Anti HIV agent - maraviroc
Antiviral medicines have transformed AIDS, into a manageable, chronic illness in those patients who can access the drugs. The amount of the virus circulating in the body can be reduced to negligible levels with regular doses of a cocktail of antiretroviral drugs that act by different mechanisms, such as protease inhibitors and reverse transcriptase inhibitors.
Antiviral medicines have transformed AIDS, into a manageable, chronic illness in those patients who can access the drugs. The amount of the virus circulating in the body can be reduced to negligible levels with regular doses of a cocktail of antiretroviral drugs that act by different mechanisms, such as protease inhibitors and reverse transcriptase inhibitors.
However, the virus mutates to evade the drugs' activity, and in the long term they lose their effectiveness. Thus further medicines that remain active are much needed.
Various different points of the virus' lifecycle have been targeted by drugs, one of the most recent being HIV entry, which suppresses viral infectivity as well as replication. The viral entry process begins with the virus attaching to the surface of the T cells then binding to the CD4 receptor through the gp120 envelope glycoprotein. This unmasks the coreceptor binding site, usually either CCR5 or CXCR4, and allows coreceptor binding, which induces further conformational changes allowing pre-formation and the fusion of virus and cell membranes.
One fusion inhibitor, enfuvirtide, is already available. Another, being developed by Pfizer, is maraviroc, which attacks a different part of the virus entry process, the chemokine CCR5 coreceptor.1 A total of 24 asymptotic HIV positive patients who used CCR5 were given 100mg maraviroc twice a day, 25mg once a day or placebo for 10 days.2 The mean saturation of CCR5 was more than 90% during the treatment period for those given the highest dose, but lower than 80% in those given the 25mg dose; the higher dose also gave a much better reduction in viral load. No serious adverse events were seen.
A further trial was carried out in 80 patients to evaluate dosing frequency and the effects of food.,3 Over a 10-day period the subjects were given doses of 25, 100 and 300mg once a day; 50, 100, 150 and 300mg twice a day or placebo. Similar dose-dependent viral load reductions were seen regardless of frequency of dosing. Plasma levels were similar to those seen in healthy volunteers. A high fat meal had no effect on antiviral activity. Phase III trials are under way.