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Background: In real-life settings, guidelines frequently cannot be followed since many patients are multimorbid and/or elderly or have other complicating conditions which carry an increased risk of drug-drug interactions. This document aimed to adapt recommendations from existing clinical practice guidelines (CPGs) to assist physicians' decision-making processes concerning specific and complex scenarios related to acute CAP.Methods: The process for the adaptation procedure started with the identification of unsolved clinical questions (PICOs) in patients with CAP and continued with critically appraising the updated existing CPGs and choosing the recommendations, which are most applicable to these specific scenarios.Results: Seventeen CPGs were appraised to address five PICOs. Twenty-seven recommendations were endorsed based on 7 high, 9 moderate, 10 low, and 1 very low-quality evidence. The most valid recommendations applicable to the clinical practice were the following ones: Respiratory virus testing is strongly recommended during periods of increased respiratory virus activity. Assessing the severity with a validated prediction rule to discriminate where to treat the patient is strongly recommended along with reassessing the patient periodically for improvement as expected. In adults with multiple comorbidities, polypharmacy, or advanced age, it is strongly recommended to check for possible drug interactions before starting treatment. Strong graded recom-mendations exist on antibiotic treatment and its duration. Recommendations on the use of biomarkers such as C -reactive protein or procalcitonin to improve severity assessment are reported.Conclusion: This document provides a simple and reliable updated guide for clinical decision-making in the management of complex patients with multimorbidity and CAP in the real-life setting.

This study aims to quantify antibiotic consumption for suspected respiratory tract superinfections in COVID-19 patients, while investigating the associated drivers of antibiotic prescribing in light of the current signs of antibiotic overuse. Adult patients with a positive COVID-19 diagnosis admitted to a Belgian 721-bed university hospital were analyzed retrospectively (March 11th–May 4th, 2020), excluding short-term admissions (

Background Seasonal human coronaviruses (hCoVs) broadly circulate in humans. Their epidemiology and effect on the spread of emerging coronaviruses has been neglected thus far. We aimed to elucidate the epidemiology and burden of disease of seasonal hCoVs OC43, NL63, and 229E in patients in primary care and hospitals in Belgium between 2015 and 2020.Methods We retrospectively analysed data from the national influenza surveillance networks in Belgium during the winter seasons of 2015-20. Respiratory specimens were collected through the severe acute respiratory infection (SARI) and the influenza-like illness networks from patients with acute respiratory illness with onset within the previous 10 days, with measured or reported fever of 38 degrees C or greater, cough, or dyspnoea; and for patients admitted to hospital for at least one night. Potential risk factors were recorded and patients who were admitted to hospital were followed up for the occurrence of complications or death for the length of their hospital stay. All samples were analysed by multiplex quantitative RT-PCRs for respiratory viruses, including seasonal hCoVs OC43, NL63, and 229E. We estimated the prevalence and incidence of seasonal hCoV infection, with or without co-infection with other respiratory viruses. We evaluated the association between co-infections and potential risk factors with complications or death in patients admitted to hospital with seasonal hCoV infections by age group. Samples received from week 8, 2020, were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Findings 2573 primary care and 6494 hospital samples were included in the study. 161 (6.3%) of 2573 patients in primary care and 371 (5.7%) of 6494 patients admitted to hospital were infected with a seasonal hCoV. OC43 was the seasonal hCoV with the highest prevalence across age groups and highest incidence in children admitted to hospital who were younger than 5 years (incidence 9.0 [95% CI 7.2-11.2] per 100 000 person-months) and adults older than 65 years (2.6 [2.1-3.2] per 100 000 person-months). Among 262 patients admitted to hospital with seasonal hCoV infection and with complete information on potential risk factors, 66 (73.3%) of 90 patients who had complications or died also had at least one potential risk factor (p=0.0064). Complications in children younger than 5 years were associated with co-infection (24 [36.4%] of 66; p=0.017), and in teenagers and adults (>= 15 years), more complications arose in patients with a single hCoV infection (49 [45.0%] of 109; p=0.0097). In early 2020, the Belgian SARI surveillance detected the first SARS-CoV-2-positive sample concomitantly with the first confirmed COVID-19 case with no travel history to China.Interpretation The main burden of severe seasonal hCoV infection lies with children younger than 5 years with co-infections and adults aged 65 years and older with pre-existing comorbidities. These age and patient groups should be targeted for enhanced observation when in medical care and in possible future vaccination strategies, and co-infections in children younger than 5 years should be considered during diagnosis and treatment. Our findings support the use of national influenza surveillance systems for seasonal hCoV monitoring and early detection, and monitoring of emerging coronaviruses such as SARS-CoV-2. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Belgian Federal Public Service Health, Food Chain Safety, and Environment; Belgian National Insurance Health Care (Institut national d'assurance maladie-invalidite/Rijksinstituut voor ziekte-en invaliditeitsverzekering); and Regional Health Authorities (Flanders Agentschap zorg en gezondheid, Brussels Commission communautaire commune, Wallonia Agence pour une vie de qualite).

