NIH – Imaging the Persistent HIV Reservoir (R01)

June 12, 2017 by School of Medicine Webmaster

The purpose of this Funding Opportunity Announcement (FOA) is to support the development of imaging approaches to identify and characterize persistent HIV reservoirs in patients undergoing suppressive antiretroviral therapy (ART) and to quantify the nature and size of these reservoirs in response to therapeutic or immunologic interventions. The FOA seeks innovative imaging strategies to identify reservoirs in human or animal models that have undergone successful, long-term viral suppression.

Identification and quantification of the persistent HIV reservoirs in virally suppressed patients currently presents a roadblock to HIV cure research. There is ongoing debate whether low-level viral replication persists in the face of suppressive antiretroviral therapy (ART), however it is clear that a transcriptionally silent, latent pool of infected cells persists in the blood and tissues of infected patients on ART. Direct imaging of productively infected cells has provided a wealth of information regarding the nature and distribution of these cells in individuals who are not on ART, however there has been only limited success imaging latently infected cells in treated individuals.

Investigators have recently recognized that peripheral tissues, in particular secondary lymphoid organs, including lymph nodes and the gut associated lymphoid tissue (GALT), as well as brain microglia and vascular cells may serve as important sources for HIV persistence and viral rebound following the discontinuation of ART. Demonstrating efficacy of strategies designed to cure HIV infection will require convenient, efficient measurement and monitoring of changes in the size of the persistent HIV reservoir, preferably using non-invasive methodologies. Recent progress in the use of single-cell analysis technologies and intravital imaging provide attractive new avenues for developing approaches for imaging and measuring persistent HIV reservoirs.

Research Objectives

Research projects and studies may include, but are not limited to the following topics:

  • In situ staining of persistent HIV or SIV/SHIV reservoirs in ART-treated individuals or non-human primates, respectively, to identify the critical cellular and anatomical sources of functional proviruses, latent proviruses, defective proviruses expressing HIV proteins, and reservoir cells undergoing homeostatic clonal proliferation.
  • Single-cell imaging of infected cells from blood and disrupted tissues of ART-treated individuals.
  • Intravital imaging of tissue reservoirs in animal models of HIV/SIV persistence.
  • PET or other whole body modalities for imaging tissue reservoirs in infected individuals on ART or in animal models.
  • Multiparameter imaging to identify cellular markers associated with persistent and latent reservoirs.
  • Multimodal correlative microscopy for high-resolution spatial imaging of infected tissues from individuals on ART.
  • Studies referenced above that include samples from patients or animal models treated with agents that reactivate latent reservoirs.
  • Non-invasive imaging of brain and tissue reservoirs in animal models and infected individuals

Deadlines:  standard AIDS dates apply


Filed Under: Funding Opportunities