Human T-cell Lymphotropic Virus Type 1 Infection Research Articles

Impact and economic analysis of human T-cell lymphotropic virus type 1 (HTLV-1)-targeted antenatal screening, England and Wales, 2021.

BackgroundHuman T-cell lymphotropic virus type 1 (HTLV-1) is a neglected virus that can cause severe disease and be transmitted from mother to child through breastfeeding. Avoidance of breastfeeding prevents 80% of vertical transmission. The United Kingdom (UK) is currently assessing whether HTLV-1-targeted antenatal screening should be implemented.AimWe aimed to assess the impact and cost-effectiveness of a targeted programme to prevent HTLV-1 vertical transmission in England and Wales.MethodsWe estimated the number of pregnant women who have high risk of HTLV-1 infection based on their or their partner's country of birth. With data from 2021, we used a mathematical model to assess cost-effectiveness of HTLV-1 antenatal screening. We also estimated the annual number of infant infections and the number that could be prevented with screening and intervention.ResultsWe estimate that ca 99,000 pregnant women in England and Wales have high risk of HTLV-1 infection. In the absence of screening, 74 (range: 25-211) HTLV-1 infections in infants would be expected to occur every year in England and Wales. Implementation of targeted screening would prevent 58 (range: 19-164) infant infections annually. The intervention is effective (incremental 0.00333 quality-adjusted life years (QALY)) and cost-saving (GBP -57.56 (EUR -66.85)).ConclusionOur findings support implementation of HTLV-1 targeted antenatal screening to reduce vertical transmission from mothers to infants in the UK.

High Ratio of Human T Cell Lymphotropic Virus Transmission and Prevalence of Human T Cell Lymphotropic Virus Type 1-Associated Diseases in Brazilian Family Groups Followed Up by the GIPH Cohort.

A silent spread of human T cell lymphotropic virus type 1 (HTLV-1) has been occurring for thousands of years, with a high prevalence in some regions due to the sexual and vertical transmission and formation of family clusters. The time from HTLV-1 infection until the onset of virus-associated diseases is extremely long, approximately one to three decades. In this study, we evaluated intrafamilial HTLV-1 transmission and associated diseases in 1,204 individuals enrolled and followed up by the GIPH cohort between 1997 and 2017. The family groups (n = 43) were composed of 279 individuals who were tested for HTLV-1/human T cell lymphotropic virus type 2 (HTLV-2) and were classified as two groups according to the index case: blood donor (blood donors referred to the GIPH cohort) and nondonor (individuals referred to the GIPH cohort by other health services). The observed rates of HTLV-1 transmission and associated diseases among the relatives were high. Of 236 family members and sexual partners tested for HTLV, 104 (44.1%) were confirmed as having HTLV infection, with 36.7% of relatives whose index case was blood donors and 56.9% of relatives with nondonor index cases. At least one case of HTLV-1-associated myelopathy was observed in 42.9% of the families with intrafamilial transmission of HTLV-1. Brazil is an endemic area for HTLV-1/2 and has implemented mandatory universal screening of blood donors for HTLV-1/2 since 1993. However, the lack of public health services offer diagnosis for HTLV to the general population and pregnant women in the country makes it difficult to identify infected people, and contributes to the silent spread of the virus.

Determination of molecular epidemiologic pattern of human T-lymphotropic virus type 1 (HTLV-1) in Alborz province, Iran.

Human T-cell lymphotropic virus type 1 (HTLV-1) is linked to two debilitating diseases, adult T-cell leukemia/lymphoma (ATLL) and HTLV-1 associated myelopathy tropical spastic paraparesis (HAM/TSP), which are prevalent in various parts of the world, including the Alborz province in Iran. Understanding the prevalence and evolutionary relationships of HTLV-1 infections in these endemic areas is of utmost importance. In the realm of phylogenetic studies, long terminal repeat (LTR) region of HTLV-1 stands out as highly conserved, yet more variable compared to other gene segments. Consequently, it is the primary focus for phylogenetic analyses. Additionally, trans-activator of transcription (Tax), an oncoprotein, holds a pivotal role in the regulation of gene expression. This cross-sectional study delved into the phylogenetic analysis of HTLV-1 among individuals in Alborz province of Iran. To confirm infection, we amplified partial sequence LTR (PLTR) and HTLV-1 bZIP factor (PHBZ). For phylogenetic analysis, we sequenced the full sequence LTR (FLTR) andfull Tax sequence (FTax). The FLTR and FTax sequences underwent analysis using BioEdit, and phylogenetic trees were constructed using MEGA-X software. Out of the roughly 15,000 annual blood donors in Alborz, 19 samples tested positive for HTLV-1, indicating a 0.13% HTLV-1 positivity rate among blood donors. Furthermore, the HTLV-1 virus prevalent in the Alborz province belongs to subtype A (cosmopolitan) subgroup A. The findings revealed that while mutations were observed in both the LTR and Tax genes, they were not significant enough to bring about fundamental alterations. Despite positive selection detected in three Alborz isolates, it has not led to mutations affecting Tax function and virulence.

