SARS-CoV-2 testing, positivity, and factors associated with COVID-19 among people with HIV across Europe in the multinational EuroSIDA cohort.

BACKGROUND: Although people with HIV might be at risk of severe outcomes from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus 2019 [COVID-19]), regional and temporal differences in SARS-CoV-2 testing in people with HIV across Europe have not been previously described. METHODS: We described the proportions of testing, positive test results, and hospitalizations due to COVID-19 between 1 January 2020 and 31 December 2021 in the EuroSIDA cohort and the factors associated with being tested for SARS-CoV-2 and with ever testing positive. RESULTS: Of 9012 participants, 2270 (25.2%, 95% confidence interval [CI] 24.3-26.1) had a SARS-CoV-2 polymerase chain reaction test during the study period (range: 38.3% in Northern to 14.6% in Central-Eastern Europe). People from Northern Europe, women, those aged <40 years, those with CD4 cell count <350 cells/mm3 , and those with previous cardiovascular disease or malignancy were significantly more likely to have been tested, as were people with HIV in 2021 compared with those in 2020. Overall, 390 people with HIV (4.3%, 95% CI 3.9-4.8) tested positive (range: 2.6% in Northern to 7.1% in Southern Europe), and the odds of testing positive were higher in all regions than in Northern Europe and in 2021 than in 2020. In total, 64 people with HIV (0.7%, 95% CI 0.6-0.9) were hospitalized, of whom 12 died. Compared with 2020, the odds of positive testing decreased in all regions in 2021, and the associations with cardiovascular disease, malignancy, and use of tenofovir disoproxil fumarate disappeared in 2021. Among study participants, 58.9% received a COVID-19 vaccine (range: 72.0% in Southern to 14.8% in Eastern Europe). CONCLUSIONS: We observed large heterogeneity in SARS-CoV-2 testing and positivity and a low proportion of hospital admissions and deaths across the regions of Europe.

Tracking changes in rhodium nanoparticles in the environment, including their mobility and bioavailability in soil.

The goals of the undertaken studies included assessment of the mobility of Rh nanoparticles (Rh NPs) and ionic forms (Rh(III)) in soil, optimization of the digestion procedure of environmental samples containing Rh NPs, and comparison of Rh NPs and Rh(III) uptake and bioaccumulation by hydroponically cultivated plants. Mass spectrometry with inductively coupled plasma (ICP MS) was used to determine the total content of Rh in solutions obtained after the processes of digestion and extraction. Transmission Electron Microscopy (TEM) supported the investigation of Rh NPs decomposition and proved the presence of uptaken nano forms in plant tissues. Adsorptive stripping voltammetry (AdSV) allowed to distinguish ionic and metallic forms of Rh, based on the fact that Rh NPs are electrochemically inactive. A two-step digestion procedure with H2SO4 and HNO3 was proposed for efficient decomposition of Rh NPs. Based on single extractions with selected extractants, it was found that independently of its chemical form Rh is substantially immobilized in soil. The mobility of Rh(III) and Rh NPs was below 38% and 0.02%, and the accumulation factor in leaves equaled 0.2 and 4.4, respectively.

Acquired immune deficiency syndrome (AIDS) and late presentation in Poland - data from Test and Keep in Care (TAK) Polska project.

