Magnetoresistance Scaling Reveals Symmetries of the Strongly Correlated Dynamics in BaFe_{2}(As_{1-x}P_{x})_{2}.

The phenomenon of T-linear resistivity commonly observed in a number of strange metals has been widely seen as evidence for the breakdown of the quasiparticle picture of metals. This study shows that a recently discovered H/T scaling relationship in the magnetoresistance of the strange metal BaFe_{2}(As_{1-x}P_{x})_{2} is independent of the relative orientations of current and magnetic field. Rather, its magnitude and form depend only on the orientation of the magnetic field with respect to a single crystallographic axis: the direction perpendicular to the magnetic iron layers.

Functional cure of HIV: the scale of the challenge.

A variety of interventions to induce a functional cure of HIV are being explored, with the aim being to allow patients to cease antiretroviral therapy (ART) for prolonged periods of time or for life. These interventions share the goal of inducing ART-free remission from HIV pathogenesis and disease progression but achieve this in quite different ways, by reducing the size of the latent reservoir (for example, small-molecule stimulation of latently infected cells), reducing the number of target cells available for the virus (for example, gene therapy) or improving immune responses (for example, active or passive immunotherapy). Here, we consider a number of these alternative strategies for inducing post-treatment control of HIV and use mathematical modelling to predict the scale of the challenge inherent in these different approaches.

PD-1 Expression in HIV-Specific CD8+ T cells Before Antiretroviral Therapy Is Associated With HIV Persistence.

Background: The persistence of latently infected T cells remains the principal barrier to HIV cure. Understanding how the early immune responses shape persistence of HIV on antiretroviral therapy (ART) will be fundamental for potential eradication. Here, we aimed to determine the relationship between CD8 T-cell function and phenotype before therapy and HIV persistence on ART.

Sex-Based Differences in Human Immunodeficiency Virus Type 1 Reservoir Activity and Residual Immune Activation.

Plasma human immunodeficiency virus type 1 (HIV-1) RNA levels in women are lower early in untreated HIV-1 infection compared with those in men, but women have higher T-cell activation and faster disease progression when adjusted for viral load. It is not known whether these sex differences persist during effective antiretroviral therapy (ART), or whether they would be relevant for the evaluation and implementation of HIV-1 cure strategies. We prospectively enrolled a cohort of reproductive-aged women and matched men on suppressive ART and measured markers of HIV-1 persistence, residual virus activity, and immune activation.

Enrichment of gut-derived Fusobacterium is associated with suboptimal immune recovery in HIV-infected individuals.

We explored the gut microbiota profile among HIV-infected individuals with diverse immune recovery profiles following long-term suppressive ART and investigated the relationship between the altered bacteria with markers of immune dysfunction. The microbiota profile of rectal swabs from 26 HIV-infected individuals and 20 HIV-uninfected controls were examined. Patients were classified as suboptimal responders, sIR (n = 10, CD4 T-cell <350 cells/ul) and optimal responders, oIR (n = 16, CD4 T-cell >500 cells/ul) after a minimum of 2 years on suppressive ART.

Are we entering a new era for qualitative research? Using qualitative evidence to support guidance and guideline development by the World Health Organization.

Qualitative approaches are one of several methodologies utilised within the social sciences. New developments within qualitative methods are widening the opportunities for using qualitative evidence to inform health policy and systems decisions. In this commentary, we discuss how, in our work with the World Health Organization (WHO), we have explored ways of broadening the types of evidence used to develop evidence-informed guidance for health systems.

PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation.

Scoping reviews, a type of knowledge synthesis, follow a systematic approach to map evidence on a topic and identify main concepts, theories, sources, and knowledge gaps. Although more scoping reviews are being done, their methodological and reporting quality need improvement. This document presents the PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) checklist and explanation.

Perceptions of HIV cure research among people living with HIV in Australia.

