HTLV-1 proviral load in peripheral blood mononuclear cells quantified in 100 HAM/TSP patients: A marker of disease progression

Abstract

A high proviral load of human T cell lymphotropic virus type 1 (HTLV-1) in peripheral blood mononuclear cells (PBMCs) has been reported in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The aim of the present study was to investigate the role of HTLV-1 proviral load in PBMCs (expressed as the number of copies per 10 6 PBMCs) in HAM/TSP disease course. One hundred consecutive HAM/TSP patients were recruited and assigned on the basis of the disability score and disease duration to either a rapid ( n = 38) or a slow ( n = 62) progression group. Thirty-four asymptomatic HTLV-1 carriers were also included. HTLV-1 proviral load was quantified in all HAM/TSP patients and asymptomatic subjects. The mean HTLV-1 proviral load was 6-fold lower in asymptomatic carriers than in HAM/TSP patients (18,224 ± 24,811 vs. 107,905 ± 96,651, p < 0.0001) and significantly higher in rapid progression patients than in slow progression patients (146,469 ± 98,943 vs. 84,270 ± 87,912, p = 0.0002). HTLV-1 proviral load in HAM/TSP patients was independent of age at the time of study, age at onset, and disease duration, and was not related to ophthalmological-associated disease or Chisholm grade. A high level of pulmonary lymphocytosis correlated with high HTLV-1 proviral load level ( p = 0.01). Our results suggest that the level of HTLV-1 proviral load in PBMCs parallels the course of HTLV-1 infection, being low in asymptomatic carriers and high and very high, respectively, in slow and rapid progression HAM/TSP patients. The magnitude of the HTLV-1 proviral load in PBMCs can be used as a biological marker of disease progression and could be a useful marker of disease activity in the monitoring of therapeutic trials.