Decoding dysregulated angiogenesis in HTLV-1 asymptomatic carriers compared to healthy individuals.

Human T-cell lymphotropic virus type 1 (HTLV-1) is the first identified human retrovirus responsible for two significant diseases: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). Although the majority of infected individuals remain asymptomatic carriers, a small percentage may develop ATLL or HAM/TSP. In tumorigenesis, a crucial process is angiogenesis, which involves the formation of new blood vessels. However, the precise mechanism of HTLV-1 associated angiogenesis remains unclear. This study aims to investigate the gene regulation involved in the angiogenesis signaling pathway associated with HTLV-1 infection. The research enrolled 20 male participants, including asymptomatic carriers and healthy individuals. Blood samples were collected and screened using ELISA for HTLV-1 confirmation, and PCR was performed for both Tax and HBZ for validation. RNA extraction and cDNA synthesis were carried out, followed by RT-qPCR analysis targeting cellular genes involved in angiogenesis. Our findings indicate that gene expression related to angiogenesis was elevated in HTLV-1 ACs patients. However, the differences in gene expression of the analyzed genes, including HSP27, Paxillin, PDK1, PTEN, RAF1, SOS1, and VEGFR2 between ACs and healthy individuals were not statistically significant. This suggests that although angiogenesis-related genes may show increased expression in HTLV-1 infection, they might not be robust indicators of ATLL progression in asymptomatic carriers. The results of our study demonstrate that angiogenesis gene expression is altered in ACs of HTLV-1, indicating potential involvement of angiogenesis in the early stages before ATLL development. While we observed elevated angiogenesis gene expression in ACs, the lack of statistical significance between ACs and healthy individuals suggests that these gene markers may not be sufficient on their own to predict the development of ATLL in asymptomatic carriers.

HTLV-1 p12 modulates the levels of prion protein (PrPC) in CD4+ T cells.

Infection with human T cell lymphotropic virus type 1 (HTLV-1) is endemic in Brazil and is linked with pro-inflammatory conditions including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic neuroinflammatory incapacitating disease that culminates in loss of motor functions. The mechanisms underlying the onset and progression of HAM/TSP are incompletely understood. Previous studies have demonstrated that inflammation and infectious agents can affect the expression of cellular prion protein (PrPC) in immune cells. Here, we investigated whether HTLV-1 infection affected PrPC content in cell lines and primary CD4+cells in vitro using flow cytometry and western blot assays. We found that HTLV-1 infection decreased the expression levels of PrPC and HTLV-1 Orf I encoded p12, an endoplasmic reticulum resident protein also known to affect post-transcriptionally cellular proteins such as MHC-class I and the IL-2 receptor. In addition, we observed a reduced percentage of CD4+ T cells from infected individuals expressing PrPC, which was reflected by IFN type II but not IL-17 expression. These results suggested that PrPC downregulation, linked to both HTLV-1 p12 and IFN-γ expression in CD4+ cells, may play a role in the neuropathogenesis of HTLV-1 infection.

Human T-cell lymphotropic virus type 1 (HTLV-1) proposed vaccines: a systematic review of preclinical and clinical studies

BackgroundNumerous vaccination research experiments have been conducted on non-primate hosts to prevent or control HTLV-1 infection. Therefore, reviewing recent advancements for status assessment and strategic planning of future preventative actions to reduce HTLV-1 infection and its consequences would be essential.MethodsMEDLINE, Scopus, Web of Science, and Clinicaltrials.gov were searched from each database's inception through March 27, 2022. All original articles focusing on developing an HTLV-1 vaccine candidate were included.ResultsA total of 47 studies were included. They used a variety of approaches to develop the HTLV-1 vaccine, including DNA-based, dendritic-cell-based, peptide/protein-based, and recombinant vaccinia virus approaches. The majority of the research that was included utilized Tax, Glycoprotein (GP), GAG, POL, REX, and HBZ as their main peptides in order to develop the vaccine. The immunization used in dendritic cell-based investigations, which were more recently published, was accomplished by an activated CD-8 T-cell response. Although there hasn't been much attention lately on this form of the vaccine, the initial attempts to develop an HTLV-1 immunization depended on recombinant vaccinia virus, and the majority of results seem positive and effective for this type of vaccine. Few studies were conducted on humans. Most of the studies were experimental studies using animal models. Adenovirus, Cytomegalovirus (CMV), vaccinia, baculovirus, hepatitis B, measles, and pox were the most commonly used vectors.ConclusionsThis systematic review reported recent progression in the development of HTLV-1 vaccines to identify candidates with the most promising preventive and therapeutic effects.

