The importance of confirmatory assays in testing blood donors for human T-cell lymphotropic virus.

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.

O conhecimento dos profissionais da Atenção Básica em Saúde sobre o Vírus T-linfotrópico Humano / The knowledge of Primary Health Care professionals about the Human T-lymphotropic virus / El conocimiento de los profesionales de la Atención Primaria de Salud sobre el virus linfotrópico T humano

Objetivo: investigar o conhecimento de profissionais de saúde presentes em unidades básicas de saúde (UBS's) sobre o HTLV e as condutas tomadas em caso de infecção. Método:pesquisa quantitativa transversal de abordagem exploratória, sendo realizada por meio de entrevista, com preenchimento de formulário via Google Forms. Realizada em julho de 2023. Resultados:estudo composto por 33 profissionais de saúde, dentre os quais 39% afirmaram desconhecer o HTLV. Essa informação é preocupante, considerando que uma unidade de saúde representa a principal porta de entrada paraos indivíduos em busca de atendimento à saúde. A maioria expressiva, representando 70%, demonstrou conhecimento sobre os meios de prevenção da doença. Porém, a vacinação não foi identificada pela maioria como um método de prevenção, destacando uma percepção menos difundida sobre o papel da vacina nesse contexto. Conclusão:é crucial divulgar pesquisas sobre o tema, criando oportunidades estratégicas para aprimorar tanto a compreensão clínica quanto a empatia no atendimento aos portadores do HTLV, contribuindo assim para a melhoria do diagnóstico, tratamento e qualidade assistencia

Objective:To investigate the knowledge of health professionals present in primary health care units (BHUs) about HTLV and the procedures taken in case of infection. Method:cross-sectional quantitative research with an exploratory approach, carried out through interviews, filling out a form via Google Forms. Carried out in July 2023. Results:study composed of 33 health professionals, of which 39% said they were unaware of HTLV. This information is worrying, considering that a health unit represents the main gateway for individuals seeking health care. The significant majority, representing 70%, demonstrated knowledge about the means of preventing the disease. However, vaccination was not identified by the majority as a prevention method, highlighting a less widespread perception about the role of the vaccine in this context. Conclusion:it is crucial to disseminate research on the topic, creating strategic opportunities to improve both clinical understanding and empathy in the care of HTLV carriers, thus contributing to the improvement of diagnosis, treatment and quality of care.

Objective:To investigate the knowledge of health professionals present in primary health care units (BHUs) about HTLV and the procedures taken in case of infection. Method:cross-sectional quantitative research with an exploratory approach, carried out through interviews, filling out a form via Google Forms. Carried out in July 2023. Results:study composed of 33 health professionals, of which 39% said they were unaware of HTLV. This information is worrying, considering that a health unit represents the main gateway for individuals seeking health care. The significant majority, representing 70%, demonstrated knowledge about the means of preventing the disease. However, vaccination was not identified by the majority as a prevention method, highlighting a less widespread perception about the role of the vaccine in this context. Conclusion:it is crucial to disseminate research on the topic, creating strategic opportunities to improve both clinical understanding and empathy in the care of HTLV carriers, thus contributing to the improvement of diagnosis, treatment and quality of care.

Sex, Age, and Risk Group Variations among Individuals Infected with HIV, HTLV-1, and HTLV-2: Review of Data Records (1983­2017) from a Public Health Laboratory in São Paulo, Brazil

The inaugural AIDS Program in Brazil was established in São Paulo in 1983, with the Instituto Adolfo Lutz appointed for laboratory assistance. Subsequently, research on HIV infections and HIV/HTLV (HIV/HTLV-1 and HIV/HTLV-2) co-infections was conducted. This narrative review focuses on studies from the Immunology Department (1983­2017) that significantly influenced AIDS diagnosis or provided epidemiological data such as prevalence rates, sex, age, and risk factors. Twelve studies, encompassing over 8000 individuals, are discussed. During 1983­1985, nearly all AIDS cases were attributed to homosexual/bisexual men aged 31 years old. Subsequently, heterosexual men and women emerged as risk groups owing to intravenous drug use (IDU) and/or unprotected sexual intercourse with AIDS patients or multiple partners per year. From 1985 onwards, vertical transmission led to child infections. HIV/HTLV co-infection rates decreased over time, initially associated with male IDU, and in the 2010s with female IDU, and individuals aged >40 years. Trends in HIV and HIV/HTLV co-infections among younger men and women (<30 years of age) were observed from 2015 to 2017. The changing characteristics and risk groups for HIV and HIV/HTLV co-infections over the years underscore the necessity for ongoing public policies to prevent retrovirus transmission, particularly among adolescents and young adults. (AU)

Human T-lymphotropic virus 1/2 infection among immigrants and refugees in Central Brazil, an emerging vulnerable population.

