DNA reservoir seeding in HIV superinfection

During HIV infection a reservoir of long-lived latently infected cells is established that persists during antiretroviral therapy and is the source of virus replication after treatment cessation. A better understanding of HIV reservoir seeding will aid efforts to target these long-lived HIV infected cells during their establishment. The goal of this study was to characterize DNA sequences in the HIV reservoir from women infected at two different times with two genetically distinct HIV strains (called superinfection) and compared them to RNA sequences throughout infection. This allows an accurate estimate of when HIV DNA entered the reservoir. In most cases we observed viruses from both the initial and superinfecting lineages in the reservoir, suggesting that reservoir seeding occurs throughout HIV infection. However, the majority of HIV sequences entered the reservoir near the time of ART initiation, suggesting that novel strategies that aim to reduce reservoir size should target viruses that enter the reservoir immediately prior to ART.