Economic analysis of antenatal screening for human T-cell lymphotropic virus type 1 in Brazil: an open access cost-utility model

Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes severe diseases, such as aggressive cancer or progressive neurological disease. HTLV-1 affects mainly people in areas with low human development index and can be transmitted from mother to child, primarily through breastfeeding. Refraining from breastfeeding is an effective intervention to reduce the risk of infection in infants. However, HTLV-1 antenatal screening is not offered globally. According to WHO, the scarcity of cost-effectiveness studies is considered one of the major barriers to the implementation of policies to prevent HTLV-1 infection. Therefore, this study aimed to assess the cost-effectiveness of antenatal screening and postnatal interventions to prevent HTLV-1 mother-to-child transmission in Brazil and to develop an open-access, editable, mathematical model that can be used by other countries and regions to assess different scenarios. In this cost-utility analysis, we constructed a decision tree and a Markov model to assess the cost-effectiveness of HTLV-1 antenatal screening and postnatal interventions (ie, avoidance of breastfeeding, by suppression of lactation with cabergoline, and provision of formula feed) to reduce transmission. For our model, we used data from Brazil and we took the perspective of the public health-care system to estimate costs. The implementation of both screening and interventions would result in the prevention of 1039 infections in infants every year in Brazil with an incremental cost-effectiveness ratio (ICER) of US$11 415 per quality-adjusted life-year (QALY). 88% of all probabilistic sensitivity analysis simulations had ICER values lower than the Brazilian cost-effectiveness threshold ($18 107·74 per QALY). HTLV-1 prevalence in pregnant women, the risk of HTLV-1 transmission when breastfeeding lasts for 6 months or more, and the cost of screening tests were the variables with the largest effect on ICER. HTLV-1 antenatal screening is cost-effective in Brazil. An open-access model was developed, and this tool could be used to assess the cost-effectiveness of such policy globally, favouring the implementation of interventions to prevent HTLV-1 mother-to-child transmission worldwide. None. For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

SARS-CoV-2 (COVID-19) infection in patients with HTLV-1 infection in Peru - case series

Introduction: Peru has suffered a prolonged sanitary emergency and has the highest COVID – 19 mortalities per capita in the world. Some risk factors (diabetes, HIV, cardiovascular diseases, etc.) are currently considered by the CDC to develop severe COVID-19 infection. CDC considers as possible risk factors (evidence is mixed), other immunodeficiency conditions, one of them would be infection by HTLV-1 (human T-cell lymphotropic virus type 1). It is not known whether subjects with HTLV – 1 infection have a higher risk for severe COVID – 19 disease. Materials and methods: We identified 51 patients with HTLV-1 and COVID-19. The patients recruited for this article belong to the HTLV-1 cohort of the Institute of Tropical Medicine Alexander von Humboldt - Cayetano Heredia Hospital and to the study cohort: "The effect of Strongyloides Stercoralis on HTLV-1 disease progression”. Periodic telemedicine follow-up was carried out on our patients during the lockdown from April 2020 to November 2021, and information related to SARS-CoV-2 infection was recorded. Results: 51 patients from cohorts were diagnosed with COVID-19 during the pandemic between April 2020 and October 2021. The majority are female (29 patients, 56.85%). 76.47% (39 patients) underwent a molecular/PCR, antigenic or serological test; while 23.53% (12 patients) developed symptoms compatible with COVID-19 in a context of family outbreak and positive direct contact. 74.51% (38 patients) developed a mild form of the disease, 15.69% (8 patients) a moderate form and 9.80% (5 patients) were asymptomatic. The most frequent symptoms were general malaise and/or fever (82.35%), headache (80.39%) and cough (76.47%). Discussion: the course of SARS-CoV-2 in patients infected with HTLV-1 follows similar patterns in percentage and symptoms compared to the general population. 81% usually develop a mild condition, while for our data 74.51% did. 14% usually develop moderate to severe disease worldwide, in our cohort, 15.69% developed moderate disease. The patients show a clinical picture similar to what is described in the literature as a common presentation of SARS-CoV-2. American studies show that the most frequent symptoms are headache (76%) and sore throat (65%); in our cohort, 80.39% reported headache and 35.29% sore throat. Conclusion: Patients with HTLV-1 who become infected with SARS-CoV-2 develop mild or moderate disease in similar proportions to the general population. More studies are needed to elucidate the risk of developing severe SARS-CoV-2 disease in patients infected with HTLV-1 and its associated comorbidities.

