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Persistent viruses are hard to be eradicated, even using effective medications, and can persist for a long time in humans, sometimes regardless of treatment. Hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and human T cell lymphotropic virus infections, the most common in our era, are still a challenge despite the increased knowledge about their biology. Most of them are highly pathogenic, some causing acute disease or, more often, leading to chronic persistent infections, and some of the occult, carrying a high risk of morbidity and mortality. However, if such infections were discovered early, they might be eradicated in the near future with effective medications and/or vaccines. This perspective review points out some specific characteristics of the most important chronic persistent viruses. It seems that in the next few years, these persistent viruses may have control by vaccination, epidemiological strategies, and/or treatment.

Human T-cell lymphotropic virus type 1 (HTLV-1) prevalence in Portugal is low and mainly affects immigrants from endemic areas where human immunodeficiency virus (HIV) infection represents a public health problem. Despite the majority of HTLV-1-infected individuals remains asymptomatic, severe pathologies may develop after prolonged viral persistence, namely an aggressive form of leukemia. An increased mortality rate and faster progression to death is often related to HTLV-1/HIV coinfection. Nevertheless, studies showed that some antiretrovirals used in HIV treatment lead to a positive immune response against HTLV-1. This study aimed to analyze epidemiological and clinical data, and to assess the diversity of HTLV-1 strains circulating in infected residents diagnosed in the Portuguese national reference laboratory between 2010 and 2021. Long terminal repeat and env proviral sequences derived from 20 individuals were used to generate phylogenetic trees along with multiples reference sequences from different geographic origins retrieved from the database. Three samples belong to Portuguese natives and 17 belong to immigrants: 15 from several countries of Africa, 1 from South America, and 1 from Europe; 6 patients (30%, mean age 40.3 years) showed HTLV-1-related diseases, and 6 (30%, mean age 45.2 years) were coinfected with HIV/AIDS. The results show that the Cosmopolitan subtype is circulating in Portugal, with 10 sequences being classified as subgroup A, that include Portuguese and natives from S. Tomé and Príncipe with a mean age of 39.4 years, and 10 sequences that segregated into the Senegal cluster derived from natives born in Guinea-Bissau with a mean age of 43.5 years. A high proportion of HTLV-1-related diseases and HIV/AIDS coinfection was observed. Risk behavior practices and the absence of specific control measures, including diagnostic and treatment, may contribute to a silent dissemination of a broad diversity of HTLV-1 strains and, therefore, the increased rate of progression to debilitating diseases. In this manner, an early diagnostic and a molecular surveillance of HTLV-1 transmission remains necessary in Portugal.

Despite the accuracy of confirmatory tests for the diagnosis of human T cell lymphotropic virus (HTLV), inconclusive or false-negative results still occur when diagnosing human T cell lymphotropic virus type 2 (HTLV-2)-positive patients. The goal of this study was to evaluate the sensitivity and accuracy of a confirmatory immunoassay, the Multi-HTLV assay. A total of 246 plasma samples were tested by real-time polymerase chain reaction (qPCR) and used to calculate the sensitivity and typing accuracy of the Multi-HTLV assay. Of the 246 plasma samples, 127 were positive for human T cell lymphotropic virus type 1 (HTLV-1), 112 were positive for HTLV-2, and 7 were positive for both HTLV-1 and HTLV-2. Thereafter, the nonparametric Mann-Whitney U test was used to calculate the concordance between the qPCR test and Multi-HTLV assay in 12 samples with discrepant and inconclusive qPCR results. The Multi-HTLV assay showed high performance in identifying HTLV-1 and HTLV-2 with sensitivities of 97% [95% confidence interval (CI): 0.92-0.98] and 94% (0.87-0.96), respectively. However, due to typing performance (98% for HTLV-1 and 94% for HTLV-2), it had 95% agreement with positive HTLV-1 qPCR results (95% CI: 90.07-97.81) and 86% (78.04-91.01) of HTLV-2 qPCR results were positive. Moreover, this test was able to recognize 80% of indeterminate samples and all HTLV-2 positive samples that showed false-negative qPCR results. Our findings, derived from a substantial number of HTLV-positive samples, underscore the inherent reliability and feasibility of the Multi-HTLV assay, regardless of the molecular testing facilities. Furthermore, the distinctive multiparametric nature of this assay, combined with its straightforward procedural execution, introduces novel perspectives for analyzing specific serological profiles in each patient, as well as the potential for immunological monitoring of disease progression.

