Antiretroviral therapy (ART) has revolutionized the treatment of HIV and has dramatically reduced morbidity and mortality. ART successfully inhibits HIV replication, resulting in undetectable viral load in peripheral blood. Interruption of ART, however, allows HIV to re-initiate replication. As such, HIV-infected individuals require ART for the duration of their life. Lifelong treatment is costly and can trigger adverse side effects in some individuals. As such, there is a need to identify strategies to cure HIV or induce “remission” and avoid lifelong treatment.
A major barrier to curing HIV is the persistence of a latent reservoir that predominantly resides in CD4+ T cells. Many different strategies have been proposed to target the HIV reservoir. Chief amongst these strategies is the `shock and kill' approach. This is a two-step strategy that involves; (1) using a latency reversing agent (LRA) to induce virus expression and make the infected or virus harboring cell visible to the immune system; and (2) utilizing immune cells to eliminate the infected or virus harboring cell. While clinical trials exploring the utility of the `shock and kill' strategy have shown LRAs to induce viral expression in ART-treated HIV-infected individuals, no trials of this approach have decreased the frequency of cells carrying integrated HIV DNA. The reason(s) that `shock and kill' strategies have not reduced the frequency of cells carrying integrated HIV DNA remains unclear. Stronger LRAs or more potent anti-viral immune responses may be required to purge the latent reservoir.
In this Frontiers Research Topic, we aim to explore novel approaches for eliminating HIV reservoirs. We invite early stage investigators to contribute their ideas as to how to tackle this important scientific problem. We aim to generate a Frontiers Research Topic comprised of short reviews introducing the reader to novel approaches to eliminating HIV reservoirs. These reviews should offer hypotheses regarding therapeutic possibilities and indicate how feasible the discussed approach is as a treatment option. Finally, each review should attempt to discuss what would be required to move the novel strategy into the clinic.
Antiretroviral therapy (ART) has revolutionized the treatment of HIV and has dramatically reduced morbidity and mortality. ART successfully inhibits HIV replication, resulting in undetectable viral load in peripheral blood. Interruption of ART, however, allows HIV to re-initiate replication. As such, HIV-infected individuals require ART for the duration of their life. Lifelong treatment is costly and can trigger adverse side effects in some individuals. As such, there is a need to identify strategies to cure HIV or induce “remission” and avoid lifelong treatment.
A major barrier to curing HIV is the persistence of a latent reservoir that predominantly resides in CD4+ T cells. Many different strategies have been proposed to target the HIV reservoir. Chief amongst these strategies is the `shock and kill' approach. This is a two-step strategy that involves; (1) using a latency reversing agent (LRA) to induce virus expression and make the infected or virus harboring cell visible to the immune system; and (2) utilizing immune cells to eliminate the infected or virus harboring cell. While clinical trials exploring the utility of the `shock and kill' strategy have shown LRAs to induce viral expression in ART-treated HIV-infected individuals, no trials of this approach have decreased the frequency of cells carrying integrated HIV DNA. The reason(s) that `shock and kill' strategies have not reduced the frequency of cells carrying integrated HIV DNA remains unclear. Stronger LRAs or more potent anti-viral immune responses may be required to purge the latent reservoir.
In this Frontiers Research Topic, we aim to explore novel approaches for eliminating HIV reservoirs. We invite early stage investigators to contribute their ideas as to how to tackle this important scientific problem. We aim to generate a Frontiers Research Topic comprised of short reviews introducing the reader to novel approaches to eliminating HIV reservoirs. These reviews should offer hypotheses regarding therapeutic possibilities and indicate how feasible the discussed approach is as a treatment option. Finally, each review should attempt to discuss what would be required to move the novel strategy into the clinic.