International Conference on Human Retrovirology: HTLV 2022

On World HTLV Day (10 November 2021) we recorded a podcast on the patient, clinician and scientist’s perspective of Human T Leukaemia Virus-1 (HTLV-1). Today we present you an update on the latest International Retrovirology Conference: HTLV 22 held in Melbourne, Australia.

HTLV-1 is a sexually and vertically transmitted virus that is distantly related to HIV and capable of causing severe, chronic and progressive diseases such as adult T cell leukaemia, HTLV-1 associated myelopathy (HAM/TSP) and bronchiectasis. The natural history of HTLV-1 is mostly asymptomatic and the majority of those who carry the virus remain undiagnosed. The mostly silent nature of the virus, compounded by a lack of public health response (e,g, of STI and antenatal care screening programmes) has led to unchecked transmission. Forty years after its discovery HTLV-1 remains a neglected human pathogen, with no specific anti-retroviral treatment or vaccine available.

The future of HTLV-1 therapeutics and recognition by national and international public health organisations is promising as discussed in this special episode of STI podcast dedicated to the 2022 International Conference on Human Retrovirology. Join Dr Fabiola Martin and her guests the Australian HTLV-1 patient representative, Ms Joanna Curteis, Dr Carolina Rosadas, HTLV-1 scientist at Imperial College London, UK and Prof Damian Purcell, HTLV-1 at Doherty Institute, Melbourne, Australia.

Highlights

HTLV-1 Epidemiology

Internationally antenatal care screening (ANC) for HTLV-1 is not routinely adopted, though there is compelling evidence from Japan and Martinique that ANC screening does reduce HTLV-1 prevalence. Prates et al reported that in Brazil a cohort of 292 HTLV-1 positive mothers followed over 24 years, the vertical transmission rate was 15%, with prolonged breastfeeding being the most significant risk factor. Determinants for the HTLV-1 maternal-to-child Transmission.
HTLV-1 is primarily sexually transmitted. A recent study measured the HTLV-1 proviral load in two discrete sites, vaginal fluid and peripheral blood mononuclear cells (PBMCs) among 57 women diagnosed with HTLV-1. The mean HTLV-1 pro-viral load was higher in PBMCs than vaginal fluid and there was a strong direct correlation between the mean pro-viral load of PBMCs with vaginal fluid. HTLV-1 proviral load in vaginal fluid correlates directly with proviral load in peripheral blood mononuclear cells of infected women.

PrEP for HTLV-1

Pre-exposure prophylaxis for HTLV-1 is feasible. Animal model studies have shown that the integrase strand transfer inhibitor (INSTI) carbotegravir prevents the transmission of HTLV-1. Cabotegravir is a long-acting injectable antiretroviral already approved for the treatment of HIV-1. Given the extended half-life of cabotegravir, these findings highlight the potential of the first PrEP agent for HTLV. Cabotegravir, the long-acting integrase strand transfer inhibitor, potently inhibits human T-cell lymphotropic virus type 1 transmission in vitro.
Combination administration of tenofovir alafenamide and dolutegravir (TAF+DTG) anti-retroviral therapy in animal models achieved high intracellular concentrations and was effective at preventing de novo infection within the humanised animal model. These data provide support for the evaluation of TAF+DTG as HTLV-1 PrEP in human studies. Combination antiretroviral therapy and MCL1 inhibition mitigate HTLV-1 infection in vivo.

HTLV-1 Advocacy

The International Retrovirology Association (IRVA) released an open letter calling for a Global Action to eliminate HTLV-1: Rapid implementation of HTLV-1 prevention strategies and effective linkage with care and research funding is requested: 371 individuals and 36 organisations so far have endorsed this letter and further signatures will be collected on the new IRVA website.
Dr Meg Doherty presented the WHO HTLV-1 position papers and recommendations about the mapping, prevention and elimination of HTLV-1.

At the opening ceremony, a message from Director General Dr Thedros Adhanom Ghebreyes informed the HTLV-1 community that at the 2022 World Health Assembly WHO will ask member states to endorse HTLV-1 as an STI. This will be a huge breakthrough in making HTLV-1 visible.