OBJECTIVES: Late presentation (LP) at HIV diagnosis is associated with worse prognosis and an increase in the number of new infections. We analyse the proportion of patients diagnosed late and factors related to LP in Poland in 2016-2017. METHODS: Data were obtained from 13 out of 17 HIV centres in Poland from 2016 and 2017, including date of diagnosis, age, sex, transmission route, anti-hepatitis C virus (anti-HCV), Venereal Diseases Research Laboratory (VDRL) antibodies, AIDS diagnosis, baseline HIV viral load and CD4 count. RESULTS: Out of 1522 patients, 88.9% were male with median age of 33.6 years. Men who have sex with men (MSM) comprised 69.4% of all new infections, heterosexual route of transmission (HTX) 18.2% and injecting drug use (IDU) 4.7%. Late presenters comprised 44.8% of the study group. Factors associated with LP were female sex [odds ratio (OR) = 1.5, 95% confidence interval (95% CI): 1.09-2.08], older age (OR = 1.59, 95% CI: 1.42-1.79 per decade), route of transmission (HTX: OR = 1.96, 95% CI: 1.50-2.56; IDU: OR = 3.17, 95% CI: 1.92-5.37), positive HCV results (OR = 1.90, 95% CI: 1.23-2.95) and syphilis diagnosis (OR = 2.06, 95% CI: 2.29-3.31). Adjusting for these factors, the only independent factors associated with LP were age (OR = 1.52, 95% CI: 1.35-1.71) and route of transmission (HTX: OR = 1.73, 95% CI: 1.23-2.44; IDU: OR = 2.24, 95% CI: 1.25-4.10). CONCLUSIONS: Late presentation in Poland follows European trends. A total of 44.8% of all newly diagnosed patients in Poland continue to present late or at the AIDS stage. Independent factors associated with LP/AIDS were older age, IDU and HTX. Patients from these groups should be targeted to improve early diagnosis and medical care.

Where are we with pre-exposure prophylaxis use in Central and Eastern Europe? Data from the Euroguidelines in Central and Eastern Europe (ECEE) Network Group.

OBJECTIVES: Pre-exposure prophylaxis (PrEP) for HIV infection is an important intervention for control of the HIV epidemic. The incidence of HIV infection is increasing in the countries of Central and Eastern Europe (CEE). Therefore, we investigated the change in PrEP use in CEE over time. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group was initiated in February 2016 to compare standards of care for HIV and viral hepatitis infections in CEE. Data on access to PrEP were collected from 23 countries through online surveys in May-June 2017 (76 respondents) and in November 2018-May 2019 (28 respondents). RESULTS: About 34.2% of respondents stated that tenofovir/emtricitabine (TDF/FTC) was licensed for use in their country in 2017, and 66.7% that it was licensed for use in 2018 (P = 0.02). PrEP was recommended in national guidelines in 39.5% of responses in 2017 and 40.7% in 2018 (P = 0.378). About 70.7% of respondents were aware of "informal" PrEP use in 2017, while 66.6% were aware of this in 2018 (P = 0.698). In 2018, there were 53 centres offering PreP (the highest numbers in Poland and Romania), whereas six countries had no centres offering PreP. The estimated number of HIV-negative people on PreP in the region was 4500 in 2018. Generic TDF/FTC costs (in Euros) ranged from €10 (Romania) to €256.92 (Slovakia), while brand TDF/FTC costs ranged from €60 (Albania) to €853 (Finland). CONCLUSIONS: Although the process of licensing TDF/FTC use for PrEP has improved, this is not yet reflected in the guidelines, nor has there been a reduction in the "informal" use of PrEP. PrEP remains a rarely used preventive method in CEE countries.

2019 update of the European AIDS Clinical Society Guidelines for treatment of people living with HIV version 10.0.

