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Maintenance of virologic efficacy and decrease in levels of β2-microglobulin, soluble CD40L and soluble CD14 after switching previously treated HIV-infected patients to an NRTI-sparing dual therapy.

Novel strategies are necessary to decrease inflammatory parameters in successfully treated HIV-infected patients. Our aim was to evaluate the maintenance of viral suppression and potential changes in inflammatory, immune-activation and coagulation biomarkers in virologically suppressed HIV-infected patients switched to a nucleoside reverse transcriptase inhibitor-sparing (NRTI) and maraviroc (MVC)-containing combined antiretroviral therapy (cART). Fifty-eight HIV-infected patients were observed after their treatment regimens were changed to MVC 150mg/once daily plus ritonavir-boosted protease …

Treatments for Long COVID autonomic dysfunction: a scoping review.

PURPOSE: For Long COVID autonomic dysfunction, we have summarized published evidence on treatment effectiveness, clinical practice guideline … 11 effectiveness studies that investigated numerous treatment regimens (fexofenadine + famotidine, maraviroc + pravastatin, selective serotonin reuptake inhibitors, nutraceutical formulations, multicomponent treatments, heart rate variability biofeedback, inspiratory muscle training, or stellate ganglion block). One randomized trial reported benefits of a …

Effect of RANTES on Vascular Contractile and Relaxant Responses in Rat Carotid Arteries.

Although regulated-upon-activation normal T-cell expressed and secreted (RANTES), a chemokine originally identified as a T-cell-specific gen … on in the presence of RANTES, while co-treatment with the C-C motif chemokine receptor 5 antagonist maraviroc slightly improved the relaxation response. These findings suggest that RANTES impairs acetylcholine-induced relaxation, likely due to the reduction of nitric oxide bioavailability and the unmasking of vasoconstrictor prostanoids through increased re …

Switching to Low Neurotoxic Antiretrovirals to Improve Neurocognition Among People Living With HIV-1-Associated Neurocognitive Disorder: The MARAND-X Randomized Clinical Trial.

BACKGROUND: The pathogenesis of HIV-associated neurocognitive (NC) impairment is multifactorial, and antiretroviral (ARV) neurotoxicity may contribute. However, interventional pharmacological studies are limited. METHODS: Single-blind, randomized (1:1), controlled trial to assess the change of NC performance (Global Deficit Score, GDS, and domain scores) in PLWH with NC impairment randomized to continue their standard of care treatment or to switch to a less neurotoxic ARV regimen: darunavir/cobicistat, maraviroc, emtricitabine (MARAND-X). Participants had plasma and cerebrospinal fluid HIV R…

Exosomes secreted by ST3GAL5high cancer cells promote peritoneal dissemination by establishing a premetastatic microenvironment.

Peritoneal dissemination of cancer affects patient survival. The behavior of peritoneal mesothelial cells (PMCs) and immune cells influences … and immunosuppression via activation of signal transducer and activator of transcription 3 (STAT3). Maraviroc, a C-C chemokine receptor type 5 (CCR5) antagonist, prevented ST3G5high -cExo-mediated MMT, T-cell suppression, and metastasis in MSs. Our results suggest ST3G5 as a suitable therapeutic target for preventing cExo-mediated peritoneal dissemination.

CCR5-mediated dynamic maintenance of resident memory T cells in the respiratory tract.

Tissue-resident memory T cells (TRM) play a key role in defense against pathogen invading barrier sites and other non-lymphoid tissues. How … axis in promoting lung-to-dLN migration. Temporary CCR5 blockade by intratracheal administration of Maraviroc, a CCR5 inhibitor, reduced the abundance of dLN TRM cells without affecting lung TRM cells. By intratracheal cell transfer, CCR5-deficient CD8+ T cells were found impaired in lung-to-dLN migration. Finally, dLN TRM cells actively participated in the …

Олигодендроглиевые клетки-прекурсоры модифицируют иммунную реакцию и раннее обезвоживание в муслиновой модели множественного склероза.

