HIV antiviral - vicriviroc
As HIV mutates and becomes resistant to existing medicines, there is a constant need for a stream of new drugs that retain their effectiveness against the virus.
As HIV mutates and becomes resistant to existing medicines, there is a constant need for a stream of new drugs that retain their effectiveness against the virus.
Celsentri (maraviroc), the first drug of a new class - CCR5 inhibitors, was launched earlier this year by Pfizer, and another member of this class, vicriviroc, is being developed by Schering-Plough.1
The mechanism is rather different from other anti-HIV medicines, as it blocks the entry of the virus into cells. CCR5 is a G-protein coupled receptor that is one of the co-receptors involved in changing the shape of the cell surface to expose it to R5 forms of the virus, which are usually responsible for initial infection.
Numerous trials have been carried out on vicriviroc, both alone and in combination with other antiretroviral drugs. In a two-week parallel group trial, 48 HIV infected patients with CD4+ counts above 200 were given 10, 25 or 50mg vicriviroc or placebo twice a day.2 The mean decreases in viral load were higher with higher doses, and CD4+ counts also increased. After the dosing schedule, the HIV load returned to baseline.
Another study was carried out to investigate its effectiveness in combination with Combivir.3 A total of 92 R5 tropic patients with HIV were given 25, 50 or 75mg vicriviroc or placebo once a day for 14 days, after which Combivir was added, and the placebo replaced with open-label efavirenz. Virological breakthrough was seen in 57%, 45% and 22% of patients given the three doses of vicriviroc.
A longer term trial was carried out to examine its safety and efficacy in HIV infected patients with drug resistance.4 In the placebo-controlled study, 118 patients who were experiencing virologic failure while receiving a regimen containing ritonavir were given 5, 10 or 15mg vicriviroc or placebo for two weeks plus optimised background therapy, after which the antiretroviral regimen was optimised.
After 14 days and 24 weeks, both doses of vicriviroc gave a greater decrease in viral load than placebo, and adverse effects were similar across all groups. Malignancies occurred in six patients given vicriviroc, and two in the placebo group.