Search

The hepatitis C virus (HCV) epidemic in Western countries is primarily perpetuated by the sub-populations of men who have sex with men (MSM) and people who inject drugs (PWID). Understanding the dynamics of transmission in these communities is crucial for removing the remaining hurdles towards HCV elimination. We sequenced 269 annotated HCV plasma samples using probe enrichment and next-generation sequencing, obtaining 224 open reading frames of HCV (OR497849-OR498072). Maximum likelihood phylogenies were generated on the four most prevalent subtypes in this study (HCV1a, 1b, 3a, 4d) with a subsequent transmission cluster analysis. The highest rate of clustering was observed for HCV4d samples (13/17 (76.47%)). The second highest rate of clustering was observed in HCV1a samples (42/78 (53.85%)) with significant association with HIV-positive MSM. HCV1b and HCV3a had very low rates of clustering (2/83 (2.41%) and (0/29)). The spread of the prevalent subtype HCV1b appears to have been largely curtailed, and we demonstrate the onwards transmission of HCV1a and HCV4d in the HIV-positive MSM population across municipal borders. More systematic data collection and sequencing is needed to allow a better understanding of the HCV transmission among the community of PWID and overcome the remaining barriers for HCV elimination in Belgium. [ABSTRACT FROM AUTHOR]

This cross-sectional survey explored the quality of life in 505 people living with HIV in Belgium. Several domains of quality of life were impaired: 26% had been diagnosed with depression and 43% had weak social support. HIV-related stigma is still widespread, with 49% believing most people with HIV are rejected and 65% having experienced discrimination due to HIV. The impact of HIV was limited on professional life, but 40% experienced a negative impact on life satisfaction and 41% a negative impact on sexual life. For several domains, people with a recent diagnosis of HIV and long-term survivors had significantly worse scores. This survey also uncovered strengths of people living with HIV, such as positive coping and HIV self-image. Expanding the scope of quality of life in people living with HIV may provide a more complete picture of relevant life domains that may be impacted by living with HIV, but this needs further validation. [ABSTRACT FROM AUTHOR]

Summary: Candidaemia is an important health problem in immunocompromised patients with an epidemiology varying with region, period and patient population involved. The occurrence of candidaemia and the associated species distribution over a 12‐year period at a large tertiary care centre in Belgium were analysed. The trend in incidence in the intensive care units (ICUs) and non‐ICUs was investigated as well as the influence of antifungal exposure on the species distribution. From 2004 until 2015, 865 candidaemia episodes occurred in 826 patients at the University Hospitals Leuven. Candida albicans (59%) remained the most important cause of candidaemia, followed by C. glabrata (22.4%) and C. parapsilosis (8%). The mean incidence in the whole hospital was 1.48 per 10 000 patient days (PD). The incidence in ICUs increased reaching up to 10.7 per 10 000 PD whereas in the non‐ICUs, the incidence decreased. Prior exposure to fluconazole and echinocandins was associated with candidaemia caused by less susceptible species. Candidaemia incidence increased in the whole hospital, driven by ICUs. Surveillance of candidaemia epidemiology on a local scale is of high value to guide empirical treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Separate transmission networks for human immunodeficiency virus (HIV) coexist. Molecular typing of viral genomes can provide insight in HIV transmission routes in donors for whom risk behavior-based donor selection failed.Study Design and Methods: This study includes all HIV-infected Dutch and Flemish donors in the period 2005 to 2014 (n = 55). Part of the HIV polymerase (pol) gene was amplified, sequenced, and compared with more than 10,000 HIV strains obtained from HIV-infected Dutch and Flemish patients. The most likely transmission route was determined based on HIV phylogeny and the donor's self-reported risk behavior during the exit interview.Results: HIV-infected donors were predominantly male (69%), were repeat donors (73%), were born in the Netherlands or Belgium (95%), and harbored HIV Subtype B (68%). Seventy-five percent of HIV-infected male donors were part of robust phylogenetic clusters linked to male-to-male sex, while only 24% of HIV-infected male donors reported male-to-male sex during posttest counseling. Sex between men and women accounted for 13% of HIV infections in male donors and 93% of HIV infections in female donors based on phylogenetic analysis. Only 40% of HIV-infected female donors had HIV Subtype B; 65% of female donors reported a foreign partner and indeed HIV sequences interspersed with sequences from HIV-endemic areas abroad, in particular sub-Saharan Africa.Conclusion: HIV typing helps to understand HIV transmission routes in donor populations. We found substantial underreporting of male-to-male sex among HIV-infected male donors. Donor education on HIV risk factors and the danger of window-period donations and a donor environment that encourages frank disclosure of sexual behavior will contribute to a decrease of HIV-infected donors. [ABSTRACT FROM AUTHOR]