Возрождение патофизиологии множественного склероза человека (MS) в моделях животных имеет решающее значение для выявления механизмов, спровоцирующих демиэлизацию, и разработки стратегий раннего вмешательства. Здесь мы стремились моделировать чрезмерно активированный Wnt (место беспутной интеграции), сигнализирующий ранее в посмертных тканях мозга пациентов с MS путем создания экспериментального аутоиммунного энцефаломиелита (EAE) в PdgfraCreER; Apcfl/fl и Olig2Cre; Apcfl/fl мыши. Эти мыши перегружены сигнализацией Wnt в клетках-прекурсорах олигодендроцитах (OPC) из-за условного выруба аденомат

Совпадение в аннотации оригинала
Reproducing the pathophysiology of human multiple sclerosis (MS) in animal models is critical to identifying mechanisms triggering demyelina … ltration. Antagonizing chemokine receptor 5 (CCR5) using a European Medicines Agency-approved drug, maraviroc, reduced immune cell infiltration, alleviated demyelination, and attenuated EAE progression. We found an OPC-orchestrated immune cellular network that instigates early demyelination, provides insight into MS pathophysiology, and suggests avenues for …

Role of the CCL5 and Its Receptor, CCR5, in the Genesis of Aldosterone-Induced Hypertension, Vascular Dysfunction, and End-Organ Damage.

BACKGROUND: Aldosterone has been described to initiate cardiovascular diseases by triggering exacerbated sterile vascular inflammation. The … NO production in isolated endothelial cells. These effects were abolished by antagonizing CCR5 with Maraviroc. Finally, aorta incubated with CCL5 displayed severe endothelial dysfunction, which is prevented by blocking NOX1, NFκB, or CCR5. CONCLUSIONS: Our data demonstrate that CCL5/CCR5, through activation of NFκB and NOX1, is critically involved in aldos …

Systematic optimization of host-directed therapeutic targets and preclinical validation of repositioned antiviral drugs.

Inhibition of host protein functions using established drugs produces a promising antiviral effect with excellent safety profiles, decreased … ntial as broad-spectrum antivirals. In vitro and in vivo tests validated the efficacy of bosutinib, maraviroc and dextromethorphan against human herpesvirus 1 (HHV-1), hepatitis B virus (HBV) and influenza A virus (IAV). Their drug synergy with clinically used antivirals was evaluated and confirmed. The results proved that low-dose dextromethorphan is bette …

Quantitative Imaging Analysis of the Spatial Relationship between Antiretrovirals, Reverse Transcriptase Simian-Human Immunodeficiency Virus RNA, and Collagen in the Mesenteric Lymph Nodes of Nonhuman Primates.

Human immunodeficiency virus (HIV) persistence in tissue reservoirs is a major barrier to HIV cure. While antiretrovirals (ARVs) suppress vi … concentration (IC50) values; however, 52% of total tissue coverage was from only one ARV, primarily maraviroc. Collagen covered ∼35% of tissue area but did not influence ARV distribution heterogeneity. Our findings are consistent with our hypothesis that ARV distribution, in addition to total-tissue drug concentration, must be considered when evaluating vir …

The inhibitory effect of antiretroviral drugs on the L-carnitine uptake in human placenta.

In spite of remarkable reduction in the number of children born with HIV due to antiretroviral therapy, concerns remain on the short- and lo … ranavir), integrase inhibitors (raltegravir, dolutegravir, elvitegravir) and viral entry inhibitor, maraviroc. Studies in choriocarcinoma BeWo cells and human placenta-derived models confirmed predominant expression and function of OCTN2 above OCTN1 in l-carnitine transport. Subsequent screenings in BeWo cells and isolated MVM vesicles revealed seven antire …

Reciprocal Effects of Antiretroviral Drugs Used To Treat HIV Infection on the Fibroblast Growth Factor 21/β-Klotho System.

Following antiretroviral therapy, HIV-infected patients show increased circulating levels of the antidiabetic hormone fibroblast growth fact … gene expression. Neither nucleoside reverse transcriptase inhibitors nor the viral entry inhibitor maraviroc had any effect. Among the integrase inhibitors, elvitegravir significantly induced FGF21 expression, whereas raltegravir had minor effects only in adipose cells. In human hepatocytes and adipocytes, known target cells of FGF21 action, efavirenz, elv …

Transmembrane protein aptamers that inhibit CCR5 expression and HIV coreceptor function.

We have exploited the ability of transmembrane domains to engage in highly specific protein-protein interactions to construct a new class of … dition, traptamers inhibited transduction mediated by a mutant R5-tropic gp120 protein resistant to maraviroc, a small-molecule CCR5 inhibitor, and they dramatically inhibited replication of an R5-tropic laboratory strain of HIV in a multicycle infection assay. Genetic experiments suggested that the active traptamers specifically interacted with the transme …

Chemokine Receptor 5 Antagonism Causes Reduction in Joint Inflammation in a Collagen-Induced Arthritis Mouse Model.

