Assessing intrinsic capacity for person‐centred HIV care: a cross‐sectional study in ageing populations in Malaysia and Hong Kong DOI Creative Commons
Reena Rajasuriar,

Syaza Fatnin Binti Hisham,

Justin Heejoon Lim

et al.

Journal of the International AIDS Society, Journal Year: 2024, Volume and Issue: 28(1)

Published: Dec. 26, 2024

Abstract Introduction WHO's Integrated Care for Older People (ICOPE) proposes we measure the functional construct of intrinsic capacity (IC) to monitor and identify individuals with age‐associated vulnerabilities. Assessments IC may be useful address evolving, non‐HV care needs ageing people HIV (PWH). However, date, its utility within context has not been assessed. Methods Participants included 200 PWH attending out‐patient (2021−2023) in Universiti Malaya Medical Centre, Malaysia 101 community controls aged 35 years above. The ICOPE framework was adapted derive aggregate scores (ranging 0–6) encompassing five domains cognition, sensory (hearing vision), mobility, mood vitality. Multivariable analyses were used explore association multiple health outcomes including frailty, difficulties performing instrumental activities daily living (IADL) inflammatory markers. Area under receiver operator characteristic (AUC‐ROC) calculated predict frailty IADL deficits current cohort an independent 275 from Hong Kong (HK). Results Median (interquartile range, IQR) age among 50 (42−56) (39−59) years, respectively. There more males (83% vs. 56%, p <0.001). All received antiretroviral therapy (ART) a median duration 11 (8−14) years. Aggregate lower but significantly different compared controls, (5.4 5.6, = 0.093) performed worse than only cognitive domain. independently associated (OR 0.17 95% CI 0.07−0.42, <0.001), 0.25 0.14−0.46, <0.001) all other patient‐reported correlated IL‐6 sCD14 sCD163 levels. well identifying (AUC‐ROC ≥ 0.80) HK Malaysian cohorts modestly 0.64) deficits. Conclusions is good composite non‐HIV, physical social vulnerabilities on ART should complement disease‐based monitoring routine care. validated larger, longitudinal diverse settings.

Language: Английский

Interventions during Early Infection: Opening a Window for an HIV Cure? DOI Creative Commons
Christopher R. Hiner, April L. Mueller, Hang Su

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(10), P. 1588 - 1588

Published: Oct. 9, 2024

Although combination antiretroviral therapy (ART) has been a landmark achievement for the treatment of human immunodeficiency virus (HIV), an HIV cure remained elusive. Elimination latent reservoirs that persist throughout infection is most challenging barrier to cure. The progressive marked by increasing size and diversity until effective immune response mobilized, which can control but not eliminate infection. stalemate between replication manifested establishment viral set point. ART initiation during early stage limits reservoir development, preserves function, improves quality life, may lead ART-free remission in few people living with (PLWH). However, overwhelming majority PLWH, alone does HIV, lifelong needed sustain suppression. A critical area research focused on determining whether could be functionally cured if additional treatments are provided alongside ART. Several interventions including Block Lock, Shock Kill, broadly neutralizing antibody (bNAb) therapy, adoptive CD8+ T cell gene have demonstrated delayed rebound and/or animal models some PLWH. Whether or their application improve success less studied. Herein, we review current state clinical investigative discuss potential likelihood post-treatment initiated

Language: Английский

Citations

2
Euphorbia helioscopia L. inhibits lung tumorigenesis through alleviating exhausted T cell induced by chronic inflammation DOI

Wenbin Duan,

Ziye Zhou, Yuqing Huang

et al.

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 338, P. 119097 - 119097

Published: Nov. 12, 2024

Language: Английский

Citations

1
Metformin in Antiviral Therapy: Evidence and Perspectives DOI Creative Commons
Iryna Halabitska, Pavlo Petakh, Oleh Lushchak

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(12), P. 1938 - 1938

Published: Dec. 18, 2024

Metformin, a widely used antidiabetic medication, has emerged as promising broad-spectrum antiviral agent due to its ability modulate cellular pathways essential for viral replication. By activating AMPK, metformin depletes energy reserves that viruses rely on, effectively limiting the replication of pathogens such influenza, HIV, SARS-CoV-2, HBV, and HCV. Its role in inhibiting mTOR pathway, crucial protein synthesis reactivation, is particularly significant managing infections caused by CMV, EBV. Furthermore, reduces oxidative stress reactive oxygen species (ROS), which are critical replicating arboviruses Zika dengue. The drug also regulates immune responses, differentiation, inflammation, disrupting life cycle HPV potentially other viruses. These diverse mechanisms suppress replication, enhance system functionality, contribute better clinical outcomes. This multifaceted approach highlights metformin’s potential an adjunctive therapy treating wide range infections.

