Rare twin cysteine residues in the HIV-1 envelope variable region 1 link to neutralization escape and breadth development.

Identifying HIV-1 envelope (Env) traits associated with neutralization cross-reactivity is crucial for vaccine design. Variable loops 1 and 2 (V1V2), positioned at the Env trimer apex, are key regions linked to neutralization. We describe non-canonical cysteine (Cys) residues in V1 that are enriched in individuals with elite neutralization breadth.

Viral and Immune Risk Factors of HIV Rebound after Interruption of Antiretroviral Therapy.

Background: Identifying risk factors for HIV rebound after treatment interruption is crucial for designing effective remission strategies.

Methods: Peripheral blood mononuclear cells from participants in the Zurich HIV Primary Infection Cohort (ZPHI, N=73) and ACTG study A5345 (N=44) were analyzed before ART interruption. We measured cell-associated HIV RNA, total HIV DNA, and proviral diversity (env gene).

Cohort Profile: The Zurich Primary HIV Infection Study.

The Zurich Primary HIV Infection (ZPHI) study is a longitudinal cohort study established in 2002, aiming to study the clinical, epidemiological, and biological characteristics of primary HIV infection. The ZPHI enrolls individuals with documented primary HIV-1 infection. At the baseline and thereafter, the socio-demographic, clinical, and laboratory data are systematically collected, and regular blood sampling is performed for biobanking.

Absence of Proviral Human Immunodeficiency Virus (HIV) Type 1 Evolution in Early-Treated Individuals With HIV Switching to Dolutegravir Monotherapy During 48 Weeks.

Human immunodeficiency virus type 1 (HIV-1) infection is treated with antiretroviral therapy (ART), usually consisting of 2-3 different drugs, referred to as combination ART (cART). Our recent randomized clinical trial comparing a switch to dolutegravir monotherapy with continuation of cART in early-treated individuals demonstrated sustained virological suppression over 48 weeks. Here, we characterize the longitudinal landscape of the HIV-1 reservoir in these participants, with particular attention to potential differences between treatment groups regarding evidence of evolution as a proxy for low-level replication.

The Gene Space database.

The hemiparasitic flowering plant (European mistletoe) is known for its very special life cycle, extraordinary biochemical properties, and extremely large genome. The size of its genome is estimated to be 30 times larger than the human genome and 600 times larger than the genome of the model plant . To achieve insights into the Gene Space of the genome, which is defined as the space including and surrounding protein-coding regions, a transcriptome project based on PacBio sequencing has recently been conducted.

Sustained Viral Suppression With Dolutegravir Monotherapy Over 192 Weeks in Patients Starting Combination Antiretroviral Therapy During Primary Human Immunodeficiency Virus Infection (EARLY-SIMPLIFIED): A Randomized, Controlled, Multi-site, Noninferiority Trial.

Background: Starting combination antiretroviral therapy (cART) during primary human immunodeficiency virus type 1 (HIV-1) infection results in a smaller HIV-1 latent reservoir, reduced immune activation, and less viral diversity compared to starting cART during chronic infection. We report results of a 4-year study designed to determine whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir (DTG) monotherapy.

Methods: EARLY-SIMPLIFIED is a randomized, open-label, noninferiority trial.

The Interplay Between Replication Capacity of HIV-1 and Surrogate Markers of Disease.

Background: HIV-1 replication capacity (RC) of transmitted/founder viruses may influence the further course of HIV-1 infection.

Methods: RCs of 355 whole-genome primary HIV-1 isolates derived from samples acquired during acute and recent primary HIV-1 infection (PHI) were determined using a novel high-throughput infection assay in primary cells. The RCs were used to elucidate potential factors that could be associated with RC during PHI.

Detecting Selection in the HIV-1 Genome during Sexual Transmission Events.

Little is known about whether and how variation in the HIV-1 genome affects its transmissibility. Assessing which genomic features of HIV-1 are under positive or negative selection during transmission is challenging, because very few virus particles are typically transmitted, and random genetic drift can dilute genetic signals in the recipient virus population. We analyzed 30 transmitter-recipient pairs from the Zurich Primary HIV Infection Study and the Swiss HIV Cohort Study using near full-length HIV-1 genomes.

Neonatal sepsis: a systematic review of core outcomes from randomised clinical trials.

Background: The lack of a consensus definition of neonatal sepsis and a core outcome set (COS) proves a substantial impediment to research that influences policy and practice relevant to key stakeholders, patients and parents.

Methods: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In the included studies, the described outcomes were extracted in accordance with the provisions of the Core Outcome Measures in Effectiveness Trials (COMET) handbook and registered.

Video recording in the delivery room: current status, implications and implementation.

