Mario Poljak

University of Ljubljana, Lubliano, Ljubljana, Slovenia

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Publications (265)693.48 Total impact

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    ABSTRACT: The HIV-1 epidemic in Slovenia, a small Central European country, has some characteristics that make it an ideal model to study HIV-1 transmission. The epidemic is predominantly affecting men who have sex with men infected with subtype B (89% of all patients), has a low prevalence (less than 1/1000) and is growing slowly. The aim of the present study was to analyze in detail the evolutionary history and the determinants of transmission. A total of 223 partial pol gene sequences from therapy naïve individuals were included, representing 52% of all patients newly diagnosed in 13 years (2000-2012) and analyzed together with genetically similar worldwide sequences, selected in a BLAST search. Combined analysis (maximum likelihood and Bayesian) of HIV-1 transmission chains revealed 8 major clusters (n ≥ 10 patients), 1 group of 4 patients, 2 trios and 12 transmission pairs, thus leaving only 43 (19.3%) Slovenian patients infected with subtype B without a local epidemiological link, indicating a predominance of local transmission of HIV-1 infection. Bayesian analysis performed on a full set of sequences estimated several introductions of HIV-1 into Slovenia, with the most recent common ancestor (tMRCA) of the earliest Slovenian cluster dated to the late 1980s, although tMRCAs obtained from separate independent analysis of each cluster showed considerably more recent estimates. These findings indicate inconsistencies in molecular clock estimation, which we further explored. We hypothesize that these inconsistent dating estimates across the tree could be caused by an evolutionary rate acceleration of HIV-1 after entering the Slovenia epidemic that is not taken into account by the molecular clock model. It could be caused by a lower transmission rate in this setting, as demonstrated by the low epidemic growth rate estimated by Bayesian skyline plot analysis. HIV-1 subtype B was introduced into Slovenia at several time points from the late 80s onward. The majority of patients had a local transmission link, indicating a closed HIV community. The observed slower epidemic rate suggests that individuals with a long-lasting infection are the driving force of the epidemic in this region.
    BMC Infectious Diseases 12/2015; 15(1). DOI:10.1186/s12879-015-0802-6 · 2.61 Impact Factor
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    ABSTRACT: The objective of this study was to define the natural genotypic variation of the HIV-1 integrase gene across Europe for epidemiological surveillance of integrase strand-transfer inhibitor (InSTI) resistance. This was a multicentre, cross-sectional study within the European SPREAD HIV resistance surveillance programme. A representative set of 300 samples was selected from 1950 naive HIV-positive subjects newly diagnosed in 2006-07. The prevalence of InSTI resistance was evaluated using quality-controlled baseline population sequencing of integrase. Signature raltegravir, elvitegravir and dolutegravir resistance mutations were defined according to the IAS-USA 2014 list. In addition, all integrase substitutions relative to HXB2 were identified, including those with a Stanford HIVdb score ≥10 to at least one InSTI. To rule out circulation of minority InSTI-resistant HIV, 65 samples were selected for 454 integrase sequencing. For the population sequencing analysis, 278 samples were retrieved and successfully analysed. No signature resistance mutations to any of the InSTIs were detected. Eleven (4%) subjects had mutations at resistance-associated positions with an HIVdb score ≥10. Of the 56 samples successfully analysed with 454 sequencing, no InSTI signature mutations were detected, whereas integrase substitutions with an HIVdb score ≥10 were found in 8 (14.3%) individuals. No signature InSTI-resistant variants were circulating in Europe before the introduction of InSTIs. However, polymorphisms contributing to InSTI resistance were not rare. As InSTI use becomes more widespread, continuous surveillance of primary InSTI resistance is warranted. These data will be key to modelling the kinetics of InSTI resistance transmission in Europe in the coming years. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    Journal of Antimicrobial Chemotherapy 07/2015; DOI:10.1093/jac/dkv202 · 5.44 Impact Factor
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    The Journal of Infectious Diseases 07/2015; DOI:10.1093/infdis/jiv363 · 5.78 Impact Factor
  • Mario Poljak
