Dolutegravir Reduces HTLV-1 Proviral Load and Improves Neurological Outcomes in a Phase II Controlled Trial.

Abstract

No specific therapy is approved for HTLV-1 infection. We tested the effect of dolutegravir (DTG) on clinical outcomes and on HTLV-1 proviral load (HPVL) in adults with HTLV-1 infection. We conducted an open-label, randomized, controlled, phase 2 trial in Salvador, Brazil. Symptomatic adults with HTLV-1 infection were randomized 1:1 to DTG 50 mg once daily or vitamin C (VTC) 500 mg once daily for 48 weeks. We evaluated changes in gait performance (Timed 10-Meter Walk Test -T10MWT). Key secondary endpoints included change in HPVL and prespecified neurofunctional and urinary outcomes. Primary analyses emphasized intra-group and between-group comparisons; exploratory per-protocol analyses were performed for neurofunctional measures. Asymptomatic participants were included for PVL and immunological evaluations. Eighty-three participants (53 symptomatic) were randomized (DTG, n=43; VTC, n=40). At week 48, there was no between-group difference in 10MWT. However, DTG use significantly reduced HPVL over 48 weeks compared with VTC (p<0.001). Exploratory per-protocol analyses found significant improvements associated with DTG use in lower-limb spasticity (p<0.001), sensory function (light touch p=0.035; pinprick p=0.001, and median nocturia frequency (p=0.012). Network analysis of cytokines expression showed a change in DTG group from baseline to week 48, with loss of negative correlations and a more balanced pattern. DTG was well tolerated, with no unexpected safety signals. In this pilot randomized trial, DTG use was associated with significantly reduced HPVL and improvement in neurofunctional and immunological characteristics of participants in exploratory analyses. These findings provide evidence supporting the use of integrase inhibitors for HTLV-1 infection.