HTLV-1 InfectionPhase 2DOT-HNCT07555431
Dolutegravir Versus Dolutegravir in Combination With Tenofovir for the Treatment of HTLV-1 Infection
A Phase 2 study testing Combination of Dolutegravir + Tenofovir DF for treatment of HTLV-1 infection and Dolutegravir (DTG) in people with HTLV-1 Infection and HTLV I Associated Myelopathies, run by Carlos Brites at 1 site in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HTLV-1 Infection, HTLV I Associated Myelopathies, HTLV I Associated T Cell Leukemia Lymphoma
- What is being tested?
- Combination of Dolutegravir + Tenofovir DF for treatment of HTLV-1 infection and Dolutegravir (DTG)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 146 participants
- Where
- 1 siteBrazil
- Study dates
- 7 May 2026to Jun 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age equal or higher than 18 years
- Confirmed HTLV-1 infection
- Clinical manifestation atributable to HTLV-1
- Ability to provide written informed consent
Who cannot join
- Active HIV, HCV (RNA+), or HBV (HBsAg+) infection
- Active tuberculosis
- Recent corticosteroid use
- Renal impairment (CrCl <50 mL/min)
- Autoimmune diseases
- Wheelchair-bound individuals
Show all 9Show fewer
- Active malignancy (except ATLL)
- Substance abuse interfering with adherence
- Any condition compromising safety
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site, 1 recruiting
- Recruiting
Hospital Universitário Professor Edgard Santos
Salvador, Estado de Bahia, 40110-060
Estela Luz, PhD, +5571999867515, crbrites@gmail.com
Delano Paiva
About this study
Official title: 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.
Read the 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.
- Conditions
- HTLV-1 Infection, HTLV I Associated Myelopathies, HTLV I Associated T Cell Leukemia Lymphoma, Neuritis
- Being tested
- Combination of Dolutegravir + Tenofovir DF for treatment of HTLV-1 infection, Dolutegravir (DTG)
- Keywords
- HTLV-1, Dolutegravir, Tenofovir, Treatment, proviral load
- Medical subject headings
- HTLV-I Infections, Paraparesis, Tropical Spastic, Leukemia-Lymphoma, Adult T-Cell, Neuritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combination of Dolutegravir + Tenofovir DF for treatment of HTLV-1 infectionCombination 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
| Study group | Role | What they receive |
|---|---|---|
| Dolutegravir | Active comparator | Dolutegravir 50 mg p.o. daily Receives: Drug: Dolutegravir (DTG) |
| Combination therapy | Experimental | Daily Dolutegravir 50 mg Daily Tenofovir 300 mg Receives: Combination Product: Combination of Dolutegravir + Tenofovir DF for treatment of HTLV-1 infection |
What is being measured
The primary outcome is the main question the study is designed to answer.
HTLV-1 Proviral Load
Measurement of HTLV-1 Proviral Load by RT-PCR. Results will be expressed as copies/ml of whole blood
Measured: 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)
Measured: 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
Measured: 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
Measured: 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)
Measured: BL, 24, 48 weeks
Secondary outcomes (3)
Nocturia frequency
Nocturia frequency across the study
Measured: 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.
Measured: 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.
Measured: Baseline and at 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2026
- Study start7 May 2026
- Primary completionMay 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HTLV-1 InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 146 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Carlos Brites
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Carlos Brites, Fundação Bahiana de Infectologia
- Investigators
- Carlos Brites, MD, PhD, Principal investigator, Hospital Universitário Professor Edgard Santos, Federal University of Bahia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07555431
- Sponsor's protocol ID
- FBAI-001/26
- Acronym
- DOT-H
- Status last verified
- May 2026
- First submitted
- 8 Apr 2026
- Last updated
- 2 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonimized clinical data can be shared with other researchers upon reasonable request
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.
PubMed 32369988Fernandez 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.
PubMed 39338913Fernandez 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.
