Selzentry (maraviroc) / ViiV Healthcare - LARVOL DELTA

Impact of the initial administration of an antiretroviral drug with latency reversal properties on the HIV reservoir size. (PubMed, Sci Rep) - "This study assessed the impact of maraviroc (MVC), an antiretroviral drug with HIV latency reversal properties, on the viral reservoir size when it is administered at ART initiation...In conclusion, starting ART with a drug with HIV latency reversing activity at detectable VL phase may contribute to a greater reduction in the HIV-DNA reservoir. These findings could inform the design of future trials targeting HIV remission via a "kick and kill" strategy."

Journal • Observational data • Human Immunodeficiency Virus • Infectious Disease

A CCR5 antagonist enhances the radiosensitivity of hepatocarcinoma in a mouse model. (PubMed, J Radiat Res) - "Maraviroc combined with CFRT significantly inhibited the differentiation of bone marrow cells into PMN-MDSCs. In conclusion, the synergistic application of CCR5 antagonist with CFRT significantly enhanced radiosensitivity in HCC, primarily through suppression of PMN-MDSCs differentiation and migration, coupled with blockade of their T-cell proliferation inhibitory functions."

Journal • Preclinical • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

The Dichotomy of Tumor Control by Recruited and Resident Tumor-Associated Macrophages. (PubMed, Res Sq) - "Finally, CCR5 blockade with the FDA-approved inhibitor Maraviroc during neoantigen vaccination improved tumor control by preventing the migration of immunosuppressive, antigen-presenting recMacs (moDCs). These findings support the development of macrophage-targeted therapies by identifying pro-tumorigenic subsets and recMac trafficking as actionable targets, while preserving macrophage populations that sustain anti-tumor immunity."

Journal • Lung Adenocarcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor • CCL2 • CX3CR1 • CXCL10 • CXCL13 • CXCL9 • MRC1

Multiomics and cellular senescence profiling of aging human skeletal muscle uncovers Maraviroc as a senotherapeutic approach for sarcopenia. (PubMed, Nat Commun) - "Lastly, we define transcription factors that govern senescence state and SASP induction in aging muscle and elucidate the key function and mechanism of JUNB in SASP activation. Altogether, our findings demonstrate the prevalence and function of cellular senescence in skeletal muscle and identify a novel pharmacological intervention for sarcopenia."

Journal • Sarcopenia • JUNB

Maraviroc Prevents Optic Nerve Injury-Induced Retinal Ganglion Cell Apoptosis by Modulating the CCL5/CCR5/CTSS Axis. (PubMed, Invest Ophthalmol Vis Sci) - "Microglial activation in glaucoma upregulates CCL5, triggering CCR5-mediated RGC apoptosis via CTSS downregulation. Maraviroc effectively reduces RGC death and optic nerve damage, offering a promising neuroprotective strategy for treatment of optic nerve injury."

Journal • Glaucoma • Ophthalmology • CTSS

CCR5-mediated dynamic maintenance of resident memory T cells in the respiratory tract. (PubMed, Sci China Life Sci) - "Temporary CCR5 blockade by intratracheal administration of Maraviroc, a CCR5 inhibitor, reduced the abundance of dLN TRM cells without affecting lung TRM cells...Finally, dLN TRM cells actively participated in the secondary response and could reconstitute lung TRM cells following influenza infection. Our results support a model in which lung-to-dLN TRM retrograde migration helps maintain the CD8+ memory resident in the respiratory tract and optimizes the local T-cell response to reinfection."