Objective: To find a subset of patients with suspected central venous catheter (CVC)-related infection (CRI) in whom CVC removal is not needed.Design: Randomized controlled trial.Setting: Thirty-three-bed ICU.Patients and Participants: One hundred and forty four patients with suspected CRI in which a change of CVCs was planned were evaluated for inclusion.Interventions: Hemodynamically stable patients without proven bacteremia, no insertion site infection, and no intravascular foreign body were randomized to a standard-of-care group (SOC, all CVCs were changed as planned) or a watchful waiting group (WW, CVCs changed when bacteremia was subsequently confirmed or hemodynamic instability occurred).Measurement and Results: Study groups were compared for incidence of CVC-related bloodstream infection (CR-BSI), resolution of fever, C-reactive protein, SOFA score, duration of ICU stay, and mortality. Of 144 patients with suspected CRI, 80 patients met exclusion criteria. Sixty-four were randomized. Forty-seven of 80 excluded patients were shown to be bacteremic, 20 (25%) of whom had a CR-BSI. Five of 64 (8%) included patients had a CR-BSI during their subsequent ICU stay (two in SOC and three in WW group). All 38 CVCs were changed in the SOC group versus 16 of 42 in the WW group (62% reduction, P<0.01). Resolution of fever, C-reactive protein, SOFA score, duration of ICU stay, and ICU mortality did not differ between SOC and WW group ( P>0.1 for all).Conclusions: The use of a simple clinical algorithm permits a substantial decrease in the number of unnecessarily removed CVCs without increased morbidity. [ABSTRACT FROM AUTHOR]

In this study we evaluated the performance of the VERSANT® HIV-1 Resistance Assays (LiPA) in detecting drug resistance in therapy-naive HIV-infected patients diagnosed in Belgium in 2000. We compared the results with population sequencing and found concordance to be in line with previous studies in treatment-experienced patients (86.87% for reverse transcriptase (RT); 92.77% for protease (PRO)). Discordance was mainly due to indeterminate reactions on LiPA (8.45% for RT; 6.85% for PRO) and minor discordances (4.13% for RT; 0.25% for PRO). Major discordances were rare (0.46% for RT; 0.12% for PRO). Indeterminate reactions were significantly associated with strains belonging to non-B subtypes. [Copyright &y& Elsevier]

The Belgian population of people living with HIV (PLHIV) has unrestricted access to direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection, since 2017. International literature claims that half of the patients remain untreated in high-income countries with unrestricted access to DAA. This study was initiated to provide an overview of the present situation in Belgium and recommendations for HCV care in PLHIV in other regions. This was a retrospective, multicenter study of PLHIV in Belgium, from January 1, 2007 to December 31, 2018. The HCV cascade of care was examined. Out of 4607 unique PLHIV, 322 (7.0%) tested positive for HCV antibody and HCV RNA positivity was seen in 289 (6.3%). Of those with a proven HCV infection, 207/289 (71.6%) initiated treatment. Of the 171 (82.6%) persons with a sustained virologic response (SVR), 16 (9.4%) subjects were reinfected. We present a care cascade of 4607 PLHIV in Belgium. Treatment initiation and SVR rates were high compared to other regions. Implementation of a national HCV register to track progress and yearly screening, especially in PLHIV with high-risk behavior, remains crucial. Identifying reasons for not initiating treatment is necessary to achieve elimination of HCV in PLHIV by 2030. [ABSTRACT FROM AUTHOR]

Presents the changes in the prevalence of non-B subtypes and recombinants for the past 2 decades in 2 Belgian University hospitals. Most prevalent subtype; Percentage rate increase of recombinants from 1983-2001; Indication of the prevalence of non-B subtypes and recombinants in patient population.

