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.
Age equal or higher than 18 years
Confirmed HTLV-1 infection
Clinical manifestation atributable to HTLV-1
Ability to provide written informed consent
Active HIV, HCV (RNA+), or HBV (HBsAg+) infection
Active tuberculosis
Recent corticosteroid use
Renal impairment (CrCl <50 mL/min)
Parallel
Combination of Dolutegravir + Tenofovir DF for treatment of HTLV-1 infection
Combination productIn 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)
DrugActive comparator will be DTG, 50 mg/day
HTLV-1 Proviral Load
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)
Change in intensity of pain measured by DN4 doleur scale (0 to 10, with values \>4 indicating neuropathic pain)
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
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
Nocturia frequency
Nocturia frequency across the study
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.
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.
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
Frequency of Adverse events and Serious adverse events
frequency of incident AE associated with the treatment drugs
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.
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Carlos Brites
Lead sponsor
Fundação Bahiana de Infectologia
Sponsor institution