    Clinical Microbiology and Infection 06/2015; DOI:10.1016/j.cmi.2015.05.041 · 5.20 Impact Factor
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    ABSTRACT: Resolving dilemma whether the rise in the number of HIV diagnoses represents an actual increase in HIV transmissions or is a result of improved HIV surveillance is crucial before implementing national HIV prevention strategies. Annual proportions of recent infections (RI) among newly diagnosed persons infected with HIV-1 in Slovenia during 27 years (1986-2012) were determined using an algorithm consisting of routine baseline CD4 and HIV viral load measurements and the Aware BED EIA HIV-1 Incidence Test (BED test). The study included the highest coverage of persons diagnosed with HIV during the entire duration of an HIV epidemic in a given country/region (71%). Out of 416 patients, 170 (40.9%) had a baseline CD4 cell count less than 200 cells/mm(3) and/or HIV-1 viral load less than 400 copies/ml and were characterized as having a long-standing infection (LSI). The remaining 246 patients were additionally tested using the BED test. Overall, 23% (97/416) of the patients were labeled RI. The characteristics significantly associated with RI were as follows: younger age, acute retroviral syndrome, CDC class A and other than C, no AIDS defining illnesses, HIV test performed in the past, a higher viral load, and a higher CD4 cell count. An interesting trend in the proportion of RI was observed, with a peak in 2005 (47% of RI) and the lowest point in 2008 (12%) in parallel with a rise in the numbers of new HIV diagnoses. This study could help promote the idea of introducing periodic HIV incidence monitoring using a simple and affordable algorithm. J. Med. Virol.© 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Journal of Medical Virology 06/2015; DOI:10.1002/jmv.24209 · 2.22 Impact Factor
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    ABSTRACT: Human papillomaviruses (HPVs) are small, non-enveloped viruses with a circular double-stranded DNA genome, etiologically associated with various benign and malignant neoplasms of the skin and mucosa. As of May 30, 2015, 201 different HPV types had been completely sequenced and officially recognized and divided into five PV-genera: Alpha-, Beta-, Gamma-, Mu-, and Nupapillomavirus. The Mupapillomavirus genus currently consists of only two HPV types: HPV1 and HPV63, identified in 1980 and 1993, respectively, both associated with sporadic cases of cutaneous warts. In this preliminary study, we announce the complete genome sequence of a novel HPV type, now officially recognized as HPV204. Based on preliminary data, the genome of HPV204 comprises a total of 7,227 bp and contains five early open reading frames (E1, E2, E4, E6, and E7) and two late ORFs (L1 and L2). No E5 ORF could be identified. Preliminary HPV204 clusters to the Mu-PV genus, species Mu-3.
    Acta dermatovenerologica Alpina, Panonica, et Adriatica 06/2015; 24(2):21-3. DOI:10.15570/actaapa.2015.7
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    ABSTRACT: Papillomaviruses (PV) are a remarkably heterogeneous family of small DNA viruses that infect a wide variety of vertebrate species and are etiologically linked with the development of various neoplastic changes of the skin and mucosal epithelia. Based on nucleotide similarity, PVs are hierarchically classified into genera, species and types. Novel human PV (HPV) types are given a unique number only after the whole genome has been cloned and deposited with the International HPV Reference Center. As of March 09, 2015, 200 different HPV types, belonging to 49 species, had been recognized by the International HPV Reference Center. In addition, 131 animal PV types identified from 66 different animal species exist. Recent advances in molecular techniques have resulted in an explosive increase in the identification of novel HPV types and novel subgenomic HPV sequences in the last few years. Among PV genera, the Gamma-PV genus has been growing most rapidly in recent years with 80 completely sequenced HPV types, followed by Alpha- and Beta-PV genera that have 65 and 51 recognized HPV types, respectively. We reviewed in detail the contemporary molecular methods most often used for identification and characterization of novel PV types, including polymerase chain reaction, rolling circle amplification and next generation sequencing. Furthermore, we present a short overview of 12 and 10 novel HPV types recently identified in Sweden and Slovenia, respectively. Finally, an update on the International Human Papillomavirus Reference Center is provided. Copyright © 2015. Published by Elsevier Ltd.
