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.

Triple Therapy with Prednisolone, Pegylated Interferon and Sodium Valproate Improves Clinical Outcome and Reduces Human T-Cell Leukemia Virus Type 1 (HTLV-1) Proviral Load, Tax and HBZ mRNA Expression in Patients with HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis

“…Furthermore, there was a statistically significant correlation between HTLV-1 PVL and the age of the patients (r= 0.59; p=0.01). Inconsistent findings have been reported in the literature regarding the correlation between PVL and age [34,35]. Although Furtado et al [34] did not find any correlation between PVL and age at blood sampling, age at disease onset, or duration of disease, Matsuzaki et al [35] reported a higher PVL in patients with a disease onset at an age of>65 years compared with those with a younger age of onset [35].…”

Utility of HTLV proviral load quantification in diagnosis of HTLV-1-associated myelopathy requires international standardization

“…Furtado et al [15] also attempted to establish a proviral load cut-off value to distinguish asymptomatic carriers from HAM/TSP patients in Minas Gerais (Brazil). Using whole blood, a cut-off of 114 HTLV-1 copies/10 4 white blood cells (1.14%), offered 78.2% sensitivity and 28% specificity in patients with HAM/TSP.…”

Leukemia and Retroviral Disease

“…HTLV-1 proviral DNA levels in PBMCs varied during the course of HTLV-1 infection [103]. High proviral DNA levels [104] along with the replication or migration of HTLV-1-infected lymphocytes to the CNS have been associated with the development of HAM/TSP [103]. Indeed, Bassi et al [105] proposed the use of HTLV-1 proviral DNA loads as a diagnostic tool for the early detection of HAM/TSP.…”

“…Several studies have indicated that HTLV-1 infection promotes HIV-1 replication, accelerating the development of AIDS, while other reports have shown that HTLV-1 actually inhibits HIV-1 infection [4]. The conflicting results reported are likely due in part to the diverse antiretroviral regimens used to treat HTLV-1/HIV-1-coinfected patients [104]. In addition, the timing with respect to the introduction of the second virus (HTLV-1 or HIV-1) may have great impact on HIV-1 replication and disease.…”