Rapid subacute myelopathy following kidney transplantation from HTLV-1 donors: role of immunosuppresors and failure of antiretrovirals

Roc, Lourdes; Mendoza, Carmen de; Fernandez‐Alonso, M.; Reina, Gabriel; Soriano, Vincent

doi:10.1177/2049936119868028

Cited by 9 publications

(8 citation statements)

References 37 publications

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“…HTLV-1 transmission can also occur through exposure to infected blood products such as in intravenous (IV) drug users, blood donations, and organ transplantation. Cases of transplant-derived HAM/TSP and ATL have been reported in many countries ( Tajima et al, 2016 ; Moreno-Ajona et al, 2018 ; Nayar et al, 2018 ; Taylor, 2018 ; Motomura et al, 2019 ; Roc et al, 2019 ; Goto et al, 2020 ). In one such report, three recipients were monitored following organ transplantation from a HTLV-1-infected individual (not known to be positive at time of donation) ( Cook et al, 2016 ).…”

Section: Human T-cell Leukemia Virus Type 1 Backgroundmentioning

confidence: 99%

The Past, Present, and Future of a Human T-Cell Leukemia Virus Type 1 Vaccine

Maksimova

Ratner

et al. 2022

Front. Microbiol.

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Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic human retrovirus which causes a lifelong infection. An estimated 5–10 million persons are infected with HTLV-1 worldwide – a number which is likely higher due to lack of reliable epidemiological data. Most infected individuals remain asymptomatic; however, a portion of HTLV-1-positive individuals will develop an aggressive CD4+ T-cell malignancy called adult T-cell leukemia/lymphoma (ATL), or a progressive neurodegenerative disease known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Few treatment options exist for HAM/TSP outside of palliative care and ATL carries an especially poor prognosis given the heterogeneity of the disease and lack of effective long-term treatments. In addition, the risk of HTLV-1 disease development increases substantially if the virus is acquired early in life. Currently, there is no realistic cure for HTLV-1 infection nor any reliable measure to prevent HTLV-1-mediated disease development. The severity of HTLV-1-associated diseases (ATL, HAM/TSP) and limited treatment options highlights the need for development of a preventative vaccine or new therapeutic interventions. This review will highlight past HTLV-1 vaccine development efforts, the current molecular tools and animal models which might be useful in vaccine development, and the future possibilities of an effective HTLV-1 vaccine.

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Section: Human T-cell Leukemia Virus Type 1 Backgroundmentioning

confidence: 99%

The Past, Present, and Future of a Human T-Cell Leukemia Virus Type 1 Vaccine

Maksimova

Ratner

et al. 2022

Front. Microbiol.

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“…AZT/3TC/raltegravir initiated within 1 week of renal transplantation from another infected donor, and continued for >18 months, did not prevent HAM development in the recipient at 8 months. A second kidney recipient, who received AZT/3TC/raltegravir in the first 2-months posttransplant, and whose allograft was removed following rejection, developed asymptomatic infection over 3 years of followup (129).…”

Section: Htlv-pep Organ Transplantationmentioning

confidence: 99%

HTLV-1 Transmission and HIV Pre-exposure Prophylaxis: A Scoping Review

Bradshaw

Taylor

2022

Front. Med.

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HIV pre-exposure prophylaxis (HIV-PrEP) is effective in reducing the likelihood of HIV acquisition in HIV-negative people at high risk of exposure. Guidelines recommend testing for sexually transmitted infections (STIs) before starting, and periodically on PrEP, including bacterial infections, HIV, hepatitis C virus, and, for those who are non-immune, hepatitis B virus. Diagnosed infections can be promptly treated to reduce onward transmission. HTLV-1 is not mentioned; however, it is predominantly sexually transmitted, causes adult T-cell leukaemia/lymphoma (ATL) or myelopathy in 10% of those infected, and is associated with an increased risk of death in those without any classically HTLV-associated condition. The 2021 WHO Technical Report on HTLV-1 called for the strengthening of global public health measures against its spread. In this scoping review, we, therefore, (1) discuss the epidemiological context of HIV-PrEP and HTLV-1 transmission; (2) present current knowledge of antiretrovirals in relation to HTLV-1 transmission prevention, including nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and integrase strand transfer inhibitors (INSTIs); and (3) identify knowledge gaps where data are urgently required to inform global public health measures to protect HIV-PrEP users from HTLV-1 acquisition. We suggest that systematic seroprevalence studies among PrEP-using groups, including men who have sex with men (MSM), people who inject drugs (PWIDs), and female sex workers (FSWs), are needed. Further data are required to evaluate antiretroviral efficacy in preventing HTLV-1 transmission from in vitro studies, animal models, and clinical cohorts. PrEP delivery programmes should consider prioritizing the long-acting injectable INSTI, cabotegravir, in HTLV-1 endemic settings.

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“…HTLV-1 transmission also may occur during allograft transplantation [ 36 ]. Despite low incidence, myelopathy cases have been reported following organ transplantation in HTLV-1 positive subjects in non-endemic countries [ 37 ]. In 2000, three patients who received organ transplants from the same donor, who was determined to be an HTLV-1 healthy carrier, then presented with clinical manifestations of myelopathy [ 38 ].…”

Section: Htlv-1 Transmissionmentioning

confidence: 99%

Hijacking Host Immunity by the Human T-Cell Leukemia Virus Type-1: Implications for Therapeutic and Preventive Vaccines

Pise-Masison¹,

Franchini²

2022

Viruses

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Human T-cell Leukemia virus type-1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and other inflammatory diseases. High viral DNA burden (VL) in peripheral blood mononuclear cells is a documented risk factor for ATLL and HAM/TSP, and patients with HAM/TSP have a higher VL in cerebrospinal fluid than in peripheral blood. VL alone is not sufficient to differentiate symptomatic patients from healthy carriers, suggesting the importance of other factors, including host immune response. HTLV-1 infection is life-long; CD4+-infected cells are not eradicated by the immune response because HTLV-1 inhibits the function of dendritic cells, monocytes, Natural Killer cells, and adaptive cytotoxic CD8+ responses. Although the majority of infected CD4+ T-cells adopt a resting phenotype, antigen stimulation may result in bursts of viral expression. The antigen-dependent “on-off” viral expression creates “conditional latency” that when combined with ineffective host responses precludes virus eradication. Epidemiological and clinical data suggest that the continuous attempt of the host immunity to eliminate infected cells results in chronic immune activation that can be further exacerbated by co-morbidities, resulting in the development of severe disease. We review cell and animal model studies that uncovered mechanisms used by HTLV-1 to usurp and/or counteract host immunity.

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Rapid subacute myelopathy following kidney transplantation from HTLV-1 donors: role of immunosuppresors and failure of antiretrovirals

Cited by 9 publications

References 37 publications

The Past, Present, and Future of a Human T-Cell Leukemia Virus Type 1 Vaccine

The Past, Present, and Future of a Human T-Cell Leukemia Virus Type 1 Vaccine

HTLV-1 Transmission and HIV Pre-exposure Prophylaxis: A Scoping Review

Hijacking Host Immunity by the Human T-Cell Leukemia Virus Type-1: Implications for Therapeutic and Preventive Vaccines

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