A new HIV treatment mechanism has been discovered and tested, though on small-scale and could prove to be the best bet on beating the epidemic. In addition, it enfolds the genetic blueprint of the virus. The antiretroviral drug interferes with the association and disassociation of the HIV capsid. Current antiretroviral treatment is effective for most people with HIV.
However, a new treatment provides more options especially for people who may have developed the resistant version of the virus. Even so, the last time an HIV drug with a different mechanism to be approved was 10 years ago. This gives more reason for the new treatment to be tried and tested. Researchers are hopeful that the new treatment may propose a new compelling and long-acting treatment opportunity.
Researcher Wingston Tse presented findings during the Conference on Retroviruses and Opportunistic Infections (CROI 2017) in Seattle. The findings were as a result of the Gilead Sciences’ ten-year capsid inhibitor development programme.
The background to the study was the indispensable role played by the HIV p24 capsid protein in the viral lifespan by developing a cone-shaped structure that encloses the viral genome.
Laboratory studies led to the unearthing of a unique class of “skillfully potent” and metabolically steady HIV capsid inhibitors with encouraging pharmacokinetic profiles. After testing capsid binding and assembly as well as X-rays of the crystal structure of capsid inhibitor candidates, the researchers were able to choose those that most readily bound to HIV.
The GS-CA1 that binds to a greatly preserved site at the interface of two neighbouring molecules within a capsid hexamer was then selected.
The Researchers Found That:
- The inhibitor acts at multiple steps in the viral replication cycle
- The inhibitor hindered with capsid assembly required for the advanced stage viral particle growth and the roles that take place after entrance into a host cell and moving viral genetic material into the cell nucleus
Antiviral potency and drug resistance were tested by laboratory human cell lines.
GS-CA1 is a greatly powerful inhibitor of HIV-1 replication and more strong than existing antiretrovirals. Additionally, GS-CA1 demonstrated similar potency against multiple HIV-1 isolated from different people with all the major viral clades.
It also maintained full activity against viral mutants resistant to all approved antiretroviral classes as well as less potent activity against HIV-2.
GS-CA1 was shown to clear slowly from the body after extensive and vigorous metabolism and pharmacokinetic was carried out. This proved that it has a long half-life making it suitable for slow-release parenteral management as well as long-acting jabs.
The study was also carried out in animals, rats to be more specific that maintained high levels of drug plasma for ten weeks. The company aims to move into human trials using low-dose jabs given just once a month. The company also aims to proceed with toxicology studies and begin phase 1 clinical trials in 2018.
The study is among many that are being done by researchers across the globe in the hope to find a cure for the dreaded HIV virus. There is hope that HIV will be curable in the years to come. For now, HIV Post-Exposure Prophylaxis treatment is commonly used to combat the HIV infection likelihood.
Reference: Tse WC et al. Discovery of novel potent HIV capsid inhibitors with long-acting potential. Conference on Retroviruses and Opportunistic Infections (CROI 2017), Seattle, abstract 38, 2017.