Association Between HTLV-1 Infection and Nasopharyngeal Carcinoma: A Case-Control Study

Background: The northeast of Iran is one of the endemic regions of human T-cell lymphotropic virus type-1 (HTLV-1). This study aimed to evaluate the relationship between nasopharyngeal carcinoma and HTLV-1 infection in northeast Iran, an endemic area for HTLV-1. Methods: In this case-control study, paraffin-embedded nasopharyngeal tissue samples of patients with definitive nasopharyngeal carcinoma were evaluated for the presence of the HTLV-1 genome by polymerase chain reaction retrospectively. Results: Thirty patients with nasopharyngeal carcinoma and 30 healthy people were evaluated. All participants were matched in terms of age and gender, and all were living in Mashhad. The HTLV-1 genome was detected in only one of the people in the healthy group. Conclusions: The HTLV-1 infection and nasopharyngeal carcinoma did not correlate significantly.

Human T Cell Lymphotropic Virus Type 1 Global Prevalence Associated with the Human Development Index: Systematic Review with Meta-Analysis.

In 2012, the number of people infected with human T cell lymphotropic virus type 1 (HTLV-1) was estimated to be 10 million worldwide. Prevalence varies according to geographic location, ethnic factors, sex, age, populations exposed to risk factors, income, and education, reaching countries with the worst socioeconomic scenarios. There is a need to determine the current global prevalence of HTLV-1 and examine its association with countries' human development index (HDI) to provide data for global health policy. Systematic review with meta-analysis is according to PRISMA 2020 recommendations. It was registered at PROSPERO, CRD42021223146. Prevalence or cross-sectional studies of HTLV-1 infection with at least 100 participants, screening, and confirmatory serologic testing were included. Studies with incomplete or unavailable results or with duplicate information were excluded. Data were selected by two independent investigators and analyzed using R software, a metapackage that generated the forest plots [95% confidence interval (CI)]. Heterogeneity was assessed using the I2 statistic, and funnel plot asymmetry was assessed using Egger's test. Countries were compared using an HDI cutoff ≥0.8. Methodological quality was assessed using Joanna Briggs Institute (JBI) criteria. The overall prevalence of HTLV-1 infection was 0.91% (95% CI: 0.80-1.02, p < .0001) and was higher in low HDI countries [1.18% (95% CI: 1.03-1.34)] than in high HDI countries [0.41% (95% CI: 0.27-0.57)]. Prevalence varied according to the populations studied: it was higher in the general population [1.65% (95% CI: 1.08-2.34)] compared to pregnant women [0.34% (95% CI: 0.17-0.57)] and blood donors [0.04% (95% CI: 0.01-0.08)]. Consistently, prevalence for each population group was higher in low HDI countries than in high HDI countries. The worldwide prevalence of HTLV-1 infection is highly heterogeneous, with a global prevalence of 0.91%. In high HDI countries, the observed prevalence is approximately three times lower than in low HDI countries. In the general population, the observed prevalence is about 5 times higher than in pregnant women and 41 times higher than in blood donors.

Safety of intraocular anti-VEGF antibody treatment under in vitro HTLV-1 infection.

HTLV-1 (human T-cell lymphotropic virus type 1) is a retrovirus that infects approximately 20 million people worldwide. Many diseases are caused by this virus, including HTLV-1-associated myelopathy, adult T-cell leukemia, and HTLV-1 uveitis. Intraocular anti-vascular endothelial growth factor (VEGF) antibody injection has been widely used in ophthalmology, and it is reportedly effective against age-related macular degeneration, complications of diabetic retinopathy, and retinal vein occlusions. HTLV-1 mimics VEGF165, the predominant isoform of VEGF, to recruit neuropilin-1 and heparan sulfate proteoglycans. VEGF165 is also a selective competitor of HTLV-1 entry. Here, we investigated the effects of an anti-VEGF antibody on ocular status under conditions of HTLV-1 infection in vitro. We used MT2 and TL-Om1 cells as HTLV-1-infected cells and Jurkat cells as controls. Primary human retinal pigment epithelial cells (HRPEpiCs) and ARPE19 HRPEpiCs were used as ocular cells; MT2/TL-Om1/Jurkat cells and HRPEpiCs/ARPE19 cells were co-cultured to simulate the intraocular environment of HTLV-1-infected patients. Aflibercept was administered as an anti-VEGF antibody. To avoid possible T-cell adhesion, we lethally irradiated MT2/TL-Om1/Jurkat cells prior to the experiments. Anti-VEGF antibody treatment had no effect on activated NF-κB production, inflammatory cytokines, chemokines, HTLV-1 proviral load (PVL), or cell counts in the retinal pigment epithelium (RPE) under MT2 co-culture conditions. Under TL-Om1 co-culture conditions, anti-VEGF antibody treatment did not affect the production of activated NF-κB, chemokines, PVL, or cell counts, but production of the inflammatory cytokine IL-6 was increased. In addition, anti-VEGF treatment did not affect PVL in HTLV-1-infected T cells. This preliminary in vitro assessment indicates that intraocular anti-VEGF antibody treatment for HTLV-1 infection does not exacerbate HTLV-1-related inflammation and thus may be safe for use.

