We caught up with Gilead‘s Mike Elliott to find out the latest in HIV medication and whether a cure is finally within our reach…
HIV capsid inhibitors – what are they and how do they work to attack the virus?
Capsid inhibitors are a new class of medicines that have the potential to be used as novel long-acting antiretroviral therapy (ART) in the future, to improve upon currently available treatments and address the unmet needs of PLWHIV while we continue to search for a cure.
Previously, the capsid was not an explored target for ART and the study presented at CROI 2017 identified a novel capsid inhibitor, GS-CA1, that has a highly potent antiviral activity and a favourable resistance profile compared to existing ARVs, in vitro.
Inside the HIV virus, a conical capsid encloses the viral (RNA) genome. This capsid is essential for viral replication and plays an important role in the early and late stages of the viral life cycle:
- Early on, when the viral and host-cell membranes fuse, the capsid is released into the host cell and ‘uncoats’, allowing for viral replication
- Following replication of the viral genome, a new capsid forms at the end of the replication process to produce a mature viral particle
The data show that GS-CA1 has a dual mechanism of action, targeting the role of the capsid in both stages of the replication process.
In addition to being a highly potent inhibitor of HIV-1 replication, in an animal model, GS-CA1, maintained target plasma concentrations for over 10 weeks, following a single subcutaneous administration.
Based on these results, we plan to initiate Phase 1 clinical trials of GS-CA1 in 2018.