Current antiretroviral therapies (ART) effectively eliminate HIV replication in CD4+ T-cells but do not eradicate non-replicating, persistent viral forms that integrate within human chromosomal DNA in latently infected cells. Latently infected HIV cells are established extremely early during infection and persist for the lifetime of the infected person. New technologies are in development to eradicate the HIV reservoir. This would allow patients to remain healthy off of ART and pose no transmission risk to their sexual partners.
With Dr. Florian Hladik, we are modeling the possibility of anti-proliferative agents as a means to decrease the size of the reservoir. We are also working with Dr. Keith Jerome who is developing DNA cleavage enzymes to target and terminally mutate viral DNA. DNA cleavage enzymes must be delivered to infected cells as gene therapy within viral delivery vectors. We are developing testable models to identify optimal dosing strategies using this approach. Finally, we are working with Dr. Hans Peter Kiem who is employing autologous transplantation of stem cells as a potential strategy to cure HIV. These cells are genetically modified ex vivo such that HIV entry is longer possible, and then transplanted back into the HIV-1 infected person. We are developing models that identify a threshold of modified cells necessary to eliminate HIV infected cells.