March/April 2017 

The capsid inhibitor—a new class to enter clinical trials

Most approved anti-HIV drugs work by interfering with an enzyme and/or protein that is needed by HIV-infected cells to make new viruses.

A journey through the cell

The capsid is the name given to the proteins that surround HIV’s genetic material. Upon HIV attaching itself to a target cell of the immune system, the virus sends its genetic material (RNA) into the cell. As the genetic material is surrounded by the capsid, it is protected from detection by the cell’s internal sensors. The capsid, along with its cargo of genetic material, then makes its way to the cell’s control centre, or nucleus. Inside the nucleus is the cell’s genetic material, which contains instructions for the operation of the cell and helps it carry out its functions. Once near the nucleus, the capsid releases its cargo, and through a series of steps HIV’s genetic material is converted into a form similar to the cell’s genetic material (DNA). The capsid proteins then help HIV’s DNA cross into the nucleus, where it integrates into the cell’s DNA. At some point in the future, perhaps through immunological stimulation, the cell becomes activated and HIV’s DNA takes over the cell and converts it into a mini-virus factory, producing new copies of HIV.

More about the capsid

The capsid has several functions, as follows:

  • it protects HIV’s genetic material
  • it helps HIV’s genetic material gain entry to the nucleus of a cell
  • it helps the new copies of HIV become infectious

Thus, a capsid inhibitor could work by interrupting or impairing three different parts of HIV’s life cycle. In theory, since the capsid inhibitor has so many anti-HIV activities, it could be used by itself in the prevention of HIV infection. However, much work lies ahead before this drug’s developer, Gilead Sciences, can be certain about that. A long-acting formulation of the capsid inhibitor has been developed and can maintain high levels in dogs for at least 10 weeks. This finding suggests that the capsid inhibitor has potential for intermittent dosing in people—perhaps every one or two months. However, this formulation likely will need further testing in animals, particularly in monkeys susceptible to SIV (simian immunodeficiency virus, which is closely related to HIV), before human studies begin. Taking all of this information into account, clinical trials with the capsid inhibitor may not begin until 2018.

—Sean R. Hosein


Tse WC, Link JO, Mulato A, et al. Discovery of novel potent HIV capsid inhibitors with long-acting potential. Conference on Retroviruses and Opportunistic Infections, 13-16 February 2017, Seattle. Abstract 33.