Antiviral agent - rilpivirine

Thanks to highly active antiretroviral therapy, or HAART, HIV infection has, for many patients, been transformed from a death sentence into a chronic condition.

By taking a cocktail of at least three different antiviral drugs, levels of the virus in the bloodstream can be suppressed to undetectable levels. These include several different classes of drug, including both nucleoside and non-nucleoside reverse transcriptase inhibitors and protease inhibitors; more recently, entry inhibitors and integrase inhibitors have been approved.

Because of the virus's ability to mutate into resistant forms, new antiviral drugs that overcome this resistance are always necessary, and Tibotec is developing a new non-nucleoside reverse transcriptase inhibitor, rilpivirine.¹ Its structural core is similar to the company's earlier drug, etravirine, which was launched a decade ago.

It has the advantages of being simple to synthesise and has high oral bioavailability, as well as having good in vitro antiviral activity.

Several trials have been carried out. These include a placebo-controlled Phase IIa trial in 47 HIV infected patients who had not previously received antiretroviral therapy.² Subjects were given doses of 25, 50, 100 or 150mg of the drug orally once a day for a week, or placebo. Those given doses of the active had a median reduction of 1.199 log copies/ml, whereas those given placebo had a small increase.

At the end of the week, four of those given rilpivirine had a viral load of below 400 copies/ml. The most common side-effects were headache and gastrointestinal problems; no significant differences in either antiviral activity or safety were seen between the different doses of the drug.

Another trial compared its activity with efavirenz.³ A total of 368 antiretroviral-naïve HIV infected patients were given doses of 25, 75 and 150mg of rilpivirinine or 600mg of efavirenz. Three-quarters of the subjects also took zidovudine and lamivudine, and the remainder tenofovir disoproxil and emtricitabine. There were no significant differences between activities of the two drugs after 48 weeks, and between 77% and 81% of patients had viral loads below 50 copies/ml. Headache and nausea were again the most common side-effects, but adverse events affecting the nervous system were less common in the rilpivirine group. Trials continue.