Background: Although most currently used regimens for Hepatitis C virus (HCV) infections can be initiated without prior knowledge of genotype and subtype, genotyping is still useful to identify patients who might benefit from a personalized treatment due to resistance to direct-acting antivirals (DAA)., Objectives: To assess the utility of full-genome next-generation sequencing (FG-NGS) for HCV genotyping., Study Design: 138 HCV plasma samples previously genotyped by VERSANT HCV Genotype Assay (LiPA) were subjected to FG-NGS and phylogenetically genotyped Genome Detective. Consensuses were analysed by HCV-GLUE for resistance-associated substitutions (RASs) and their impact on treatment response was investigated., Results: 102/138 (73.9%) samples were sequenced to a genome coverage and depth of >90% of the HCV open reading frame covered by >100 reads/site. Concordant genotype and subtype results were assigned in 97.1% and 79.4% of samples, respectively. FG-NGS resolved the subtype of 13.7% samples that had ambiguous calls by LiPA and identified one dual infection and one recombinant strain. At least one RAS was found for the HCV genes NS3, NS5A, and NS5B in 2.91%, 36.98% and 27.3% samples, respectively. Irrespective of the observed RAS, all patients responded well to DAA treatment, except for HCV1b-infected patients treated with Zepatier (33.3% failure rate (5/15))., Conclusion: While LiPA and FG-NGS showed overall good concordance, FG-NGS improved specificity for subtypes, recombinant and mixed infections. FG-NGS enabled the detection of RAS, but its predictive value for treatment outcome in DAA-naïve patients remains uncertain. With additional refinements, FG-NGS may be the way forward for HCV genotyping., Competing Interests: Declaration of Competing Interest The authors declare no commercial or financial relationship that could be construed as potential conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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.

Background Once daily (QD) ritonavir or cobicistat-boosted darunavir (DRV/b), in combination with other antiretrovirals (ARVs), is recommended as a first-line option for human immunodeficiency virus-infected patients in European and USA guidelines. The objective of this study was to analyse the outcomes of DRV/r QD-based antiretroviral therapy (ART) regimens in real-life settings. Methods This is an observational, non-interventional, non-comparative, retrospective, multicentre cohort study. Data were collected from the databases of eight Belgian AIDS Reference Centres. All patients who received at least one dose of DRV/r QD, regardless of background ARV regimen, with a minimum follow-up of 6 months were included. Results Data from 1701 subjects were collected. Most were male (66.5%) with a mean age of 42.9 years, 33.1% were treatment-naïve and 66.9% were ART experienced. During a median follow-up of 2.45 years (95% CI: 1.50-3.34), the probability to remain on treatment was 87% for the first year, 79% for the second year. DRV/r was well tolerated with few discontinuations due to adverse events (6.9%) or virological failure (0.8%). Among the 1138 treatment-experienced patients, 111 (9.8%) patients received DRV/r QD monotherapy. Conclusions This retrospective cohort analysis confirms the long-term effectiveness and good tolerability of DRV/r QD in a real-life setting. No unexpected adverse events were reported.

We aimed to study epidemic trends and predictors for transmitted drug resistance (TDR) in our region, its clinical impact and its association with transmission clusters. We included 778 patients from the AIDS Reference Center in Leuven (Belgium) diagnosed from 1998 to 2012. Resistance testing was performed using population-based sequencing and TDR was estimated using the WHO-2009 surveillance list. Phylogenetic analysis was performed using maximum likelihood and Bayesian techniques. The cohort was predominantly Belgian (58.4%), men who have sex with men (MSM) (42.8%), and chronically infected (86.5%). The overall TDR prevalence was 9.6% (95% confidence interval (CI): 7.7-11.9), 6.5% (CI: 5.0-8.5) for nucleoside reverse transcriptase inhibitors (NRTI), 2.2% (CI: 1.4-3.5) for non-NRTI (NNRTI), and 2.2% (CI: 1.4-3.5) for protease inhibitors. A significant parabolic trend of NNRTI-TDR was found (p = 0.019). Factors significantly associated with TDR in univariate analysis were male gender, Belgian origin, MSM, recent infection, transmission clusters and subtype B, while multivariate and Bayesian network analysis singled out subtype B as the most predictive factor of TDR. Subtype B was related with transmission clusters with TDR that included 42.6% of the TDR patients. Thanks to resistance testing, 83% of the patients with TDR who started therapy had undetectable viral load whereas half of the patients would likely have received a suboptimal therapy without this test. In conclusion, TDR remained stable and a NNRTI up-and-down trend was observed. While the presence of clusters with TDR is worrying, we could not identify an independent, non-sequence based predictor for TDR or transmission clusters with TDR that could help with guidelines or public health measures.

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.

