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

Ann Clin Transl Neurol. 2021 Oct;8(10):1970-1985. doi: 10.1002/acn3.51437. Epub 2021 Sep 25.


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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Female
  • Humans
  • Integrase Inhibitors / administration & dosage
  • Integrase Inhibitors / pharmacology*
  • Male
  • Middle Aged
  • Paraparesis, Tropical Spastic / drug therapy*
  • Pilot Projects
  • Raltegravir Potassium / administration & dosage
  • Raltegravir Potassium / pharmacology*
  • Treatment Outcome


  • Integrase Inhibitors
  • Raltegravir Potassium

Associated data


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