Antiviral drug resistance pathways. Long range objective is to understand the mechanisms by which lentiviruses become resistant to antiviral drugs and to utilize this information to help develop improved strategies for chemotherapy of AIDS; strategies to combat viral resistance to AIDS therapy. A major barrier to successful treatment of the acquired immune deficiency syndrome (AIDS) with antiviral drugs is the emergence of drug-resistant mutants of the human immunodeficiency virus type-1 (HIV-1). The long-range objective of this laboratory is to understand the mechanisms by which lentiviruses become resistant to and/or evade antiviral drugs and to utilize this information to help develop improved strategies for chemotherapy of AIDS. We have developed model systems using chimeric viruses based on simian immunodeficiency virus (SIV) containing the HIV reverse transcriptase (RT-SHIV) for studies of Highly Active AntiRetroviral Therapy (HAART) in rhesus macaques. We are using this model to characterize reservoirs of viral latency and sites of residual replication during HAART. In a related project we have developed novel entry inhibitors of HIV with a combinatorial chemistry approach, and we are developing methods to “evolve” these inhibitors in response to emergence of drug-resistant HIV mutants. These approach provides a new strategy to help combat viral resistance to AIDS therapy.
Visit Dr. North's website: http://faculty.vetmed.ucdavis.edu/faculty/twnorth/