AntiViral-HyperActivation Limiting Therapeutics (AV-HALTs) are an investigational class of
antiretroviral drugs
The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of mult ...
used to treat
Human Immunodeficiency Virus
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause AIDS, acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of th ...
(
HIV
The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...
) 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
The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
hyperactivation now believed to drive the loss of
CD4
In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as helper T cells, monocytes, macrophages, and dendritic c ...
+
T helper cells
The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...
leading to disease progression and
Acquired Immunodeficiency Syndrome
The human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a preventable disease. It can ...
(
AIDS
The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...
).
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.
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 (e.g. didanosine) with a cytostatic agent (e.g.
hydroxyurea
Hydroxycarbamide, also known as hydroxyurea, is an antimetabolite medication used in sickle-cell disease, essential thrombocythemia, chronic myelogenous leukemia, polycythemia vera, and cervical cancer. In sickle-cell disease it increases fe ...
).
Examples
* VS411, investigational first generation combination AV-HALT (low-dose hydroxyurea + didanosine) (
Phase II) - ViroStatics, srl
[
]
* VS1-002, investigational second generation single-drug AV-HALT (Pre-clinical) - ViroStatics, srl
Synonyms
* virostatics (antiVIRal + cytOSTATICS)
References
{{DEFAULTSORT:Av-Halt
Antiretroviral drugs