Spectrum of Non-Nucleoside Reverse Transcriptase Inhibitor-Associated Drug Resistance Mutations in Persons Living with HIV-1 Receiving Rilpivirine.

Introduction: Few data are currently available on the nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) resistance mutations selected in persons living with HIV-1 (PLWH) who develop virological failure while receiving rilpivirine (RPV).

Methods: We analyzed pooled HIV-1 RT genotypic data from 280 PLWH in the multicenter EuResist database and 115 PLWH in the Stanford HIV Drug Resistance Database (HIVDB) who received RPV as their only NNRTI.

Results: Among the 395 PLWH receiving RPV, 180 (45.

HIV-1 diversity in viral reservoirs obtained from circulating T-cell subsets during early ART and beyond.

Even during extended periods of effective immunological control, a substantial dynamic of the viral genome can be observed in different cellular compartments in HIV-1 positive individuals, indicating the persistence of active viral reservoirs. To obtain further insights, we studied changes in the proviral as well as in the viral HIV-1 envelope (Env) sequence along with transcriptional, translational and viral outgrowth activity as indicators for viral dynamics and genomic intactness. Our study identified distinct reservoir patterns that either represented highly sequence-diverse HIV-1 populations or only a single / few persisting virus variants.

Incorporating temporal dynamics of mutations to enhance the prediction capability of antiretroviral therapy's outcome for HIV-1.

Motivation: In predicting HIV therapy outcomes, a critical clinical question is whether using historical information can enhance predictive capabilities compared with current or latest available data analysis. This study analyses whether historical knowledge, which includes viral mutations detected in all genotypic tests before therapy, their temporal occurrence, and concomitant viral load measurements, can bring improvements. We introduce a method to weigh mutations, considering the previously enumerated factors and the reference mutation-drug Stanford resistance tables.

SARS-CoV-2 Test-to-Stay in Daycare.

Background And Objectives: Test-to-stay concepts apply serial testing of children in daycare after exposure to SARS-CoV-2 without use of quarantine. This study aims to assess the safety of a test-to-stay screening in daycare facilities.

Methods: 714 daycare facilities and approximately 50 000 children ≤6 years in Cologne, Germany participated in a SARS-CoV-2 Pool-polymerase chain reaction (PCR) screening from March 2021 to April 2022.

Torque Teno Virus Load Is Associated With Centers for Disease Control and Prevention Stage and CD4+ Cell Count in People Living With Human Immunodeficiency Virus but Seems Unrelated to AIDS-Defining Events and Human Pegivirus Load.

Background: Torque teno virus (TTV) is part of the human virome. TTV load was related to the immune status in patients after organ transplantation. We hypothesize that TTV load could be an additional marker for immune function in people living with HIV (PLWH).

Five-year single-center analysis of cytomegalovirus viremia in kidney transplant recipients and possible implication for novel prophylactic therapy approaches.

Background: Cytomegalovirus (CMV) infections are a common complication after kidney transplantation (KTx) and negatively affecting patient outcome. Valganciclovir (VGC) prophylaxis is often limited by drug-induced side effects and dose reduction due to decline in kidney function.

Method: In the present study, episodes of CMV viremia in the first year after KTx in a cohort of 316 recipients were analyzed retrospectively to identify risk factors linked to persistent infections.

The Role of Late Presenters in HIV-1 Transmission Clusters in Europe.

Background: Investigating the role of late presenters (LPs) in HIV-1 transmission is important, as they can contribute to the onward spread of HIV-1 virus before diagnosis, when they are not aware of their HIV status.

Objective: To characterize individuals living with HIV-1 followed up in Europe infected with subtypes A, B, and G and to compare transmission clusters (TC) in LP vs. non-late presenter (NLP) populations.

SARS-CoV-2 trends in Italy, Germany and Portugal and school opening during the period of Omicron variant dominance: A quasi experimental study in the EuCARE project.

Objectives: We investigated the impact of school reopening on SARS-CoV-2 transmission in Italy, Germany, and Portugal in autumn 2022 when the Omicron variant was prevalent.

