Long-term kinetics of proviral load in HTLV-1 carriers: defining risk for the development of adult T-cell leukemia/lymphoma.

Biomark Res

Division of Hematopoietic Disease Control, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo, 108-8639, Japan.

Published: February 2025

Background: Assessment of adult T-cell leukemia/lymphoma (ATL) development among human T-lymphotropic virus 1 (HTLV-1)-infected individuals (carriers) constitute a significant issue. A high HTLV-1 proviral load (PVL) in carriers has been used as a risk factor for ATL development and PVLs are considered to remain unchanged over time among carriers.

Methods: This single-center analysis used a cohort from a prospective observational study of HTLV-1 carriers in Japan (JSPFAD). Carriers whose PVL was measured at least twice between October 2004 and March 2023 were included. We used trajectory analysis to construct a kinetic model of the PVL.

Results: Analysis of 1371 samples from 252 carriers revealed a slight but significant increase in the PVL with age (P < 0.001). Trajectory analysis of PVL kinetics classified the carriers into six groups, in three of which increased over time. When we applied the model to 15 carriers who subsequently developed ATL, 12 (80%) were classified into the highest PVL group, with an estimated 15-year ATL development of 47.5% (95% confidence interval: 20.4-74.2%). Notably, younger patients are at greater risk of developing ATL if their PVL values are comparable. Our risk estimation model is available online ( https://atlriskpredictor.shinyapps.io/ATL_risk_calculator/ ).

Conclusions: This study demonstrated that the PVLs increases over time, allowing for prospective risk estimation for ATL development. Further validation is needed to assess the validity of this model.

Trial Registration: Retrospectively registered.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11863581PMC
http://dx.doi.org/10.1186/s40364-025-00747-5DOI Listing

Publication Analysis

Top Keywords

proviral load
8
htlv-1 carriers
8
adult t-cell
8
t-cell leukemia/lymphoma
8
atl development
8
carriers
6
long-term kinetics
4
kinetics proviral
4
load htlv-1
4
carriers defining
4

Similar Publications

Background: We investigated the efficacy of dolutegravir/lamivudine for maintenance treatment for people with HIV and previous lamivudine resistance.

Methods: Open-label, single arm, multicentric clinical trial including virologically suppressed PWH with historical lamivudine resistance (confirmed by genotypic testing or suspected based on clinical history), no integrase resistance and CD4+ >200 cells/mm3 whose ART was changed to dolutegravir/lamivudine if the M184V/I mutation was not detected in baseline proviral DNA population sequencing. Proviral DNA next-generation sequencing (NGS) was retrospectively performed in baseline samples.

View Article and Find Full Text PDF

Long-term kinetics of proviral load in HTLV-1 carriers: defining risk for the development of adult T-cell leukemia/lymphoma.

Biomark Res

February 2025

Division of Hematopoietic Disease Control, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo, 108-8639, Japan.

Background: Assessment of adult T-cell leukemia/lymphoma (ATL) development among human T-lymphotropic virus 1 (HTLV-1)-infected individuals (carriers) constitute a significant issue. A high HTLV-1 proviral load (PVL) in carriers has been used as a risk factor for ATL development and PVLs are considered to remain unchanged over time among carriers.

Methods: This single-center analysis used a cohort from a prospective observational study of HTLV-1 carriers in Japan (JSPFAD).

View Article and Find Full Text PDF

We evaluated the HIV-1 reservoir in people with four-class drug-resistant (4DR) virus compared with those without drug resistance. Using the intact proviral DNA assay, we found that both groups had similar levels of intact HIV-1 DNA, suggesting that multidrug-resistant HIV does not significantly alter the size of the reservoir. These findings are a first step in studying the HIV-1 reservoir in the population with multidrug-resistant virus, and further studies are needed to confirm our results.

View Article and Find Full Text PDF

Persisting HIV reservoir viruses in resting CD4 T cells and other cellular subsets are a barrier to cure efforts. Early antiretroviral therapy (ART) enables post-treatment viral control in some cases, but mechanisms remain unclear. We hypothesised that ART initiated before peak viremia impacts HIV-1 subtype C reservoirs.

View Article and Find Full Text PDF

The HIV reservoir consists of infected cells in which the HIV-1 genome persists as provirus despite effective antiretroviral therapy (ART). Studies exploring HIV cure therapies often measure intact proviral DNA levels, time to rebound after ART interruption, or ex vivo stimulation assays of latently infected cells. This study utilizes barcoded HIV to analyze the reservoir in humanized mice.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!