A MAJOR advance in human T-cell lymphotropic virus type 1 (HTLV-1) research has identified existing HIV antiretrovirals and a targeted cancer drug as potential tools to prevent and treat HTLV-1 subtype C (HTLV-1c), offering a long-overdue path forward in addressing this neglected but serious infection.
HTLV-1, a retrovirus that infects an estimated 5–20 million people worldwide, is linked to lifelong infection and a range of debilitating outcomes, including adult T-cell leukaemia/lymphoma and chronic inflammatory diseases such as HTLV-1-associated myelopathy and bronchiectasis. The HTLV-1c subtype, endemic to Indigenous populations in central Australia and parts of Oceania, has been associated with particularly aggressive disease and disproportionately high rates of pulmonary complications, yet treatment options remain non-existent.
In this study, researchers developed the first humanised mouse model for HTLV-1c and compared it directly with the globally dominant HTLV-1a subtype. HTLV-1c caused slightly more aggressive disease in vivo, particularly in lung tissue, mirroring the real-world clinical burden observed in endemic communities. Using this model, the team tested clinically relevant interventions. A combination of tenofovir and dolutegravir, standard drugs used for HIV pre-exposure prophylaxis (PrEP), significantly reduced HTLV-1c transmission and slowed disease progression in the mice.
Crucially, the study also found that HTLV-1c-infected cells rely on MCL-1, a protein that prevents apoptosis. When treated with a specific MCL-1 inhibitor, infected cells were selectively destroyed both in vitro and in vivo. When combined with tenofovir and dolutegravir, MCL-1 inhibition further delayed disease progression, suggesting a possible therapeutic synergy that could pave the way for curative strategies.
This research represents a significant milestone in HTLV-1 science. For healthcare professionals working in infectious disease, oncology, and public health, it signals the potential repurposing of available drugs to address a virus long overlooked in global health strategies.
Reference
Cooney JP et al. Combination antiretroviral therapy and MCL-1 inhibition mitigate HTLV-1 infection in vivo. Cell. 2025; DOI:10.1016/j.cell.2025.06.023.
