Clinical trial of raltegravir, an integrase inhibitor, in HAM/TSP

• Published in: Annals of clinical and translational neurology Vol. 8; no. 10; pp. 1970 - 1985
• Main Authors: Enose‐Akahata, Yoshimi, Billioux, Bridgette Jeanne, Azodi, Shila, Dwyer, Jennifer, Vellucci, Ashley, Ngouth, Nyater, Nozuma, Satoshi, Massoud, Raya, Cortese, Irene, Ohayon, Joan, Jacobson, Steven
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-10-2021; John Wiley and Sons Inc; Wiley
• Subjects: Adult; African Americans; Aged; Antibodies; Antiretroviral drugs; Cell growth; Clinical trials; Demographics; Female; HIV; Human immunodeficiency virus; Humans; Infections; Integrase Inhibitors - administration & dosage; Integrase Inhibitors - pharmacology; Lymphocytes; Male; Middle Aged; Paraparesis, Tropical Spastic - drug therapy; Pilot Projects; Raltegravir Potassium - administration & dosage; Raltegravir Potassium - pharmacology; Software; Treatment Outcome
• ISSN: 2328-9503; 2328-9503
• DOI: 10.1002/acn3.51437

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.