    Clinical Microbiology and Infection 05/2015; DOI:10.1016/j.cmi.2015.05.011 · 5.20 Impact Factor
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    ABSTRACT: Several countries are in the process of switching to hrHPV (high-risk human papillomavirus) testing for cervical cancer screening. Given the multitude of available tests, validated assays which assure high-quality screening need to be identified. A systematic review was conducted to answer the question which hrHPV tests fulfill the criteria defined by an international expert team in 2009, based on reproducibility and relative sensitivity and specificity compared to Hybrid Capture-2 or GP5+/6+ PCR-EIA. These hrHPV DNA assays were validated in large randomized trials and cohorts with follow-up of eight years or more. Eligible studies citing the 2009-guideline were retrieved from www.scopus.com and from a meta-analysis assessing the relative accuracy of new hrHPV assays versus the standard comparator tests to detect high-grade cervical intraepithelial neoplasia or cancer in primary screening. The cobas 4800 HPV Test and RealTime High Risk HPV test were consistently validated in two and three studies, respectively, whereas PapilloCheck HPV-screening test, BD Onclarity HPV assay and the HPV Risk Assay were validated each in one study. Other tests which partially fulfil the 2009-guidelines are: Cervista HPV HR Test, PCR-LMNX, a homebrew E6/E7 RT qPCR and MALDI-TOF. The APTIMA HPV assay targeting E6/E7 mRNA of hrHPV was also fully validated. However, the cross-sectional equivalency criteria of the 2009-guidelines were set up for HPV DNA assays. Demonstration of a low risk of CIN3+ after a negative APTIMA test over a longer period is waited for to inform about its utility in cervical cancer screening at five year or longer intervals. Copyright © 2015. Published by Elsevier Ltd.
    Clinical Microbiology and Infection 05/2015; DOI:10.1016/j.cmi.2015.04.015 · 5.20 Impact Factor
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    ABSTRACT: BACKGROUND: Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes. METHODS AND FINDINGS: We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05-1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06-1.25), North America (OR = 1.19; 95% CI: 1.12-1.26), Europe (OR = 1.07; 95% CI: 1.01-1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12-1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92-1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions-a proxy for recent infection-yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs-K101E, K103N, Y181C, and G190A-accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling. CONCLUSIONS: Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen.
    PLoS Medicine 04/2015; 12(4):e1001810. DOI:10.1371/journal.pmed.1001845 · 14.00 Impact Factor
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    ABSTRACT: Data regarding factors predicting unfavorable outcomes in adult herpetic meningoencephalitis (HME) cases is scarce in the literature. We conducted a multicenter study to provide insights into the predictors of outcome with special emphasis to use and timing of antivirals. Overall, 501 patients with molecular confirmation from the cerebrospinal fluid were included from 35 referral centers in 10 countries. Overall, 438 patients were found to be eligible for the analysis. Finally, 232 (52.9%) patients experienced unfavorable outcomes; 44 died and 188 survived with sequlae. Age (OR 1.04, 95% CIs 1.02-1.05), Glasgow coma scale (OR 0.84, 95% CIs 0.77-0.93), symptomatic period of 2-7 days (OR 1.80, 95% CIs 1.16-2.79) and over seven days (OR 3.75, 95% CIs 1.72-8.15) until treatment commenced, predicted unfavorable outcomes. The outcome in HME patients is related to a combination of therapeutic and host factors. This study suggests that rapid diagnosis and early administration of antiviral treatment in HME patients are keys to favorable outcome. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Antimicrobial Agents and Chemotherapy 03/2015; 59(6). DOI:10.1128/AAC.05016-14 · 4.45 Impact Factor
