Anti-HIV agent - darunavir
The number of people around the world living with HIV continues to rise, with the World Health Organization estimating that the worldwide total is more than 40 million and that a further five million people will become infected with the virus.
The number of people around the world living with HIV continues to rise, with the World Health Organization estimating that the worldwide total is more than 40 million and that a further five million people will become infected with the virus.
Resistant strains are rising, however, and new drugs to use in the cocktail of medicines that keeps the virus' effects at bay in infected people are still much needed if antiretroviral combination therapy is to remain successful. These include a mixture of reverse transcriptase inhibitors along with a new protease inhibitor, darunavir, which is being developed by Johnson & Johnson subsidiary Tibotec.1 The non-peptide drug has potent antiviral activity, including against resistant strains.
An open label randomised Phase IIa study was carried out in 50 patients who had expirence of multiple protease inhibitors.2 The subjects were given 300, 600 or 900mg of the new drug plus 100mg ritonavir in place of their failing protease inhibitors, with their other antiviral drugs being unchanged. A fourth group continued to receive their failing regimen. A total of 97% of all those patients given combinations including darunavir had a reduction of at least 0.5 log10 copies/ml. The drug was generally well tolerated, with the most common adverse effects being gastrointestinal disturbances.
A further trial is being carried out in a group of 497 patients who had previously received at least three classes of antiretrovirals and had one or more protease inhibitor mutations and limited treatment options.3 In the Phase IIb dose finding study patients were given 400 or 800mg darunavir plus 100mg ritonavir once a day, 400 or 600mg darunavir plus 100mg ritonavir twice a day, or a control of doctor-selected protease inhibitor. After 24 weeks significant mean reductions in viral load were seen in all those given darunavir. The best reduction, 1.85 log10 copies/ml, and up to 47% of all those given the new drug had undetectable virus levels, compared with just 10% of those receiving older protease inhibitors. The most common side-effects were headache and diarrhoea. The study is continuing for a total of 96 weeks and will be entering Phase III trials.