[HTML][HTML] Lessons for understanding central nervous system HIV reservoirs from the last gift program
PK Riggs, A Chaillon, G Jiang, SL Letendre… - Current HIV/AIDS …, 2022 - Springer
Current HIV/AIDS Reports, 2022•Springer
Abstract Purpose of Review Deep tissue HIV reservoirs, especially within the central
nervous system (CNS), are understudied due to the challenges of sampling brain, spinal
cord, and other tissues. Understanding the cellular characteristics and viral dynamics in
CNS reservoirs is critical so that HIV cure trials can address them and monitor the direct and
indirect effects of interventions. The Last Gift program was developed to address these
needs by enrolling altruistic people with HIV (PWH) at the end of life who agree to rapid …
nervous system (CNS), are understudied due to the challenges of sampling brain, spinal
cord, and other tissues. Understanding the cellular characteristics and viral dynamics in
CNS reservoirs is critical so that HIV cure trials can address them and monitor the direct and
indirect effects of interventions. The Last Gift program was developed to address these
needs by enrolling altruistic people with HIV (PWH) at the end of life who agree to rapid …
Purpose of Review
Deep tissue HIV reservoirs, especially within the central nervous system (CNS), are understudied due to the challenges of sampling brain, spinal cord, and other tissues. Understanding the cellular characteristics and viral dynamics in CNS reservoirs is critical so that HIV cure trials can address them and monitor the direct and indirect effects of interventions. The Last Gift program was developed to address these needs by enrolling altruistic people with HIV (PWH) at the end of life who agree to rapid research autopsy.
Recent Findings
Recent findings from the Last Gift emphasize significant heterogeneity across CNS reservoirs, CNS compartmentalization including differential sensitivity to broadly neutralizing antibodies, and bidirectional migration of HIV across the blood–brain barrier. Our findings add support for the potential of CNS reservoirs to be a source of rebounding viruses and reseeding of systemic sites if they are not targeted by cure strategies.
Summary
This review highlights important scientific, practical, and ethical lessons learned from the Last Gift program in the context of recent advances in understanding the CNS reservoirs and key knowledge gaps in current research.
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