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    ABSTRACT: Gammapapillomavirus (Gamma-PV) is a diverse and rapidly expanding PV-genus, currently consisting of 76 fully characterized human papillomavirus (HPV) types. In this study, DNA genomes of two novel HPV types, HPV179 and HPV184, obtained from two distinct facial verrucae vulgares specimens of a 64 year-old renal-transplant recipient, were fully cloned, sequenced and characterized. HPV179 and HPV184 genomes comprise 7,228-bp and 7,324-bp, respectively, and contain four early (E1, E2, E6 and E7) and two late genes (L1 and L2); the non-coding region is typically positioned between L1 and E6 genes. Phylogenetic analysis of the L1 nucleotide sequence placed both novel types within the Gamma-PV genus: HPV179 was classified as a novel member of species Gamma-15, additionally containing HPV135 and HPV146, while HPV184 was classified as a single member of a novel species Gamma-25. HPV179 and HPV184 type-specific quantitative real-time PCRs were further developed and used in combination with human beta-globin gene quantitative real-time PCR to determine the prevalence and viral load of the novel types in the patient's facial warts and several follow-up skin specimens, and in a representative collection, a total of 569 samples, of HPV-associated benign and malignant neoplasms, hair follicles and anal and oral mucosa specimens obtained from immunocompetent individuals. HPV179 and HPV184 viral loads in patients' facial warts were estimated to be 2,463 and 3,200 genome copies per single cell, respectively, suggesting their active role in the development of common warts in organ-transplant recipients. In addition, in this particular patient, both novel types had established a persistent infection of the skin for more than four years. Among immunocompetent individuals, HPV179 was further detected in low-copy numbers in a few skin specimens, indicating its cutaneous tissue tropism, while HPV184 was further detected in low-copy numbers in one mucosal and a few skin specimens, suggesting its dual tissue tropism.
    PLoS ONE 03/2015; 10(3):e0119154. DOI:10.1371/journal.pone.0119154 · 3.23 Impact Factor
  • Rajko Saletinger · Mario Poljak · Franc Strle
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    ABSTRACT: After a primary infection, human cytomegalovirus (HCMV) remains latent in certain human cells. Different stimuli, including immune deficiency and severe infection, can trigger the reactivation of latent HCMV infection. In the last decade, the role of the reactivation in immunocompetent patients with serious illness has been intensely studied; however, the knowledge of the potential role of moderately severe infections on HCMV dynamics is limited. In the prospective study, 80 HCMV-seropositive, immunocompetent adult patients with community-acquired pneumonia (CAP), treated outside the intensive care unit (ICU), were monitored with real-time polymerase chain reaction (PCR) for the presence of HCMV DNA. Detection of HCMV DNA in whole blood and/or plasma was interpreted as reactivation of latent HCMV infection. HCMV DNA was detected in 6 of 80 (7.5%) patients. All HCMV DNA-positive patients were classified according to the pneumonia severity index (PSI) as high-risk classes IV or V; thus, HCMV DNAaemia rate within these two PSI classes was 16.7%. All of the patients had positive whole blood samples, whereas plasma samples were positive in a single patient. We did not detect any significant differences comparing six patients with proven HCMV DNAaemia and 74 patients in whom HCMV DNAaemia was not demonstrated regarding the levels of inflammatory parameters on admission, length of treatment with supplemental oxygen, and length of hospital stay. In conclusion, the finding of HCMV DNAaemia in patients with CAP treated outside the ICU is a rare event and occurs only in patients with PSI classes designating more severe pneumonia. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
    Clinical Microbiology and Infection 01/2015; 21(1):97-102. DOI:10.1016/j.cmi.2014.09.001 · 5.20 Impact Factor
  • B Kopilović · M Poljak · K Seme · I Klavs
    Eurosurveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 01/2015; 20(22). · 4.66 Impact Factor
