Open AccessClinical trial of raltegravir, an integrase inhibitor, in HAM/TSP
Author(s) -
EnoseAkahata Yoshimi,
Billioux Bridgette Jeanne,
Azodi Shila,
Dwyer Jennifer,
Vellucci Ashley,
Ngouth Nyater,
Nozuma Satoshi,
Massoud Raya,
Cortese Irene,
Ohayon Joan,
Jacobson Steven
Publication year - 2021
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.51437
Subject(s) - raltegravir , medicine , integrase inhibitor , tropical spastic paraparesis , myelopathy , peripheral blood mononuclear cell , cohort , immune system , clinical trial , viral load , gastroenterology , immunology , virology , pharmacology , virus , antiretroviral therapy , in vitro , spinal cord , biochemistry , chemistry , psychiatry
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.