Objectives: This 5-year follow-up study aimed to assess clinical outcomes of HIV-1 infected adults treated with atazanavir (ATV) in clinical practice in Belgium, to describe patient profiles and characteristics, as well as treatment safety. Methods: A multicenter, non-interventional, non-comparative, retrospective cohort study was performed in HIV-1 positive adult patients treated with ATV between 2006 and 2012. Data were collected from 8 AIDS reference centers’ databases. All analyses were on-treatment. Sub-analyses were carried out in unboosted ATV treated patients and in females. The primary endpoint was defined as the time-to-treatment-discontinuation. Furthermore, virological suppression, immunological response, time to loss of virological response, reasons for ATV initiation, and discontinuation were also assessed. Results: 2264 ARV-naive and ARV-experienced patients (median age: 41 years) were included. Females and non-Caucasians were broadly represented (40 and 45%, respectively). The probability to remain on treatment was 0.78 (CI: 0.76; 0.78) for the first and 0.69 (CI: 0.66; 0.71) for the second year and was similar between males and females. Overall, 771 patients (34.1%) discontinued ATV over time, the median (Q1-Q3) time to discontinuation being 0.8 (0.3–1.5) year. In unboosted ATV-treated patients, results were comparable to the overall ATV population, except for a higher rate of discontinuation-over-time (45.1%). Conclusions: Clinical and safety data from this 5 year-cohort study show that the vast majority of patients remained on ATV treatment for the first and second years, overall as well as patients treated with unboosted ATV and females.

Summary Background Effective two-drug regimens could decrease long-term drug exposure and toxicity with HIV-1 antiretroviral therapy (ART). We therefore aimed to evaluate the efficacy and safety of a two-drug regimen compared with a three-drug regimen for the treatment of HIV-1 infection in ART-naive adults. Methods We conducted two identically designed, multicentre, double-blind, randomised, non-inferiority, phase 3 trials: GEMINI-1 and GEMINI-2. Both studies were done at 192 centres in 21 countries. We included participants (≥18 years) with HIV-1 infection and a screening HIV-1 RNA of 500 000 copies per mL or less, and who were naive to ART. We randomly assigned participants (1:1) to receive a once-daily two-drug regimen of dolutegravir (50 mg) plus lamivudine (300 mg) or a once-daily three-drug regimen of dolutegravir (50 mg) plus tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Both drug regimens were administered orally. We masked participants and investigators to treatment assignment: dolutegravir was administered as single-entity tablets (similar to its commercial formulation, except with a different film colour), and lamivudine tablets and tenofovir disoproxil fumarate and emtricitabine tablets were over-encapsulated to visually match each other. Primary endpoint was the proportion of participants with HIV-1 RNA of less than 50 copies per mL at week 48 in the intention-to-treat-exposed population, using the Snapshot algorithm and a non-inferiority margin of −10%. Safety analyses were done on the safety population. GEMINI-1 and GEMINI-2 are registered with ClinicalTrials.gov, numbers NCT02831673 and NCT02831764, respectively. Findings Between July 18, 2016, and March 31, 2017, 1441 participants across both studies were randomly assigned to receive either the two-drug regimen (n=719) or three-drug regimen (n=722). At week 48 in the GEMINI-1 intention-to-treat-exposed population, 320 (90%) of 356 participants receiving the two-drug regimen and 332 (93%) of 358 receiving the three-drug regimen achieved plasma HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −2·6%, 95% CI −6·7 to 1·5); in GEMINI-2, 335 (93%) of 360 in the two-drug regimen and 337 (94%) of 359 in the three-drug regimen achieved HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −0·7%, 95% CI −4·3 to 2·9), showing non-inferiority at a −10% margin in both studies (pooled analysis: 655 [91%] of 716 in the two-drug regimen vs 669 [93%] of 717 in the three-drug regimen; adjusted treatment difference −1·7%, 95% CI −4·4 to 1·1). Numerically, more drug-related adverse events occurred with the three-drug regimen than with the two-drug regimen (169 [24%] of 717 vs 126 [18%] of 716); few participants discontinued because of adverse events (16 [2%] in the three-drug regimen and 15 [2%] in the two-drug regimen). Two deaths were reported in the two-drug regimen group of GEMINI-2, but neither was considered to be related to the study medication. Interpretation The non-inferior efficacy and similar tolerability profile of dolutegravir plus lamivudine to a guideline-recommended three-drug regimen at 48 weeks in ART-naive adults supports its use as initial therapy for patients with HIV-1 infection. Funding ViiV Healthcare.

