Relationship between pre-existing viral reservoirs and the re-emergence ofplasma viremia after discontinuation of highly active anti-retroviral therapy

We examined the pathogenic significance of the latent viral reservoir in th e resting CD4(+) T cell compartment of HIV-1-infected individuals as well a s its involvement in the rebound of plasma viremia after discontinuation of highly active anti-retroviral therapy (HAART). Using heteroduplex mobility and tracking assays, we show that the detectable pool of latently infected , resting CD4(+) T cells does not account entirely for the early rebounding plasma HIV in infected individuals in whom HAART has been discontinued. In the majority of patients examined, the rebounding plasma virus was genetic ally distinct from both the cell-associated HIV RNA and the replication-com petent virus within the detectable pool of latently infected, resting CD4() T cells. These results indicate the existence of other persistent HIV res ervoirs that could prompt rapid emergence of plasma viremia after cessation of HAART and underscore the necessity to develop therapies directed toward such populations of infected cells.