Many factors determine the performance and success of delivery room management of newborn babies. Improving the quality of care in this challenging surrounding has an important impact on patient safety and on perinatal morbidity and mortality. Video recording (VR) offers the advantage to record and store work as done rather than work as recalled.

Neonatal sepsis definitions from randomised clinical trials.

Introduction: Neonatal sepsis is a leading cause of infant mortality worldwide with non-specific and varied presentation. We aimed to catalogue the current definitions of neonatal sepsis in published randomised controlled trials (RCTs).

Method: A systematic search of the Embase and Cochrane databases was performed for RCTs which explicitly stated a definition for neonatal sepsis.

The gene space of European mistletoe (Viscum album).

European mistletoe (Viscum album) is a hemiparasitic flowering plant that is known for its very special life cycle and extraordinary biochemical properties. Particularly, V. album has an unusual mode of cellular respiration that takes place in the absence of mitochondrial complex I.

Efficacy of occlusive wraps used for delivery room care.

Background: Guidelines advise for more than 20 years to use occlusive plastic wraps for temperature management during delivery room care but data on efficacy of different types of wrap are still scarce.

Methods: A random sample of seven different types of plastic wrap was tested using prewarmed aluminium blocks.

Results: The most effective wrap increased the time to cool by 2°C by one-third for the core and by 100% for the surface whereas the least effective wrap led to even faster heat loss compared with no wrap at all.

Knowledge gaps in late-onset neonatal sepsis in preterm neonates: a roadmap for future research.

Late-onset neonatal sepsis (LONS) remains an important threat to the health of preterm neonates in the neonatal intensive care unit. Strategies to optimize care for preterm neonates with LONS are likely to improve survival and long-term neurocognitive outcomes. However, many important questions on how to improve the prevention, early detection, and therapy for LONS in preterm neonates remain unanswered.

Evaluation of Broadly Neutralizing Antibody Sensitivity by Genotyping and Phenotyping for Qualifying Participants to HIV Clinical Trials.

Background: HIV envelope (env) diversity represents a significant challenge for the use of broadly neutralizing antibodies (bNAbs) in HIV treatment and cure studies. Screening for viral sensitivity to bNAbs to select eligible trial participants will be important to improve clinical efficacy; however, no universal approach has been established.

Methods: Pre-antiretroviral therapy plasma virus from participants in the Zurich Primary HIV Infection (ZPHI) study was genotyped and phenotyped for sensitivity to the bNAbs elipovimab (EVM, formerly GS-9722) and 3BNC117.

A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells.

HIV-1 replication capacity is an important characteristic to understand the replication competence of single variants or virus populations. It can further aid in the understanding of HIV-1 pathogenicity, disease progression, and drug resistance mutations. To effectively study RC, many assays have been established.

HIV-1 integration sites in CD4+ T cells during primary, chronic, and late presentation of HIV-1 infection.

HIV-1 is capable of integrating its genome into that of its host cell. We examined the influence of the activation state of CD4+ T cells, the effect of antiretroviral therapy (ART), and the clinical stage of HIV-1 infection on HIV-1 integration site features and selection. HIV-1 integration sites were sequenced from longitudinally sampled resting and activated CD4+ T cells from 12 HIV-1-infected individuals.

Delivery Room Management of Infants with Very Low Birth Weight in 3 European Countries-The Video Apgar Study.

Objective: To assess delivery room management of infants born preterm at 4 Level III perinatal centers in 3 European countries.

Study Design: This was a prospective, multicenter observational study. Management at birth was video-recorded and evaluated (Interact version 9.

Single-centre prospective observational study on postdelivery room care.

Objectives: As quality of care in the delivery room has major impact on outcome of preterm infants, multiple guidelines have been established in recent years. There is, however, little evidence on how to proceed during postdelivery room care, the time of transfer and admission to the neonatal intensive care unit (NICU). The aim of this study was to identify processes taking place during this period with potential impact on outcome.

Three-dimensional head shape acquisition in preterm infants - Translating an orthodontic imaging procedure into neonatal care.

Background: Head shape and head volume of preterm infants give important information on short- and long-term development. Three-dimensional (3D) assessment of a preterm infant's head would therefore provide more information than currently used two-dimensional methods.

Aims: To evaluate a contactless 3D imaging system to assess head shape and volume in preterm infants.

Widespread B cell perturbations in HIV-1 infection afflict naive and marginal zone B cells.

Perturbations in B cells are a hallmark of HIV-1 infection. This is signified by increased numbers of exhausted CD21 memory B cells, driven by continuous antigen-specific and bystander activation. Using high-dimensional flow cytometry, we demonstrate that this exhausted phenotype is also prevalent among peripheral antigen-inexperienced naive and marginal zone (MZ) B cells in acute and chronic HIV-1 infection.