Ex Vivo Studies of HIV Infection and Pathogenesis Within the Mission of NIDDK

May 2023 Council

Lead Division/Office


Point(s) of Contact

Peter Perrin, Ph.D.; Deepak Nihalani, Ph.D.; Saul Malozowski, M.D., Ph.D., M.B.A.

Executive Summary

HIV research involving human subjects or nonhuman primate models are often complicated by multiple factors that impact experimental design and interpretation of results. In vitro cell culture studies of biochemical, molecular biological, and cellular mechanisms can be somewhat reductionist and not fully recapitulate in vivo events. This is particularly important in conditions such as HIV, where interactions between different organ systems, inflammatory pathways, and immune processes contribute to viral reservoir dynamics and pathogenic processes. This initiative seeks to stimulate the use of ex vivo technologies such as organoids and micro-physiological systems for elucidating the complex biological processes occurring during HIV infection in tissues within NIDDKs mission. For example, these types of models could be derived from individual people with HIV with well-characterized medical histories.; they could interrogate mechanisms operative under varying conditions, such as long-term viral suppression, the presence of multiple comorbidities and coinfections, polypharmacy, interactions between different tissue compartments (ex: gut-distal organ axes and impact of adiposity), diet, and others. Moreover, ex vivo infection of organoids or micro-physiological systems from people without HIV could provide model systems that circumvent confounders such as medical history, diet, or other factors.