Challenges and strategies for the eradication of the HIV reservoir

Despite the success of highly active antiretroviral therapy (HAART) for inhibiting HIV replication and improving clinical outcomes, it fails to cure infection due to the existence of a stable latent proviral reservoir in memory CD4⁺ T cells. Because of the longevity of these cells harboring transcriptionally silent proviruses, devising strategies to induce viral gene expression so the host immune response can mediate clearance of the infected cells or the cells can undergo virus-induced cell death, has been of considerable recent interest. Here, we review current knowledge of latency, and the challenges to virus induction and eradication. Novel strategies to reactivate HIV reservoirs more effectively, in combination with immunotherapy, could lead to better clearance of the latent HIV reservoir.