Dolutegravir Reduces Human T-Cell Lymphotropic Virus Type 1 Proviral Load and Improves Neurological Outcomes in a Phase 2 Controlled Trial

Abstract

Background: No specific therapy is approved for human T-cell lymphotropic virus type 1 (HTLV-1) infection. We tested the effect of dolutegravir (DTG) on clinical outcomes and on HTLV-1 proviral load (PVL) in adults with HTLV-1 infection.

Methods: 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 PVL and prespecified neurofunctional and urinary outcomes. Primary analyses emphasized intragroup and between-group comparisons; exploratory per-protocol analyses were performed for neurofunctional measures. Asymptomatic participants were included for PVL and immunological evaluations.

Results: Eighty-three participants (53 symptomatic) were randomized (DTG, n = 43; VTC, n = 40). At week 48, there was no between-group difference in T10MWT. However, DTG use significantly reduced PVL over 48 weeks compared with VTC (P < .001). Exploratory per-protocol analyses found significant improvements associated with DTG use in lower limb spasticity (P < .001), sensory function (light touch, P = .035; pinprick, P = .001), and median nocturia frequency (P = .012). Network analysis of cytokine expression showed a change in the 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.

Conclusions: In this pilot randomized trial, DTG use was associated with significantly reduced PVL 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. Clinical Trials Registration. Brazilian Clinical Trial Register (ReBEC), code RBR-5x7ccxp.

Keywords: HTLV-1; dolutegravir; immune modulation; neurofunctional outcomes; proviral load.