Introduction: Migratory flows play a significant role in the spread of human T-lymphotropic virus 1/2 (HTLV-1/2). In the last decade, a substantial migration of individuals occurred from Haiti and Venezuela to Brazil. However, data on the prevalence of HTLV-1/2 infection among these international migrants in Brazil are scarce. This study describes the prevalence of this infection among immigrants and refugees in Central Brazil. Methods: A cross-sectional study was conducted with 537 international migrants in the State of Goiás, Central Brazil. Participants were interviewed, and blood samples were collected. Serological screening for anti-HTLV-1/2 was performed using an enzyme-linked immunosorbent assay (ELISA; Murex HTLV-I + II, DiaSorin, Dartford, UK), and seropositive samples were submitted for confirmation by a line immunoassay (INNO-LIA HTLV I/II, Fujirebio, Europe N.V., Belgium). Results: The majority of participants were males (54.4%), between 18 and 50 years old (78%; mean age: 29.1 years), self-declared black (55.1%), reported 1 to 12 years of formal education (70.9%), and were either Venezuelans (47.9%) or Haitians (39.7%). Additionally, 50.1% were immigrants, 49% were refugees, and five were Brazilian children (0.9%) born to Haitian immigrant parents. The overall prevalence of anti-HTLV-1/2 was 0.95% (95% CI: 0.31-2.28), with HTLV-1 at 0.19% and HTLV-2 at 0.76%. All seropositive individuals (n = 5) were refugees from Venezuela, resulting in a rate of 2.26% for anti-HTLV-1/2, HTLV-1 (0.45%) and HTLV-2 (1.81%) among Venezuelan refugees. Of the demographic and behavioral characteristics evaluated, unprotected sexual intercourse and having more than one sexual partner (≥2) in the previous 12 months were associated with HTLV-1/2 seropositivity among Venezuelans. Conclusion: This study revealed, despite the low seroprevalence of HTLV-1/2 among international migrants in Central Brazil, evidence of HTLV-1 and HTLV-2 infections in Venezuelan refugees. In addition, their characteristics highlight that specific social and health programs should be implemented for these emergent and socially vulnerable migrant groups.

Human T-lymphotropic virus 2 (HTLV-2) prevalence of blood donors in the state of Pará, Brazil.

INTRODUCTION: The present study had the objective to describe the molecular prevalence and epidemiological aspects of the human T-lymphotropic virus 2 (HTLV-2) infection in the blood donor population of the Pará state. METHODS: The present study is a descriptive, retrospective, and cross-sectional review of epidemiological, serological, and molecular data on inapt blood donors in the State Center for Hematology and Hemotherapy from January 2015 to December 2021. The data were digitalized to create a database using the Statistical Package for Social Sciences program. The prevalence of HTLV-2 was calculated based on the total number of donations during the study period. Descriptive frequency was used to analyze the qualitative data. RESULTS: A total of 665,568 blood donations were made. Out of these, 1884 (0.2%) samples presented serological detection to HTLV and further were evaluated using molecular confirmatory tests. Out of these, 36 samples were positive for HTLV-2 using qPCR Taqman assay based on pol gene region (0.005%). The HTLV-2 was found to be more prevalent in women (63.9%); aged between 39 and 59 years (55.6%); residents of the metropolitan region of Belém (80.6%); with self-declared race as brown (80.6%); individuals who had completed high school (58.6%); and first-time donors (58.3%) CONCLUSION: The present study identified the presence of HTLV-2 (1 HTLV-2 case/20,000 donations; 0.005%) in the specific population of blood donors in Pará state. These findings can contribute to the existing literature on the subject both for specific population groups under study and for understanding the prevalence of HTLV-2 in the general population.

Evaluation of human T-cell leukemia virus in vitro diagnostics using plasma specimens collected in Japan.

