HIV Drugs Offer Hope for Neglected HTLV-1 Virus

Breakthrough Study Identifies Potential Treatments to Halt Transmission and Clear Infection

A major scientific advance may soon provide the first preventative treatments for the human T-cell leukaemia virus type 1 (HTLV-1), a widespread and dangerous infection that currently lacks effective therapies. The research also points toward a future cure.

Promising Suppression Found

New research, co-led by Australian scientists, has discovered that existing HIV medications can significantly reduce the transmission of the HTLV-1 virus in laboratory mice. This groundbreaking work, published in the journal Cell, could pave the way for crucial interventions, particularly for First Nations communities where the virus is endemic.

The study by WEHI and the Peter Doherty Institute for Infection and Immunity also pinpointed a novel drug target. This could lead to strategies for eradicating HTLV-1 from infected individuals, thereby preventing the progression of associated diseases.

Key Findings Unveiled

Researchers found that two specific HIV antivirals, already approved for human use, effectively suppressed HTLV-1 transmission in mice. This marks the first identification of a prophylactic treatment against HTLV-1. Furthermore, when combined with a compound that triggers cell death, these HIV drugs eliminated infected cells, suggesting a potential curative approach.

These unprecedented results may allow these existing drugs to be tested in clinical trials, aiming to prevent the establishment of pathogenic levels of HTLV-1 infection.

Understanding HTLV-1

HTLV-1 infects T cells, a vital component of the immune system responsible for fighting off infections, much like HIV. While most infected individuals remain asymptomatic, a small percentage develop severe conditions such as adult T-cell leukemia and inflammatory conditions affecting the spinal cord.

Dr Marcel Doerflinger, a study co-lead author and WEHI laboratory head, stated the findings offer much-needed hope. Our study marks the first time any research group has been able to suppress this virus in a living organism, he commented. As HTLV-1 symptoms can take decades to appear, by the time a person knows they have the infection the immune damage is already in full swing. He added that stopping the virus at transmission could prevent irreversible immune damage.

Developing a New Model

Over a decade, the research team developed a world-first humanized mouse model for HTLV-1. This innovative model allowed them to observe the virus’s behavior within a human-like immune system. The mice, engrafted with human immune cells susceptible to HTLV-1, developed leukemia and lung disease when infected with both international and Australian strains of the virus.

Treatment with tenofovir and dolutegravir, both HIV antivirals, demonstrated powerful suppression of HTLV-1. What’s most exciting is that these antivirals are already in use for millions of HIV patients, meaning there’s a direct path for the clinical translation of our findings, said Dr Doerflinger. We won’t have to start from scratch because we already know these drugs are safe and effective. And now we’ve shown that their use can very likely be extended to HTLV-1.

A Dual Approach to Treatment

Remarkably, the study also revealed that combining HIV drugs with a therapy targeting the MCL-1 protein, which helps rogue cells survive, could selectively destroy HTLV-1-infected human cells. The team is now exploring precision RNA therapies to target MCL-1, aiming to create combination treatments for clinical testing and a potential cure.

Crucial Insights into Viral Strains

The development of the crucial humanized mouse models was led by first author Dr James Cooney and study lead author, WEHI Honourary Fellow and Executive Director at Centenary Institute, Professor Marc Pellegrini. Professor Pellegrini highlighted the models’ importance not only for identifying therapeutic targets but also for understanding how different HTLV-1 strains influence disease outcomes, particularly the unique Australian variant, HTLV-1c.

It’s long been hypothesised that differences in viral subtype may influence disease outcomes, but a lack of research into HTLV-1 has made it difficult for us to find the evidence needed to support this claim – until now, stated Professor Pellegrini. Our study provides critical insights that enable us to better understand the consequences of the distinct molecular make-up of the virus affecting our First Nations communities.

Advocacy and Future Directions

Associate Professor Lloyd Einsiedel, a Clinician Scientist at the Doherty Institute, played a key role in obtaining human HTLV-1 samples for the mouse models through his extensive clinical work in Central Australia. This research, co-led by Professor Damian Purcell from the University of Melbourne, identified significant genetic differences in the HTLV-1c strain compared to international strains, with the Australian variant showing more aggressive disease characteristics in the mice. Notably, the identified drug therapies proved equally effective against both strains.

Professor Purcell and Associate Professor Einsiedel, in collaboration with the National Aboriginal Community Controlled Health Organisation (NACCHO) and the Australian Department of Health, successfully advocated for the World Health Organization (WHO) to classify HTLV-1 as a Threatening Pathogen to Humans in 2021. This led to global policies aimed at reducing transmission and the development of clinical guidelines for HTLV-1c in Central Australia.

Despite Australia’s high burden of HTLV-1, the virus and its associated diseases are still not notifiable in most states and true infection rates in the nation remain unknown, observed Professor Purcell. People at risk from HTLV-1 deserve biomedical tools like those that provide game-changing therapeutic and prevention options for other blood-borne persistent viral infections, such as HIV. He emphasized the significant opportunity to prevent HTLV-1 transmission and end its associated diseases.

The research team is currently in discussions with pharmaceutical companies to include HTLV-1 patients in ongoing HIV antiviral clinical trials. Success in these discussions could establish these drugs as the first approved pre-exposure prophylaxis for HTLV-1 acquisition.

The research was supported by The Australian Centre for HIV and Hepatitis Virology Research, The Phyllis Connor Memorial Trust, Drakensberg Trust, and the National Health and Medical Research Council (NHMRC).