A broad drug arsenal to attack a strenuous latent HIV reservoir

• Published in: Current opinion in virology 2019-10, Vol.38, p.37-53
• Main Authors: Stoszko, Mateusz, Ne, Enrico, Abner, Erik, Mahmoudi, Tokameh
• Format: Article
• Language: English
• ISSN: 1879-6257; 1879-6265
• DOI: 10.1016/j.coviro.2019.06.001

•Chromatin repression, transcription initiation, transcription elongation.•Distinct mechanistic steps in HIV transcription to target for synergistic activation.•LRAs needed to target blocks in HIV RNA processing in addition to transcription.•Combination strategies to reverse, eliminate and lock latent cells needed. HIV cure is impeded by the persistence of a strenuous reservoir of latent but replication competent infected cells, which remain unsusceptible to c-ART and unrecognized by the immune system for elimination. Ongoing progress in understanding the molecular mechanisms that control HIV transcription and latency has led to the development of strategies to either permanently inactivate the latent HIV infected reservoir of cells or to stimulate the virus to emerge out of latency, coupled to either induction of death in the infected reactivated cell or its clearance by the immune system. This review focuses on the currently explored and non-exclusive pharmacological strategies and their molecular targets that 1. stimulate reversal of HIV latency in infected cells by targeting distinct steps in the HIV-1 gene expression cycle, 2. exploit mechanisms that promote cell death and apoptosis to render the infected cell harboring reactivated virus more susceptible to death and/or elimination by the immune system, and 3. permanently inactivate any remaining latently infected cells such that c-ART can be safely discontinued.