ABSTRACT
ELENA E. PASKALEVA, XUDONG LIN, WEN LI, ROBIN COTTER, MICHAEL T. KLEIN, EMILY ROBERGE, ER K. YU, BRUCE CLARK, JEAN-CLAUDE VEILLE, YANZE LIU, DAVID Y-W LEE, AND MARIO CANKI
11.1 BACKGROUND
Macrophages and T cells are major targets for HIV-1 infection [1]. While macrophages are key cellular reservoir and a source of newly replicating HIV-1 throughout the infection, a global decline in T cell population leads to the eventual collapse of the immune system, development of clinical manifestations of AIDS, and the ultimate death of the host. Highly active antiretroviral therapy (HAART) has greatly extended the lifespan of HIVinfected individuals, however the AIDS epidemic continues to expand
globally and the long-term control of HIV-1 infection remains an elusive goal. Current HAART regiments, with the exception of recent fusion inhibitor (T-20), include inhibitors of two key viral enzymes, reverse transcriptase and protease [2-4]. By using combinations of reverse transcriptase and protease inhibitors in HAART, dramatic reductions in the level of chronic HIV-1 viremia have been achieved in a majority of patients [2,4]. However, both reverse transcriptase and protease inhibitors have significant clinical side effects [5-7]. Initial optimism that the natural decay of virus-producing cells in the presence of HAART would lead to eradication of virus was short-lived [8,9]. Long-term follow-up of HAART-treated individuals revealed very slow rates of decline of HIV-1 in some individuals, with continued low-level replication of virus in macrophages and T cells, and viral persistence in several tissue compartments, such as the CNS, not readily accessible to current therapies [5,9-11]. Studies in a macaque model of simian immunodeficiency virus (SIV) viral persistence in the brain, have suggested that in individuals on HAART with suppressed viral load, the CNS may act as a long-term viral reservoir [12].
