Clinical trial of raltegravir, an integrase inhibitor, in HAM/TSP
| العنوان: | Clinical trial of raltegravir, an integrase inhibitor, in HAM/TSP |
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| المؤلفون: | Raya Massoud, Irene Cortese, Bridgette Jeanne Billioux, Shila Azodi, Nyater Ngouth, Yoshimi Enose-Akahata, Jennifer E. Dwyer, Steven Jacobson, Satoshi Nozuma, Joan Ohayon, Ashley Vellucci |
| المصدر: | Annals of Clinical and Translational Neurology Annals of Clinical and Translational Neurology, Vol 8, Iss 10, Pp 1970-1985 (2021) |
| بيانات النشر: | John Wiley and Sons Inc., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, Integrase inhibitor, Neurosciences. Biological psychiatry. Neuropsychiatry, Integrase Inhibitors, Pilot Projects, Gastroenterology, Virus, Myelopathy, Immune system, immune system diseases, Internal medicine, Raltegravir Potassium, Tropical spastic paraparesis, Medicine, Humans, IL-2 receptor, RC346-429, Aged, business.industry, General Neuroscience, virus diseases, Middle Aged, medicine.disease, Raltegravir, Paraparesis, Tropical Spastic, Clinical trial, Treatment Outcome, Female, Neurology. Diseases of the nervous system, Neurology (clinical), business, RC321-571, medicine.drug, Research Article |
| الوصف: | Objective Human T‐cell lymphotropic virus 1 (HTLV‐1)‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive myelopathy. A high proviral load (PVL) is one of the main risk factors for HAM/TSP. Recently, it was shown that raltegravir could inhibit cell‐free and cell‐to‐cell transmission of HTLV‐1 in vitro. Given the substantial clinical experience in human immunodeficiency virus infection and its excellent safety profile, this agent may be an attractive therapeutic option for HAM/TSP patients. Methods Sixteen subjects with HAM/TSP received raltegravir 400 mg orally twice daily in an initial 6‐month treatment phase, followed by a 9‐month post‐treatment phase. HTLV‐1 PVLs were assessed using droplet digital PCR from the PBMCs every 3 months, and from the CSF at baseline, month 6, and month 15. We also evaluated the ability of raltegravir to regulate abnormal immune responses in HAM/TSP patients. Results While a downward trend was observed in PBMC and/or CSF PVLs of some patients, raltegravir overall did not have any impact on the PVL in this HAM/TSP patient cohort. Clinically, all patients’ neurological scores and objective measurements remained relatively stable, with some expected variability. Immunologic studies showed alterations in the immune profiles of a subset of patients including decreased CD4+CD25+ T cells and spontaneous lymphoproliferation. Interpretation Raltegravir was generally well tolerated in this HAM/TSP patient cohort. A subset of patients exhibited a mild decrease in PVL as well as variations in their immune profiles after taking raltegravir. These findings suggest that raltegravir may be a therapeutic option in select HAM/TSP patients. Clinical Trial Registration Number NCT01867320. |
| اللغة: | English |
| تدمد: | 2328-9503 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d4a35dc4496412d3c811f72826c530ef http://europepmc.org/articles/PMC8528465 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d4a35dc4496412d3c811f72826c530ef |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23289503 |
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