Protease inhibitor — fosamprenavir
The propensity of the human immunodeficiency virus (HIV) to mutate and become resistant to the drugs used to treat it has led to the need for a steady stream of new therapeutic agents to take over when existing drugs become ineffective. Combination therapy, including reverse transcriptase inhibitors like AZT and the newer protease inhibitors, has revolutionised the treatment of HIV-infected patients. The amount of virus present can now, at least in the short to medium term, be reduced to near undetectable levels, and the time it takes for progression from HIV infection to full-blown AIDS can be greatly extended.1
Protease inhibitors affect the HIV-1 virus's life-cycle late on when infected cells release virions, and if the enzyme is not working properly then the virions produced are not mature or infectious.
A new protease inhibitor currently in Phase III trials at GlaxoSmithKline, who licensed the compound from Vertex Pharmaceuticals, is fosamprenavir. The compound is a prodrug of the already licensed protease inhibitor amprenavir, which has serious bioavailability problems as it has a high lipophilicity and a low water solubility. The inactive phosphate ester is extremely water-soluble, and is converted to the active non-phosphated compound in the body. It is administered as the Na or Ca salt
In a randomised study in 85 adults infected with HIV who had not already received antiretroviral treatment, patients were given either amprenavir or fosamprenavir. Good improvements were seen in HIV-1, CD-4+ and RNA counts. Side-effects were similar, though the fosamprenavir group showed a lower incidence of abdominal pain and moderate nausea, and a slightly higher incidence of transient headache and sleep problems.2
Further Phase III studies of the drug are under way, including trials in patients who have already received antiretroviral treatment, and into the effectiveness of the compound in combination with ritonavir.