BACKGROUND: The European AIDS Clinical Society (EACS) Guidelines cover key aspects of HIV management with major updates every two years. GUIDELINE HIGHLIGHTS: The 2019 Guidelines were extended with a new section focusing on drug-drug interactions and other prescribing issues in people living with HIV (PLWH). The recommendations for treatment-naïve PLWH were updated with four preferred regimens favouring unboosted integrase inhibitors. A two-drug regimen with dolutegravir and lamivudine, and a three-drug regimen including doravirine were also added to the recommended initial regimens. Lower thresholds for hypertension were expanded to all PLWH and for cardiovascular disease prevention, the 10-year predicted risk threshold for consideration of antiretroviral therapy (ART) modification was lowered from 20% to 10%. Frailty and obesity were added as new topics. It was specified to use urine albumin to creatinine ratio to screen for glomerular disease and urine protein to creatinine ratio for tubular diseases, and thresholds were streamlined with the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations. Hepatitis C virus (HCV) treatment recommendations were split into preferred and alternative treatment options. The algorithm for management of recently acquired HCV infection was updated and includes recommendations for early chronic infection management. Treatment of resistant tuberculosis (TB) was streamlined with the World Health Organization (WHO) recommendations, and new tables on immune reconstitution inflammatory syndrome, on when to start ART in the presence of opportunistic infections and on TB drug dosing were included. CONCLUSIONS: The EACS Guidelines underwent major revisions of all sections in 2019. They are available in four different formats including a new interactive web-based version and are translated into Chinese, French, German, Japanese, Portuguese, Russian and Spanish.

HIV care in times of the COVID-19 crisis - Where are we now in Central and Eastern Europe?

INTRODUCTION: The SARS-CoV-2 pandemic has hit the European region disproportionately. Many HIV clinics share staff and logistics with infectious disease facilities, which are now on the frontline in tackling COVID-19. Therefore, this study investigated the impact of the current pandemic situation on HIV care and continuity of antiretroviral treatment (ART) supplies in CEE countries. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group was established in February 2016 to review standards of care for HIV in the region. The group consists of professionals actively involved in HIV care. On March 19, 2020 we decided to review the status of HIV care sustainability in the face of the emerging SARS-CoV-2 pandemic in Europe. For this purpose, we constructed an online survey consisting of 23 questions. Respondents were recruited from ECEE members in 22 countries, based on their involvement in HIV care, and contacted via email. RESULTS: In total, 19 countries responded: Albania, Armenia, Belarus, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Estonia, Georgia, Greece, Hungary, Lithuania, Macedonia, Poland, Republic of Moldova, Russia, Serbia, Turkey, and Ukraine. Most of the respondents were infectious disease physicians directly involved in HIV care (17/19). No country reported HIV clinic closures. HIV clinics were operating normally in only six countries (31.6%). In 11 countries (57.9%) physicians were sharing HIV and COVID-19 care duties. None of the countries expected shortage of ART in the following 2 weeks; however, five physicians expressed uncertainty about the following 2 months. At the time of providing responses, ten countries (52.6%) had HIV-positive persons under quarantine. CONCLUSIONS: A shortage of resources is evident, with an impact on HIV care inevitable. We need to prepare to operate with minimal medical resources, with the aim of securing constant supplies of ART. Non-governmental organizations should re-evaluate their earlier objectives and support efforts to ensure continuity of ART delivery.

The EuroSIDA study: 25 years of scientific achievements.

The EuroSIDA study was initiated in 1994 and follows adult people living with HIV (PLHIV) in 100 collaborating clinics across 35 countries covering all European regions, Israel and Argentina. The study aims to study the long-term virological, immunological and clinical outcomes of PLHIV and to monitor temporal changes and regional differences in outcomes across Europe. Annually collected data include basic demographic characteristics, information on AIDS- and non-AIDS-related clinical events, and details about antiretroviral therapy (ART), hepatitis C treatment and other medications, in addition to a range of laboratory values. The summer 2016 data set held data from a total of 23 071 individuals contributing 174 481 person-years of follow-up, while EuroSIDA's unique plasma repository held over 160 000 samples. Over the past 25 years, close to 300 articles have been published in peer-reviewed journals (h-index 52), covering a range of scientific focus areas, including monitoring of clinical and virological outcomes, ART uptake, efficacy and adverse events, the influence of hepatitis virus coinfection, variation in the quality of HIV care and management across settings and regions, and biomarker research. Recognizing that there remain unresolved issues in the clinical care and management of PLHIV in Europe, EuroSIDA was one of the cohorts to found The International Cohort Consortium of Infectious Disease (RESPOND) cohort consortium on infectious diseases in 2017. In celebration of the EuroSIDA study's 25th anniversary, this article aims to summarize key scientific findings and outline current and future scientific focus areas.