PubMed 41413309Brites C, Montano-Castellon I, Arriaga MB, Marconi C, Mayoral R, Luz E, Figueredo CA, Fiuza BSD, Netto EM. Dolutegravir Reduces Human T-Cell Lymphotropic Virus Type 1 Proviral Load and Improves Neurological Outcomes in a Phase 2 Controlled Trial. Clin Infect Dis. 2026 May 20;82(5):e910-e920. doi: 10.1093/cid/ciag163.
PubMed 41834485
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dolutegravir Versus Dolutegravir in Combination With Tenofovir for the Treatment of HTLV-1 Infection (DOT-H): an Open-label, Randomized, Controlled Study.
- ClinicalTrials.gov ID
- NCT07555431
- Acronym / sponsor ID
- DOT-H / FBAI-001/26
- Conditions
- HTLV-1 Infection, HTLV I Associated Myelopathies, HTLV I Associated T Cell Leukemia Lymphoma, Neuritis
- Keywords
- HTLV-1, Dolutegravir, Tenofovir, Treatment, proviral load
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 146 participants (estimated)
- Lead sponsor
- Carlos BritesUniversity, hospital or other
- Study start
- 7 May 2026 (actual)
- Primary completion
- May 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 29 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dolutegravir | Active comparator | Drug: Dolutegravir (DTG)Dolutegravir 50 mg p.o. daily |
| Combination therapy | Experimental | Combination Product: Combination of Dolutegravir + Tenofovir DF for treatment of HTLV-1 infectionDaily Dolutegravir 50 mg Daily Tenofovir 300 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age equal or higher than 18 years
- Confirmed HTLV-1 infection
- Clinical manifestation atributable to HTLV-1
- Ability to provide written informed consent
Key exclusion criteria (9 listed)
- Active HIV, HCV (RNA+), or HBV (HBsAg+) infection
- Active tuberculosis
- Recent corticosteroid use
- Renal impairment (CrCl <50 mL/min)
- Autoimmune diseases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Combination of Dolutegravir + Tenofovir DF for treatment of HTLV-1 infectionIn 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 product | Combination therapy |
| Dolutegravir (DTG)Active comparator will be DTG, 50 mg/day | Drug | Dolutegravir |
Primary outcome
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
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)
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
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
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)
3 secondary outcomes
Nocturia frequency
Time frame: Baseline, 24 and 48 weeks
Cytokines levels
Time frame: BL, 24 and 48 weeks
RAND 36-Item Health Survey
Time frame: Baseline and at 48 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2026.
- Background: PubMed 32369988Marino-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.
- Background: PubMed 39338913Fernandez 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.
- Background: PubMed 41413309Fernandez 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.
- Background: PubMed 41834485Brites C, Montano-Castellon I, Arriaga MB, Marconi C, Mayoral R, Luz E, Figueredo CA, Fiuza BSD, Netto EM. Dolutegravir Reduces Human T-Cell Lymphotropic Virus Type 1 Proviral Load and Improves Neurological Outcomes in a Phase 2 Controlled Trial. Clin Infect Dis. 2026 May 20;82(5):e910-e920. doi: 10.1093/cid/ciag163.
- Individual participant dataSharing planned: Yes. Anonimized clinical data can be shared with other researchers upon reasonable request
Related trials for HTLV-1 Infection
RecruitingObservational study
Evaluation of Patients With HAM/TSP
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RecruitingPhase 1
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Acute Adult T-Cell Leukemia/Lymphoma, Adult T-Cell Leukemia/Lymphoma
Active, not recruitingObservational study
Clinico-biological Characterization and Survival of Patients With Adult T-cell Leukemia / Lymphoma (ATL) and Patients Chronically Infected With the HTLV-1 Virus (HTLV-OBS)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Carlos Brites, MD, PhD principal investigator
Hospital Universitário Professor Edgard Santos, Federal University of Bahia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Combination of Dolutegravir + Tenofovir DF for treatment of HTLV-1 infection and Dolutegravir (DTG) in people with HTLV-1 Infection and HTLV I Associated Myelopathies, run by Carlos Brites at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Carlos Brites, MD, PhD (+5571992329552, crbrites@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HTLV-1 Proviral Load (time frame: From baseline to the end of treatment at 48 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07555431, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2026.