The capacity of HIV-1 to establish a state of latent infection at the level of individual cells provides a mechanism for viral persistence in the face of highly active antiretroviral therapy (HAART). In previous studies, we have shown that resting memory CD4+ T cells carrying latent, replication-competent pro-virus are present at low frequency in all infected individuals. Longitudinal studies of patients on HAART have shown that this reservoir of latently infected cells is reservoir might be subject to modulation by therapeutic strategies that enhance the immune response to HIV-1. It is extraordinary stability of the latent reservoir reflects that fact that it is being continually replenished by a low level of ongoing viral replication that continues even in patients on HAART who have undetectable levels of plasma virus. If this is the case, then enhanced immune responses to HIV-1 may contribute to the control of this ongoing replication and may lead to a measurable decrease in the size of the latent reservoir. The latent reservoir may be the only virologic parameter that can be measured in patients with undetectable plasma virus. We will therefore determine whether in the setting of HAART immunization with viral antigens can affect the size and rate of the decay of the patent reservoir in HIV-1-infected humans and HIV-infected macaques. Specifically, in collaboration with Dr. MacGregor, we will determine whether th4e frequency of latently infected cells is decreased in individuals on HAART who have been immunized with DNA and pox virus based vaccines encoding HIV-1 antigens.
