Challenges and Opportunities for T-Cell-Mediated Strategies to Eliminate HIV Reservoirs.
HIV's ability to establish latent reservoirs of reactivation-competent virus is the major barrier to cure. "Shock and kill" methods consisting of latency-reversing agents (LRAs) followed by elimination of reactivating cells through cytopathic effects are under active development. However, the clinical efficacy of LRAs remains to be established. Moreover, recent studies indicate that reservoirs may not be reduced efficiently by either viral cytopathic or CD8(+) T-cell-mediated mechanisms. In this perspective, we highlight challenges to T-cell-mediated elimination of HIV reservoirs, including characteristics of responding T cells, aspects of the cellular reservoirs, and properties of the latent virus itself. We also discuss potential strategies to overcome these challenges by targeting the antiviral activity of T cells toward appropriate viral antigens following latency.
Faculty of Health Sciences, Simon Fraser University , Burnaby, BC , Canada ; BC Centre for Excellence in HIV/AIDS , Vancouver, BC , Canada.
Mark A
MA
Brockman
Department of Microbiology, Immunology and Tropical Medicine, The George Washington University , Washington, DC , USA.
R Brad
RB
Jones
Faculty of Health Sciences, Simon Fraser University , Burnaby, BC , Canada ; BC Centre for Excellence in HIV/AIDS , Vancouver, BC , Canada.
Zabrina L
ZL
Brumme
CTL escape; HIV latency; T cells; immune evasion; immune-based therapy