BACKGROUND: In vitro diagnostics (IVDs) for primary detection test/screening of human T-cell leukemia virus (HTLV) have recently been updated to new-generation products in Japan. In this study, the performance of these products was evaluated and discussed in terms of the usability of HTLV diagnosis in Japan. METHODS: The performance of 10 HTLV IVDs for primary detection test and confirmatory/discriminatory test was evaluated. Plasma specimens that had been declared ineligible for transfusion were provided by the Japanese Red Cross Blood Center. RESULTS: The diagnostic specificity of the IVDs was 100% (160/160). Six sandwich assays resulted in all HTLV-1/HTLV-positive specimens being positive (46/46). On the other hand, one sandwich assay, IVD under development 2 (UD2), resulted in one HTLV-1-positive and one HTLV-positive specimen being negative (44/46, 95.7%). One indirect assay, HISCL HTLV-1, could not detect one HTLV-positive specimen (45/46, 97.8%), but the updated product, UD1, correctly detected it (46/46, 100%). Serodia HTLV-I, based on a particle agglutination assay, resulted in 44 of the 46 positive specimens, but could not detect two specimens (44/46, 95.7%). ESPLINE HTLV-I/II, based on an immunochromatography assay (ICA), was able to diagnose all specimens as positive (46/46, 100%). CONCLUSIONS: Six sandwich assays and an ICA demonstrated high diagnostic sensitivity and specificity and are recommended for use in HTLV diagnosis in conjunction with confirmatory/discriminatory test using the INNO-LIA HTLV-I/II Score.

Novel Zn(II)-complex with hybrid chalcone-thiosemicarbazone ligand: Synthesis, characterization, and inhibitory effect on HTLV-1-infected MT-2 leukemia cells.

Chalcone and thiosemicarbazone have attracted attention due to their easy synthetic procedure and high success in the development of antiviral and antitumor, however, there are few biological data on the evaluation of chalcone-thiosemicarbazone hybrids and their complexation with metal ions. In this sense, the present work reports the synthesis and characterization of the hybrid (Z)-2-((E)-3-(4-chlorophenyl)-1-phenylallylidene)hydrazine-1-carbothioamide (CTCl) and its Zn(II)-complex (CTCl-Zn). The compounds were cell-based evaluated in terms of cytotoxicity against human T-cell lymphotropic virus type 1 (HTLV-1) infected leukemia cells (MT-2) and the experimental data were correlated with molecular docking calculations. The ligand and Zn(II)-complex were easily synthesized with a good yield - 57% and 79%, respectively. The dynamic of E/Z isomers with respect to the imine bond configuration of CTCl was evidenced by 1H NMR experiments in DMSO­d6, while the X-ray diffraction of CTCl-Zn showed that Zn(II) ion is tetracoordinated to two ligands in a bidentate mode and the metal ion lies on an intermediate geometry between the see-saw and trigonal pyramid. The ligand and complex exhibited low toxicity and the Zn(II)-complex is more cytotoxic than the ligand, with the corresponding IC50 value of 30.01 and 47.06 µM. Both compounds had a pro-apoptotic effect without the release of reactive oxygen species (ROS) and they can interact with DNA via minor grooves driven by van der Waals forces.

Comparison of two new HTLV-I/II screening methods, Abbott Alinity i rHTLV-I/II and Diasorin LIAISON® XL murex recHTLV-I/II, to Abbott architect rHTLVI/II assay.

BACKGROUND: Diagnosis of Human T-cell Lymphotropic Virus (HTLV) types I and II infection requires sequencial testing with firstly a screening using an Enzyme immunoassay followed by a confirmatory test. OBJECTIVES: To compare the performances of the Alinity i rHTLV-I/II (Abbott®) and LIAISON® XL murex recHTLV-I/II serological screening tests to the ARCHITECT rHTLVI/II test followed if positive by HTLV BLOT 2.4, MP Diagnostics as the reference. STUDY DESIGN: 119 serum samples from 92 known HTLV-I infected patients and 184 from uninfected patients with HTLV were analyzed in parallel with, Alinity i rHTLV-I/II, LIAISON® XL murex recHTLV-I/II and ARCHITECT rHTLVI/II. RESULTS: Alinity i rHTLV-I/II and LIAISON® XL murex recHTLV-I/II exhibited a total agreement with ARCHITECT rHTLVI/II for both positive and negative samples. Both tests are suitable alternatives for HTLV screening.

The slowdown of new infections by human retroviruses has reached a plateau in Spain.