Determination of pararosaniline hydrochloride in workplace air.

Pararosaniline hydrochloride (CPR) is a dye used for colouring paper, leather and natural and artificial fibres. It is also used in analytical and microbiological laboratories. It is a carcinogenic substance of category 1B. In analytical chemistry, it is used for detecting the following among others: bromates, formaldehyde, ozone, sulphite and sulfur dioxide. CPR is a dye commonly used in microbiology for staining preparations, for staining bacteria, antibodies or other organisms. In Poland, about 800 employees were exposed to this substance. The lack of methods for the determination of pararosaniline hydrochloride in workplace air makes it impossible to assess the occupational exposure of workers to this substance. For this reason, a determination method has been developed, which allows for the determination of pararosaniline hydrochloride in the air. This method makes it possible to determine the concentration of CPR in the air at the workplace within the range from 0.002 to 0.04 mg/m3 (for an air sample of 120 L). The method is based on the adsorption of pararosaniline hydrochloride present in the workplace air on a polypropylene filter, eluting the substance deposited on the filter with methanol and analysing the solution thus obtained using high-performance liquid chromatography with a diode array detector (wavelength of 544 nm). Using an Ultra C18 (250 mm length) chromatographic column at a temperature of 23 °C and the mobile phase of methanol:0.1% phosphoric acid(V) (95:5, v/v) at flow rate of 0.6 mL/min makes it possible to determine the content of pararosaniline hydrochloride in the presence of aniline, nitrobenzene and 4-tolylamine. Limit of detection and limit of quantification were 0.17 ng/mL and 0.51 ng/mL, respectively.

HIV health care providers are ready to introduce pre-exposure prophylaxis in Central and Eastern Europe and neighbouring countries: data from the Euroguidelines in Central and Eastern Europe (ECEE) Network Group.

OBJECTIVES: Pre-exposure prophylaxis (PrEP) for HIV infection has been introduced in only a few European countries. We investigated the potential to provide PrEP in the Central and Eastern European region, and in neighbouring countries. METHODS: The Euroguidelines in Central and Eastern Europe (ECEE) Network Group was formed in February 2016 to review standards of care for HIV infection in the region. Information related to PrEP was collected through on-line surveys. Respondents were recruited by ECEE members based on their involvement in HIV care. RESULTS: Seventy-six respondents from 23 countries participated in the survey. Twenty-six (34.2%) respondents reported that PrEP [tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)] was registered by the drug registration authority in their country. Fifty-three (70.7%) respondents reported being aware of 'informal' PrEP use in their country. If they had access to PrEP, 56 (74.7%) would advise its use in their practice. Forty-five (59.2%) respondents had concerns regarding PrEP use, and 10 (13.3%) expressed the need for more training. Most of the respondents (88.2%) would provide PrEP to people with high-risk behaviours. CONCLUSIONS: PrEP is already used informally in some countries in the region. Physicians are keen to use PrEP if and when it is accessible. Obstacles towards implementing PrEP in those countries were mostly related to lack of national guidelines, drug registration and governmental strategy.

Promoting high standards of care for women living with HIV: position statement from the Women Against Viruses in Europe Working Group.

OBJECTIVES: Gender-related factors can influence management decisions, treatment outcomes and the overall long-term wellbeing of people living with HIV (PLWH). The Women Against Viruses in Europe (WAVE) Working Group was established to promote the health and wellbeing of women living with HIV (WLWH). WAVE is part of the European AIDS Clinical Society (EACS) and organizes annual workshops to discuss different issues in the management of WLWH. METHODS: In 2016, 34 WAVE members including community representatives, HIV clinicians and researchers met to discuss standards of care for WLWH and to review current guidelines. Participants focused on three different themes: (1) access to and engagement and retention in care; (2) monitoring of women on antiretroviral therapy and management of comorbidities; and (3) review of EACS treatment guidelines. RESULTS: Five priority areas for optimizing the care of WLWH were identified: (1) psychosocial aspects of HIV diagnosis and care; (2) mental health and wellbeing; (3) pharmacokinetics, toxicity and tolerability of antiretroviral therapy; (4) coinfections and comorbidities; and (5) sexual and reproductive health. WAVE recommendations are provided for each of these areas, and gaps in knowledge and needs for changes in currently existing standards are discussed. CONCLUSIONS: This position statement provides an overview of the key recommendations to optimize the care of WLWH that emerged during the 2016 WAVE workshop.