SummaryStigma and discrimination within health care settings remain a public health challenge across diverse cultural environments and may have deleterious effects on mental and physical health. This study explores the causes, forms and consequences of HIV-related stigma and discrimination among migrant sub-Saharan African women living with HIV in Belgium. A qualitative study was conducted with 44 HIV-positive sub-Saharan African migrant women between April 2013 and December 2014 in health care settings in Belgium. Data were analysed using thematic content analysis. Twenty-five of the women reported overt stigma and discrimination and fifteen reported witnessing behaviours that they perceived to be stigmatizing and discriminatory in health care settings. The themes that emerged as to the causes of stigma and discrimination were: public perceptions of migrants and HIV, fear of contamination and institutional policies on HIV management. Reported forms of stigma and discrimination included: delayed or denied care, excessive precautions, blame and humiliation. The consequences of stigma and discrimination were: emotional stress, inconsistent health-care-seeking behaviour and non-disclosure to non-HIV treating personnel. Stigma and discrimination in health care settings towards people with HIV, and more specifically towards HIV-positive sub-Saharan African migrant women, impedes sustainable preventive measures. Specialized education and training programmes for non-HIV health care providers require in-depth investigation.

Contains fulltext : 154919.pdf (Publisher’s version ) (Closed access) OBJECTIVE: This study aimed to evaluate the effect of dendritic cell (DC) vaccination against HIV-1 on host gene expression profiles. DESIGN: Longitudinal PBMC samples were collected from participants of the DC-TRN trial for immunotherapy against HIV. Microarray-assisted gene expression profiling was performed to evaluate the effects of vaccination and subsequent interruption of antiretroviral therapy on host genome expression. Data from the DC-TRN trial were compared with results from other vaccination trials. METHODS: We used Affymetrix GeneChips for microarray gene expression analysis. Data were analyzed by principal component analysis and differential gene expression was assessed using linear modeling. Gene ontology enrichment and gene set analysis were used to characterize differentially expressed genes. Transcriptome analysis included comparison with PBMCs obtained from DC-vaccinated melanoma patients and of healthy individuals who received seasonal influenza vaccination. RESULTS: DC-TRN immunotherapy in HIV-infected individuals resulted in a major shift in the transcriptome. Longitudinal analysis demonstrated that changes in the transcriptome sustained also during interruption of antiretroviral therapy. After DC-vaccination, the transcriptome was enriched for cellular immunity associated genes that were also induced in healthy adults who received live attenuated influenza virus vaccination. These beneficial responses were accompanied by detrimental signals of general immune activation. CONCLUSIONS: The DC-TRN induced changes in the transcriptome were profound, lasting, and consisted of both protective signals and signatures of inflammation and immune exhaustion, with a net result of decreased viral load, without clinical benefit. Thus transcriptome analysis provides useful information, dissecting both positive and negative effects, for the evaluation of safety and efficacy of immunotherapeutic strategies.

Spirituality/religion serves important roles in coping, survival and maintaining overall wellbeing within African cultures and communities, especially when diagnosed with a chronic disease like HIV/AIDS that can have a profound effect on physical and mental health. However, spirituality/religion can be problematic to some patients and cause caregiving difficulties. The objective of this paper was to examine the role of spirituality/religion as a source of strength, resilience and wellbeing among sub-Saharan African (SSA) migrant women with HIV/AIDS. A qualitative study of SSA migrant women was conducted between April 2013 and December 2014. Participants were recruited through purposive sampling and snowball techniques from AIDS Reference Centres and AIDS workshops in Belgium, if they were 18 years and older, French or English speaking, and diagnosed HIV positive more than 3 months beforehand. We conducted semi-structured interviews with patients and did observations during consultations and support groups attendances. Thematic analysis was used to analyse the data. 44 women were interviewed, of whom 42 were Christians and 2 Muslims. None reported religious/spiritual alienation, though at some point in time many had felt the need to question their relationship with God by asking "why me?" A majority reported being more spiritual/religious since being diagnosed HIV positive. Participants believed that prayer, meditation, regular church services and religious activities were the main spiritual/religious resources for achieving connectedness with God. They strongly believed in the power of God in their HIV/AIDS treatment and wellbeing. Spiritual/religious resources including prayer, meditation, church services, religious activities and believing in the power of God helped them cope with HIV/AIDS. These findings highlight the importance of spirituality in physical and mental health and wellbeing among SSA women with HIV/AIDS that should be taken into consideration in providing a caring and healthy environment.

