Pilot study of Raltegravir, an Integrase inhibitor, in Human T-cell lymphotrophic virus-1 (HTLV-1) associated myelopathy, tropical spastic paraparesis (HAM/TSP). (P6.300)

OBJECTIVE: In this study, we seek to assess the use of Raltegravir, an HIV-1 integrase inhibitor, as a possible treatment for HAM/TSP. BACKGROUND: HAM/TSP is a disabling myelopathy, occurring in up to 3[percnt] of HTLV-1 infected subjects. It results from immune-mediated bystander damage of the neural tissues in association with an elevated HTLV-1 proviral load (PVL), which is known to be the main risk factor for developing HAM/TSP in infected subjects. Thus PVL reduction is a reasonable therapeutic goal. Raltegravir was shown to reduce cell-free and cell-to-cell transmission of HTLV-1 in vitro . Active HTLV-1 replication, through the retroviral life cycle with new virus integration, occurs in vivo and might contribute to the total HTLV-1 PVL in infected subjects. DESIGN/METHODS: In this 15 month, open label, baseline versus treatment pilot clinical trial, sixteen subjects with HAM/TSP will receive Raltegravir at 400 mg twice daily for 6 months and will be followed for an additional 9 months. The primary outcome measure is HTLV-1 PVL at month 6 as compared to baseline as determined using droplet digital PCR. Secondary outcome measures include safety and tolerability of Raltegravir in HAM/TSP, its effects on PVL in the different lymphocyte subsets and the cerebrospinal fluid (CSF), its effects on viral expression, and its effects on HTLV-1 associated immune activation in the peripheral blood and CSF. RESULTS: We have 8 patients enrolled in this trial. Currently, we are examining the effect of Raltegravir on the PVL in the PBMCs, CSF, and different lymphocyte populations using a third generation PCR, droplet digital PCR. Studies to elucidate the effects of Raltegravir treatment on viral expression and on immune activation are also underway. CONCLUSIONS: It remains to be determined if Raltegravir will be a promising therapeutic for HAM/TSP patients. Disclosure: Dr. Massoud has nothing to disclose. Dr. Caruso has nothing to disclose. Dr. Akahata has nothing to disclose. Dr. Ohayon has nothing to disclose. Dr. Jacobson has nothing to disclose.