Journal • Infectious Disease • Influenza • Respiratory Diseases • CD69 • CD8 • CXCR3 • ITGAE

Understanding residual risk of cardiovascular disease in people with HIV. (PubMed, Curr Opin HIV AIDS) - "Despite antiretroviral and statin therapy, residual ASCVD risk in PWH underscores the need for targeted interventions. Anti-inflammatory therapies, including IL-6 and IL-1β inhibitors, CCR5 antagonists (e.g., maraviroc, cenicriviroc mesylate), and immunomodulatory agents like methotrexate and colchicine, are being explored. Understanding HIV-driven immune dysregulation may lead to novel strategies to mitigate cardiovascular risk in this population."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease • Inflammation • APOA1 • CASP1 • CD14 • CRP • IL10 • IL1B • IL6

IMPACT-LC: Investigating Measurable PRO Acuity Trial (IMPACT) is a Multi-Center Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of Maraviroc and Atorvastatin to Improve Neurocognitive and Physical Function of Subjects With Long COVID-19/Post-Acute Sequelae of COVID-19 (PASC). (clinicaltrials.gov) - P2/3 | N=252 | Not yet recruiting | Sponsor: HealthBio, Inc.

New P2/3 trial • Infectious Disease • Novel Coronavirus Disease

Paradoxical role of CD8+ T cells and lung cancer-derived IFN-? in the downregulation of tumor-specific immune responses (IMMUNOLOGY 2025) - "Furthermore, Maraviroc, an FDA-approved CCR5 antagonist, significantly reduces lung tumor growth...Surprisingly, we identified lung tumor cells themselves as prominent producers of IFN-γ, and knockout of IFN-γ from LLC cells significantly reduced their growth in vivo. Our data suggests that immunoregulation of lung cancer is unique and may require novel immunomodulating strategies for future treatments.Keywords: Animals Rodent; Cells T Cells T Cells, Cytotoxic; Molecules Cytokines; Tissues Lung"

Lung Cancer • Melanoma • Oncology • Solid Tumor • CCL3 • CD4 • CD8 • FOXP3 • IFNG • TNFA

Discovery and exploration of disubstituted [1,2,5]oxadiazolo-[3,4-b]pyrazines as novel C-C chemokine receptor type 5 signaling inhibitors targeting the intracellular allosteric binding pocket. (PubMed, Eur J Med Chem) - "The therapeutic potential of C-C chemokine receptor type 5 inhibition has been demonstrated by antagonists targeting the extracellular domain, notably maraviroc, a Food and Drug Administration-approved Human Immunodeficiency Virus entry inhibitor...Molecular dynamics simulations and a competition assay with a Gαq11 mimetic were used to confirm the intracellular binding mode of these compounds. This novel class of C-C chemokine receptor type 5-selective intracellular antagonists offers a foundation for developing molecular tools and therapeutic agents, potentially overcoming the limitations of current extracellular C-C chemokine receptor type 5 antagonists."

Journal • Cardiovascular • Human Immunodeficiency Virus • Infectious Disease • Oncology

Male-Dominant Spinal Microglia Contribute to Neuropathic Pain by Producing CC-Chemokine Ligand 4 Following Peripheral Nerve Injury. (PubMed, Cells) - "Intrathecal administration of maraviroc, an inhibitor of the CCL4-CC-chemokine receptor 5 (CCR5) signaling pathway, after PSL, significantly suppressed mechanical allodynia only in male mice. Furthermore, intrathecal administration of CCL4 induced mechanical allodynia in both sexes, accompanied by increased expression of c-fos, a neuronal excitation marker, in the SDH. These findings highlight a sex-biased difference in the gene expression profile of spinal microglia following peripheral nerve injury, with elevated CCL4 expression in male mice potentially contributing to pain exacerbation."

Journal • Inflammation • Neuralgia • Pain • CCL4 • FOS

Traffic control: Mechanisms of ligand-specific internalization and intracellular distribution of CCR5. (PubMed, Mol Pharmacol) - "A CCR5 inhibitor Maraviroc has been approved for blocking HIV entry; however, inhibitors for the treatment of other diseases have had limited success, likely because of the complexity of CCR5 pharmacology and biology...It responds to different ligands with distinct signaling and trafficking behaviors; notably, some ligands induce retention of the receptor inside the cell. This study reveals the cellular basis for receptor sequestration that can be exploited as a therapeutic strategy for inhibiting CCR5 function."

