QUANTIFICATION OF LATENT TISSUE RESERVOIRS AND TOTAL-BODY VIRAL LOAD IN HIV-1 INFECTION

The capacity of HIV-1 to establish latent infection of CD4(+) T cells may allow viral persistence despite immune responses and antiretrovira l therapy. Measurements of infectious virus(1,2) and viral RNA(3,4) in plasma and of infectious virus(1), viral DNA(5-10) and viral messenge r RNA species(11-14) in infected cells all suggest that HIV-1 replicat ion continues throughout the course of infection. Uncertainty remains over what fraction of CD4(+) T cells are infected and whether there ar e latent reservoirs for the virus. We show here that during the asympt omatic phase of infection there is an extremely low total body load of latently infected resting CD4(+) T cells with replication-competent i ntegrated provirus (< 10(7) cells). The most prevalent form of HIV-1 D NA in resting and activated CD4(+) T cells is a full-length, linear, u nintegrated form that is not replication competent. The infection prog resses even though at any given time in the lymphoid tissues integrate d HIV-1 DNA is present in only a minute fraction of the susceptible po pulations, including resting and activated CD4(+) T cells and macropha ges.