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

NCT07555431 | Not Yet Recruiting Phase 2

• 1 other identifier: FBAI-001/26
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

HTLV-1; Dolutegravir; Tenofovir; Treatment; proviral load

Outcome Measures

Primary Outcomes (5)

• HTLV-1 Proviral Load

  Measurement of HTLV-1 Proviral Load by RT-PCR. Results will be expressed as copies/ml of whole blood

  From baseline to the end of treatment at 48 weeks

• Changes in Pain intensity (DN4 doleur scale)

  Change in intensity of pain measured by DN4 doleur scale (0 to 10, with values \>4 indicating neuropathic pain)

  Baeline, 24 and 48 weeks

• Changes in Spasticity

  Changes in limbs spasticity, as measured by Ashworth scale. The Ashworth Scale uses a simple ordinal scale ranging from 0 to 4, where the highest values mean increased spasticity

  BL, 24 and 48 weeks

• Changes in muscle strenght

  Evaluation of muscle strenght by Kendall Muscle Grading system (Kendal scale), which ranges from 0 to 10, with highest values indicating better muscle strenght

  BL, 24 and 48 weeks

• Changes in motor score scales

  Evaluation of changes in motor performance using the lower extremity motor score (LEMS) is a subscale of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) that assesses lower extremity muscle strength.The score range is 0-5 for each of 5 key muscles (hip flexors, knee extensors, ankle dorsi-flexors, long toe extensors and ankle plantar flexors) of each leg, with a maximum score of 50 (the lower values indicates worse motor function)

  BL, 24, 48 weeks

Secondary Outcomes (3)

• Nocturia frequency

  Baseline, 24 and 48 weeks

• Cytokines levels

  BL, 24 and 48 weeks

• RAND 36-Item Health Survey

  Baseline and at 48 weeks

Other Outcomes (3)

• Quantification of HTLV-1

  BL, at 24 and 48 weeks

• Frequency of Adverse events and Serious adverse events

  baseline to 48 weeks

• Measurement of Levels of sCD14 and sCD163

  BL, 24 and 48 weeks

Study Arms (2)

Dolutegravir

ACTIVE COMPARATOR

Dolutegravir 50 mg p.o. daily

Drug: Dolutegravir (DTG)

Combination therapy

EXPERIMENTAL

Daily Dolutegravir 50 mg Daily Tenofovir 300 mg

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

Interventions

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

In a previous study Dolutegravir was able to reduce HTLV-1 proviral load, but a few patients did not respond to therapy. We intend to use a combination of Dolutegravir + TDF to improve the response rate. There is no previous evidence on the use of such combination for treating HTLV-1 infection.

Combination therapy

Dolutegravir (DTG) DRUG

Active comparator will be DTG, 50 mg/day

Dolutegravir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Carlos Brites: lead

Study Sites (1)

Hospital Universitário Professor Edgard Santos

Salvador, Estado de Bahia, 40110-060, Brazil

Location

Related Publications (4)

• Marino-Merlo F, Balestrieri E, Matteucci C, Mastino A, Grelli S, Macchi B. Antiretroviral Therapy in HTLV-1 Infection: An Updated Overview. Pathogens. 2020 May 1;9(5):342. doi: 10.3390/pathogens9050342.

  PMID: 32369988 BACKGROUND

• Fernandez T, Marconi C, Montano-Castellon I, Deminco F, Brites C. A Systematical Review on ART Use in HTLV Infection: Clinical, Virological, and Immunological Outcomes. Pathogens. 2024 Aug 27;13(9):721. doi: 10.3390/pathogens13090721.

  PMID: 39338913 BACKGROUND

• Fernandez T, Arriaga MB, Mayoral R, Netto EM, Brites C. Dolutegravir use is related to lower HTLV-1 proviral load in people co-infected by HIV-1. Commun Med (Lond). 2025 Dec 18;6(1):54. doi: 10.1038/s43856-025-01312-9.

  PMID: 41413309 BACKGROUND

• Brites C, Montano-Castellon I, Arriaga MB, Marconi C, Mayoral R, Luz E, Figueredo CA, Fiuza BSD, Netto EM. Dolutegravir Reduces HTLV-1 Proviral Load and Improves Neurological Outcomes in a Phase II Controlled Trial. Clin Infect Dis. 2026 Mar 9:ciag163. doi: 10.1093/cid/ciag163. Online ahead of print.

  PMID: 41834485 BACKGROUND

MeSH Terms

Conditions

HTLV-I Infections; Paraparesis, Tropical Spastic; Leukemia-Lymphoma, Adult T-Cell; Neuritis

Interventions

Tenofovir; dolutegravir

Condition Hierarchy (Ancestors)

Deltaretrovirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Myelitis; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases; Leukemia, T-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Peripheral Nervous System Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Carlos Brites, MD, PhD

  Hospital Universitário Professor Edgard Santos, Federal University of Bahia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carlos Brites, MD, PhD

CONTACT

+5571992329552; crbrites@gmail.com

Estela Luz

CONTACT

+5571999867515; eluz5@yahoo.com.br

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Health professionals who will evaluate patient´s neuro-functional performance will be blinded on treatment arm
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Full Professor - Infectious Diseases

Study Record Dates

• First Submitted: April 8, 2026
• First Posted: April 29, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: IPD will be available from January 2029 to June 2029
• Access Criteria: Researchers with an approved protocol will be abel to access the databank upon reasonable request to the study PI

Locations

BR (1)