AntiViral-HyperActivation Limiting Therapeutics (AV-HALTs): A New Class of Antiviral Drugs

This paper will review recent discoveries in the field of viral pathogenesis and the development of a new antiretroviral class known as AntiViral-HyperActivation Limiting Therapeutics (AV-HALTs) that has been specifically designed in response to these findings. AV-HALTs are characterized by the combination of two distinct activities – the direct inhibition of viral replication (antiviral activity) and the reduction of excessive chronic immune system hyperactivation (hyperactivation limiting effect). These two effects can be achieved by combining two drugs (a first-generation AV-HALT) or by a single molecule (second-generation AV-HALTs).

The medical need for AV-HALTs is best illustrated in the treatment of the Human ImmunoDeficiency Virus Type 1 (HIV-1). Paradoxically, it is the chronic, excessive hyperactivation of the immune system, resulting in cellular hyperproliferation and systemic inflammation – throughout the course of HIV disease – that is now recognized as the major driver of not only the continual loss of CD4⁺ T cells and progression to the Acquired Immunodeficiency Syndrome (AIDS), but also of the emergence of both AIDS-defining and non-AIDS-defining events that negatively impact upon both morbidity and mortality despite otherwise successful (ie, fully virus suppressive) HIV therapy. This review will focus upon the establishment of the human proof of concept for AV-HALTs using a two-drug, first-generation AV-HALT (VS411) and the development of single-molecule, second-generation AV-HALTs for the treatment of HIV-1 disease and other chronic viral infections.

Keywords: Immunotherapy, disease-modifying treatment, AV-HALT, inflammation, HIV.