Journal • Human Immunodeficiency Virus • Infectious Disease • Oncology

Preclinical systematic review of CCR5 antagonists as cerebroprotective and stroke recovery enhancing agents. (PubMed, Elife) - "CCR5 antagonists demonstrate promise; however, rigorously designed preclinical studies that better align with STAIR/SRRR recommendations and downstream clinical trials are warranted. Prospective Register of Systematic Reviews (PROSPERO CRD42023393438)."

Journal • Preclinical • Review • Cardiovascular

ALKBH5 Regulates Macrophage Senescence and Accelerates Atherosclerosis by Promoting CCL5 m6A Modification. (PubMed, Arterioscler Thromb Vasc Biol) - "The ALKBH5 inhibitor IOX1 and the CCR5 antagonist maraviroc were identified as potential clinical interventions for inhibiting senescent foamy macrophage formation and atherosclerosis progression. Myeloid ALKBH5 deletion attenuates atherosclerosis progression by suppressing the formation of senescent foamy macrophages and the recruitment of CD8+IFNγ+ T cells. These findings identify ALKBH5, CCL5, and CCR5 as novel therapeutic targets for atherosclerosis."

Journal • Atherosclerosis • Cardiovascular • ALKBH5 • APOE • CD68 • CD8 • IFNG • LYZ

Oligodendroglial precursor cells modulate immune response and early demyelination in a murine model of multiple sclerosis. (PubMed, Sci Transl Med) - "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 early interventions."

Journal • Preclinical • CNS Disorders • Immunology • Multiple Sclerosis • Solid Tumor • CD4 • ITGAM • OLIG2 • PDGFRA • WIF1

Impact of Antiretroviral Therapy (ART) Intensification on HIV-1 Virologic Markers (ACTG 5324) (CROI 2025) - "Background The A5324 trial investigated intensification with dolutegravir (DTG) +/- maraviroc (MVC) on neuropsychological performance (NP) in persons with HIV (PWH) and neurocognitive impairment (NCI) on suppressive ART. One limitation of this finding is that the DTG+MVC arm exhibited a lower percentage of CA-2LTR detectable at baseline, despite randomization (Figure). The reduction of CA-2LTR detection with DTG+MVC may indicate suppression of residual replication, but other mechanisms are possible like altered migration of CA-2LTR-postive CD4+ T cells."

Alzheimer's Disease • Cognitive Disorders • Human Immunodeficiency Virus • Infectious Disease • CD4

MARAVIROC: This Study is Assessing the Safety and Efficacy of Immune Inhibition as a Treatment to Prevent Primary Graft Dysfunction (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: University of California, San Francisco

New P2 trial • Acute Lung Injury • Respiratory Diseases • Transplantation

Maraviroc enhances Bortezomib sensitivity in multiple myeloma by inhibiting M2 macrophage polarization via PI3K/AKT/RhoA signaling pathway in macrophages. (PubMed, Cell Div) - "MVC reduced macrophage polarization and enhanced Bortezomib sensitivity in MM cells."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • CCL3 • CCR5 • RHOA

Investigating drug-liposome interactions using liposomal electrokinetic chromatography. (PubMed, Anal Bioanal Chem) - "Canagliflozin, which initially showed no electrophoretic mobility, migrated toward the anode in the presence of negatively charged liposomes. Mobility of positively charged substances, ambroxol and maraviroc, was suppressed by the interactions with liposomes...However, the effects were complex due to changes in API ionization and liposome surface charge, complicating the distinction between pH effects and liposome presence on API behavior. Our findings emphasize the significance of liposome composition, temperature, and pH in studying the interactions of liposomes with drugs, which is crucial for optimizing liposome-based drug delivery systems."

