CD24-Fc resolves inflammation and rescues CD8 T cells with polyfunctionality in humanized mice infected with HIV-1 under cART.

The persistence of HIV-1 reservoirs during combination anti-retroviral therapy (cART) leads to chronic immune activation and systemic inflammation in people with HIV (PWH), associating with a suboptimal immune reconstitution as well as an increased risk of non-AIDS events. This highlights the needs to develop novel therapy for HIV-1 related diseases in PWH. In this study, we assessed the therapeutic effect of CD24-Fc, a fusion protein with anti-inflammatory properties that interacts with danger-associated molecular patterns (DAMPs) and siglec-10, in chronic HIV-1 infection model using humanized mice undergoing suppressive cART.

High Rates of High-risk HPV Anal Infection and Abnormal Cytology in a Cohort of Transgender People Assigned Male at Birth.

Background: Transgender people assigned male at birth (TG-AMAB) have higher rates of anal human papillomavirus (HPV) infection and anal cancer compared with cisgender populations. In a cohort of TG-AMAB in Washington DC, we determined the prevalence and epidemiological factors associated with anal high-risk HPV (HR-HPV) infection and cytological abnormalities.

Methods: In an urban academic-community clinic, we recruited adults identifying as a gender different than their sex assigned at birth.

Fighting fire with fire: using infectious agents to treat persistent infection.

Infectious diseases lead to significant morbidity and mortality. Often, resolution of the acute stage of the disease leads to microbial persistence, resulting in chronic debilitating disease. Management of persistent infections frequently requires lifelong therapy with antimicrobial agents.

Paradoxical Psoriasis.

Cytokine blocking therapies have revolutionized the management of psoriasis and atopic dermatitis but can lead to the development of paradoxic psoriasis (PP). Patients treated with biologics should be closely monitored for the development of PP and other paradoxical eruptions (including inflammatory joint disease, inflammatory bowel disease, eczematous eruptions, lupus like eruptions, sarcoidal eruptions, and others) and occasionally the development of cutaneous T-cell lymphoma. Further understanding the immunologic mechanism of these processes will ultimately drive our understanding of and ability to predict and manage PPs.

RNA Interference Therapeutics for Chronic Hepatitis B: Progress, Challenges, and Future Prospects.

Chronic hepatitis B (CHB) is a global health challenge that can result in significant liver-related morbidity and mortality. Despite a prophylactic vaccine being available, patients already living with CHB often must engage in lifelong therapy with nucleoside analogues. However, the potential of RNA interference (RNAi) therapeutics as a promising avenue for CHB treatment is being explored.

IFNα induces CCR5 in CD4 T cells of HIV patients causing pathogenic elevation.

Background: Among people living with HIV, elite controllers (ECs) maintain an undetectable viral load, even without receiving anti-HIV therapy. In non-EC patients, this therapy leads to marked improvement, including in immune parameters, but unlike ECs, non-EC patients still require ongoing treatment and experience co-morbidities. In-depth, comprehensive immune analyses comparing EC and treated non-EC patients may reveal subtle, consistent differences.

Safety and efficacy of the oral TLR8 agonist selgantolimod in individuals with chronic hepatitis B under viral suppression.

Background & Aims: Selgantolimod (GS-9688) is a Toll-like receptor 8 (TLR8) agonist that suppresses HBV in vitro. In a phase II study, we evaluated the safety and efficacy of weekly selgantolimod treatment in virally suppressed individuals with chronic HBV taking oral antiviral treatment.

Methods: Forty-eight patients were randomized into two cohorts (hepatitis B e antigen [HBeAg]-positive and -negative [n = 24 each]) to receive oral selgantolimod 3 mg, 1.

Use of a machine learning model to predict retention in care in an urban HIV clinic.

Identifying barriers to retention in care (RIC) is critical to ending the HIV epidemic in the United States. Therefore, we developed a machine learning model (MLM) to identify predictive factors for RIC in an urban HIV clinic. Our MLM yielded a positive predictive value of 84%, higher than previously reported MLMs.

Neuronal and Glial Metabolite Abnormalities in Participants With Persistent Neuropsychiatric Symptoms After COVID-19: A Brain Proton Magnetic Resonance Spectroscopy Study.

Background: The aim of this study was to determine whether neurometabolite abnormalities indicating neuroinflammation and neuronal injury are detectable in individuals post-coronavirus disease 2019 (COVID-19) with persistent neuropsychiatric symptoms.

Methods: All participants were studied with proton magnetic resonance spectroscopy at 3 T to assess neurometabolite concentrations (point-resolved spectroscopy, relaxation time/echo time = 3000/30 ms) in frontal white matter (FWM) and anterior cingulate cortex-gray matter (ACC-GM). Participants also completed the National Institutes of Health Toolbox cognition and motor batteries and selected modules from the Patient-Reported Outcomes Measurement Information System.

Quantifying the Neuropsychiatric Symptoms in Post-Acute Sequelae of COVID-19 (PASC) using the NIH Toolbox and PROMIS.