Language: Английский

Citations

1
Combined Dendritic Cell And Anti-TIGIT Immunotherapy Potentiate Trail+ Memory NK Cells Against HIV-1 Infected Cells DOI Open Access
Ildefonso Sánchez‐Cerrillo, Olga Popova,

María Agudo-Lera

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 9, 2024

ABSTRACT Natural Killer (NK) cells are promising tools for the development of immunotherapies targeting persistently infected CD4+ T to potentially achieve remission in people with HIV-1 (PWH). However, chronicity infection limits functional properties NK cells, and additional approaches needed potentiate their cytotoxic activity against HIV-1-infected cells. In present study, we analyzed reinvigoration from PWH after priming autologous dendritic (DC) stimulated nanoparticles containing Poly I:C (Nano-PIC). We show that improved natural function cell associates increased proportions NKG2C+CD57- precursors memory NK, which eliminate mainly through TRAIL receptor. addition, expression TIGIT but not TIM3 limited increase NKG2C+ associated persistent dysfunctionality stimulation Nano PIC-DC. Blockade restored capacities eliminating vitro . Moreover, combining Nano-PIC-DC anti-TIGIT mAbs immunotherapy expansion humanized immunodeficient NSG mice transplanted vivo Such viral control was preserved NKG2C precursors, granzyme B on tissue mice. Together, combination Nano-PIC DC antibodies may be a strategy efficacy aimed at cure. One sentence summary Stimulation ability

Language: Английский

Citations

0
Dasatinib interferes with HIV-1 proviral integration and the inflammatory potential of monocyte-derived macrophages from people with HIV DOI Creative Commons
Sara Rodríguez-Mora, Clara Sánchez-Menéndez,

Guiomar Bautista-Carrascosa

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 229, P. 116512 - 116512

Published: Sept. 1, 2024

HIV-1 infection is efficiently controlled by the antiretroviral treatment (ART) but viral persistence in long-lived reservoirs formed CD4 + T cells and macrophages impedes eradication creates a chronic inflammatory environment. Dasatinib tyrosine kinase inhibitor clinically used against myeloid leukemia (CML) that has also showed an anti-inflammatory potential. We previously reported dasatinib very efficient at interfering with of preserving antiviral activity SAMHD1, innate immune factor blocks T-cell activation proliferation inactivated phosphorylation T592 (pSAMHD1). observed short-term vitro significantly reduced pSAMHD1 monocyte-derived (MDMs) isolated from people HIV (PWH) healthy donors, infection. This inhibition was based on low levels 2-LTR circles proviral integration, while reverse transcription not affected. MDMs CML long-term were resistant to In addition, decreased potential reducing release M1-related cytokines like TNFα, IL-1β, IL-6, CXCL8, CXCL9, through normal IL-12 IFNγ. Due production M2-related IL-1RA IL-10 impaired, appeared interfere differentiation. The use along ART could be reservoir alleviate inflammation characteristic PWH.

Language: Английский

Citations

0
Low-Level Viremia Increases the Risk of Diabetes Mellitus in People with HIV in China: A 7-Year Retrospective Longitudinal Cohort Study DOI

Chunxing Tao,

Aidan Nong,

Minn Thit Aung

et al.

Published: Jan. 1, 2024

Language: Английский

Citations

0
Rapamycin Enhances CAR-T Control of HIV Replication and Reservoir Elimination in vivo. DOI Open Access
Wenli Mu,

Shallu Tomer,

Jeffrey Harding

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 3, 2024

ABSTRACT Chimeric Antigen Receptor (CAR) T cell therapy has emerged as a powerful immune for various diseases. Our studies in humanized mice and non-human primates (NHPs) demonstrate that hematopoietic stem (HSCs) modified with anti-HIV CAR leads to lifelong engraftment supply of functional anti-viral CAR-T cells, leading significantly reduced viral rebound after ART withdrawal. However, exhaustion, driven by chronic activation, remains major challenge the continuous efficacy therapy, necessitating additional measures achieve cure. We recently showed vivo treatment low dose rapamycin inflammation improved function HIV-infected mice. Here, we report both vitro . In mitochondria respiration cytotoxicity. low-dose HIV-infected, CAR-HSC treated inflammation, prevented exhaustion cells control replication compared CAR-HSCs alone. RNAseq analysis sorted from transcriptome, including downregulation multiple check point inhibitors upregulation key genes related survival. also observed delayed withdrawal diminished HIV reservoir were Taken together, our data indicate HSCs-based combined is promising approach treating persistent improving replication.

