The capacity of HIV-1 to establish latent infection at the level of individual cells allows viral persistence in the presence of an active immune response and anti-retroviral therapy. Understanding the size and composition of the latent reservoir is essential for predicting whether virus eradication is possible. Using extremely pure cell populations isolated from lymph nodes of 14 infected individuals, we analyzed the total body load of latently infected CD4+ T cells carrying integrated and unintegrated provirus. We also measured the extent of infection in macrophages and activated CD4+ T cells in the lymphoid tissues where active virus replication occurs. The asymptomatic phase of infection is characterized by a steady state in which there is an extremely low total body load of latently infected resting CD4+ T cells with replication-competent integrated provirus (<10-7 infected cells). The most prevalent form of provirus in resting and activated CD4+ T cells is a full length, unintegrated form that is not replication-competent, probably because of defects that prevent recognition by integrase. The infection progresses even though at any given time integrated provirus is present in only a minute fraction (<0.I%) of the susceptible populations in the lymphoid tissues including resting and activated CD4+ T cells and macrophages. The extremely low frequency of cells with stably integrated provirus provides an optimistic perspective on the possibility of virus eradication and immune reconstitution.
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