Antiviral effect of raltegravir on HTLV-1 carriers

Abstract

BACKGROUND: In vitro studies support that integrase inhibitors, such as raltegravir, may inhibit human T cell lymphotropic virus type 1 (HTLV-1) replication. However, this hypothesis has not been tested in vivo. METHODS: HTLV-1-infected individuals were invited to participate in a pilot, open study that examined whether 400 mg of raltegravir twice daily could exhibit any recognizable virological effect over 12 months. Proviral DNA was measured by a real-time PCR targeting the pol region. HTLV-1 integrase sequences were obtained from peripheral blood mononuclear cells (PBMCs) at baseline and during follow-up. RESULTS: A total of five HTLV-1-infected individuals entered the study. All were infected with HTLV-1 subtype a. Two patients had HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), the rest being asymptomatic. The HTLV-1 proviral load was high in all cases (median 758 HTLV-1 DNA copies/10(4) PBMCs). Following the initiation of raltegravir therapy and for up to 6 months, both of the HAM/TSP patients experienced a transient decline in the HTLV-1 proviral load (2248 to 519 and 1033 to 861 copies/10(4) PBMCs, respectively), returning to baseline levels on subsequent determinations. No significant changes in the HTLV-1 proviral load were noticed in the three asymptomatic individuals (median proviral load of 755 copies/10(4) PBMCs over time). A total of 20 integrase sequences could be obtained from the five patients, and no genotypic substitutions were recognized comparing baseline and follow-up specimens under raltegravir. CONCLUSIONS: Treatment with raltegravir in HTLV-1-infected individuals does not result in a significant reduction of proviral load beyond 6 months of therapy. The lack of continuous viral replication cycles in chronic HTLV-1 carriers most likely explains our findings.