The gut microbiome and its resistome as predictors of clinical infections and phenotypic antibiotic resistance in hematopoietic stem cell transplant recipients.

A relationship between the gut microbiome composition, its resistome, and risk of clinical infections may exist and was explored here using 663 shotgun-sequenced fecal samples from 276 stem cell transplant patients. E. faecium, E.

Risk of cancer in people with HIV experiencing varying degrees of immune recovery with sustained virological suppression on antiretroviral treatment for more than 2 years: an international, multicentre, observational cohort.

Background: The impact of long-term virological suppression and CD4 count recovery on non-AIDS defining cancers (NADC) is unclear. We determined whether poor immune recovery was associated with incident cancer risk in people with HIV with virological suppression (VS).

Methods: Participants from the D:A:D and RESPOND collaborations in Europe and Australia who achieved ≥2 years of VS on ART between Dec 1999 and Dec 2022 were included.

SARS-Cov-2 vaccination strategies in hospitalized recovered COVID-19 patients: a randomized clinical trial (VATICO Trial).

The impact on immunogenicity and efficacy of SARS-CoV-2 vaccination in people with prior COVID-19 could differ depending on timing of vaccination and number of doses. The VATICO study randomized 66 hospitalized recovered COVID-19 individuals to receive either immediate or deferred vaccination, with one or two doses of mRNA SARS-CoV-2 vaccines. We measured binding and neutralizing antibodies against SARS-CoV-2 at enrollment and longitudinally.

A simple tool to evaluate the effectiveness of HIV care for settings with gaps in data availability (ESTIHIV).

Many HIV clinics with poor IT-infrastructure are unable to report data on individuals in care with HIV, on antiretroviral treatment (ART) and virologically suppressed (VS), with the aim of monitoring the HIV Continuum of Care to estimate efficacy of HIV treatment programmes. We developed an estimation-tool, ESTIHIV, and determined the minimal data required for a random sample, to produce representative estimates, with a specified level of precision, of people with HIV on ART and VS. For proof of concept, 8852 HIV positive persons from seven clinics in seven different countries, with a follow-up visit during 2017, were included.

Possible scenarios for the spread of mpox outside the endemic focus in Africa.

The recent expansion of mpox in Africa is characterized by a dramatic increase in zoonotic transmission (clade Ia) and the emergence of a new clade Ib that is transmitted from human to human by close contact. Clade Ia does not pose a threat in areas without zoonotic reservoirs. But clade Ib may spread widely, as did clade IIb which has spread globally since 2022 among men who have sex with men.

Deployment and validation of the CLL treatment infection model adjoined to an EHR system.

Research algorithms are seldom externally validated or integrated into clinical practice, leaving unknown challenges in deployment. In such efforts, one needs to address challenges related to data harmonization, the performance of an algorithm in unforeseen missingness, automation and monitoring of predictions, and legal frameworks. We here describe the deployment of a high-dimensional data-driven decision support model into an EHR and derive practical guidelines informed by this deployment that includes the necessary processes, stakeholders and design requirements for a successful deployment.

Development of antibody levels and subsequent decline in individuals with vaccine induced and hybrid immunity to SARS-CoV-2.

Objectives: This study aimed to compare antibody trajectories among individuals with SARS-CoV-2 hybrid and vaccine-induced immunity.

Methods: Danish adults receiving three doses of BTN162b2 or mRNA-1237 were included prior to first vaccination (Day 0). SARS-CoV-2 anti-spike IgG levels were assessed before each vaccine dose, at Day 90, Day 180, 28 days after 3rd vaccination (Day 251), Day 365, and prior to 4th vaccination (Day 535).

Trends in underlying causes of death in allogeneic hematopoietic cell transplant recipients over the last decade.

Objectives: Improved survival after hematopoietic cell transplantation (HCT) and an increasingly comorbid transplant population may give rise to new trends in the causes of death.

Methods: This study includes all adult allogeneic HCT recipients transplanted at Rigshospitalet between January 1, 2010 and December 31, 2019. Underlying causes of death were determined using the Classification of Death Causes after Transplantation (CLASS) method.

Predicting type 2 diabetes risk before and after solid organ transplantation using polygenic scores in a Danish cohort.

Type 2 diabetes mellitus (T2DM) can be multifactorial where both genetics and environmental factors play a role. We aimed to investigate the use of polygenic risk scores (PRS) in the prediction of pre-transplant T2DM and post-transplant diabetes mellitus (PTDM) among solid organ transplant (SOT) patients. Using non-genetic risk scores alone; and the combination with PRS, separate logistic regression models were built and compared using receiver operator curves.

Metabolic Profiling Early Post-Allogeneic Haematopoietic Cell Transplantation in the Context of CMV Infection.

Immune dysfunction resulting from allogeneic haematopoietic stem cell transplantation (aHSCT) predisposes one to an elevated risk of cytomegalovirus (CMV) infection. Changes in metabolism have been associated with adverse outcomes, and in this study, we explored the associations between metabolic profiles and post-transplantation CMV infection using plasma samples collected 7-33 days after aHSCT. We included 68 aHSCT recipients from Rigshospitalet, Denmark, 50% of whom experienced CMV infection between days 34-100 post-transplantation.

Potential cost-effectiveness of community availability of tenofovir, lamivudine, and dolutegravir for HIV prevention and treatment in east, central, southern, and west Africa: a modelling analysis.