Seroprevalence of maternal peripartum human T-cell lymphotropic virus type-1 infection: a systematic review and meta-analysis of the Nigerian literature.

The peripartum period is both a highly vulnerable stage and a significant indicator of a population's health status. Interest is increasing in human T-cell lymphotropic virus type-1 (HTLV-1) transmission due to its adverse health impacts. However, nationally representative data on HTLV-1 that are important for health planning are unavailable for this subpopulation. This study aimed to conduct a pooled estimate of HTLV-1 prevalence among pregnant women in Nigeria to quantify its clinical burden and public health implications. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 statement. After a systematic review of the Nigerian literature, 12 studies (2,821 pregnant or postnatal women) were included in the final evidence synthesis. The estimated HTLV-1 prevalence in Nigerian peripartum women following a positive screening test by enzyme-linked immunosorbent assay was 5.44% (95% confidence interval [CI], 3.16%-9.20%). A subgroup analysis of the 2 major regions showed a slightly higher prevalence in the Western versus Southern region (5.55% [95% CI, 2.49%-11.87%]; and 4.91% [95% CI, 2.11%-11.02%]; P=0.84). However, a subgroup analysis by geopolitical zone revealed that Southwestern and Northwestern Nigeria had the highest prevalence (9.23% [95% CI, 4.35%-18.55%; I2=93%] and 7.15% [95% CI, 1.54%-27.54%]; I2=92%). Our decade-old subgroup analysis found inconsistencies in the HTLV-1 prevalence. Furthermore, our literature review revealed a prevalence of HTLV infection among patients with various clinical types of lymphomas/leukemias and myelopathy of 2%-22%. These findings have important implications in defining the epidemiological patterns of HTLV-1 infection in Nigeria. They also suggest the presence of HTLV-endemic clusters near low-endemic areas, even within the same geopolitical zones.

Assess the Knowledge of Medical Students About HTLV-1 in Mashhad University of Medical Science

Introduction: Human T-cell lymphotropic virus type 1 (HTLV-1) is known to be endemic in the population of northeastern Iran. This study was conducted with the aim of investigating the knowledge and attitude of medical students of Mashhad University of Medical Sciences about the HTLV-1 virus.Material and Methods: The present study was a descriptive-analytical study that was conducted in Mashhad Medical School from April to June 2014. The research population included all medical students studying at the time of the study (307 people). The tool of data collection was a questionnaire including 4 parts of demographic characteristics, the amount of information resources used, the level of awareness about HTLV-1 infection and measuring the attitude of students towards HTLV-1 infection. The data was analyzed in the form of descriptive statistics using SPSS 16.0 software.Results: A total of 271 people responded to the questionnaire (response rate: 88/27). Among the participants, 130 were male and 141 were female. The majority of students, 161 people got their information from the classroom and 157 people were natives of Mashhad. The information obtained from the description of the questions and the percentage of correct answers to the questions showed that the level of students' knowledge about this infection was average with an average score of 16.66 out of 40 points, and the average score of the students' attitude was reported as 68.11 with an average level.Conclusion: The obtained results reported the level of knowledge of the target group as medium-low, and the level of attitude of this group as medium-high. Also, there was a direct relationship between the amount of information and the level of attitude with the year of entering the university and studying in the university, which reports the slope of this change as low.

