Multiphasic HIV decrease in individuals treated with anti-retroviral drugs has been modeled as the independent decay, with different half-lives, of distinct pools of cells infected before the initiation of treatment. We analyzed the kinetics of plasma HIV RNA in individuals receiving combinations of up to five drugs. The initial rates of decline increased substantially with the efficacy of treatment. Decline rates decreased with time, approaching zero in some cases. These observations are better explained if most of the virus is produced by cells infected after the initiation of therapy. Accordingly, treatment results in ongoing HIV infection cycles of decreasing amplitude, but the decrease progressively attenuates and may cease altogether at some viral load. We propose that HIV replication occurs in multiple local bursts, associated with immune activation in response to antigens. Current anti-retroviral drugs substantially reduce the size of these bursts and diminish their frequency but fail to abolish them.