Cytokine gene polymorphism associations with congenital cytomegalovirus infection and sensorineural hearing loss.

Cytomegalovirus (CMV) is the most common viral agent of congenital infections and a leading nongenetic cause of sensorineural hearing loss (SNHL). The host immunologic factors that render a developing foetus prone to intrauterine CMV infection and development of hearing loss are unknown. The aim of this study was to assess the potential associations between the polymorphisms within cytokine and cytokine receptors genes, and the risk of congenital CMV infection, and the hearing outcome. A panel of 11 candidate single nucleotide polymorphisms (SNPs): TNF rs1799964, TNF rs1800629, TNFRSF1A rs4149570, IL1B rs16944, IL1B rs1143634, IL10 rs1800896, IL10RA rs4252279, IL12B rs3212227, CCL2 rs1024611, CCL2 rs13900, CCR5 rs333 was genotyped in 470 infants (72 with confirmed intrauterine CMV infection and 398 uninfected controls), and related to congenital CMV infection, and the outcome. In multivariate analysis, the IL1B rs16944 TT and TNF rs1799964 TC genotypes were significantly associated with intrauterine CMV infection (aOR = 2.32; 95% CI, 1.11-4.89; p = 0.032, and aOR = 2.17, 95% CI, 1.25-3.77; p = 0.007, respectively). Twenty-two out of 72 congenitally infected newborns had confirmed SNHL. Carriers of CT or TT genotype of CCL2 rs13900 had increased risk of hearing loss at birth and at 6 months of age (aOR = 3.59; p = 0.028 and aOR = 4.10; p = 0.039, respectively). This is the first study to report an association between SNPs in IL1B, TNF, and CCL2, and susceptibility to congenital CMV infection (IL1B and TNF) and SNHL (CCL2).

Euroguidelines in Central and Eastern Europe (ECEE) conference and the Warsaw Declaration - a comprehensive meeting report.

OBJECTIVES: The objective of this paper is to summarize the outcomes of the Euroguidelines in Central and Eastern Europe (ECEE) conference held in Warsaw in February 2016. The main aim of this conference was to facilitate a discussion on European AIDS Clinical Society (EACS) guidelines implementation across the region and neighbouring countries and to present the current obstacles in benchmarking HIV care in Europe. METHODS: During a 2-day meeting, there were country-based presentations using a predefined template so as to make the data comparable and focus the discussion. Areas covered were country epidemiology, surveillance, national strategy for treatment and prevention, standards of care, access to care and treatment availability. Each participant filled in a questionnaire investigating HIV guidelines usage per country. RESULTS: In total, 16 Central and Eastern Europe (CEE) and neighbouring countries were represented at the conference: Albania, Armenia, Belarus, Croatia, Czech Republic, Estonia, Georgia, Hungary, Lithuania, Moldova, Poland, Romania, Russia, Serbia, Slovakia and Turkey. EACS guidelines version 7.1 were used in 14 (87%) countries. In 11 (69%) countries, national guidelines were available, of which eight had been recently updated. Half of the countries declared that they use World Health Organization (WHO) and Department of Health and Human Services (DHHS) guidelines, over one-third the European Centre for Disease Prevention and Control (ECDC) HIV testing guidelines and one in five the International Antiviral Society-USA (IAS-USA) Panel guidelines from 2012. CONCLUSIONS: Participants declared their will to promote the widespread use of EACS guidelines for HIV infection in the CEE region and neighbouring countries by signing the Warsaw Declaration. They also emphasized the need to increase publishing of data from national cohorts in that region.

