Virus maturation is the process that occurs during the last stages of HIV reproduction, after HIV has been released from the infected cell. It involves the processing of viral proteins and is required for the virus to become infectious. By blocking, or inhibiting, the virus maturation process, new virus cannot go on to infect other cells in the body.

Bevirimat, a derivative of a Chinese herb called Syzigium claviflorum, is the first HIV maturation inhibitor to enter phase II clinical trials. Because bevirimat works differently than currently available HIV drugs, it will likely be effective for people who have HIV that is resistant to currently available treatment options.

In one small phase IIa study, HIV-positive patients were selected to receive a liquid formulation of bevirimat (25mg, 50mg, 100mg, or 200mg), or a placebo, once daily for ten days, without any other antiretrovirals. At the 200mg dose, the average viral load reduction after ten days of treatment was 1.03 log. The average viral load reductions using the three lower doses were less than 0.5 log.

In a phase IIb study, patients on a failing HIV drug regimen took either placebo or a 400mg tablet version of bevirimat that was thought to be equivalent to the 200mg liquid version used in the phase IIa study. After 14 days, however, the blood concentrations of the drug – along with its effects on viral load – were poorer than anticipated. This suggested to the researchers that the tablet formulation used in the study did not deliver the drug as expected.

The phase IIb study is continuing, but with the use of the original liquid formulation of the drug. Results involving treatment-experienced patients taking either placebo or a 250mg liquid dose for 14 days were reported in the most recent press release from the company.

Viral loads decreased by an average of 0.68 log in the bevirimat-treated patients, compared to a 0.18 log drop in the placebo-treated patients. Among those taking the 400mg tablet version of the drug, the average viral load drop was 0.36 log after 14 days of treatment.

In the press release, Alan Dunton, MD, Chief Executive Officer of Panacos, is quoted as saying, "This confirms our belief that the lower than expected plasma concentrations observed in the earlier 400mg tablet cohort were caused by the prototype tablet formulation, and not by bevirimat itself."

Panacos plans to continue its phase IIb study, increasing the liquid dose of the drug by 50mg in each group of patients enrolled in the trial.

Source: Panacos Pharmaceuticals