Clinical Characteristics and Outcomes of Infection with Human T-Cell Lymphotropic Virus (HTLV) in a Non-Endemic Area: A Single Institution Study

Introduction: The first human oncogenic retrovirus discovered, human T cell lymphotropic virus (HTLV) remains poorly understood. Etiologically associated with adult T-cell leukemia (ATL), HTLV type 1 (HTLV-1) causes lifelong latent infection in CD4+ T cells and is estimated to affect between 5 to 20 million individuals globally. Despite being closely related, HTLV-2 infection has not been casually linked to clinical disease. In recent years, there has been an increased incidence of HTLV in the United States, however, affected patients are often under- and mis-diagnosed. While great strides have been made in understanding the virology, epidemiology, and clinical course of HTLV-1 and HTLV-2 infection, much of our current knowledge of HTLV and HTLV-related diseases is based on research in endemic areas, particularly Japan. We sought to characterize the epidemiology, clinical features, comorbidities, and survival of HTLV-1- or HTLV-2-positive individuals identified in a non-endemic area, using patient information from our academic institution. Methods: Our study was a single institution, retrospective case-control analysis of HTLV-1 or HTLV-2 patients between 1998 and 2020. We utilized two HTLV-negative controls, matched for age, sex, and race, for each one HTLV-positive case. Hematologic, neurologic, and rheumatologic covariates, including viral co-infection, opportunistic illnesses, malignancy, and clinical characteristics, were evaluated as variables affecting overall survival (OS). Results: We identified 38 cases of HTLV infection, of whom 23 were HTLV-1 and 15 were HTLV-2 positive. Median follow up was 39.7 months and median OS was 67.2 months for HTLV-seropositive patients, compared to 49.6 months and 131.2 months, respectively, for HTLV-seronegative patients. HTLV-1 positive patients had lower median OS compared to HTLV-2 patients (47.7 months vs. 77.36 months). During follow-up, 21 of 38 HTLV-seropositive patients died, compared to 33 of 76 HTLV-seronegative patients who died. Underlying reasons for HTLV testing were grouped into eight mutually exclusive categories: transplant evaluation, neurologic deficit(s), hematologic disorder, dermatologic, gastrointestinal, lymphadenopathy, infection, and other/unknown. Notably, the majority (53.9%) of patients in our control group received HTLV testing for transplant evaluation testing, compared to 23.7% of HTLV-seropositive patients. In evaluation of co-morbidities associated with HTLV, hepatitis C seropositivity was higher in HTLV-seropositive patients compared to controls (OR 16.8, 95% CI = 3.4 - 81.8, p < 0.001). There were no cases of HIV infection in our study. In Kaplan Meier analysis, hepatitis C and HTLV co-infection resulted in decreased 1-year and 3-year OS, compared to no infection, hepatitis C infection alone, or HTLV infection alone (Figure 1). Similarly, patients with any cancer diagnosis and HTLV infection had worse 1-year OS compared to patients with cancer or HTLV alone. There was no significance in 1-year OS with other risk factors, including CMV/HTLV co-infection or blood stream bacterial/HTLV co-infection. In univariate analysis, the hazard for 1-year all-cause mortality was increased among patients with HTLV-seropositivity (unadjusted HR 3.4, 95% CI 1.4- 8.2, P = 0.006), ATL (unadjusted HR 4.8, 95% CI 1.8 - 13.3, P = 0.08), AML (unadjusted HR 4.3, 95% CI 1.6-11.9, P = 0.01), and hepatitis C infection (unadjusted HR 3.2, 95% CI 1.2-8.5, P = 0.03) (Table 1). When corrected, multivariate analysis showed that HTLV seropositivity was no longer associated with 1-year all-cause mortality; however association with AML (adjusted HR 10.0, 95% CI 2.8-35.2, P = 0.0003) and hepatitis C infection (adjusted HR 7.0, 95% CI 1.5 - 32.0, P = 0.01) remained significant. Conclusions: HTLV-seropositivity was not associated with increased 1-year mortality in multivariate analysis. Our study is limited by our small patient sample size, as well as the biased patient control population due to HTLV testing. These studies warrant continued evaluation of clinical characteristics and outcomes of HTLV infection in non-endemic regions. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Integrative and Multidisciplinary Care for People Living With Human T-Cell Lymphotropic Virus in Bahia, Brazil: 20 Years of Experience.