Patients with HIV not only have to deal with the challenges of living with an incurable disease but also with the dilemma of whether or not to disclose their status to their partners, families and friends. This study explores the extent to which sub-Saharan African (SSA) migrant women in Belgium disclose their HIV positive status, reasons for disclosure/non-disclosure and how they deal with HIV disclosure. A qualitative study consisting of interviews with twenty-eight SSA women with HIV/AIDS was conducted. Thematic content analysis was employed to identify themes as they emerged. Our study reveals that these women usually only disclose their status to healthcare professionals because of the treatment and care they need. This selective disclosure is mainly due to the taboo of HIV disease in SSA culture. Stigma, notably self-stigma, greatly impedes HIV disclosure. Techniques to systematically incorporate HIV disclosure into post-test counseling and primary care services are highly recommended.

SummaryGranulocytic sarcoma or chloroma is defined as an extramedullar solid tumor, composed of granulocytic precursor cells at various levels of differentiation. Granulocytic sarcoma is mostly associated with acute and chronic leukemia, rarely with polycythemia vera and myelofibrosis. The use of special immunohistochemical stains is mandatory, because this tumor is often misdiagnosed as malignant lymphoma.We report two cases of granulocytic sarcoma (tonsil and ovary) associated with chronic myelogenous leukemia. We describe the first reported association of atypical CML and granulocytic sarcoma.

In a phase I/IIa clinical trial, 17 HIV-1 infected patients, stable on cART, received 4 vaccinations with autologous dendritic cells etectroporated with mRNA encoding Tat, Rev and Nef, after which cART was interrupted. Vaccination was safe and feasible. During the analytical treatment interruption (All), no serious adverse events were observed. Ninety-six weeks following ATI, 6/17 patients remained off therapy. Although induced and/or enhanced CD4(+) and CD8(+) T-cell responses specific for the immunogens were observed in most of the patients, we found no correlation with the number of weeks off cART. Moreover, CD4(+) T-cell counts, plasma viral load and the time remaining off cART following ATI did not differ from historical control data. To conclude, the vaccine was safe, well tolerated and resulted in vaccine-specific immune responses. Since no correlation with clinical parameters could be found, these results warrant further research in order to optimize the efficacy of vaccine-induced T-cell responses. (C) 2011 Elsevier Inc. All rights reserved.

The limitations of highly active anti-retroviral therapy (HAART) have necessitated the development of alternative therapeutic strategies. One of the approaches that has gained prominence in recent years is therapeutic vaccination. We decided to assess the capacity of mature dendritic cells, derived from blood monocytes of HIV-1 infected patients, to generate functional T-cell responses. For this purpose, we constructed a chimeric mRNA encoding the proteins Tat, Rev and Nef. The TaReNef encoding information was linked to the HLA class II-targeting sequence of DC-LAMP. Broadly directed HIV-specific CD4(+) and CD8(+) cytotoxic T cells exhibiting a poly-functional cytokine secretion pattern were generated by co-culturing with autologous chimeric mRNA electroporated dendritic cells. Thus, administration of ex vivo generated dendritic cells expressing the early proteins Tat, Rev and Nef might offer a promising approach for therapeutic vaccination in HIV-1 infection. (C) 2008 Elsevier Ltd. All rights reserved.

Three commercial assays for quantifying plasma human immunodeficiency virus type 1 (HIV-1) RNA were evaluated. The assays differed in their sample volumes, the means of preparing samples, and methods of amplification and detection. Plasma samples were obtained from 36 HIV-1-infected patients representing all stages of HIV-1 infection and were analyzed as coded specimens. Measurement of HIV-1 RNA baseline levels revealed no significant difference in sensitivity between the three assays. The assays were also applied to the quantitation of HIV-1 RNA levels in the plasma of patients who were changing their antiretroviral therapy. The changes measured in HIV-1 RNA levels in plasma in response to therapy were comparable by the three assays. No close correlation was found between the amount of HIV-1 RNA and the CD4 T-cell count; HIV-1 RNA assays were more sensitive than p24 antigen assays as an indicator of plasma viremia. Overall, the study demonstrates that all three quantitative assays for HIV-1 RNA can be used to measure the HIV-1 RNA copy number representing the HIV-1 viremia status in patients with HIV-1 infection. Since this copy number is likely to be useful in monitoring the effectiveness of antiviral therapy, these quantitative assays for HIV-1 RNA are ready to be built into clinical trials.