Participation in HIV cure-related clinical trials that involve antiretroviral treatment (ART) interruption may pose substantial individual risks for people living with HIV (PLHIV) without any therapeutic benefit. As such, it is important that the views of PLHIV are considered in the design of HIV cure research trials. Examining the lived experience of PLHIV provides unique and valuable perspectives on the risks and benefits of HIV cure research.

Population Pharmacokinetics and Pharmacodynamics of Disulfiram on Inducing Latent HIV-1 Transcription in a Phase IIb Trial.

Disulfiram (DSF) was well tolerated and activated viral transcription (cell-associated unspliced (CA-US) and plasma human immunodeficiency virus (HIV) RNA) in a phase II dose-escalation trial in HIV+ antiretroviral therapy (ART)-suppressed participants. Here, we investigated whether exposure to DSF and its metabolites predicted these changes in HIV transcription. Participants were administered 500 (N = 10), 1,000 (N = 10), or 2,000 (N = 10) mg of DSF for 3 consecutive days.

Cardiac MRI T2* in Liver Transplant Candidates: Application and Performance of a Novel Imaging Technique to Identify Patients at Risk for Poor Posttransplant Cardiac Outcomes.

Background: In end-stage liver disease, alterations in iron metabolism can lead to iron overload and development of iron overload cardiomyopathy. In liver transplant candidates, evaluation for cardiac iron overload and dysfunction can help to identify candidates at increased risk for peritransplant morbidity and mortality, though recommendations for pretransplant evaluation of cardiac iron overload are not standardized. Cardiac Magnetic Resonance Imaging T2* (CMRI-T2*) is a validated method to quantify cardiac iron deposition, with normal T2* value of 20 ms or greater.

Myeloid Dendritic Cells Induce HIV Latency in Proliferating CD4 T Cells.

HIV latency occurs predominantly in long-lived resting CD4 T cells; however, latent infection also occurs in T cell subsets, including proliferating CD4 T cells. We compared the establishment and maintenance of latent infection in nonproliferating and proliferating human CD4 T cells cocultured with syngeneic myeloid dendritic cells (mDC). Resting CD4 T cells were labeled with the proliferation dye eFluor 670 and cultured alone or with mDC, plasmacytoid dendritic cells, or monocytes in the presence of staphylococcal enterotoxin B (SEB).

Association Between Plasma Antibody Responses and Risk for Cryptococcus-Associated Immune Reconstitution Inflammatory Syndrome.

Background: Initiation of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected individuals with cryptococcal meningitis places them at risk for Cryptococcus-associated immune reconstitution inflammatory syndrome (C-IRIS). The relationship between antibody immunity and C-IRIS risk has not been investigated.

Methods: We compared plasma levels of immunoglobulins, C.

Variation in cell-associated unspliced HIV RNA on antiretroviral therapy is associated with the circadian regulator brain-and-muscle-ARNT-like-1.

Objective(s): To determine whether variation in cell-associated unspliced (CA-US) HIV RNA in HIV-infected individuals on antiretroviral therapy (ART) has a circadian basis.

Methods: Prospective observational study of HIV-infected individuals on ART. Blood was collected on three occasions and CA-US HIV RNA and mRNA of the circadian-locomotor-output-cycles-kaput (CLOCK)-associated genes quantified by real time PCR.

Barriers and strategies to achieve a cure for HIV.

9 years since the report of a cure for HIV after C-C chemokine receptor type 5 Δ32 stem cell transplantation, no other case of HIV cure has been reported, despite much research. However, substantial progress has been made in understanding the biology of the latent HIV reservoir, and in measuring the amount of virus that persists after antiretroviral therapy (ART) with increasingly sophisticated approaches. This knowledge is being translated into a long pipeline of clinical trials seeking to reduce viral persistence in participants on suppressive treatment and ultimately to allow safe cessation of ART.

Explaining the relation between pathological gambling and depression: Rumination as an underlying common cause.