Background: Post-exposure prophylaxis (PEP) offers protection from HIV after condomless sex, but is not widely available in a timely manner in east, central, southern, and west Africa. To inform the potential pilot implementation of such an approach, we modelled the effect and cost-effectiveness of making PEP consisting of tenofovir, lamivudine, and dolutegravir (TLD) freely and locally available in communities without prescription, with the aim of enabling PEP use within 24 h of condomless sex. Free community availability of TLD (referred to as community TLD) might also result in some use of TLD as pre-exposure prophylaxis (PrEP) and as antiretroviral therapy for people living with HIV.

Associations of functional human leucocyte antigen class I groups with HIV viral load in a heterogeneous cohort.

Objective: Human leucocyte antigen (HLA) class I alleles are the main host genetic factors involved in controlling HIV-1 viral load (VL). Nevertheless, HLA diversity has proven a significant challenge in association studies. We assessed how accounting for binding affinities of HLA class I alleles to HIV-1 peptides facilitate association testing of HLA with HIV-1 VL in a heterogeneous cohort.

Trends in Cancer Incidence in Different Antiretroviral Treatment-Eras amongst People with HIV.

Despite cancer being a leading comorbidity amongst individuals with HIV, there are limited data assessing cancer trends across different antiretroviral therapy (ART)-eras. We calculated age-standardised cancer incidence rates (IRs) from 2006-2021 in two international cohort collaborations (D:A:D and RESPOND). Poisson regression was used to assess temporal trends, adjusted for potential confounders.

Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.

Background: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure.

Methods: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA.

Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection.

Background: For people with HIV and CD4 counts >500 cells/mm, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4 counts are <350 cells/mm. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain.

Methods: The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4 counts .

Mild induced hypothermia and coagulation and platelet function in patients with septic shock: Secondary outcome of a randomized trial.

Coagulation abnormalities and microthrombi contribute to septic shock, but the impact of body temperature regulation on coagulation in patients with sepsis is unknown. We tested the hypothesis that mild induced hypothermia reduces coagulation and platelet aggregation in patients with septic shock. Secondary analysis of randomized controlled trial.

Impact of Antibiotic Treatment on the Gut Microbiome and its Resistome in Hematopoietic Stem Cell Transplant Recipients.

Antibiotic-resistant bacterial infections are increasingly an issue in allogenic hematopoietic stem cell transplant patients. How antibiotic treatment impacts antibiotic resistance in the human gut microbiome remains poorly understood in vivo. Here, a total of 577 fecal samples from 233 heavily antibiotic-treated transplant patients were examined using high-resolution prescription data and shotgun metagenomics.

Recommendations for defining preventable HIV-related mortality for public health monitoring in the era of Getting to Zero: an expert consensus.

Getting to Zero is a commonly cited strategic aim to reduce mortality due to both HIV and avoidable deaths among people with HIV. However, no clear definitions are attached to these aims with regard to what constitutes HIV-related or preventable mortality, and their ambition is limited. This Position Paper presents consensus recommendations to define preventable HIV-related mortality for a pragmatic approach to public health monitoring by use of national HIV surveillance data.

Deep-sequencing of viral genomes from a large and diverse cohort of treatment-naive HIV-infected persons shows associations between intrahost genetic diversity and viral load.

Background: Infection with human immunodeficiency virus type 1 (HIV) typically results from transmission of a small and genetically uniform viral population. Following transmission, the virus population becomes more diverse because of recombination and acquired mutations through genetic drift and selection. Viral intrahost genetic diversity remains a major obstacle to the cure of HIV; however, the association between intrahost diversity and disease progression markers has not been investigated in large and diverse cohorts for which the majority of the genome has been deep-sequenced.

Investigation of Causal Effects of Protein Biomarkers on Cardiovascular Disease in Persons With HIV.

Background: There is an incompletely understood increased risk for cardiovascular disease (CVD) among people with HIV (PWH). We investigated if a collection of biomarkers were associated with CVD among PWH. Mendelian randomization (MR) was used to identify potentially causal associations.

Pre-Transplant Prediction of Acute Graft-versus-Host Disease Using the Gut Microbiome.

Gut microbiota is thought to influence host responses to allogeneic hematopoietic stem cell transplantation (aHSCT). Recent evidence points to this post-transplant for acute graft-versus-host disease (aGvHD). We asked whether any such association might be found pre-transplant and conducted a metagenome-wide association study (MWAS) to explore.

Association between ten-eleven methylcytosine dioxygenase 2 genetic variation and viral load in people with HIV.

Introduction: Identifying genetic factors that influence HIV-pathogenesis is critical for understanding disease pathways. Previous studies have suggested a role for the human gene ten-eleven methylcytosine dioxygenase 2 (TET2) in modulating HIV-pathogenesis.

Methods: We assessed whether genetic variation in TET2 was associated with markers of HIV-pathogenesis using both gene level and single nucleotide polymorphism (SNP) level association in 8512 HIV-positive persons across five clinical trial cohorts.

Chest x-ray imaging score is associated with severity of COVID-19 pneumonia: the MBrixia score.

Spatial resolution in existing chest x-ray (CXR)-based scoring systems for coronavirus disease 2019 (COVID-19) pneumonia is low, and should be increased for better representation of anatomy, and severity of lung involvement. An existing CXR-based system, the Brixia score, was modified to increase the spatial resolution, creating the MBrixia score. The MBrixia score is the sum, of a rule-based quantification of CXR severity on a scale of 0 to 3 in 12 anatomical zones in the lungs.