Objective: To quantify neuropsychiatric symptoms reported by individuals with Post-Acute Sequelae of COVID-19 (PASC) using the NIH Toolbox for Assessment of Neurological and Behavioral Function (NIHTB) and Patient-Reported Outcomes Measurement Information System (PROMIS).

Methods: 30 PASC (20 women, 21-63 years) and 27 control (16 women, 25-68 years) participants completed three NIHTB batteries and selected PROMIS tests. Group differences on fully corrected T-scores were evaluated using analysis of covariance and Cohen's effect sizes.

Ongoing oxidative stress in individuals with post-acute sequelae of COVID-19.

Objectives: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is associated with lower plasma glutathione (GSH) levels due to oxidative stress. However, plasma levels may not reflect brain GSH levels. Individuals with post-acute sequelae of COVID-19 (PASC) have a higher prevalence of cognitive fatigue, which might be related to altered brain γ-aminobutyric-acid (GABA) levels.

Undertreatment of opioid use disorder in patients hospitalized with injection drug use-associated infections.

Objective: To evaluate the association between medication for opioid use disorder (MOUD) initiation and addiction consultation and outcomes for patients hospitalized with infectious complications of injecting opioids.

Method: This was a retrospective cohort study performed at four academic medical centers in the United States. The participants were patients who had been hospitalized with infectious complications of injecting opioids in 2018.

Genotype Frequencies in Asian Populations Support Shorter Duration Therapy with Sofosbuvir-Based Hepatitis C Virus Regimens to Increase the Number Cured.

Globally, ∼56.8 million people are chronically infected with hepatitis C virus (HCV), with about half residing in Asia. The cost and efficiency of delivering regimens based on direct-acting antiviral agents for HCV are important considerations in implementing these curative treatments.

Use of nonstigmatizing language is associated with improved outcomes in hospitalized people who inject drugs.

Background: Stigma surrounding opioid use disorder (OUD) is a barrier to treatment. The use of stigmatizing language may be evidence of negative views toward patients.

Objective: We aimed to identify associations between language and clinical outcomes in patients admitted for infectious complications of OUD.

Early Elevated IFNα Identified as the Key Mediator of HIV Pathogenesis and its low level a Hallmark of Elite Controllers.

Advances in HIV therapy came from understanding its replication. Further progress toward "functional cure" -no therapy needed as found in Elite Controllers (EC)- may come from insights in pathogenesis and avoidance by EC. Here we show that all immune cells from HIV-infected persons are impaired in non-EC, but not in EC.

IFNα induces CCR5 in CD4 T-cells, causing its anti- HIV inefficiency and its subsequent pathogenic elevation, partially controlled by anti-HIV therapy.

Like EC, we find that ART-treated patients control serum IFNα concentration and show few immune cell alterations enabling a healthy but fragile medical status. However, treatment interruption leads to elevated IFNα reflecting virus production indicating that like EC, ART does not achieve a virological cure. The immune system becomes overwhelmed by multiple immune cell abnormalities as found in untreated patients.

Changes in Brain Activation Patterns During Working Memory Tasks in People With Post-COVID Condition and Persistent Neuropsychiatric Symptoms.

Background And Objectives: Post-COVID condition (PCC) is common and often involves neuropsychiatric symptoms. This study aimed to use blood oxygenation level-dependent fMRI (BOLD-fMRI) to assess whether participants with PCC had abnormal brain activation during working memory (WM) and whether the abnormal brain activation could predict cognitive performance, motor function, or psychiatric symptoms.

Methods: The participants with PCC had documented coronavirus disease 2019 (COVID-19) at least 6 weeks before enrollment.

CD38: an ecto-enzyme with functional diversity in T cells.

CD38, a nicotinamide adenine dinucleotide (NAD)+ glycohydrolase, is considered an activation marker of T lymphocytes in humans that is highly expressed during certain chronic viral infections. T cells constitute a heterogeneous population; however, the expression and function of CD38 has been poorly defined in distinct T cell compartments. We investigated the expression and function of CD38 in naïve and effector T cell subsets in the peripheral blood mononuclear cells (PBMCs) from healthy donors and people with HIV (PWH) using flow cytometry.

Immune drivers of HBsAg loss in HBeAg-negative CHB patients after stopping nucleotide analog and administration of Peg-IFN.

Background: The stoppage of nucleoside analog (NA) can lead to immune flare and loss of HBsAg in a proportion of HBeAg-negative chronic hepatitis B (CHB) patients. HBsAg loss could be improved by instituting Peg-Interferon therapy in those who show an immune flare after the stoppage of NA. We investigated the immune drivers of HBsAg loss in NA-treated HBeAg-negative CHB patients after stopping NAs and administration of Peg-IFN-α2b therapy.

Blockade of CCR4 breaks immune tolerance in chronic hepatitis B patients by modulating regulatory pathways.

Background: Immunotargets including checkpoint inhibitors and toll-like receptor 8 agonists have recently gained attention for the recovery of hepatitis B virus (HBV)-specific T cell exhaustion in chronic hepatitis B(CHB). Chemokine receptors have a similar significant role during viral infections; however, their role in CHB remains poorly understood. Therefore, in this study we evaluated the role of chemokine receptor 4 (CCR4) in deriving immunosuppression during CHB.