The 2022 annual meeting of the HTLV & HIV-2 Spanish Network was held in Madrid on December 14. We summarize here the main information presented and discussed at the workshop and review time trends for human retroviral infections in Spain. As transmissible agents, infections by human retroviruses are of obligatory declaration. Until the end of 2022, the Spanish national registry had recorded 451 cases of HTLV-1, 821 of HTLV-2, and 416 of HIV-2. For HIV-1, estimates are of 150 000 people currently living with HIV-1 and 60 000 cumulative deaths due to AIDS. During year 2022, new diagnoses in Spain were of 22 for HTLV-1, 6 for HTLV-2, and 7 for HIV-2. The last updated figures for HIV-1 are from 2021 and counted 2786 new diagnoses. The slowdown in yearly infections for HIV-1 in Spain points out that new strategies are needed to achieve the United Nations 95-95-95 targets by 2025. For the remaining neglected human retroviral infections, their control might be pushed throughout four interventions: (1) expanding testing; (2) improving education and interventions aimed to reduce risk behaviors; (3) facilitating access to antiretrovirals as treatment and prevention, including further development of long-acting formulations; and (4) increasing vaccine research efforts. Spain is a 47 million population country in South Europe with strong migration flows from HTLV-1 endemic regions in Latin America and Sub-Saharan Africa. At this time universal HTLV screening has been implemented only in the transplantation setting, following the report of 5 cases of HTLV-associated myelopathy shortly after transplantation of organs from HTLV-1 positive donors. There are four target populations for expanding testing and unveiling asymptomatic carriers responsible for silent HTLV-1 transmissions: (1) migrants; (2) individuals with sexually transmitted infections; (3) pregnant women; and (4) blood donors.

Trend in seroprevalence of HTLV-1/2 in Taiwanese blood donors-A 10-year follow-up.

OBJECTIVES: This study evaluated the Human T-lymphotropic virus (HTLV) screening policy impact on the HTLV seroprevalence from 2009 to 2018 as well as the differences between administrative districts in terms of prevalence distribution in Taiwan. BACKGROUND: Since February 1996, the Taiwan Blood Services Foundation (TBSF) had conducted HTLV screening of blood donors. The HTLV seroprevalence was 0.032% in 1999. MATERIALS AND METHODS: This cross-sectional study included donors' data collected from blood donation centres across Taiwan from 2009 to 2018. Enzyme immunoassay and Western blot assay were used for screening and confirmation of HTLV infections. In this study, the researchers calculated the trends in the HTLV rates of first-time and repeat donors across time as well as the HTLV prevalence distribution across the 22 administrative districts of Taiwan. RESULTS: Amongst 17 977 429 employed blood donations, 739 HTLV-seropositive donations (4.11 per 100 000 donations) were identified. The HTLV-positive donors were aged between 17 and 64 years, with a median age of 49 years. The overall seropositivity rates of first-time and repeat donors were 34.36/100 000 and 1.27/100 000. HTLV seroprevalence in first-time blood donors significantly decreased by 57% (crude odds ratio [95% confidence interval] (crude OR [95% CI]) = 0.43 [0.28-0.64]) within 10 years. A slight decline was also identified in repeat donors (crude OR [95% CI] = 0.73 [0.4-1.32]). Donors from different districts showed significantly varied prevalence. Most districts with high prevalence are situated in eastern Taiwan, for both donation types. Older blood donors were more likely to be infected with HTLV than younger ones in first time and repeat donors. Middle age donors (50-65 years) had an 18.47-39.65 greater risk than those aged <20 years. Significant higher risk of female was observed in both donation types. Amongst different age groups, first-time female donors increase 1.31-1.88 times infection risk and female in repeat donor group had 1.55-3.43 times greater risk. CONCLUSION: Over years of implementation of the HTLV blood donor screening policy by the TBSF, the HTLV seroprevalence of first-time donors has decreased consistently. Moreover, the HTLV seroprevalence of repeat donors has dropped considerably. This implies that the screening policy provides continued benefit. Females and older blood donors were more likely infected with HTLV than males and younger blood donors. The influence of age on infection was greater amongst first-time donors than amongst repeat donors. Therefore, appropriate measures should be taken to ensure public safety.

Concluding Remarks for Special Issue HTLV-HIV Co-Infections.

During the early 1980s, the first 3 human retroviruses were identified: human T-lymphotropic virus 1 and 2 (HTLV-1 and HTLV-2) and human immunodeficiency virus (HIV) [...].