This study is the first prospective study to assess the prevalence, epidemiology, and risk factors of HIV-1 drug resistance in newly diagnosed HIV-infected patients in Belgium. In January 2003 it was initiated as part of the pan-European SPREAD program, and continued thereafter for four inclusion rounds until December 2006. Epidemiological, clinical, and behavioral data were collected using a standardized questionnaire and genotypic resistance testing was done on a sample taken within 6 months of diagnosis. Two hundred and eighty-five patients were included. The overall prevalence of transmitted HIV-1 drug resistance in Belgium was 9.5% (27/285, 95% CI: 6.6-13.4). Being infected in Belgium, which largely coincided with harboring a subtype B virus, was found to be significantly associated with transmission of drug resistance. The relatively high rate of baseline resistance might jeopardize the success of first line treatment as more than 1 out of 10 (30/285, 10.5%) viruses did not score as fully susceptible to one of the recommended first-line regimens, i.e., zidovudine, lamivudine, and efavirenz. Our results support the implementation of genotypic resistance testing as a standard of care in all treatment-naive patients in Belgium.

Multidrug-resistant (MDR) Acinetobacter baumannii are emerging as important nosocomial pathogens. These organisms have a capacity for long-term survival in the hospital environment. The purpose of this study was to describe the course and control of an outbreak with MDR A. baumannii in a Belgian university hospital after transfer of two trauma patients from Greece. Wounds in both patients were colonised with MDR A. baumannii. Over an 11 month period from September 2004 to July 2005, carbapenem-non-susceptible A. baumannii (producing carbapenem-hydrolysing oxacillinase OXA-58) were isolated from 28 patients, despite early implementation of contact precautions. MDR A. baumannii was detected in routine clinical diagnostic samples from 26 patients and in screening specimens from an additional two patients. Twenty patients (71.4%) were colonised or infected during their stay in intensive care. Twenty-four (85.7%) respiratory samples were positive for MDR A. baumannii. Careful review of all procedures related to the respiratory tract did not identify a common route of transmission. Outbreak control required multiple interventions, including contact isolation of colonised and infected patients, monitoring the practice of personnel, screening of asymptomatic patients, use of isolation rooms and enhanced environmental disinfection. Introduction of single-use ventilator circuits was considered but the outbreak was controlled before implementation.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating neurologic disorder caused by a polyomavirus, called JC virus. PML affects mainly immunocompromised hosts. We report a case of PML as first manifestation of sarcoidosis in a previously healthy man. Treatment with cidofovir, resulted in a neurological and radiological stabilization. To our knowledge the association of PML and sarcoidosis without previous immunosuppressive treatment has only been described in a few cases, none of them were treated with cidofovir. (C) 2007 Elsevier B.V. All rights reserved.

We report our single institution's effort to standardize the method of collecting peripheral blood progenitor cells (PBPC) used for autologous transplantation. PBPC were mobilized by different types of chemotherapy followed by G-CSF (24 patients) or G-CSF alone (six patients) in 30 patients with various underlying neoplastic diseases. A median of three aphereses (range: 2-7), using the CS3000 cell separator was performed and a blood volume of 101 was processed. We studied the relationship between the absolute numbers of circulating leukocytes, mononuclear cells and CD34+ cells and the amount of PBPC collected during a single apheresis procedure. CD34+ cells were quantified by leukocyte subset analysis based on flow cytometry. Both CFU-GM and CD34+ cell contents of the apheresis products (69 procedures analyzed) correlated strongly: rho = 0.936, P = 0.0001). Regression analysis showed that the total number of CD34+ cells or CFU-GM content of the apheresis products could be predicted (r = 0.915, P = 0.0001) from the absolute number of CD34+ cells in the blood. A number of 10 circulating CD34+ cells per mm3 blood ensured a minimum of 0.5 x 10(6) CD34+ cells per kg, collected on the same day. Of the 30 patients, 17 received an autologous graft that contained only PBPC in 13. Long-term and complete hematological reconstitution was observed in all patients who had a minimum of 2 x 10(6) CD34+ cells per kg reinfused.