title: Monitoring the HTLV-1 proviral load in the peripheral blood of asymptomatic carriers and patients with HTLV-associated myelopathy/tropical spastic paraparesis from a Brazilian cohort: ROC curve analysis to establish the threshold for risk disease.
abstract: Human T-lymphotropic virus 1 (HTLV-1) infection is associated with HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which affects approximately 5% of carriers. High proviral load is a risk marker for HAM/TSP, although there is an overlap of proviral load levels in peripheral blood between asymptomatic carriers and HAM/TSP patients. In this study, receiver operating characteristic curve analysis was used to define a set point of HTLV-1 proviral load that better indicates an increased risk for HAM/TSP. Proviral load was quantified in 75 asymptomatic carriers and 78 HAM/TSP patients in a Brazilian cohort. The cut-off of proviral load was defined as 114 copies/10(4)  cells, with 78.2% sensitivity to identify true HAM/TSP patients. The mean proviral load levels were not significantly different between males and females with the same clinical status, and there was no significant correlation between proviral load and age at blood sampling, age at the onset of illness, or duration of disease. In HAM/TSP patients, proviral load was significantly higher in wheelchair-bound patients than in individuals able to walk without support and in those with the worst spinal cord injuries. Follow-up of HTLV-1-infected individuals showed that proviral load was more stable in asymptomatic carriers than in HAM/TSP patients. In a cohort study, periodically quantifying proviral load in asymptomatic carriers is necessary to identify those at risk for developing neurological disease, and it is necessary for HAM/TSP patients to monitor spinal injury and progression to walking disability. The measure of proviral load in clinical practice implicates the definition of the cut-off of proviral load and its validation during follow-up.
authors.affiliation: Research Department, Minas Gerais State Blood Center (Fundação Hemominas), Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Marina dos Santos Brito Silva
authors.initials: Mdos S
authors.lastname: Furtado
authors.forename: Rafaela Gomes
authors.initials: RG
authors.lastname: Andrade
authors.forename: Luiz Cláudio Ferreira
authors.initials: LC
authors.lastname: Romanelli
authors.forename: Maisa Aparecida
authors.initials: MA
authors.lastname: Ribeiro
authors.forename: João Gabriel
authors.initials: JG
authors.lastname: Ribas
authors.forename: Elídio Barbosa
authors.initials: EB
authors.lastname: Torres
authors.forename: Edel Figueiredo
authors.initials: EF
authors.lastname: Barbosa-Stancioli
authors.forename: Anna Bárbara de Freitas Carneiro
authors.initials: AB
authors.lastname: Proietti
authors.forename: Marina Lobato
authors.initials: ML
authors.lastname: Martins
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001769:Blood / Q000821:virology*; D001938:Brazil; D002353:Carrier State / Q000175:diagnosis / Q000821:virology; D019411:Clinical Laboratory Techniques / Q000379:methods*; D005260:Female; D015490:HTLV-I Infections / Q000175:diagnosis* / Q000821:virology*; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011533:Proviruses / Q000302:isolation & purification*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D019562:Viral Load; D055815:Young Adult