Low risk of human T-lymphotropic virus infection in U.S. blood donors; Is it time to consider a one-time selective testing approach?

BACKGROUND: U.S. blood donors are tested at each donation for human T-lymphotropic virus (HTLV) antibodies. Depending on donor incidence and other mitigation/removal technologies, a strategy of one-time selective donor testing should be considered. METHODS: Antibody seroprevalence was calculated for HTLV-confirmed-positive American Red Cross allogeneic blood donors from 2008 to 2021. Incidence was estimated for seven 2-year time periods using confirmed-positive repeat donors having seroconverted in 730 days. Leukoreduction failure rates were obtained from internal data from July 1, 2008-June 30, 2021. Residual risks were calculated using a 51-day window period. RESULTS: Between 2008 and 2021, >75 million donations (>18 million donors) yielded 1550 HTLV seropositives. HTLV seroprevalence was 2.05 antibody-positives per 100,000 donations (0.77 HTLV-1, 1.03 HTLV-2, 0.24 HTLV-1/2), and 10.32 per 100,000 among >13.9 million first-time donors. Seroprevalence differed significantly by virus type, sex, age, race/ethnicity, donor status, and U.S. census region. Over 14 years and 24.8 million person-years of observation, 57 incident donors were identified (25 HTLV-1, 23 HTLV-2, and 9 HTLV-1/2). Incidence decreased from 0.30 (13 cases) in 2008-2009 to 0.25 (7 cases) in 2020-2021. Female donors accounted for most incident cases (47 vs. 10 males). In the last 2-year reporting period, the residual risk was 1 per 2.8 million donations and 1 per 3.3 billion donations when coupled with successful leukoreduction (0.085% failure rate). CONCLUSIONS: HTLV donation seroprevalence for the years 2008-2021 varied by virus type and donor characteristics. Low HTLV residual risk and use of leukoreduction processes support the conclusion that a selective one-time donor testing strategy should be considered.

Development and validation of a duplex real-time PCR for the rapid detection and quantitation of HTLV-1.

BACKGROUND: The HTLV-1 prevalence in China varies geographically, while HTLV-2 infection has rarely been found so far. Proviral load is one of the determining factors of pathogenesis and progression of HTLV-1 related diseases. However, neither molecular assays nor commercial kits are available for HTLV-1 diagnosis in China. The objective of the present study was to develop and validate a TaqMan qPCR assay for HTLV-1 proviral load quantification. RESULTS: A plasmid containing both the HTLV-1 of interest and a fragment of the RNase P (RPPH1) gene was constructed and used to establish the standard curves. The assay has a wide dynamic range (2.5 × 108 copies/reaction ~ 25 copies/reaction) and sensitive to 1 copy for HTLV-1 and RPPH1. The limit of detection for Hut102 cell concentration was 0.0218% (95% confidence interval 0.0179-0.0298%). The assay gave coefficient of variation (CV) for both the HTLV-1 and RPPH1 Ct values. All of the HTLV-1 sero-negative samples and MOT cell line (infected with HTLV-2) amplified only the RPPH1 gene by our method, presenting 100% specificity. 85 Samples confirmed positive or indeterminate by LIA were performed by established qPCR assay and WB. 90.0% (27/30) of LIA-HTLV-1-positive, 33% (2/6) of LIA-untypeable and 2% (1/49) of LIA-indeterminate samples were defined as qPCR-positive. The median PVL of LIA-positive samples (n = 27, 1.780 copies/100 cells) was much higher than that of LIA-untypeable and (n = 2, 0.271 copies/100 cells) indeterminate samples (n = 1, 0.017 copies/ 100 cells). Additionally, compared to WB, the duplex qPCR verified more positive samples, demonstrating a better sensitivity. CONCLUSION: The duplex qPCR developed here with high sensitivity, good specificity and reproducibility could accurately and quantitatively detect the HTLV-1 PVLs, which can be used to confirm the initial reactive samples for an improved cost/benefit ratio as well as to monitor the clinical progression and efficacy of therapy in patients with HTLV-1 related disease.