Methods: A prospective international study was conducted using the case reproduction number (R) calculated with the time parametrization of Omicron. For Germany and Italy, staggered difference-in-differences analysis was employed to explore the causal relationship between school reopening and R changes, accounting for varying reopening dates.

Torque teno virus-DNA load as individual cytomegalovirus risk assessment parameter upon allogeneic hematopoietic stem cell transplantation.

Background: Immune recovery following allogeneic hematopoietic stem cell transplantation (allo-HSCT) decisively influences the occurrence of opportunistic infections, one of the leading causes of death among this group of patients. Yet, today, there are no laboratory parameters mirroring immune function sufficiently. Torque teno virus (TTV) has already proven itself as a functional immune marker in other settings.

Acute orchitis deciphered: Coxsackievirus B strains are the main etiology and their presence in semen is associated with acute inflammation and risk of persistent oligozoospermia.

Although various viruses are considered to be the clinical cause for acute orchitis, it is completely unclear to what extent and which viruses are etiologically involved in acute orchitis and what the clinic and course of these patients are like. Therefore, a prospective study was set up to decipher acute isolated orchitis. Between July 2007 and February 2023, a total of 26 patients with isolated orchitis were recruited and compared with 530 patients with acute epididymitis.

Generating synthetic clinical data that capture class imbalanced distributions with generative adversarial networks: Example using antiretroviral therapy for HIV.

Objective: Clinical data's confidential nature often limits the development of machine learning models in healthcare. Generative adversarial networks (GANs) can synthesise realistic datasets, but suffer from mode collapse, resulting in low diversity and bias towards majority demographics and common clinical practices. This work proposes an extension to the classic GAN framework that includes a variational autoencoder (VAE) and an external memory mechanism to overcome these limitations and generate synthetic data accurately describing imbalanced class distributions commonly found in clinical variables.

Cohort Profile: A European Multidisciplinary Network for the Fight against HIV Drug Resistance (EuResist Network).

The EuResist cohort was established in 2006 with the purpose of developing a clinical decision-support tool predicting the most effective antiretroviral therapy (ART) for persons living with HIV (PLWH), based on their clinical and virological data. Further to continuous extensive data collection from several European countries, the EuResist cohort later widened its activity to the more general area of antiretroviral treatment resistance with a focus on virus evolution. The EuResist cohort has retrospectively enrolled PLWH, both treatment-naïve and treatment-experienced, under clinical follow-up from 1998, in nine national cohorts across Europe and beyond, and this article is an overview of its achievement.

Anti-angiogenic agents for NSCLC following first-line immunotherapy: Rationale, recent updates, and future perspectives.

The implementation of immune checkpoint inhibitors (ICIs), with or without chemotherapy, as first-line treatment for patients who do not have actionable mutations has proved to be a major paradigm shift in the management of advanced non-small cell lung cancer (NSCLC). However, the transition of ICIs, such as pembrolizumab and nivolumab, to a first-line setting has left an unmet need for effective second-line treatment options, which is an area of intense research. In 2020, we reviewed the biological and mechanistic rationale for anti-angiogenic agents in combination with, or following, immunotherapy with the aim of eliciting a so called 'angio-immunogenic' switch in the tumor microenvironment.

CMV-IgG pre-allogeneic hematopoietic stem cell transplantation and the risk for CMV reactivation and mortality.

Cytomegalovirus (CMV) represents one of the most common infectious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Currently, a common diagnostic test used to stratify the risk for CMV infection in allo-HSCT recipients is the qualitative CMV serology of donor and recipient. A positive serostatus of the recipient is the most important risk factor for CMV reactivation and associated with reduced overall survival post-transplantation (TX).

In-depth virological and immunological characterization of HIV-1 cure after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation.

