Vpu Inhibitor Candidate

A Vpu inhibitor candidate shows promise against HIV & HCV

by Jeannie Wraight

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[dropcap]B[/dropcap]IT225 is a new type of antiviral called a Vpu inhibitor, which researchers are investigating to treat both HIV and HIV/hepatitis C (HCV) co-infection. This potential therapy is among the more compelling drugs in the HIV pipeline, offering two mechanisms of action for the treatment of HIV. In addition, data shows that BIT225 has a 100-percent sustained virologic response (SVR) in difficult to treat HCV genotype 3a in combination with ribavirin and interferon.

HIV
Reported data of BIT225 in HIV patients has produced interesting results and demonstrates two potential means of controlling HIV from the use of one unique drug. Studies found that BIT225 can reverse HIV-induced impairment of the immune system. In addition, BIT225 has been found to inhibit viral production in myeloid cells in viral reservoirs.

Decreasing inflammation
HIV antiretroviral therapy (ART) effectively decreases the level of HIV in the body with the goal of near complete viral suppression in the blood. This allows the immune system to rebuild or, at least, prevent further damage from occurring.

Inflammation is likely the most catastrophic effect of HIV in the post-ART era. Inflammation is the overactivation of the immune system in response to continual pathogens, in this case HIV. Despite decreased levels of HIV in the body due to ART, the immune system sees the remaining ongoing HIV replication as a threat and tries to neutralize it, causing a continual activation of the immune system. This activation results in inflammation.
Inflammation is extremely harmful to the body and causes what we refer to as co- morbidities. These illnesses include heart disease, cancers, neurological conditions and bone disorders.

In a Phase 1a/2b study in Thailand, twenty-one ART-naïve individuals were given either BIT225 or placebo for ten days. Researchers found that levels of sCD163—a marker of immune activation in macrophage cells, of which myeloid cells are a precursor—were significantly reduced in those receiving BIT225, thus showing that the drug successfully reduced inflammation effected by macrophages in the viral reservoir. This is the first time a drug has been able to achieve such a reduction.

“The aim of drug treatment for HIV is to not only reduce virus levels, but also to dampen down the associated immune activation. BIT225 can potentially target both sides of the problem, resulting in reduction of virus and a normal functioning immune system,” said Dr. John Wilkinson, Senior Virologist at Biotron, the biotech that is developing the agent.

The reduction of viral reservoirs
Because macrophages, those long-lived cells that are believed to make up part of the HIV viral reservoir, live much longer than other cells, some researchers believe that they may be a vital factor to the persistence of viral reservoirs. The reservoir maintains a very low level of replication despite the decrease of HIV in blood due to ART. The latent cells that harbor resting HIV are thought to be the primary obstacle to developing a strategy to eradicate HIV.

In the same study as described above, researchers found that BIT225 decreased the level of HIV in monocytes. The highest reduction was seen in study participants who had the greatest levels of HIV.

BIT225 would likely be used in combination with other antiretroviral medications in order to reduce the amount of HIV in the blood and prevent continued replication in viral reservoirs. Biotron suggests, “BIT225 is a candidate agent that could be useful in future eradication strategies.”

Hepatitis C
Approximately twenty-five percent of HIV- positive people in the U.S. are co-infected with hepatitis C. Co-infected individuals have historically not responded to HCV treatment as well as those with HCV mono-infection. BIT225 is being studied specifically for people who are co-infected.
In a small study of HIV/HCV co-infected individuals with genotype 3a who were given BIT225 along with interferon and ribavarin, all of the study participants achieved sustained virologic response (SVR) HCV RNA levels at twelve weeks. The rate of SVR in patients with genotype 3a in Thailand, where this study took place, is 68.8 percent. In comparison, researchers saw a 100-percent SVR rate when BIT225 was added to interferon and ribavirin.

BIT225 was also tested in patients with genotype 1, the most common HCV genotype (approximately 83.4 million people worldwide are living with it).
In this study, 100-percent of study participants who received 400 mg of BIT225 in combination with interferon and ribavirin maintained SVR at forty-eight weeks.

Studies with newer HCV therapies are needed. If results continue to be positive, BIT225 could be used in several different ways to treat people with HIV as well as people co-infected with HCV/HIV. The reduction of inflammation as well as the ability to reduce reservoir virus levels would make this drug a novel and advantageous addition to the present arsenal of HIV therapies and a potential player in the possible eradication of HIV.


 

Jeannie Wraight is the former editor-in-chief and co-founder of HIV and HCV Haven (www.hivhav- en.com) and a blogger and writer for TheBody. com. She is a member of the Board of Directors of Health People, a community-based organization in the South Bronx and an advisor to TRW (Teach me to Read and Write), a community-based organization in Kampala, Uganda. She lives with her husband in New York City.