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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
146
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.
Active comparator will be DTG, 50 mg/day
Hospital Universitário Professor Edgard Santos
Salvador, Estado de Bahia, Brazil
RECRUITINGHTLV-1 Proviral Load
Measurement of HTLV-1 Proviral Load by RT-PCR. Results will be expressed as copies/ml of whole blood
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: BL, 24, 48 weeks
Nocturia frequency
Nocturia frequency across the study
Time frame: 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.
Time frame: 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.
Time frame: Baseline and at 48 weeks
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