Brazil is home to the highest absolute number of human T-cell lymphotropic virus type-1 (HTLV-1)-infected individuals worldwide; the city of Salvador, Bahia, has the highest prevalence of HTLV-1 infection in Brazil. Due to the complex nature of several diseases associated with this retrovirus, a multidisciplinary health care approach is necessary to care for people living with HTLV-1. The Bahia School of Medicine and Public Health’s Integrative Multidisciplinary HTLV Center (CHTLV) has been providing support to people living with HTLV and their families since 2002, striving to ensure physical and mental well-being by addressing biopsychosocial aspects, providing clinical care and follow-up, including to pregnant/postpartum women, as well as comprehensive laboratory diagnostics, psychological therapy, and counseling to family members. To date, CHTLV has served a total of 2,169 HTLV-infected patients. The average patient age is 49.8 (SD 15.9) years, 70.3% are female, most are considered low-income and have low levels of education. The majority (98.9%) are HTLV-1 cases, and approximately 10% have been diagnosed with tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM), while 2.2% have infective dermatitis and 1.1% have adult T-cell lymphoma. In all, 178 pregnant/postpartum women [mean age: 32.7 (±6.5) years] have received care at CHTLV. Regarding vertical transmission, 53% of breastfed infants screened for HTLV tested positive in their second year of life, nearly 18 times the rate found in non-breastfed infants. This article documents 20 years of experience in implementing an integrative and multidisciplinary care center for people living with HTLV in Bahia, Brazil. Still, significant challenges remain regarding infection control, and HTLV-infected individuals continue to struggle with the obtainment of equitable and efficient healthcare.

Clinical course of HTLV-1 infection associated intermediate uveitis

ObjectiveTo describe the clinical features at presentation, delivered treatment and follow-up of a case series of human T-cell lymphotropic virus type 1 (HTLV-1) associated intermediate uveitis. Patients and methodsRetrospective, descriptive and longitudinal study of patients with HTLV-1 associated intermediate uveitis treated at a reference ophthalmology facility in Lima, Peru, during the years 2012 to 2018. ResultsA total of 18 patients (28 eyes) were included, the average age at presentation was 57.3 years, 66.6% were women, and the average follow-up time was 1,280 days. The most frequent symptoms were blurred or diminished vision (78.6%) and floaters (57.1%). Best corrected visual acuity was 20/40 or better in 53.6%. The mean initial intraocular pressure was 14.95 mmHg. Keratic precipitates were observed in 50% of eyes, 17.9% were of the stellate type. The most frequent treatment was periocular corticosteroid injections (53.6%). Complications such as epimacular membrane (50%), cataract (21.4%) and glaucoma (7.1%) occurred. At the end of follow-up, only 2 eyes lost one line of vision; the final best corrected visual acuity was 20/40 or better in 85.7%, and 20/70 or better in 96.4%. Patients with both eyes affected increased from 33% at presentation to 55.5%. The course of the disease was chronic in 60.7%. ConclusionHTLV-1 associated intermediate uveitis mainly occurred in patients in the second half of life, developing a chronic course and with good visual prognosis.

Cabotegravir, the Long-Acting Integrase Strand Transfer Inhibitor, Potently Inhibits Human T-Cell Lymphotropic Virus Type 1 Transmission in vitro.

Human T-cell lymphotropic virus type 1 (HTLV-1) is a deltaretrovirus most prevalent in southwestern Japan, sub-Saharan Africa, Australia, South America, and the Caribbean. Latest figures approximate 10 million people worldwide to be infected with HTLV-1. This is likely a significant underestimation due to lack of screening in endemic areas and absence of seroconversion symptoms. The two primary diseases associated with HTLV-1 infection are adult T cell leukaemia-lymphoma, a malignant and, sometimes, aggressive cancer; and HTLV-1 associated myelopathy/tropical spastic paraparesis, a debilitating neurological degenerative disease. Unfortunately, despite the poor prognosis, there is currently no effective treatment for HTLV-1 infection. We previously showed that integrase strand transfer inhibitors (INSTIs) clinically used for human immunodeficiency virus type 1 (HIV-1) prophylaxis and treatment are also effective against HTLV-1 transmission in vitro. In 2021 a new INSTI, cabotegravir, was approved by the FDA for HIV-1 treatment. We thus set out to evaluate its efficacy against HTLV-1 infection in vitro. Strand transfer assays performed using recombinant HTLV-1 integrase treated with increasing concentrations of cabotegravir, effectively inhibited strand transfer activity, displaying an IC50 of 77.8 ± 22.4 nM. Furthermore, cabotegravir blocked HTLV-1 transmission in tissue culture; we determined an EC50 of 0.56 ± 0.26 nM, similar to bictegravir. Alu-PCR confirmed the block in integration. Thus, there are four INSTIs and one reverse transcriptase inhibitor approved by the FDA for HIV-1 treatment, that potently block HTLV-1 infection in vitro. This should strongly encourage the establishment of a new standard of HTLV-1 treatment – particularly for pre-exposure prophylaxis and prevention of mother-to-child transmission.

Evaluation of antioxidant status and oxidative stress markers in HTLV-1 infected individuals: correlation with the severity of virus-induced complications.

