HIV - MK-0518
HIV infection has been transformed from a death sentence to a manageable, chronic disease by the use of cocktails of antiviral drugs.
HIV infection has been transformed from a death sentence to a manageable, chronic disease by the use of cocktails of antiviral drugs.
However, because of the development of resistance to the drugs used there is a continuing need for new antiviral agents, both in the same classes as the existing reverse transcriptase inhibitors and protease inhibitors, but also drugs that act by new mechanisms.
A third enzyme that is involved in HIV replication, integrase, is also a potential target for drugs. This enzyme mediates the integration of the virus's reverse transcribed DNA into the genome of the host cell. Several companies are looking at this as a target, and the one with the most advanced integrase inhibitor is Merck, which is now in Phase III trials.
Its safety, activity and pharmacokinetics were investigated in a multicentre randomised, double blind Phase II trial of the drug as monotherapy.1 A total of 35 treatment naïve patients were given the drug in doses of 100, 200, 400 or 600mg twice a day for 10 days. Those given the drug at all doses had dramatically improved HIV RNA counts, and it was generally well tolerated, with dizziness and headache being the most commonly reported sid- effects. In the second part of this trial, the same doses are being compared with efavirenz, with both agents being given in combination with tenofovir/lamivudine.
In another study, MK-0518's safety and efficacy in HIV patients with resistance to antiretroviral drugs was investigated.2 In a multicentre, double blind, dose-ranging trial, 178 patients were given the 200, 400 or 600mg of the drug orally twice a day or placebo, along with optimised background therapy. All three doses had potent antiviral activity, and it was generally well tolerated. Numerous Phase III studies are also under way, both in treatment naïve patients and in combination with other drugs.