and 54 socio‐demographically matched healthy (HIV−) comparators (age M = 43, SD = 12 years), with cohort education mean of 16 years (SD = 12). Age at seroconversion ranged 20–55 years old. ANOVA assessed additive and synergistic effects of age and HIV in 133 ROIs. Bivariate statistics examined relationships of FC indices vulnerable to age‐HIV interactions and neurocognitive domains T‐scores (attention, executive, memory, psychomotor, semantic skills). Multivariate logistic models determined covariates of FC. This study found no statistically significant age‐HIV effects on RS‐FC after correcting for multiple comparisons except for synergistic effects on connectivity within cingulo‐opercular network (CON) at the trending level. However, for uncorrected RS connectivity analyses, we observed HIV‐related strengthening between regions of fronto‐parietal network (FPN) and default mode network (DMN), and particular DMN regions and sensorimotor network (SMN). Simultaneously, FC weakening was observed within FPN and between other regions of DMN‐SMN, in HIV+ vs. HIV‐ individuals. Ten ROI pairs revealed age‐HIV interactions, with FC decreasing with age in HIV+, while increasing in controls. FC correlated with particular cognitive domains positively in HIV+ vs. negatively in HIV‐ group. Proportion of life prior‐to‐after HIV‐seroconversion, post‐infection years, and treatment determined within‐FPN and SMN‐DMN FC. In sum, highly functioning HIV+/cART+ patients do not reveal significantly altered RS‐FC from healthy comparators. Nonetheless, the current findings uncorrected for multiple comparisons suggest that HIV infection may lead to simultaneous increases and decreases in FC in distinct brain regions even in patients successfully stabilized on cART. Moreover, RS‐fMRI ROI‐based analysis can be sensitive to age‐HIV interactions, which are especially pronounced for inter‐network FC in relation to neurocognition. Aging and treatment‐related factors partially explain RS‐FC in aging HIV+ patients. HighlightsHIV infection may lead not only to weakened but also strengthened RS connectivity.RS‐fMRI FC is sensitive to age‐HIV synergistic effects in patients stable on cART.Age‐HIV interactions change directionality rather than exacerbate HIV effects on FC.Negative relations between FC and cognitive domains in health are positive in HIV.Infection duration, proportion of life prior‐to‐after conversion, cART determine FC.

Factors associated with urinary tract infections among HIV-1 infected patients

Background Urinary tract infections remain an important yet underinvestigated clinical problem among HIV infected patients. Here we analyze factors associated with its occurrence and the spectrum of bacterial pathogens identified in the group of patients followed at the HIV Out-Patient Clinic in Warsaw. Methods Clinic database collected all medical information on patients routinely followed since 1994 to 2015. All patients with available urine culture were included into analyses, only the first culture was included. In statistical analyses logistic regression models were used to identify factors associated with positive culture. Results In total 608 patients had urine culture performed, 176 (28.9%) were females and 432 (71,1%) were males, 378 (62.2%) registered in care before/in 2007, 258 (42.4%) infected through homosexual contact. Median baseline lymphocyte CD4+ count was 385 (IQR:204–565) cells/μl and median nadir lymphocyte CD4+ count 197 (86–306) cells/μl. One hundred and eighteen patients were actively infected with HCV, as defined by positive real-time PCR. In total 141 (23.2%) patients had positive urine culture, the most common bacterial pathogen was E.coli (58.2%) and E. faecalis (12.8%). Patients with urinary tract infection were more likely to be female (51.8% vs. 22.1%, p<0.0001), infected through other than homosexual mode (80.1% vs. 50.7%, p<0.0001), with lower nadir CD4 count (139 vs. 221 cells/μl, p<0.0001) and lower baseline HIV RNA (4.02 vs. 4.35 log copies/ml, p = 0.01) and less likely to be HCV RNA positive (26.9% vs. 49.2%, p = 0.01). In multivariate regression model being registered before/in 2007 (OR = 2.10; [95%CI: 1.24–3.56]), infected through other than homosexual mode (2.05;[1.18–3.56]) and female gender (2.14;[1.33–3.44]) were increasing and higher nadir CD4+ count decreasing (0.92;[0.85–0.99]) the odds of urinary tract infection. Conclusions We have identified that almost one third of patients had urinary tract infections with non-typical bacterial pathogens. Population with increased odds of urinary tract infections are women, patients infected through other than homosexual contacts and those registered before 2007.

Effects of age, HIV, and HIV-associated clinical factors on neuropsychological functioning and brain regional volume in HIV+ patients on effective treatment

It is yet unclear if people infected with human immunodeficiency virus (HIV+) on stable, combined antiretroviral therapies (cARTs) decline with age at the same or greater rate than healthy people. In this study, we examined independent and interactive effects of HIV, age, and HIV-related clinical parameters on neuropsychological functioning and brain regional volume in a sizable group of Polish HIV+ men receiving cART. We also estimated the impact of nadir CD4 cell count, CD4 cell count during participation in the study, duration of HIV infection, or duration of cART along with age. Ninety-one HIV+ and 95 control (HIV−) volunteers ages 23–75 completed a battery of neuropsychological tests, and 54 HIV+ and 62 HIV− of these volunteers participated in a brain imaging assessment. Regional brain volume in the cortical and subcortical regions was measured using voxel-based morphometry. We have found that HIV and older age were independently related to lower attention, working memory, nonverbal fluency, and visuomotor dexterity. Older age but not HIV was associated with less volume in several cortical and subcortical brain regions. In the oldest HIV+ participants, age had a moderating effect on the relationship between the duration of cART and visuomotor performance, such as that older age decreased speed of visuomotor performance along with every year on cART. Such results may reflect the efficacy of cART in preventing HIV-associated brain damage. They also highlight the importance of monitoring neuropsychological functioning and brain structure in HIV+ patients. This is particularly important in older patients with long adherence to cART.