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NCT Number: NCT07555431

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

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.

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Key information

Conditions

HTLV-1 Infection Central Nervous System Diseases Central Nervous System Infections Deltaretrovirus Infections HTLV I Associated Myelopathies HTLV I Associated T Cell Leukemia Lymphoma HTLV-I Infections Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunologic Deficiency Syndromes Immunoproliferative Disorders Infections Leukemia Leukemia, Lymphoid Leukemia, T-Cell Leukemia-Lymphoma, Adult T-Cell Lymphatic Diseases Lymphoproliferative Disorders Myelitis Neoplasms Neoplasms by Histologic Type Nervous System Diseases Neuritis Neuroinflammatory Diseases Neuromuscular Diseases Paraparesis, Tropical Spastic Peripheral Nervous System Diseases RNA Virus Infections Retroviridae Infections Spinal Cord Diseases Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Hospital Universitário Professor Edgard Santos

Salvador, Estado de Bahia, 40110-060, Brazil

Location status: Recruiting

Location contact

Delano Paiva

CONTACT

Estela Luz, PhD

CONTACT

[email protected]

+5571999867515

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Dolutegravir (DTG)

Drug

Active comparator will be DTG, 50 mg/day

Primary outcomes

  1. HTLV-1 Proviral Load

    Time frame: From baseline to the end of treatment at 48 weeks

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

  2. Changes in Pain intensity (DN4 doleur scale)

    Time frame: Baeline, 24 and 48 weeks

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

  3. Changes in Spasticity

    Time frame: BL, 24 and 48 weeks

    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

  4. Changes in muscle strenght

    Time frame: BL, 24 and 48 weeks

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

  5. Changes in motor score scales

    Time frame: BL, 24, 48 weeks

    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)

Secondary outcomes

  1. Nocturia frequency

    Time frame: Baseline, 24 and 48 weeks

    Nocturia frequency across the study

  2. Cytokines levels

    Time frame: BL, 24 and 48 weeks

    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.

  3. RAND 36-Item Health Survey

    Time frame: Baseline and at 48 weeks

    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.

Other outcomes

  1. Quantification of HTLV-1

    Time frame: BL, at 24 and 48 weeks

    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

  2. Frequency of Adverse events and Serious adverse events

    Time frame: baseline to 48 weeks

    frequency of incident AE associated with the treatment drugs

  3. Measurement of Levels of sCD14 and sCD163

    Time frame: BL, 24 and 48 weeks

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Carlos Brites, MD, PhD

CONTACT

[email protected]

+5571992329552

Estela Luz

CONTACT

[email protected]

+5571999867515

Sponsors and collaborators

Lead sponsor

Carlos Brites

Other

Registry information

Official study title

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

Acronym: DOT-H

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Apr 29, 2026
Registry last updated
Jun 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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