The source of persistent HIV in patients on suppressive therapy is debated. Recent studies of treatment intensification have produced varied results: no reduction in low-level plasma viremia indicating the source of persistent viremia is long-lived HIV-infected cells that release HIV when activated and increase in episomal HIV DNA indicating active replication persists in some infected individuals on suppressive therapy. In addition, clonal HIV sequences found in plasma from patients on long-term suppressive therapy are rarely found in CD4 memory T cells. These results indicate that persistent viremia may arise from several different sources. Recent studies emphasize the complexity of HIV latency. Current strategies for HIV eradication focus on compounds that activate viral transcription in memory CD4 T cells by many routes, including inhibiting histone deacetylation and activating nuclear factor kappa B. Several compounds and combinations of these compounds appear to induce the expression of integrated HIV in different latency models. This review focuses on recent advances in HIV research and therapy that seek to eradicate persistent HIV in patients on suppressive therapy.
Many researchers currently investigate the source and dynamics of residual viremia. A well defined latent reservoir of HIV is memory CD4 T cells. However, other cell types such as hematopoietic stem cells and cells of the monocyte/macrophage lineage may also serve as long-term reservoirs of HIV. Several mechanisms appear to play a role in maintaining HIV latency including viral integration sites, chromatin environment, and downregulated transcription factors. Further studies are necessary to better understand the mechanisms that promote HIV latency in vivo. Recent studies shed new light on persistent HIV reservoirs and the mechanisms of latency. These studies highlight an important conclusion: any long-term strategy for HIV eradication must take HIV latency and its implications into account. Importantly, approaches to eradication of latent HIV reservoirs should not lead to new HIV infection as a result of activating latently infected cells or cause global T-cell activation. Although many challenges remain, it is encouraging to note that new research and debate have begun to seriously address HIV eradication and/or remission.