Despite scientific evidence originating from two patients published to date that CCR5Δ32/Δ32 hematopoietic stem cell transplantation (HSCT) can cure human immunodeficiency virus type 1 (HIV-1), the knowledge of immunological and virological correlates of cure is limited. Here we characterize a case of long-term HIV-1 remission of a 53-year-old male who was carefully monitored for more than 9 years after allogeneic CCR5Δ32/Δ32 HSCT performed for acute myeloid leukemia. Despite sporadic traces of HIV-1 DNA detected by droplet digital PCR and in situ hybridization assays in peripheral T cell subsets and tissue-derived samples, repeated ex vivo quantitative and in vivo outgrowth assays in humanized mice did not reveal replication-competent virus.

European Cohorts of patients and schools to Advance Response to Epidemics (EuCARE): a cluster randomised interventional and observational study protocol to investigate the relationship between schools and SARS-CoV-2 infection.

Background: Contradictory results were reported on the role of school closure/reopening on the overall SARS-CoV-2 transmission rate, as well as on which kind and level of mitigation measures implemented in schools may be effective in limiting its diffusion. Some recent studies were reassuring, showing that opening did not increase the community spread, although teachers and families are worried about the high class density. On the other hand, distance learning was associated with a negative impact on learning, sociability and psychological health, especially in vulnerable children.

Analysis of mutational history of multidrug-resistant genotypes with a mutagenetic tree model.

Human immunodeficiency virus (HIV) can develop resistance to all antiretroviral drugs. Multidrug resistance, however, is a rare event in modern HIV treatment, but can be life-threatening, particular in patients with very long therapy histories and in areas with limited access to novel drugs. To understand the evolution of multidrug resistance, we analyzed the EuResist database to uncover the accumulation of mutations over time.

Nintedanib plus docetaxel after progression on first-line immunochemotherapy in patients with lung adenocarcinoma: Cohort C of the non-interventional study, VARGADO.

Background: Immune checkpoint inhibitors (ICIs) with or without chemotherapy represent first-line standard of care for patients with advanced non-small cell lung cancer (NSCLC) without targetable driver mutations. The most appropriate second-line therapy after failing immunochemotherapy remains an open question. Nintedanib, an oral triple angiokinase inhibitor that targets the vascular endothelial growth factor receptor, fibroblast growth factor receptor, and, platelet-derived growth factor receptor, in combination with docetaxel, is approved for treatment of advanced NSCLC (adenocarcinoma histology) following progression on first-line chemotherapy.

The Health Gym: synthetic health-related datasets for the development of reinforcement learning algorithms.

In recent years, the machine learning research community has benefited tremendously from the availability of openly accessible benchmark datasets. Clinical data are usually not openly available due to their confidential nature. This has hampered the development of reproducible and generalisable machine learning applications in health care.

Molecular Epidemiology of HIV-1 in Eastern Europe and Russia.

The HIV epidemic in Eastern Europe and Russia is large and not well-controlled. To describe the more recent molecular epidemiology of HIV-1, transmitted drug resistance, and the relationship between the epidemics in this region, we sequenced the and genes of HIV-1 from 812 people living with HIV from Ukraine ( = 191), Georgia ( = 201), and Russia ( = 420) before the initiation of antiretroviral therapy. In 190 Ukrainian patients, the gene sequence was also determined.

Implementing the Lolli-Method and pooled RT-qPCR testing for SARS-CoV-2 surveillance in schools: a pilot project.

Purpose: School closures have been used as part of lockdown strategies to contain the spread of SARS-CoV-2, adversely affecting children's health and education. To ensure the accessibility of educational institutions without exposing society to the risk of increased transmissions, it is essential to establish SARS-CoV-2 testing strategies that are child-friendly, scalable and implementable in a daily school routine. Self-sampling using non-invasive saliva swabs combined with pooled RT-qPCR testing (Lolli-Method) has been proven to be a sensitive method for the detection of SARS-CoV-2.

Effective high-throughput RT-qPCR screening for SARS-CoV-2 infections in children.

Systematic SARS-CoV-2 testing is a valuable tool for infection control and surveillance. However, broad application of high sensitive RT-qPCR testing in children is often hampered due to unpleasant sample collection, limited RT-qPCR capacities and high costs. Here, we developed a high-throughput approach ('Lolli-Method') for SARS-CoV-2 detection in children, combining non-invasive sample collection with an RT-qPCR-pool testing strategy.