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    ABSTRACT: An increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) was observed in several population-based registries and has been attributed to human papillomavirus (HPV) infection. In the present study, we aimed to assess the contribution of HPV infection to the burden of mucosal head and neck squamous cell carcinoma (HNSCC) in Slovenia. For this purpose, data from the nationwide Cancer Registry of Slovenia for cases diagnosed between 1983 and 2009 were analyzed to determine time trends of age-adjusted incidence rates and survival in terms of annual percentage change (APC) for HNSCC in potentially HPV-related and HPV-unrelated sites. In addition, determination of p16 protein, HPV DNA and E6/E7 mRNA was performed in a cohort of OPSCC patients identified from the prospective database for the years 2007-2008. In total, 2,862 cases of HNSCC in potentially HPV-related sites and 7,006 cases in potentially HPV-unrelated sites were identified with decreased incidence observed over the time period in both groups (-0.58; 95 % CI -1.28 to -0.13 and -0.90; 95 % CI -1.23 to -0.57). Regardless of the group, incidence trends for both genders showed a significant decrease in men and increase in women. In a cohort of 99 OPSCC patients diagnosed between 2007 and 2008, 20 (20.2 %) patients had HPV positive tumors and exhibited a superior outcome compared to HPV-negative patients. In conclusion, results of the epidemiologic and histopathologic study confirmed that HPV infection had no major impact on the incidence trends in the Slovenian patients with HNSCC and, specifically, OPSCC during the studied period.
    Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 12/2014; DOI:10.1007/s00405-014-3459-7 · 1.61 Impact Factor
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    ABSTRACT: To determine the prevalence of a broad spectrum of human papillomavirus (HPV) types in conjunctival papillomas and a possible difference in clinical and histopathological presentation of HPV-positive and HPV-negative papillomas. Formalin-fixed, paraffin-embedded papilloma tissue specimens obtained from 25 patients were analysed using six different PCR-based methods targeting 87 HPV types from four different papillomavirus (PV) genera: α-PV, β-PV, γ-PV and µ-PV, and in situ hybridisation for HPV-6/HPV-11. Slides were reviewed for pedunculated or sessile growth, the presence of goblet cells, keratinising or non-keratinising epithelium, elastosis, atypia and koilocytes. α-PV types HPV-6 and HPV-11 were detected in 19/25 (76%) conjunctival papilloma tissue specimens, 9 (47%) of which were also HPV-6/HPV-11 positive with in situ hybridisation. Six different β-PV types-HPV-9, HPV-12, HPV-20, HPV-21, HPV-22, HPV-24-were additionally detected in four cases, all of which were also HPV-6/HPV-11 positive. No γ-PVs or µ-PVs were found in any of the tested tissues samples. Extralimbal location (p=0.021), presence of goblet cells (p=0.005), non-keratinising squamous epithelium (p=0.005), and absence of elastosis (p=0.005) were associated with the presence of HPV-6/HPV-11. We demonstrated that certain clinical and histological features are more frequently associated with HPV infection and that HPV genera other than α-PV are most probably not significant factors in conjunctival papilloma occurrence. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    British Journal of Ophthalmology 12/2014; 99(3). DOI:10.1136/bjophthalmol-2014-306087 · 2.81 Impact Factor
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    ABSTRACT: Abstract Background: HIV-1 subtype CRF01_AE originated in Africa and then passed to Thailand where it established a major epidemic. Despite the global presence of CRF01_AE little is known about its subsequent dispersal pattern. Methods: We assembled a global dataset of 2,736 CRF01_AE sequences by pooling sequences from public databases and patient-cohort studies. We estimated viral dispersal patterns using statistical phylogeography run over bootstrap trees estimated by the maximum likelihood (ML) method. Results: We show that Thailand has been the source of viral dispersal to most areas worldwide, including 17 out of 20 sampled countries in Europe. Japan, Singapore, Vietnam and other Asian countries have played a secondary role in the viral dissemination. In contrast, China and Taiwan have mainly imported infections from neighbouring Asian countries, North America and Africa without any significant exporting transmissions. Discussion: The central role of Thailand in the global spread of CRF01_AE can be probably explained by the popularity of Thailand as a vacation destination characterized by sexual tourism and by Thai emigration to the Western world. Our study highlights the unique case of CRF01_AE, the only globally distributed non-B clade for which its global dispersal was not originated in Africa.
