ABX464: a good drug candidate instead of a magic bullet

Despite the significant number of antiviral drugs that are currently available in the clinics of developed countries, none of these affect the production stage of HIV-1 replication, more specifically the process of viral gene expression. For instance, several early attempts failed to generate inhibitors of the viral Tat protein, the small activator of viral transcription from the long terminal repeat (LTR) promoter. A recent study published in Retrovirology by Campos et al. presents a new small molecule inhibitor, ABX464, that targets the other small viral protein essential for viral gene expression, the Rev protein (Retrovirology 12:30, 2015). Targeting of multiple virus replication steps and silencing the generation of new progeny may be of particular value for current attempts to develop novel therapeutic strategies that provide a cure or functional cure for HIV-1 infection (Nat Rev Immunol 12: 607-614, 2012). We will briefly review some of the unique antiviral properties of ABX464, with the focus on its surprising ability to exhibit a sustained antiviral effect in a humanized mouse model. Although ABX464 may remain an important new addition to the anti-HIV arsenal, we do present a sobering alternative explanation for the long-lasting reduction in viral load after treatment cessation.