Abstract Body

HIV proviruses persist in vivo in latent and transcriptionally active forms. Little is known regarding the fraction of infected cells in blood and in tissues that are quiescent versus those that actively express HIV RNA in either ART treated or untreated individuals, although it is known that the majority of proviruses are defective for viral replication due to deletion or hypermutation. It is thought that cells expressing HIV, defective or not, are susceptible to cell killing by cytopathic effects or immune responses. It stands to reason, therefore, that long-lived latently-infected cells may accumulate over the course of HIV infection and persist after ART is initiated. Indeed, many studies have demonstrated the persistence of latently-infected cells during ART and, it is believed that such cells, when activated, are the source of viral rebound when ART is interrupted. However, it has been reported that HIV-expressing cells in lymph nodes may be protected from the cytotoxic T-cell immune response, and therefore, may persist during ART despite HIV expression and, therefore, may be the primary source of viral rebound when treatment is stopped. It was also recently discovered that HIV infected T-cells can persist in vivo through cellular proliferation, which occurs both prior to and during ART. In one case thus far, a highly expanded infected CD4+ T cell clone was shown to be the source of persistent infectious viremia during ART, demonstrating that at least some members within clones can express HIV RNA and produce virus particles. This talk will summarize emerging data from studies investigating the fraction of HIV infected cells that express HIV RNA in blood and tissues both prior to and during ART and the fraction of HIV expressing cells within cell clones, including those carrying replication-competent proviruses. Understanding the fractions of viral RNA expressing cells and levels of HIV RNA expressed by them during ART will lead to a better understanding of the HIV reservoir, the nature of latency, and the sources of rebound viremia when ART is interrupted.