Rheumatoid arthritis (RA) is a chronic inflammatory disease mainly affecting the synovial joints. A highly potent antagonist of C-C chemokine receptor 5 (CCR5), maraviroc (MVC), plays an essential role in treating several infectious diseases but has not yet been evaluated for its potential effects on RA development. This study focused on evaluating the therapeutic potential of MVC on collagen-induced arthritis (CIA) in DBA/1J mice. Following CIA induction, animals were treated intraperitoneally with MVC (50 mg/kg) daily from day 21 until day 35 and evaluated for clinical score and histopatholo…

In vitro susceptibility to fostemsavir is not affected by long-term exposure to antiviral therapy in MDR HIV-1-infected patients.

OBJECTIVES: Fostemsavir is the prodrug of the HIV-1 attachment inhibitor temsavir and is currently under clinical assessment in heavily trea … ART was 26 years (23-27) and 11 (46%) had a previous AIDS diagnosis. Exposure to entry inhibitors (maraviroc and/or enfuvirtide) had occurred in 19 (79%) patients. Among 23/24 gp120 sequences obtained, temsavir resistance-associated mutations (RAMs) were detected in three cases (two M426L and one S375N). Pseudotyped viruses were obtained from 23/24 samples …

HIV-1 anchor inhibitors and membrane fusion inhibitors target distinct but overlapping steps in virus entry.

HIV-1 entry into cells is mediated by the envelope glycoprotein (Env) and represents an attractive target for therapeutic intervention. Two drugs that inhibit HIV entry are approved for clinical use: the membrane fusion-inhibitor T20 (Fuzeon, enfuvirtide) and the C-C chemokine receptor type 5 (CCR5) blocker maraviroc (Selzentry). Another class of entry inhibitors supposedly target the fusion peptide (FP) and are termed anchor inhibitors. These include the VIRIP peptide and VIRIP derivatives such as VIR165, VIR353, and VIR576. Here, we investigated the mechanism of inhibition by VIR165. We show…

Macrophage-sensory neuronal interaction in HIV-1 gp120-induced neurotoxicity‡.

BACKGROUND: Human immunodeficiency virus (HIV)-associated sensory neuropathy (SN) is the most frequent neurological complication of HIV dise … implicated in other painful polyneuropathies. The C-C chemokine receptor type 5 (CCR5) antagonist, maraviroc, concentration-dependently inhibited gp120-induced tumour necrosis factor-α gene expression, indicating that these effects occurred via gp120 activation of CCR5. CONCLUSIONS: Our findings highlight macrophages in the pathogenesis of HIV-SN and upst …

2018 update to the HIV-TRePS system: the development of new computational models to predict HIV treatment outcomes, with or without a genotype, with enhanced usability for low-income settings.

OBJECTIVES: Optimizing antiretroviral drug combination on an individual basis can be challenging, particularly in settings with limited acce … timing windows, the use of a new filter to exclude probable non-adherent cases and the addition of maraviroc, tipranavir and elvitegravir to the system. RESULTS: The no-genotype models achieved area under the receiver operator characteristic curve (AUC) values of 0.82 and 0.81 using the standard and relaxed baseline data windows, respectively. The genotyp …

Anti-chemokine small molecule drugs: a promising future?

IMPORTANCE OF THE FIELD: Chemokines have principally been associated with inflammation due to their role in the control of leukocyte migrati … ess, and get a glimpse of the outlook for the future. TAKE HOME MESSAGE: In 2007, the FDA approved maraviroc, an inhibitor of CCR5 for the prevention of HIV infection, the first triumph for a small-molecule drug acting on the chemokine system. The time to market, 11 years from discovery of CCR5, was fast by industry standards. A second small-molecule drug, …

Clinical impact of tropism testing in a real-life cohort of HIV infected patients: a retrospective observational study.

BACKGROUND: The circumstances of prescription of tropism tests clinically relevant in treatment-experienced patients are unclear. METHODS: We performed a monocentric retrospective analysis of all tropism tests performed between 2006 and 2015 in HIV-infected patients on antiretroviral therapy (ART) without MVC. The motivation of tropism determination was collected. Factors associated with MVC prescription were determined using logistic regression analysis. RESULTS: Five hundred sixty-three tests were performed in experienced patients not receiving MVC. Reasons for tropism performance were: vi