CCR5-∆32, CCR2-64I, SDF1-3'A, and IFNλ4 rs12979860 and rs8099917 gene polymorphisms in individuals with HIV-1, HIV/HTLV-1, and HIV/HTLV-2 in São Paulo, Brazil

Background. Chemokine and chemokine-receptor polymorphisms have been associated with protection against HIV infection and delayed progression to AIDS, whereas polymorphisms in IFNλ4 (formerly IL28B) have been associated with human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy (HAM) development. Evolutionary selection against ancestral genes differs among human populations, resulting in varying risks of acquiring and developing viral diseases. Methods. DNA samples from 434 patients infected with HIV-1 and/or co-infected with HTLV-1/-2, and samples from 74 HIV and HTLV non-infected individuals from São Paulo, Brazil, were divided into five groups: HIV-naïve, n=160; HIV-ART, n=180; HIV/HTLV-1, n=53; HIV/HTLV-2, n=41; and control, n=74. These samples were analyzed for CCR5-∆32deletion, CCR2-64I, SDF1-3'A, and IFNλ4 rs12979860 and rs8099917 single nucleotide polymorphisms using PCR and PCR-RFLP techniques. These polymorphisms' genotype and allele frequencies were calculated and compared among groups using logistic regression analysis. Results. All polymorphism profiles described in the literature were detected in this study. The wild-type genotype predominated in all genes analyzed except for IFNλ4 rs12979860. Statistical differences in allele frequencies among groups were detected in the CCR5 and CCR2 genes, with a high frequency of ∆32 in HIV-naïve vs. HIV-ART (OR 2.45, P=0.037) and a minus mutant allele A (CCR2-64I) in HIV-naïve vs. HIV/HTLV-1 (OR 1.90, P=0.048), HIV-ART vs. HIV/HTLV-1 (OR 2.62, P=0.003), and HIV/ART vs. HIV/HTLV-2 (OR 2.42, P=0.016). Conclusions. The polymorphism profiles detected in the study groups corroborate the profiles described in racial admixed populations. High CCR2-64I mutant allele frequencies were detected in HIV/HTLV-1/-2 co-infected individuals, and CCR5-∆32 showed predictive value for ART initiation. (AU)

HTLV-2 Enhances CD8+ T Cell-Mediated HIV-1 Inhibition and Reduces HIV-1 Integrated Proviral Load in People Living with HIV-1.

People living with HIV-1 and HTLV-2 concomitantly show slower CD4+ T cell depletion and AIDS progression, more frequency of the natural control of HIV-1, and lower mortality rates. A similar beneficial effect of this infection has been reported on HCV coinfection reducing transaminases, increasing the spontaneous clearance of HCV infection and delaying the development of hepatic fibrosis. Given the critical role of CD8+ T cells in controlling HIV-1 infection, we analysed the role of CD8+ T cell-mediated cytotoxic activity in coinfected individuals living with HIV-1. One hundred and twenty-eight individuals living with HIV-1 in four groups were studied: two groups with HTLV-2 infection, including individuals with HCV infection (N = 41) and with a sustained virological response (SVR) after HCV treatment (N = 25); and two groups without HTLV-2 infection, including individuals with HCV infection (N = 25) and with a sustained virological response after treatment (N = 37). We found that CD8+ T cell-mediated HIV-1 inhibition in vitro was higher in individuals with HTLV-2. This inhibition activity was associated with a higher frequency of effector memory CD8+ T cells, higher levels of granzyme A and granzyme B cytolytic enzymes, and perforin. Hence, cellular and soluble cytolytic factors may contribute to the lower HIV-1 pre-ART viral load and the HIV-1 proviral load during ART therapy associated with HTLV-2 infection. Herein, we confirmed and expanded previous findings on the role of HTLV-2 in the beneficial effect on the pathogenesis of HIV-1 in coinfected individuals.

HTLV infection in Brazil's second-largest indigenous reserve.