Introduction. Human T-cell lymphotropic virus type 1 (HTLV-1), a well-known member of the retroviridae family, potentially causes serious outcomes including adult T-cell leukaemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM-TSP). Oxidative stress plays a key role in progression and clinical exacerbation of several chronic infections. We have previously shown a reduction in serum total antioxidant capacity (TAC) during HTLV-1 infection and this study was set out to investigate the reasons for TAC reduction.Hypothesis/Gap Statement. Oxidant/antioxidant imbalance during HTLV-1 infection may result from disruptions in oxidant levels or antioxidant defence system.Aim. This study aimed to analyse the key enzymes and oxidant molecules playing important roles in virus-induced oxidative stress.Methodology. We measured serum activities of the major antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) as well as serum concentrations of the main oxidant markers: nitric oxide (NO) and malondialdehyde (MDA). Totally 40 HTLV-1 infected patients and 40 healthy controls were enrolled in this study. The patient group consisted of chronic carriers and patients with HAM-TSP (N=20).Results. The current study found that serum levels of MDA and NO were significantly higher in patient groups particularly in HAM-TSP patients (P<0.05). In addition, a reductive trend was observed in the serum activities of CAT, SOD, and GPX in HTLV-1 infected patients compared with healthy controls (P<0.05).Conclusion. Reduced activities of CAT, SOD, and GPX antioxidant enzymes along with the observed elevated concentrations of oxidant molecules may contribute to oxidative stress and worse outcomes during HTLV-1 infection.

Possible deterioration of Apolipoproteins expression by HTLV-1 infection in favor of infected leukemic cells in adult T-cell leukemia/lymphoma (ATLL)

BackgroundIt has been suggested that human T-cell lymphotropic virus type 1 (HTLV-1) infection can affect the lipid profile. Therefore, in this study, the main apolipoproteins and HTLV-1 regulatory factors were assessed in infected subjects. Methods and resultsA cross-sectional study was performed on 12 adult T-cell leukemia/lymphoma (ATLL) and 10 HAM/TSP patients, and 10 HTLV-1 asymptomatic carriers (ACs). The peripheral blood mononuclear cells (PBMCs) were assessed for proviral load (PVL) measurement and the expression of HBZ, ABCA, APOA, and APOE, using the qRT-PCR, Taqman method.The ABCA1 expression level in the ATLL group was significantly higher than ACs and HAM/TSP, (P = 0.034 and P = 0.019, respectively). The APOA1 expression, in ATLL (0.89 ± 0.30) and HAM/TSP patients (0.31 ± 0.25), was lower than HTLV-1 ACs (1.15 ± 0.63); but not significant. The APOE expression in the ACs' group (22.66 ± 7.88) was strongly higher than ATLL (0.003 ± 0.0004) and HAM/TSP (1.81 ± 0.60) subjects (P = 0.007 and P = 0.012, respectively); ATLL and HAM/TSP groups had no significant differences (P = 0.957). All of the ATLL patients expressed HBZ, but not Tax, on the other hand more than 70% of HAM/TSPs and ACs expressed Tax but only one AC and one HAM/TSP patient expressed HBZ. The PVL median in ATLL patients was higher (2983.87 ± 1797.07copies/104PBMCs), than ACs (17.00 ± 10.00copies/104) (P = 0.016), and HAM/TSP (314.00 ± 185.00) (P = 0.05). ConclusionsThe HBZ probably altering the expression of ABCA1 and APOE, which particularly, can deteriorate the lipid profile in ATLL patients. The importance of APOE in healthy condition and its negative correlation with PVL in ATLL patients could be a novel target in therapy.

Genome analysis suggests HTLV-1aA introduction in Chile related to migrations of ancestral indigenous populations

The human T cell lymphotropic virus type 1 (HTLV-1), unlike other RNA viruses such as HIV, has a stable genome and has infected humans since remote times. Although the HTLV-1 infection is endemic in South America, there is scarce information about HTLV-1 in Chile and its history of introduction. This study assessed the genomic content of HTLV-1 from Chile and its relationship with HTLV-1 lineages circulating worldwide by phylogenetic reconstruction and dating analyses. A total of 30 HTLV-1 genomes collected from the four continents were used to conduct dating analyses, including the first HTLV-1 genome from Amerindian/Mapuche ethnicity. Estimation was performed using a Bayesian Markov Chain Monte Carlo coalescent-based approach as implemented in the BEAST program. The time of the most recent ancestor of HTLV-1 from Chile was ∼1409 years ago, which coincides with the period of Amerindian population expansion across South America. Our results suggest HTLV-1aA was possibly introduced in Chile during the migrations of the ancestral indigenous populations.