A fluorescent HTS assay for phosphohydrolases based on nucleoside 5'-fluorophosphates: its application in screening for inhibitors of mRNA decapping scavenger and PDE-I.

Several nucleotide-specific phosphohydrolases can cleave P-F bonds in substrate analogues containing a fluorophosphate moiety to release fluoride ions. In this work, by employing a fluoride-sensitive molecular sensor, we harnessed this cleavage reaction to develop a fluorescence assay to screen for phosphohydrolase inhibitors. The assay is rapid, sensitive, and based on simple and synthetically available reagents. The assay was adapted to the high-throughput screening (HTS) format and its utility was demonstrated by screening an 'in-house' library of small nucleotides against two enzymes: DcpS, a metal-independent mRNA decapping pyrophosphatase of the histidine triad (HIT) family; and PDE-I, a divalent cation-dependent nuclease. Our screening results agreed with the known specificities of DcpS and PDE-I, and led to the selection of several inhibitors featuring low-micromolar IC50 values. For DcpS, we also verified the results by using an alternative method with the natural substrate. Notably, the assay presented here is the first fluorescence-based HTS-adaptable assay for DcpS, an established therapeutic target for spinal muscular atrophy. The assay should be useful for phosphohydrolase specificity profiling and inhibitor discovery, particularly in the context of DcpS and other HIT-family enzymes, which play key roles in maintaining cellular functions and have been linked to disease development.

Fish consumption in mid-childhood and its relationship to neuropsychological outcomes measured in 7-9 year old children using a NUTRIMENTHE neuropsychological battery.

BACKGROUND: Long-chain polyunsaturated fatty acids (LCPUFA), particularly n-3 LCPUFA, play a central role in neuronal growth and the development of the human brain. Fish is the main dietary source of n-3 LCPUFA. To assess the relation between fish consumption, estimated dietary n-3 LCPUFA intake and cognition and behaviour in childhood in a multi-centre European sample. METHODS: Children from 2 European studies, CHOP and NUHEAL, were assessed at 8 and 7.5 years of age, respectively. Different outcomes of neuropsychological development (assessed with the standardized NUTRIMENTHE Neuropsychological Battery (NNB) consisting of 15 subtests) were related with outcomes from a food-frequency questionnaire (FFQ) focussing on the consumption of fish. RESULTS: A total of 584 children completed the FFQ and the neuropsychological tests. We found no associations with calculated DHA or EPA intakes for any of the neuropsychological domains. Children who consumed 2 fish meals per week including one of fatty fish, showed no substantive differences in the cognitive domains from the children who did not. However negative associations with fatty fish consumption were found for social problems (p = 0.019), attention problems (p = 0.012), rule-breaking problems (p = 0.019) and aggressive behaviour problems (p = 0.032). No association was observed with internalizing problems. Higher levels of externalizing problems (p = 0.018) and total problems (p = 0.018) were associated with eating less fatty fish. CONCLUSIONS: Children who consumed 2 fish meals per week including one of fatty fish were less likely to show emotional and behavioural problems than those who did not.

Molybdenum targets produced by mechanical reshaping.

Targets required to determine the parameters of the 100Mo(p,xn)99mTc reaction and to estimate the yield of the 99mTc production were prepared starting with powder material. Material, melted with electron beam gun into solid bead, was reshaped into foil mechanically. Targets were prepared by powder melting and hot flattening of the droplet followed by cold rolling. Procedure allowed preparation of thick (in the range of hundreds of microns) and thin (down to 250 nm) foils.

Factors responsible for incomplete linkage to care after HIV diagnosis: preliminary results from the Test and Keep in Care (TAK) project.

