Host-directed approaches in the pursuit of a cure for HIV

The success of antiretroviral therapy (ART) for people with HIV has been a result of direct acting antiviral small molecules that target key components of the viral life cycle, however ART must be taken life long and there is no cure. The major barrier to a cure for HIV is the persistence of a long lived and proliferating reservoir of latently infected cells that persist on ART. Cure strategies for HIV currently target host proteins to either reduce the size of the reservoir or enhance HIV-specific immunity. A major challenge of targeting a host protein is the lack of specificity for HIV and therefore increased risk of adverse events. However, cure strategies are designed to be time limited, as opposed to ART which is lifelong. Here we review host-directed cure strategies that modulate HIV transcription and infection, enhance cell death and/or increase HIV-specific immune control. Ultimately a cure strategy will require a combination of these interventions.