    The Journal of Infectious Diseases 12/2014; 211(11). DOI:10.1093/infdis/jiu666 · 5.78 Impact Factor
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    ABSTRACT: In approximately 10% of newly diagnosed individuals in Europe, HIV-1 variants harboring transmitted drug resistance mutations (TDRM) are detected. For some TDRM it has been shown that they revert to wild type while other mutations persist in the absence of therapy. To understand the mechanisms explaining persistence we investigated the in vivo evolution of frequently transmitted HIV-1 variants and their impact on in vitro replicative capacity. We selected 31 individuals infected with HIV-1 harboring frequently observed TDRM such as M41L or K103N in reverse transcriptase (RT) or M46L in protease. In all these samples, polymorphisms at non-TDRM positions were present at baseline (median protease: 5, RT: 6). Extensive analysis of viral evolution of protease and RT demonstrated that the majority of TDRM (51/55) persisted for at least a year and even up to eight years in the plasma. During follow-up only limited selection of additional polymorphisms was observed (median: 1). We demonstrate limited in vivo evolution of protease and RT harbouring frequently observed TDRM in the plasma. This is in line with the high in vitro replication capacity of patient-derived viruses harbouring TDRM compared to site-directed mutant viruses harbouring TDRM. As site-directed mutant viruses have a lower replication capacity than the patient-derived viruses with similar mutational patterns, we propose that (baseline) polymorphisms function as compensatory mutations improving viral replication capacity.
    Retrovirology 11/2014; 11(1):105. DOI:10.1186/s12977-014-0105-9 · 4.77 Impact Factor
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    ABSTRACT: Background The purpose of this study was to assess the efficacy and toxicity of docetaxel, cisplatin/5-fluorouracil (TPF) induction chemotherapy and concomitant immunochemoradiotherapy with cetuximab and cisplatin in unresectable head and neck carcinoma. Methods Treatment consisted of TPF induction chemotherapy (docetaxel 75 mg/m(2) day 2; cisplatin, 75 mg/m(2) day 2; and 5-fluorouracil 750 mg/m(2) days 1-4; 4 cycles), followed by radiotherapy (RT) and concomitant weekly cetuximab, (250 mg/m(2), after a loading dose of 400 mg/m(2)) and cisplatin (30 mg/m(2)). ResultsTwenty-five of 30 patients completed 4 cycles of induction chemotherapy. Six or more concomitant infusions of cisplatin and cetuximab were administered in 13 of 25 and 18 of 25 patients, respectively. The 2-year locoregional control, disease-free survival (DFS), and overall survival (OS) were 47%, 47%, and 50%, respectively. Patients with grade 2 skin reaction to cetuximab had a superior outcome. Conclusion The tested regimen was effective; however, cetuximab and low-dose cisplatin after induction TPF increased the treatment toxicity. A grade 2 skin rash correlated with improved efficacy. (c) 2013 Wiley Periodicals, Inc. Head Neck 36: 1555-1561, 2014
    Head & Neck 11/2014; 36(11). DOI:10.1002/hed.23506 · 3.01 Impact Factor
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    ABSTRACT: Background Betapapillomaviruses (β-PV) are etiologically associated with epidermodysplasia verruciformis and a proportion of skin precancerous lesions and cancer, mainly in immunocompromised individuals. Objectives The prevalence and persistence of anal β-PV infection and β-PV type distribution were determined in a cohort of men who have sex with men (MSM). A correlation with HIV-1 infection status and selected demographic and behavioral risk factors were additionally established. Study design A total of 181 anal swabs (135 initial and 46 follow-up swabs) obtained from 135 Slovenian MSMs (17.0% HIV-1 positive) were tested for the presence of 25 different β-PV types using Diassay RHA Kit Skin (beta) HPV assay and, if negative, with an in-house nested Ma/Ha PCR. Results β-PVs were detected in 88/135 (65.2%) initial anal swabs. Infection with multiple β-PV types was found in 26 samples; the number of β-PVs ranged from 2 to 9. A total of 29 distinct β-PVs were detected: HPV-36 and HPV-38 were the most prevalent, followed by HPV-23, HPV-24, and HPV-93. HIV-1 positive status, promiscuity and use of alkyl nitrites were significantly associated with a higher prevalence of anal β-PV infection. Three partial DNA sequences suggesting putative new HPV types were identified. Conclusion To the best of our knowledge, this is the first study to investigate and characterize β-PV infections in the anal region. We showed that anal β-PV infection is highly prevalent in the MSM population and that β-PVs can establish persistent infection in the anal region for up to 4.8 years.
