AV-HALTs in the treatment of HIV/AIDS

AV-HALTs in the Treatment of HIV/AIDS

Highly active antiretroviral therapy (HAART) constitutes the current standard of care for treating the Human Immunodeficiency Virus (HIV). Although HAART is quite effective in reducing viral load and raising CD4+ cell counts, latent virus reservoirs persist and as many as 60 years therapy may be required to eradicate the virus. People receiving HAART are also likely to experience drug-related toxicity and may have to change therapy due to the emergence of drug-resistant strains. For these reasons, the search for new therapeutic approaches continues.

What are "AV-HALT" drugs?

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 the Acquired Immunodeficiency Syndrome (AIDS). It is believed that immune system hyperactivation is primarily driven by processes such as the "leaking" of microbes and pieces of microbes (ie, microbial translocation) across the gut. Once passing the gut, these antigens create an elevated systemic immune response that persists throughout HIV infection and drives the loss of CD4+ T helper cells that eventually leads to AIDS, opportunistic infections and death.

ViroStatics is developing new AntiViral-HyperActivation Limiting Therapeutics (AV-HALT) drugs and drug combinations designed to both reduce the amount of HIV replication and to slow this progressive loss of immune system function.

AV-HALTs Pathogenic rationale in HIV/AIDS
HAART does an excellent job of reducing viral replication, but does not significantly reduce the excessive immune activation that is actually driving HIV disease progression.		AV-HALTS not only reduce viral replication, but also directly limit the hyper-activation of the immune system that drives disease progression.

Clinical Proof-of-Concept AV-HALT: VS411 - A two-drug combination

The combination of dideoxyinosine, an antiviral, and hydroxycarbamide, an antiproliferative agent, has been suggested as a potential therapeutic approach to accomplish the dual goals of decreasing viral replication and down-regulating immune hyperactivation. ViroStatics has successfully developed VS411, a fixed drug combination of didanosine and hydroxycarbamide, to establish the clinical Proof of Concept for the AV-HALT platform.

		In a multinational Phase 2 a Study of VS411 presented at the International AIDS Society's "AIDS 2010" conference in Vienna, VS411 safely lowered HIV replication by 1.5 logs (96.8%) without inducing drug resistance, significantly increased CD4+ T cells by up to 135 cells/mm3 in the dideoxyinosine 200 mg/hydroxycarbamide 900 mg cohort (doses lower than traditionally investigated) in only 28 days. VS411 also rapidly and significantly reduced four key markers of excessive immune activation, becoming the first HIV/AIDS therapy to achieve both goals of an AV-HALT after only four weeks of therapy.