Clinical Trial of Raltegravir, an Integrase Inhibitor, in HAM/TSP

Overview

Journal Ann Clin Transl Neurol

Specialty Neurology

Date 2021 Sep 25

PMID 34562313

Citations 4

Authors

Yoshimi Enose-Akahata

Bridgette Jeanne Billioux

Shila Azodi

Jennifer Dwyer

Ashley Vellucci

Nyater Ngouth

Satoshi Nozuma

Raya Massoud

Irene Cortese

Joan Ohayon

Steven Jacobson

Affiliations

Soon will be listed here.

Abstract

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.

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