Dolutegravir Versus Dolutegravir in Combination With Tenofovir for the Treatment of HTLV-1 Infection (DOT-H)

Carlos Brites

Status and phase: Enrolling; Phase 2

Conditions: Neuritis; HTLV-1 Infection; HTLV I Associated T Cell Leukemia Lymphoma; HTLV I Associated Myelopathies

Treatments: Combination Product: Combination of Dolutegravir + Tenofovir DF for treatment of HTLV-1 infection; Drug: Dolutegravir (DTG)

Study type: Interventional

Funder types: Other

Identifiers

NCT07555431

FBAI-001/26

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 146 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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146 participants in 2 patient groups

Dolutegravir

Active Comparator group

Description:

Dolutegravir 50 mg p.o. daily

Treatment:

Drug: Dolutegravir (DTG)

Combination therapy

Experimental group

Description:

Daily Dolutegravir 50 mg Daily Tenofovir 300 mg

Treatment:

Combination Product: Combination of Dolutegravir + Tenofovir DF for treatment of HTLV-1 infection