Background and aims Symptoms of pathological gambling (SPG) and depression often co-occur. The nature of this relationship remains unclear. Rumination, which is well known to be associated with depression, might act as a common underlying factor explaining the frequent co-occurrence of both conditions.

The GRADE Evidence to Decision (EtD) framework for health system and public health decisions.

Objective: To describe a framework for people making and using evidence-informed health system and public health recommendations and decisions.

Background: We developed the GRADE Evidence to Decision (EtD) framework for health system and public health decisions as part of the DECIDE project, in which we simultaneously developed frameworks for these and other types of healthcare decisions, including clinical recommendations, coverage decisions and decisions about diagnostic tests.

Developing The Framework: Building on GRADE EtD tables, we used an iterative approach, including brainstorming, consultation of the literature and with stakeholders, and an international survey of policy-makers.

HIV latency reversing agents act through Tat post translational modifications.

Background: Different classes of latency reversing agents (LRAs) are being evaluated to measure their effects in reactivating HIV replication from latently infected cells. A limited number of studies have demonstrated additive effects of LRAs with the viral protein Tat in initiating transcription, but less is known about how LRAs interact with Tat, particularly through basic residues that may be post-translationally modified to alter the behaviour of Tat for processive transcription and co-transcriptional RNA processing.

Results: Here we show that various lysine and arginine mutations reduce the capacity of Tat to induce both transcription and mRNA splicing.

Programmed cell death-1 contributes to the establishment and maintenance of HIV-1 latency.

Objective: In HIV-infected individuals on antiretroviral therapy (ART), latent HIV is enriched in CD4 T cells expressing immune checkpoint molecules, in particular programmed cell death-1 (PD-1). We therefore assessed the effect of blocking PD-1 on latency, both in vitro and in vivo.

Methods: HIV latency was established in vitro following coculture of resting CD4+ T cells with myeloid dendritic cells.

Individuals with HIV-1 Subtype C Infection and Cryptococcal Meningitis Exhibit Viral Genetic Intermixing of HIV-1 Between Plasma and Cerebrospinal Fluid and a High Prevalence of CXCR4-Using Variants.

The genotypic properties of human immunodeficiency virus type 1 (HIV-1) subtype C in individuals presenting with cryptococcal meningitis (CM) are not well established. Employing single-genome amplification as well as bulk PCR, cloning and sequencing strategies, we evaluated the genetic properties of HIV-1 subtype C env in 16 antiretroviral therapy-naive study participants with CM. Eleven of the 16 participants had matched blood plasma and cerebrospinal fluid (CSF) evaluated, with the rest having either a plasma or CSF sample evaluated.

The Pathway To Establishing HIV Latency Is Critical to How Latency Is Maintained and Reversed.

HIV infection requires lifelong antiretroviral therapy because of the persistence of latently infected CD4 T cells. The induction of virus expression from latently infected cells occurs following T cell receptor (TCR) activation, but not all latently infected cells respond to TCR stimulation. We compared two models of latently infected cells using an enhanced green fluorescent protein (EGFP) reporter virus to infect CCL19-treated resting CD4 (rCD4) T cells (preactivation latency) or activated CD4 T cells that returned to a resting state (postactivation latency).

The effect of antiretroviral intensification with dolutegravir on residual virus replication in HIV-infected individuals: a randomised, placebo-controlled, double-blind trial.

Background: Whether ongoing virus replication occurs in HIV-infected individuals on antiretroviral therapy (ART) is unclear; therefore, whether residual virus replication is a barrier to achieving a cure for HIV is also unknown. We aimed to establish whether ART intensification with dolutegravir would reveal or affect residual virus replication in HIV-infected individuals on suppressive treatment.

Methods: In this randomised, placebo-controlled, double-blind trial, we enrolled HIV-infected adults (aged 18 years and older) receiving combination ART (at least three agents) for at least 3 years from the Alfred Hospital and Melbourne Sexual Health Centre, Melbourne, VIC, Australia.