Paper

Modeling HIV infection, treatment, rebound, and intervention in human immune organoids

Davis, Mark M, Mangalanathan, Uma M, Fish, Rachel S, Schrum, Jacob E, Kim, Jocelyn T, Pi, Ruoxi, Selehi, Ahmad, Blish, Catherine A, Sola, Elsa, Zack, Jerome A, Lehman, Dara A, Sackey, Sarah A

2026

Overview

Targeting the HIV-infected reservoir in lymphoid tissues (LT) will be critical to developing a cure for people living with HIV (PLWH). LT explants used to study HIV infection enable the evaluation of human-specific disease progression and treatment response; however, their short lifespan makes it challenging to assess long-term treatment interventions. We therefore established an immune organoid model of HIV infection using human tonsil or spleen cells, demonstrating productive HIV infection and viral integration into CD4+ T cells. Treatment with a protease inhibitor fully suppressed ongoing viral production, with virologic rebound occurring within days of treatment interruption. The transfer of healthy allogeneic NK cells to target the reservoir upon treatment interruption reduced the number of infected cells, intact viral genomes, and production of de novo infectious viral particles. Adoption of this immune organoid platform will accelerate the evaluation of cure-based strategies to eliminate the HIV reservoir in tissues for PLWH.Competing Interest StatementJ.A.Z is a co-founder of CDR3 Therapeutics. C.A.B is a member of the Scientific Advisory Boards of ImmuneBridge and DeepCell, Inc. on topics unrelated to this project.Funder Information DeclaredNIH, R01 AI161803, R01 AI183381, T32AI007290, T32 AI007502NCRR, 1S10OD032300-01

• Publisher: Cold Spring Harbor Laboratory Press
• Subject: CD4 antigen / Complementarity-determining region 3 / Explants / HIV / Human immunodeficiency virus / Infections / Life span / Lymphocytes T / Lymphoid tissue / Organoids / Proteinase inhibitors