Grant: Chair: GlaxoSmithKline Partnered

The human immunodeficiency virus-1 (HIV-1) epidemic has infected approximately 75 million people worldwide, of which more than 35 million have died from acquired immunodeficiency syndrome (AIDS)-related complications. The development of antiretroviral therapy has been a great achievement of modern medicine, significantly prolonging the life span of infected individuals and reducing AIDS-related mortalities. However, ART is not curative, as evidenced by the rapid rebound in viremia seen in patients after therapy interruption, despite months of undetectable viremia. One possible explanation is that viral replication may persist at low levels in tissues where drug bioavailability is suboptimal. Indeed, recent findings show that antiretrovirals are largely ineffective at suppressing HIV infection when it is transmitted through cell-to-cell contact between infected and uninfected cells. Given the densely packed nature of lymphoid tissues, where explosive viral replication occurs, it is thus conceivable that cell-to-cell HIV transmission plays an important role in viral dissemination in humans. In this proposal, we will test this hypothesis, using innovative in vitro and in vivo imaging approaches, to study the cellular dynamics of contact-mediated viral spread. The implications are that the development of new therapeutic strategies must be able to remain effective against, or specifically target, this form of transmission.