Background and Objectives: Serological HTLV-1/2 screening is mandatory for blood donor candidates in Brazil. Our objective was to analyse HTLV test results in blood donors submitted for screening and confirmatory assays in a Brazilian blood bank., Materials and Methods: Retrospective analysis (2017-2022) results of chemiluminescence immunoassays and confirmatory tests for HTLV-1/2 in reactive donors were performed. During the analysed period, three sets of assays were used: (1) Architect rHTLV-I/II + HTLV Blot 2.4 (Western blot [WB]); (2) Alinity s HTLV I/II Reagent Kit + INNO-line immunoassay (LIA) HTLV I/II Score (LIA); (3) Alinity + WB., Results: The analysed period comprised a total of 1,557,333 donations. The mean percentage of HTLV reactive donors using the Architect assay was 0.14%. With the change to the Alinity assay, that percentage dropped 2.3-fold (0.06%). The reactivity rate in the confirmatory tests (1064 samples) ranged from 13.5% to 30.2%, whereas 58.3%-85.9% of samples were non-reactive. The highest rates of positive (30.2%) and indeterminate (11.5%) results were seen using LIA. Considering all analysed samples, those with signal/cut-off ratio (S/CO) >50 were positive in confirmatory tests (positive predictive value, PPV = 100%), whereas samples with S/CO ≤6 are very unlikely to be truly positive (PPV = 0)., Conclusion: The use of the Alinity assay reduced the frequency of false-positive results. Confirmatory tests are important to identify true HTLV infection in blood donors, because more than 58% of initially reactive individuals are confirmed as seronegative. Categorizing S/CO values is useful for assessing the likelihood of true HTLV-1/2 infection., (© 2024 International Society of Blood Transfusion.)

Background: Whether human T-lymphotropic virus type 1 (HTLV-1) carriers can develop sufficient humoral immunity after coronavirus disease 2019 (COVID-19) vaccination is unknown., Methods: To investigate humoral immunity after COVID-19 vaccination in HTLV-1 carriers, a multicenter, prospective observational cohort study was conducted at five institutions in southwestern Japan, an endemic area for HTLV-1. HTLV-1 carriers and HTLV-1-negative controls were enrolled for this study from January to December 2022. During this period, the third dose of the COVID-19 vaccine was actively administered. HTLV-1 carriers were enrolled during outpatient visits, while HTLV-1-negative controls included health care workers and patients treated by participating institutions for diabetes, hypertension, or dyslipidemia. The main outcome was the effect of HTLV-1 infection on the plasma anti-COVID-19 spike IgG (IgG-S) titers after the third dose, assessed by multivariate linear regression with other clinical factors., Results: We analyzed 181 cases (90 HTLV-1 carriers, 91 HTLV-1-negative controls) after receiving the third dose. HTLV-1 carriers were older (median age 67.0 vs. 45.0 years, p < 0.001) and more frequently had diabetes, hypertension, or dyslipidemia than did HTLV-1-negative controls (60.0% vs. 27.5%, p < 0.001). After the third dose, the IgG-S titers decreased over time in both carriers and controls. Multivariate linear regression in the entire cohort showed that time since the third dose, age, and HTLV-1 infection negatively influenced IgG-S titers. After adjusting for confounders such as age, or presence of diabetes, hypertension, or dyslipidemia between carriers and controls using the overlap weighting propensity score method, and performing weighted regression analysis in the entire cohort, both time since the third dose and HTLV-1 infection negatively influenced IgG-S titers., Conclusions: The humoral immunity after the third vaccination dose is impaired in HTLV-1 carriers; thus, customized vaccination schedules may be necessary for them., (© 2024. The Author(s).)

Human T-cell leukaemia virus type 1 (HTLV-1) is a human retrovirus that causes adult T-cell lymphoma and HTLV-associated myelopathy. In this issue, Rosadas et al. use data from a recent WHO report to describe how blood banks test for HTLV-1 and how this testing contributes to public health surveillance for the virus. Commentary on: Rosadas et al. HTLV-1 screening of blood donations: we are systematically missing opportunities. Br J Haematol 2023;202:1220-1223., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)