How Might We Cure HIV?

Antiretroviral therapy (ART) does not eliminate HIV-1 from latently infected reservoirs, and this remains the critical obstacle to the eradication of infection. Although ART is effective in suppressing viral load, life-long ART is burdensome in many respects. Given expanding numbers of HIV-infected individuals on ART worldwide, there is an urgent need to examine the possibility that innovative therapies might eradicate infection, and obviate the need for life-long medical therapy for HIV-positive people around the world. Several approaches to eradicating the latent HIV reservoir and curing infection have been proposed and are under study. An initial strategy seeks to induce the expression of the latent integrated proviral genomes within resting CD4+ T cells, so that viral proteins or particles may be revealed and allow these cellular reservoirs to be cleared. The inducing agents that have been studied recently are inhibitors of histone deacetylase (HDAC) such as suberoylanilide hydroxamic acid (SAHA). Such induction of viral expression seems unlikely in itself to efficiently clear all latently infected cells. Therefore, it seems likely that parallel efforts to augment the HIV-specific immune response with specific immunotherapies or vaccination may be required. Recently, efforts to achieve immune augmentation by ex vivo expansion of viral specific cytotoxic T-cell lymphocytes derived from HIV-infected patients have yielded an augmented HIV-specific immune response in vivo, as have cellular vaccinations delivered by administration of dendritic cells. As HIV latency and the persistence of infection despite effective ART is multifactorial, the eradication of HIV infection may require multiple approaches.