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

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.

Study Overview

• Status: Recruiting
• Conditions: Neuritis; HTLV-1 Infection; HTLV I Associated T Cell Leukemia Lymphoma; HTLV I Associated Myelopathies
• Intervention / Treatment: Drug: Dolutegravir (DTG); Combination product: Combination of Dolutegravir + Tenofovir DF for treatment of HTLV-1 infection

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 146
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Carlos Brites, MD, PhD; Phone Number: +5571992329552; Email: crbrites@gmail.com
• Study Contact Backup: Name: Estela Luz; Phone Number: +5571999867515; Email: eluz5@yahoo.com.br

Study Locations

• Brazil
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 40110-060
      • Recruiting
      • Hospital Universitário Professor Edgard Santos
      • Contact: Estela Luz, PhD; Phone Number: +5571999867515; Email: crbrites@gmail.com
      • Contact: Delano Paiva

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dolutegravir; Dolutegravir 50 mg p.o. daily	Drug: Dolutegravir (DTG); Active comparator will be DTG, 50 mg/day
Experimental: Combination therapy; Daily Dolutegravir 50 mg Daily Tenofovir 300 mg	Combination product: Combination of Dolutegravir + Tenofovir DF for treatment of HTLV-1 infection; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nocturia frequency	Nocturia frequency across the study	Baseline, 24 and 48 weeks
Cytokines levels	Measurement of levels of (Tumon Necrosis Factor-Alpha) TNF-alpha, IL-6, IL-2, IL-4, IL-10, Interferon γ-induced Protein (IP-10), Gamma-Interferon (Gamma-IFN), in picogram/cubic milimiter. Values may varies from undetectable levels to any detectable concentration, expressed in pg/mm3.	BL, 24 and 48 weeks
RAND 36-Item Health Survey	The RAND Corporation Health-Related Quality of Life (RAND-36) domains are scored on a 0 to 100 range, so that a high score defines a more favorable health-related quality of life (HRQoL). The scale measure several domains of HRQoL.	Baseline and at 48 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Adverse events and Serious adverse events	frequency of incident AE associated with the treatment drugs	baseline to 48 weeks
Quantification of HTLV-1	To evaluate active replication of HTLV-1, we will measure the number of copies of Long Terminal Repeat (LTR) circles to detect HTLV-1 unintegrated proviral genome and HTLV-1 plasma RNA levels. Presence of any number of copies of LTR indicates ongoing active viral replication	BL, at 24 and 48 weeks
Measurement of Levels of sCD14 and sCD163	Levels of soluble cluster of diferentiation 14 (sCD14) and 163 (sCD14), expressed in ng/mL, will be measured to evaluate levels of monocytes´ activation across the trial. Higher levels indicate increased monocytes´ activation.	BL, 24 and 48 weeks

Collaborators and Investigators

• Sponsor: Carlos Brites
• Investigators: Principal Investigator: Carlos Brites, MD, PhD, Hospital Universitário Professor Edgard Santos, Federal University of Bahia

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: April 8, 2026
• First Submitted That Met QC Criteria: April 24, 2026
• First Posted (Actual): April 29, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Treatment; Tenofovir; Dolutegravir; HTLV-1; proviral load
• Additional Relevant MeSH Terms: Neuroinflammatory Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neuromuscular Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Peripheral Nervous System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Retroviridae Infections; Immunologic Deficiency Syndromes; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Spinal Cord Diseases; Central Nervous System Infections; Myelitis; Deltaretrovirus Infections; Leukemia, T-Cell; Hemic and Lymphatic Diseases; Paraparesis, Tropical Spastic; HTLV-I Infections; Leukemia-Lymphoma, Adult T-Cell; Neuritis; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Purines; Organophosphorus Compounds; Organophosphonates; Adenine; Tenofovir; dolutegravir
• Other Study ID Numbers: FBAI-001/26

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonimized clinical data can be shared with other researchers upon reasonable request
• IPD Sharing Time Frame: IPD will be available from January 2029 to June 2029
• IPD Sharing Access Criteria: Researchers with an approved protocol will be abel to access the databank upon reasonable request to the study PI
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No