Language: Английский

Citations

0
Anti-HIV-1 HSPC-based gene therapy with safety kill switch to defend against and attack HIV-1 infection DOI Creative Commons
Qi Guo, Keval Parikh,

Jian Zhang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 13, 2024

Hematopoietic stem/progenitor cell (HSPC)-based anti-HIV-1 gene therapy holds promise to provide life-long remission following a single treatment. Here we report multi-pronged HSPC-based designed defend against and attack HIV-1 infection. We developed lentiviral vector capable of co-expressing three genes. Two are prevent infection, including short-hairpin RNA (CCR5sh1005) knock down co-receptor CCR5 membrane anchored fusion inhibitor (C46). The third is CD4-based chimeric antigen receptor (CAR) infected cells. Our also includes non-signaling truncated human epidermal growth factor (huEGFRt) which acts as negative selection-based safety kill switch transduced Anti-HIV-1 vector-transduced CD34+ HSPC efficiently reconstituted multi-lineage hematopoietic cells in humanized bone marrow/liver/thymus (huBLT) mice. viral load was significantly reduced (1-log fold reduction, p <0.001) transplanted huBLT Anti-huEGFR monoclonal antibody Cetuximab (CTX) administration huEGFRt+ vector-modified (>4-fold <0.01) These results demonstrate that our strategy highly effective for inhibition, CTX-mediated selection can deplete the event unwanted adverse effects

Language: Английский

Citations

0
Association Between Left Ventricular Diastolic Dysfunction, Systemic Inflammation, and Gastrointestinal Symptoms in HIV-Positive Patients on Antiretroviral Therapy DOI Creative Commons

Madalina-Ianca Suba,

Bogdan Gheorghe Hogea, Ahmed Abu-Awwad

et al.

Diseases, Journal Year: 2024, Volume and Issue: 12(12), P. 313 - 313

Published: Dec. 3, 2024

Background/Objectives: Despite advancements in antiretroviral therapy (ART), HIV-positive individuals face heightened risks of cardiovascular and gastrointestinal (GI) complications, often linked to persistent systemic inflammation. Left ventricular diastolic dysfunction (LVDD), prevalent HIV patients, exacerbates this inflammatory state may contribute worsened GI symptoms. This study aims explore the association between LVDD, inflammation, symptoms patients undergoing ART. The primary objective is analyze how LVDD contributes burden its impact on health population. Methods: cross-sectional included 320 participants divided into three groups: with (n = 80), without 120), HIV-negative controls 120). Levels biomarkers—CRP, IL-6, TNF-α, fibrinogen, IL-1β, IFN-γ, D-dimer—were measured, were assessed. Echocardiographic evaluations performed determine presence severity, while multivariate logistic regression identified predictors complications. Results: Patients + group exhibited significantly elevated levels CRP, D-dimer compared other groups, correlating higher incidences nausea, diarrhea, abdominal pain. TNF-α emerged as strongest predictor symptoms, underscoring role pathophysiology linking distress Persistent inflammation coagulation abnormalities ART suggest that alone not fully mitigate these Conclusions: Our findings emphasize compounded highlighting need for integrated approaches address both Anti-inflammatory therapies targeting specific biomarkers like could improve clinical outcomes, supporting a more comprehensive strategy managing HIV-related comorbidities beyond viral suppression.

Language: Английский

Citations

0
Low-level Viremia Increases the Risk of Diabetes Mellitus in People with HIV in China: A 7-Year Retrospective Longitudinal Cohort Study DOI Creative Commons

Chunxing Tao,

Aidan Nong,

Minn Thit Aung

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 4, 2024

Abstract Background It is unclear whether low-level viremia (LV) during antiretroviral therapy (ART), increase the incidence of diabetes mellitus (DM). This study aims to assess association between HIV exposure ART and DM using retrospective cohort data. Methods People with (PWH) who started in 2003 or later were identified from China’s National Free Program database. Participants on ≥ 6 months without at enrolment included this study. According two consecutive viral load (VL) measurements after ART, participants categorized into three groups: suppression (VS), transient episode (Blips), persistent (LLV). Blips LLV collectively classified as LV group. We analyzed depending Cox proportional hazard models adjusted for age, sex, baseline VL, CD4 count, initial regimen, WHO stage. Heterogeneous linear mixed fast blood glucose (FBG) trajectory patterns follow-up. Results During 26,097 person-years follow-up, we observed 1297 cases 8731 participants, median follow-up: 2.4 years [IQR:1.2, 4.5]. Two distinct FBG trajectories, labeled “Stable” “Rapid increase”, identified. The group had a significantly higher proportion increase” (OR: 2.53, P < 0.001). Both (cHR: 1.40, 0.001) 1.74, groups increased than VS After propensity score matching, showed risk (HR: 1.27, = 0.011). When restricted 35–49 age group, was even both 2.24, p 0.006) 1.43, 0.011) Conclusions Low-level substantially (DM), particularly middle-aged individuals. Monitoring VL crucial prevent development improve life expectancy among patients.

Language: Английский

Citations

0