Human T-lymphotropic viruses 1 and 2 (HTLV-1/2) have a worldwide distribution. HTLV-1 has been associated with several diseases, including an aggressive malignant disease known as adult T-cell leukemia/lymphoma and a chronic inflammatory neurological disease called HTLV-1-associated myelopathy, while HTLV-2 has not been definitively associated with diseases. HTLV-2 is most prevalent in specific groups such as injecting drug users and the indigenous population. In Brazil, most studies about HTLV in indigenous are carried out in indigenous communities from the north of the country. Mato Grosso do Sul (MS), Central Brazil, has the second-largest indigenous population in Brazil. However, there is no available data about HTLV infection in this group. We conducted the first investigation of HTLV-1/2 infection prevalence in the indigenous population from Jaguapiru and Bororó villages in Dourados City, MS, to provide the prevalence and molecular characterization of HTLV. For that, a total of 1875 indigenous participated in the study. All the serum samples were screened by an enzyme-linked immunosorbent assay commercial kit for the presence of anti-HTLV-1/2 antibodies. Positive samples were confirmed by HTLV-1/2 Western Blot assay. The HTLV-1 5'LTR region was detected by nested PCR amplification and sequenced by Sanger. Most of the study population declared belonging to Guarani-Kaiowá ethnicity (69.18%), 872 (46.51%), and 1003 (53.49%) were from Jaguapiru and Bororó villages, respectively. The median age of participants was 31 years, and 74.24% were females. Two individuals were detected with HTLV-1 (0.1%; CI 95% 0.1-0.2). The phylogenetic analysis revealed that isolates belong to the Cosmopolitan subtype and the Transcontinental subgroup (HTLV-1aA). The low HTLV-1 prevalence found in this study is similar to that observed among blood donors, and pregnant populations from Mato Grosso do Sul. The absence of HTLV-2 infection among these Brazilian indigenous communities would suggest a distinct behavior pattern from other indigenous populations in Brazil.

Prevalence and Risk Factors for HTLV-1/2 Infection inRiverside and Rural Populations of the State of Pará.

Human T-lymphotropic viruses 1 and 2 (HTLV-1 and HTLV-2) infection has been described in several Amazonian populations; however, there is still a lack of data on the prevalence of the virus in riparian populations living in rural areas of the state of Pará. The present study aimed to evaluate the prevalence of HTLV-1/2 infection in four riverine communities and one rural area in the state of Pará and to describe the possible risk factors for infection. A total of 907 individuals responded to an epidemiological survey and gave blood samples collected for anti-HTLV-1/2 antibodies by immunoenzymatic assay (EIA). The serum-reactive samples were subjected to confirmation by an in-line assay (Inno-Lia) and by proviral DNA screening using real-time PCR (qPCR). The total prevalence was 0.8% (7/907) for HTLV-1/2 (CI: 0.2-1.3%), with 0.66% HTLV-1 and 0.11% HTLV-2. The prevalence by sex was 0.7% in women (4/565) and 0.9% in men (3/342). Among seropositive patients, 83.3% (5/7) reported being sexually active, and 57.1% (4/7) reported not having the habit of using condoms during their sexual relations. Intrafamily infection was also observed. The results reinforce the need for public policies to prevent and block the spread of HTLV, especially in riparian communities that are subject to difficulties in accessing the Unified Health System (Sistema Único de Saúde/SUS) because infected individuals need clinical monitoring for surveillance and early diagnosis of symptoms associated with HTLV-1.

Biomarkers in a Cohort of HIV-Infected Patients Single- or Co-Infected with HTLV-1, HTLV-2, and/or HCV: A Cross-Sectional, Observational Study.

HIV, HTLV-1/-2, and HCV share routes of transmission, and such virus co-infections could account for worse outcomes of associated diseases. Measuring cytokines/chemokines, CD4 and CD8 T cells, and HIV viral load (VL) in HIV single-infected and co-infected individuals has prognostic value. We analyzed such biomarkers in 129 blood samples of HIV-infected individuals matched for age and sex and divided into six groups (G1 (69 HIV); G2 (9 HIV/HTLV-1); G3 (6 HIV/HTLV-2); G4 (11 HIV/HCV); G5 (19 HIV/HCV/HTLV-1); and G6 (15 HIV/HCV/HTLV-2)). Eight cytokines/chemokines from fifteen analytes could be compared. The highest levels of Th1 and pro-inflammatory cytokines were detected in G2 (IFN-γ) and G6 (IL-6 and IL1-ß) and of chemokines in G1 (MIG, IP10, RANTES), G4 (MCP1), and G6 (MIP1-ß). The highest CD4 cells number and the lowest HIV VL were identified in G3 and the opposite results in G2. Positive correlations between CD4 and CD8 cells counts and IL-6 levels were detected in G2 and G5 and of HIV VL and RANTES in G4. Negative correlations were detected between CD8 and IFN-γ in G4 and HIV VL and RANTES in G6. Despite the small number of the cohort analyzed, and although the cross-sectional study design does not allow firm conclusions, the homogeneity of the characteristics of HIV/HTLV-co-infected individuals regarding age, time and route of HIV acquisition, and criteria for introducing ART enable us to suggest a negative impact of HTLV-1 and a possible protective role of HTLV-2 in HIV infection progression in such patients.