OBJECTIVES: Linkage to care after HIV diagnosis remains underinvestigated in Europe, yet delays in linkage to care are an important obstacle to controlling the HIV epidemic. The Test and Keep in Care (TAK) project aims to determine the prevalence of HIV-positive persons who are lost or late to care and factors associated with this. METHODS: Data from community-based voluntary counselling and testing that occurred in 2010-2011 were linked with data from HIV clinics using unique test numbers. Persons not registered in HIV clinics were considered lost to care (LTC). For statistical analysis, nonparametric tests were used for comparison, and a multivariable logistic regression model was developed that included all variables with P<0.1 from the univariable models. RESULTS: A total of 110 persons were diagnosed as HIV-positive: 91% lived in central Poland, 5% were female and 71% were men who have sex with men (MSM). Forty-seven (42%) persons were LTC, seven of whom did not collect their enzyme-linked immunosorbent assay (ELISA) test result. Of those who registered, 75% registered within 1 month from HIV diagnosis, and 54% were late presenters. LTC individuals were more likely to have heterosexual or bisexual orientation, to have >20 sexual partners, to not be in a relationship with an HIV-positive partner, to not use condoms, and to be taking their first HIV test. In a logistic regression model, after adjusting for these factors, using condoms in a stable relationship decreased the odds of LTC by 72% (odds ratio 0.28; confidence interval 0.11-0.67). CONCLUSIONS: Integration into care after HIV diagnosis requires improvement. Our results suggest that broadening awareness and counselling about sexual risks may have a positive impact.

Decreasing mortality and changing patterns of causes of death in the Swiss HIV Cohort Study.

BACKGROUND: Mortality among HIV-infected persons is decreasing, and causes of death are changing. Classification of deaths is hampered because of low autopsy rates, frequent deaths outside of hospitals, and shortcomings of International Statistical Classification of Diseases and Related Health Problems (ICD-10) coding. METHODS: We studied mortality among Swiss HIV Cohort Study (SHCS) participants (1988-2010) and causes of death using the Coding Causes of Death in HIV (CoDe) protocol (2005-2009). Furthermore, we linked the SHCS data to the Swiss National Cohort (SNC) cause of death registry. RESULTS: AIDS-related mortality peaked in 1992 [11.0/100 person-years (PY)] and decreased to 0.144/100 PY (2006); non-AIDS-related mortality ranged between 1.74 (1993) and 0.776/100 PY (2006); mortality of unknown cause ranged between 2.33 and 0.206/100 PY. From 2005 to 2009, 459 of 9053 participants (5.1%) died. Underlying causes of deaths were: non-AIDS malignancies [total, 85 (19%) of 446 deceased persons with known hepatitis C virus (HCV) status; HCV-negative persons, 59 (24%); HCV-coinfected persons, 26 (13%)]; AIDS [73 (16%); 50 (21%); 23 (11%)]; liver failure [67 (15%); 12 (5%); 55 (27%)]; non-AIDS infections [42 (9%); 13 (5%); 29 (14%)]; substance use [31 (7%); 9 (4%); 22 (11%)]; suicide [28 (6%); 17 (7%), 11 (6%)]; myocardial infarction [28 (6%); 24 (10%), 4 (2%)]. Characteristics of deceased persons differed in 2005 vs. 2009: median age (45 vs. 49 years, respectively); median CD4 count (257 vs. 321 cells/µL, respectively); the percentage of individuals who were antiretroviral therapy-naïve (13 vs. 5%, respectively); the percentage of deaths that were AIDS-related (23 vs. 9%, respectively); and the percentage of deaths from non-AIDS-related malignancies (13 vs. 24%, respectively). Concordance in the classification of deaths was 72% between CoDe and ICD-10 coding in the SHCS; and 60% between the SHCS and the SNC registry. CONCLUSIONS: Mortality in HIV-positive persons decreased to 1.33/100 PY in 2010. Hepatitis B or C virus coinfections increased the risk of death. Between 2005 and 2009, 84% of deaths were non-AIDS-related. Causes of deaths varied according to data source and coding system.

Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo.

Vaccination with in vitro transcribed RNA coding for tumor antigens is considered a promising approach for cancer immunotherapy and has already entered human clinical testing. One of the basic objectives for development of RNA as a drug is the optimization of immunobioavailability of the encoded antigen in vivo. By analyzing the effect of different synthetic 5' mRNA cap analogs on the kinetics of the encoded protein, we found that m(2)(7,2'-O)Gpp(S)pG (beta-S-ARCA) phosphorothioate caps, in particular the D1 diastereoisomer, profoundly enhance RNA stability and translational efficiency in immature but not mature dendritic cells. Moreover, in vivo delivery of the antigen as beta-S-ARCA(D1)-capped RNA species is superior for protein expression and for efficient priming and expansion of naïve antigen-specific T cells in mice. Our findings establish 5' mRNA cap analogs as yet another module for tuning immunopharmacological properties of recombinant antigen-encoding RNA for vaccination purposes.

Implementing the number needed to harm in clinical practice: risk of myocardial infarction in HIV-1-infected patients treated with abacavir.

OBJECTIVES: The D:A:D study group reported a 1.9-fold increased relative risk (RR) of myocardial infarction (MI) associated with current or recent use of abacavir. The number needed to harm (NNH) incorporates information about the underlying risk of MI and the increased RR of MI in patients taking abacavir. METHODS: NNH was calculated as the reciprocal of the difference between the underlying risks of MI with and without abacavir use. A parametric statistical model was used to calculate the underlying risk of MI over 5 years. RESULTS: The relationship between NNH and underlying risk of MI is reciprocal, resulting in wide variation in the NNH with small changes in underlying risk of MI. The smallest changes in NNH are in the medium- and high-risk groups of MI. The NNH changes as risk components are modified; for example, for a patient who smokes and has a systolic blood pressure (sBP) of 160 mmHg and a 5-year risk of MI of 1.3% the NNH is 85, but the NNH increases to 277 if the patient is a nonsmoker and to 370 if sBP is within the normal range (120 mmHg). CONCLUSIONS: We have illustrated that the impact of abacavir use on risk of MI varies according to the underlying risk and it may be possible to increase considerably the NNH by decreasing the underlying risk of MI using standard of care interventions, such as smoking cessation or control of hypertension.

Search for a plant for phytoremediation--what can we learn from field and hydroponic studies?

The main aim of the study was to evaluate the strategies for coping with arsenic toxicity developed by the mine species (Calamagrostis arundinacea, Fragaria vesca, Stachys sylvatica, and Epilobium parviflorum), and to compare results obtained from plants exposed to arsenic present in contaminated soil (2000-3500 mg/kg dw) and in hydroponic solution (2 microM and 12 microM arsenate). Here we report basic differences in plant responses to arsenic depending on growth conditions (hydroponic/soil) with respect to uptake, root-to-shoot translocation, distribution, and detoxification/speciation. Calamagrostis has the highest level of As-tolerance among the tested species. When grown in soil, it accumulated the highest amount of As in roots and shoots relative to other species, however, when exposed to arsenic in hydroponics, it had lower As concentrations. The efficiency of arsenic root-to-shoot translocation was also different, being less effective in soil-grown Calamagrostis compared with hydroponics. Furthermore, in Calamagrostis exposed to arsenate in liquid medium, As(III) was the predominant arsenic form, in contrast to plants grown in As-contaminated soil, in which As(V) predominated. In addition, comparison of the level of phytochelatins showed that only PC2 was detected in plants from hydroponics, whereas in those from soil, additionally PC3 and PC4 were found. The results show that the basic components of a plant's response to arsenic, including uptake, accumulation as well as detoxification, change depending on the experimental conditions (arsenic in liquid medium or contaminated soil).