Journal

Repurposing lapatinib as a triple antagonist of chemokine receptors 3, 4, and 5. (PubMed, Mol Pharmacol) - "Although only the CCR5 antagonist maraviroc is US Food and Drug Administration-approved (for HIV), we curated data on CCR3, CCR4, and CCR5 antagonists from ChEMBL to develop and validate machine learning models. Using these models, we identified lapatinib as a potent inhibitor of CCR3, CCR4, and CCR5. Our study illustrates the potential of machine learning in identifying molecules for repurposing as antagonists for G protein-coupled receptors, including CCR3, CCR4, and CCR5, which have various therapeutic applications."

Journal • Age-related Macular Degeneration • Alzheimer's Disease • Asthma • Cardiovascular • CNS Disorders • Human Immunodeficiency Virus • Immunology • Infectious Disease • Macular Degeneration • Oncology • Ophthalmology • Pulmonary Disease • Respiratory Diseases • Retinal Disorders • CCR4

Skeletal muscle stem cells modulate niche function in Duchenne muscular dystrophy mouse through YY1-CCL5 axis. (PubMed, Nat Commun) - "Maraviroc-mediated pharmacological blockade of the CCL5/CCR5 axis effectively mitigates muscle dystrophy and improves muscle performance. Lastly, we demonstrate YY1 represses Ccl5 transcription by binding to its enhancer thus facilitating promoter-enhancer looping. Altogether, our study demonstrates the critical role of MuSCs in actively shaping their niche and provides novel insight into the therapeutic intervention of muscle dystrophy."

Journal • Preclinical • Duchenne Muscular Dystrophy • Fibrosis • Genetic Disorders • Immunology • Inflammation • Muscular Dystrophy • TGFB1 • YY1

Predicted environmental concentration (PEC), environmental risk assessment (ERA) and prioritization of antiretroviral drugs (ARVs) in seawater from Guarujá (Brazilian coastal zone). (PubMed, Mar Environ Res) - "Regarding the results of the mixture of ARVs, the ERA showed a high acute and/or chronic risk for all five classes tested, i.e., (i) nucleoside/nucleotide reverse transcriptase inhibitors; ii) non-nucleoside reverse transcriptase inhibitors; iii) protease inhibitors; (iv) integrase strand transfer inhibitors; and (v) chemokine receptor antagonists. Ultimately, the final ranking of the OPBT approach was etravirine (the highest-priority ARV in seawater from Guarujá), followed by: nevirapine > efavirenz > ritonavir > lopinavir > maraviroc > atazanavir > darunavir > abacavir > dolutegravir > zidovudine > tenofovir > lamivudine."

Journal • Human Immunodeficiency Virus • Infectious Disease

CCL5 Induces a Sarcopenic-like Phenotype via the CCR5 Receptor. (PubMed, Antioxidants (Basel)) - "The participation of CCR5 was evaluated using the antagonist maraviroc (MVC)...When the CCR5 was antagonized, the effects produced by rCCL5 were prevented. In conclusion, we report for the first time that CCL5 is a novel myokine that exerts a sarcopenic-like effect through the CCR5 receptor."

Journal • Sarcopenia • Targeted Protein Degradation • CCL5

Maraviroc/cisplatin combination inhibits gastric cancer tumoroid growth and improves mice survival. (PubMed, Biol Res) - "This finding suggests that MVC/CDDP combination could be a potential complementary therapy for GC."

Journal • Preclinical • Gastric Cancer • Oncology • Solid Tumor

Sex Affects Cognitive Outcomes in HIV-1 Tat Transgenic Mice: Role of CCR5. (PubMed, ASN Neuro) - "Well-powered cohorts of male and female mice were placed on a diet containing doxycycline to induce Tat expression for 8-wks...Deficits in the males were fully reversed by the CCR5 antagonist, maraviroc (MVC)...Based on earlier work, we hypothesized that MVC might increase brain-derived neurotrophic factor (BDNF), which is essential in maintaining synaptodendritic function. MVC did increase the mBDNF to proBDNF ratio in males, perhaps contributing to improved cognition."

Journal • Preclinical • CNS Disorders • Cognitive Disorders • Developmental Disorders • Human Immunodeficiency Virus • Infectious Disease • BDNF • CD4