AV-HALT
Encyclopedia
AntiViral-HyperActivation Limiting Therapeutics (AV-HALTs) are an investigational class of antiretroviral drugs used to treat Human Immunodeficiency Virus (HIV
) infection. Unlike other antiretroviral agents given to reduce viral replication, AV-HALTs are single or combination drugs designed to reduce the rate of viral replication while, at the same time, also directly reducing the state of immune system
hyperactivation now believed to drive the loss of CD4
+ T helper cells leading to disease progression and Acquired Immunodeficiency Syndrome (AIDS
).
This process is believed to be key to the pathogenesis of HIV infection and the progression to Acquired Immunodeficiency Syndrome (AIDS).
There is a growing recognition that successful long-term therapy for the treatment of HIV infection should not only reduce viral replication, but also limit the hyper-activation of the immune system now proposed as the cause of the eventual progression to AIDS. AV-HALTs are designed to accomplish two goals – the reduction of viral load (decreased viral load) and the reduction of immune system hyperactivation (decreased markers of cellular activation and proliferation). First generation AV-HALTs accomplish this by combining an antiviral drug (eg, didanosine) with a cytostatic agent (eg, hydroxyurea
). Second generation AV-HALTs emerging from drug discovery combine antiviral and anti-immune system hyperactivation in a single molecule.
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
) infection. Unlike other antiretroviral agents given to reduce viral replication, AV-HALTs are single or combination drugs designed to reduce the rate of viral replication while, at the same time, also directly reducing the state of immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
hyperactivation now believed to drive the loss of CD4
CD4
CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...
+ T helper cells leading to disease progression and Acquired Immunodeficiency Syndrome (AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
).
Mechanism
Chronic immune stimulation due to persistent HIV replication and microbial translocation across impaired gut-associated lymphoid tissues (GALT) induces continuous T-cell activation and proliferation of both HIV-infected and bystander cells, ultimately resulting in the exhaustion of the immune system.This process is believed to be key to the pathogenesis of HIV infection and the progression to Acquired Immunodeficiency Syndrome (AIDS).
There is a growing recognition that successful long-term therapy for the treatment of HIV infection should not only reduce viral replication, but also limit the hyper-activation of the immune system now proposed as the cause of the eventual progression to AIDS. AV-HALTs are designed to accomplish two goals – the reduction of viral load (decreased viral load) and the reduction of immune system hyperactivation (decreased markers of cellular activation and proliferation). First generation AV-HALTs accomplish this by combining an antiviral drug (eg, didanosine) with a cytostatic agent (eg, hydroxyurea
Hydroxyurea
Hydroxycarbamide or hydroxyurea is an antineoplastic drug, first synthesized in 1869, used in myeloproliferative disorders, specifically polycythemia vera and essential thrombocythemia...
). Second generation AV-HALTs emerging from drug discovery combine antiviral and anti-immune system hyperactivation in a single molecule.
Types
AntiViral-HyperActivation Limiting Therapeutics come in two forms:- Combination (multi-drug) AV-HALTs
- Single-drug AV-HALTs
Examples
- VS411, investigational first generation combination AV-HALT (low-dose hydroxyurea + didanosine) (Phase IIPhase IIPhase II may refer to:* Phase II clinical trial* Drug metabolism Phase II* Star Trek: Phase II, a planned Star Trek television series that eventually evolved into Star Trek: The Motion Picture...
) - ViroStaticsViroStaticsViroStatics, srl is an Italian/USA biopharmaceutical company with a focus on research and development for the treatment of infectious diseases such as HIV and hepatitis C and cancer...
, srl - VS1-002, investigational second generation single-drug AV-HALT (Pre-clinical) - ViroStaticsViroStaticsViroStatics, srl is an Italian/USA biopharmaceutical company with a focus on research and development for the treatment of infectious diseases such as HIV and hepatitis C and cancer...
, srl