    BMC Infectious Diseases 10/2014; 61(2). DOI:10.1016/j.jcv.2014.07.009 · 2.61 Impact Factor
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    ABSTRACT: Cervical infections with non-high-risk human papillomavirus (non-HR-HPV) types have been associated with genital warts and a fraction of atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions. The pre-vaccination prevalence of cervical infections with 25 non-HR-HPV types has been estimated, regardless of and without the coexistence of infection with HR-HPV types among Slovenian women 20-64 years old in cervical cancer screening, overall and according to age and cytology result. One thousand cervical specimens selected randomly from 4,455 specimens collected in 2010 in the Slovenian HPV prevalence survey were tested with Linear Array HPV Genotyping Test. Prevalence of cervical infections with any of the 25 non-HR-HPV types was 10.0% (95% CI: 8.1-11.9%) and with exclusively non-HR-HPV types 4.5% (95% CI: 3.2-5.8%). Prevalence of infections with any non-HR-HPV types among women with normal cytology was 8.8%, with atypical squamous cells of undetermined significance 30.4%, with low-grade squamous intraepithelial lesions 60.0%, and with high-grade squamous intraepithelial lesions 7.7%. Non-HR-HPV types without coexisting HR-HPV types were found in 4.0% of women with normal cytology, 26.1% with atypical squamous cells of undetermined significance, 6.7% with low-grade squamous intraepithelial lesions, and none with high-grade squamous intraepithelial lesion. Non-HR-HPV type cervical infections without coexisting HR-HPV infections were common among Slovenian women in cervical cancer screening with atypical squamous cells of undetermined significance, while rare in those with low-grade squamous intraepithelial lesions or worse. J. Med. Virol. © 2014 Wiley Periodicals, Inc.
    Journal of Medical Virology 10/2014; 86(10). DOI:10.1002/jmv.23997 · 2.22 Impact Factor

Publication Stats

3k Citations
693.48 Total Impact Points

Institutions

  • 1997–2015
    • University of Ljubljana
      • • Institute of Microbiology and Immunology
      • • Institute of Pathology
      Lubliano, Ljubljana, Slovenia
  • 2013
    • University of Latvia
      • Faculty of Medicine
      Riga, Riga, Latvia
  • 1997–2013
    • Slovenia Medical
      Maribor, Maribor, Slovenia
  • 2011
    • National Forensic Laboratory Slovenia
      Lubliano, Ljubljana, Slovenia
  • 1996–2011
    • Ljubljana University Medical Centre
      • • Department of Neurology
      • • Department of Gastroenterolgy
      • • Clinic of Otorhinolaryngology and Cervicofacial Surgery
      Lubliano, Ljubljana, Slovenia
  • 2007–2009
    • Zagreb University Hospital for Infectious Diseases
      Zagrabia, Grad Zagreb, Croatia
  • 1995–2000
    • Geološki zavod Slovenije
      Lubliano, Ljubljana, Slovenia