Dolutegravir Versus Dolutegravir in Combination With Tenofovir for the Treatment of HTLV-1 Infection

Dolutegravir Versus Dolutegravir in Combination With Tenofovir for the Treatment of HTLV-1 Infection (DOT-H): an Open-label, Randomized, Controlled Study.

This phase 2b, open-label, randomized controlled trial evaluates the efficacy and safety of dolutegravir (DTG) alone versus dolutegravir combined with tenofovir disoproxil fumarate (TDF) in individuals with HTLV-1 infection and associated clinical manifestations. The primary objective is to compare changes in HTLV-1 proviral load at 24 and 48 weeks. Secondary outcomes include clinical, functional, immunological, and quality-of-life measures.

Human T-lymphotropic virus type 1 (HTLV-1) infection is a neglected condition associated with severe neurological and hematological diseases, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Currently, no effective antiviral therapy exists.

Preclinical and clinical data suggest that integrase inhibitors such as dolutegravir may reduce HTLV-1 proviral load. Additionally, combination therapy with tenofovir may enhance antiviral activity. This study builds on prior pilot data demonstrating partial virological response to DTG.

Participants will be randomized (1:1) to receive DTG alone or DTG plus TDF for 48 weeks. Outcomes will include virological, immunological, clinical, and patient-reported measures. The study aims to provide evidence for therapeutic strategies targeting HTLV-1.

Inclusion Criteria:

• Age equal or higher than 18 years
• Confirmed HTLV-1 infection
• Clinical manifestation atributable to HTLV-1
• Ability to provide written informed consent

Exclusion Criteria:

• Active HIV, HCV (RNA+), or HBV (HBsAg+) infection
• Active tuberculosis
• Recent corticosteroid use
• Renal impairment (CrCl <50 mL/min)
• Autoimmune diseases
• Wheelchair-bound individuals
• Active malignancy (except ATLL)
• Substance abuse interfering with adherence
• Any condition compromising safety