Known human immunodeficiency virus (HIV) transmission histories are invaluable models for investigating the evolutionary and transmission dynamics of the virus and to assess the accuracy of phylogenetic reconstructions. Here we have characterized an HIV-1 transmission chain consisting of nine infected patients, almost all of whom were treated with antiviral drugs at later stages of infection. Partial pol and env gp41 regions of the HIV genome were directly sequenced from plasma viral RNA for at least one sample from each patient. Phylogenetic analyses in pol using likelihood methods inferred an evolutionary history not fully compatible with the known transmission history. This could be attributed to parallel evolution of drug resistance mutations resulting in the incorrect clustering of multidrug-resistant virus. On the other hand, a fully compatible phylogenetic tree was reconstructed from the env sequences. We were able to identify and quantify the molecular footprint of drug-selective pressure in pol using maximum likelihood inference under different codon substitution models. An increased fixation rate of mutations in the HIV population of the multidrug-resistant patient was demonstrated using molecular clock modeling. We show that molecular evolutionary analyses, guided by a known transmission history, can reveal the presence of confounding factors like natural selection and caution should be taken when accurate descriptions of HIV evolution are required.

Using criteria designed for invasive aspergillosis (IA) in patients with cancer, we aimed to determine the impact of IA in patients without malignancy in a medical intensive care unit (ICU). In this retrospective study, 127 patients out of 1,850 admissions (6.9%) hospitalized between 2000 and 2003 had microbiological or histopathologic evidence of Aspergillus during their ICU stay. There were 89 cases (70%) without hematologic malignancy. These patients were classified as proven IA (n = 30), probable IA (n = 37), possible IA (n = 2), or colonization (n = 20). In these patients, mean SAPS II score was 52 with a predicted mortality of 48%. The observed mortality was 80% (n = 71). Mortality of the proven and the probable IA was 97 and 87%, respectively. Postmortem examination was done in 46 out of 71 patients, and 27 autopsies (59%) showed hyphael invasion with Aspergillus. Aspergillus infections occurred in five critically ill patients with proven IA who did not have any predisposing factors according to the currently available definitions. Three of these patients had Child C liver cirrhosis. IA is an emerging and devastating infectious disease in patients in the ICU without malignancy. In those patients, host criteria for probable fungal infections should probably be adapted.

In this study we evaluated the performance of the VERSANT HIV-1 Resistance Assays (LiPA) in detecting drug resistance in therapy-naive HIV-infected patients diagnosed in Belgium in 2000. We compared the results with population sequencing and found concordance to be in line with previous studies in treatment-experienced patients (86.87% for reverse transcriptase (RT); 92.77% for protease (PRO)). Discordance was mainly due to indeterminate reactions on LiPA (8.45% for RT; 6.85% for PRO) and minor discordances (4.13% for RT; 0.25% for PRO). Major discordances were rare (0.46% for RT; 0.12% for PRO). Indeterminate reactions were significantly associated with strains belonging to non-B subtypes.

HIV-1 group M strains are usually subtyped based on gag and/or env gene sequences. In our lab, part of the pol gene sequence was available in order to determine the genotypic anti-HIV drug resistance profile. To estimate the prevalence of the different HIV-1 subtypes in patients visiting the University Hospitals in Leuven in 1999 and for whom a genotypic drug resistance test was needed, we tried to use the pol sequence for subtyping. Recombination was investigated by similarity plots and bootscanning and subtyping was performed by phylogenetic analysis. The overall region spanning the entire protease and 747 nucleotides of the reverse transcriptase proved very suitable for subtyping, although there was a low phylogenetic signal at the beginning of the reverse transcriptase (nucleotides 0-250), as we demonstrated by likelihood mapping. Of the 41 samples analyzed, 21 belonged to subtype B. Of the other 20 non-B strains, 9 belonged to subtype C, 2 to subtype D and 1 to subtype A, G, H and J, respectively, 3 were CRF&#95;02 (Circulating Recombinant Form), 1 was recombinant with a novel breakpoint and 1 sample was untypable. Although subtype B is still the most prevalent subtype in Belgium, it seems to be responsible for only half of the infections in this study. We could also document that the prevalence of subtype C is high in the Belgian native patients, especially among the heterosexually infected population. This could possibly be an indication for an epidemic spread of HIV-1 subtype C in Belgium, as for one third of these patients, no link to an endemic region could be found. The other non-B subtypes and the recombinants are mainly introduced by immigrants or by Belgian citizens traveling abroad.