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

• Published in: Frontiers in medicine 2022-04, Vol.9, p.889621
• Main Authors: Schneiderman, Bethany S, Barski, Michal S, Maertens, Goedele N
• Format: Article
• Language: English
• Subjects: cabotegravir; HTLV-1; INSTI; integrase; Medicine; MTCT; tenofovir disoproxil fumarate
• ISSN: 2296-858X; 2296-858X
• DOI: 10.3389/fmed.2022.889621

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 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 . Strand transfer assays performed using recombinant HTLV-1 integrase treated with increasing concentrations of cabotegravir, effectively inhibited strand transfer activity, displaying an IC of 77.8 ± 22.4 nM. Furthermore, cabotegravir blocked HTLV-1 transmission in tissue culture; we determined an EC 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 . 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.