Ludwik Hirszfeld Memorial Lecture: HIV-1 reservoirs: major molecular obstacles to viral eradication.

Over the last 18 years of study in one of our laboratories, we have observed the development of residual disease and latent reservoirs as major problems in the long-term therapy of HIV-1-infected individuals on highly active antiretroviral therapy (HAART). It was shown in the early 1990 's that HAART, as it is presently configured, is unlikely to lead to viral eradication due to several mechanisms of viral persistence. The two general mechanisms involved with persistence during HAART include low-level residual, cryptic replication and proviral latently-infected cells. As such, these are key areas of potential studyfor depletion and, hopefully in the future, eradication of residual disease in patients on suppressive HAART. To deplete these residual disease mechanisms will require multipronged approaches. These will include induction of HIV-1 latent proviruses, suppression of residual viral replication and destruction of long-lived cellular sanctuaries, such astissue-bound macrophages.