Approximately 4-5 million people worldwide are known to be co-infected with HIV and Hepatitis C (HCV). Managing HCV could be made easier by treating it with the same medication used for HIV. BIT-225 is one such treatment and is being studied for both illnesses.
Shown at the International Conference on Antiviral Research (ICAR) this April in Sapporo, Japan, BIT-225 is a VPU inhibitor in development by Biotron, a small Australia-based biotechnology company. Accumulating research from various institutions and researchers has highlighted the importance of VPU in HIV production.
VPU is an HIV accessory protein involved in the release of viral particles. All of the available HIV drugs target a step of the HIV lifecycle, preventing the virus from doing its job and thus stopping HIV from continuing to infect cells. For example, nucleoside analogs and non- nucleoside analogs target nucleoside reverse transcriptase and protease inhibitors target the protease enzyme.
VPU helps with the assembly of new virus particles, assisting them to bud from the infected cell. Without VPU, HIV remains attached to the surface of the human cell in which it has replicated. It is possible for HIV to replicate and bud without this particular protein, but only 10% or 20% as many new virus particles are produced. Without the VPU gene, the virus actually kills off the infected cell quicker, delaying the cytopathic (cell-killing) effects of infection that keeps the cell alive slightly longer so that it can produce more virus particles.
The goal of BIT-225 is to gain entry into cell reservoirs where current ARV’s cannot. This would allow the drug to kill off infected cells in reservoirs while other ARV’s prevent the spread of active virus. Penetrating reservoirs is a strategy that many feel is among the best options for curing HIV.
Recent results from a study of BIT-225 show the VPU inhibitor to be promising for the treatment of HCV. An HIV trial is also currently underway and another planned for this year in people co-infected with HIV and HCV.
In a Phase IIa trial, BIT 225 was used in combination with interferon and ribavirin (standard treatment). The drug was given to 24 people for four weeks. The participants were then followed for an additional 44 weeks while they took interferon and ribavirin. Participants received either 200 or 400 mg. of BIT-225 along with interferon and ribavirin, with a third group given interferon, ribavirin and placebo.
At the end of the 4 weeks, eighty-seven percent of people in the 400 mg. arm had an undetectable viral load compared to sixty-three percent of people who received interferon and ribavirin with a placebo. An additional 1 log decrease in HCV viral load was seen in study participants who added BIT 225 to interferon and ribavirin.
Follow-up data at 12 weeks showed the viral decrease was sustained two months after BIT 225 was stopped. Those who participated in this study had a HCV- 1, the most common genotype in the U.S., Europe and South America. Additional follow-up data is expected to be presented in the second half of 2012.
A phase Ia/IIb clinical trial is scheduled to begin dosing in June, with results expected later this year. BIT 225 will be given to 24 HIV treatment naive people in Bangkok, the same clinic where the HCV trial was conducted.
A Phase IIa study is planned for mid 2012 of BIT 225 in people with HIV and HCV co-infection. The study will be extended to include HCV-2 and HCV-3.