| Abstrakt: |
Objectives Investigate whether dolutegravir (DTG), tenofovir alafenamide (TAF), and lenacapavir (LEN) are able to block HTLV-1 transmission in vitro. Methods The persistently HTLV-1 infected MT-2 cell line was co-cultured with pre-treated Jurkat cells for 18h. Following depletion of MT-2 cells, Jurkat cells were cultured for 10 days before harvest and extraction of genomic DNA. Dose-response curves were generated by measuring the proviral load (PVL). Integration was measured by quantifying Alu-qPCR. Results We report that DTG and TAF potently inhibit HTLV-1 infection in cell culture. Conclusion As it stands, there is no therapeutic or preventative regimen for HTLV-1. However, antiretrovirals (ARVs) have been developed for and revolutionised HIV treatment, and the conserved mechanistic properties of retroviral polynucleotide-processing enzymes mean some HIV-1 drugs have the potential to treat or prevent HTLV-1. We previously reported that both first- and second-generation integrase strand transfer inhibitors (INSTIs), including raltegravir and bictegravir, as well as the long-acting INSTI, cabotegravir, and the nucleoside reverse transcriptase inhibitor (NRTI) formulation tenofovir disoproxil fumarate (TDF), effectively blocked intercellular transmission of HTLV-1 in cell culture. In this study, we report that dolutegravir, the INSTI currently recommended as the foundation in all first-line combination therapy by the World Health Organisation, also potently inhibits HTLV-1 infection in cell culture. We also show that the latest formulation of tenofovir, tenofovir alafenamide (TAF), is as effective as TDF in blocking transmission. Our results, if replicated in a clinical setting, suggest vertical transmission rates of HTLV-1, and future caseloads of ATLL, could be dramatically cut by the appropriation of already widely available HIV pills. Considering this work with the old medical adage 'it's better to prevent than cure', we are calling for the inclusion of INSTIs and NRTIs in upcoming HTLV-1 clinical trials. [ABSTRACT FROM AUTHOR] |
