Protease inhibitor — tipranavir
A study in the US reported that up to 87% of people with HIV taking antiviral drugs harboured drug resistant forms of the virus,1 so a steady stream of novel antiviral agents is needed. Also, increasing numbers of people are being infected with resistant forms of the virus, so their susceptibility may be lowered even though they have received no antiviral therapy.2
One such new antiviral agent, being developed by Boehringer-Ingelheim, is tipranavir. It is the first non-peptidic protease inhibitor to be developed for treating HIV. It is thought that it uses fewer hydrogen bonds when binding to the active site, and this more flexible binding may explain its resistance profile. Four key mutations have been linked with resistance to peptidic protease inhibitors, and tipranavir appears to be active against viruses with these mutations.
In a study on 41 treatment-experienced patients, who were failing on their second protease inhibitor-based regimen, 85% who had a decreased susceptibility to multiple protease inhibitors and at least one nucleoside reverse transcriptase inhibitor remained fully susceptible to tipranavir throughout the study. In an open label Phase II clinical trial, the 41 patients were randomly given 500mg tipranavir and 100mg ritonavir twice daily, or 1000mg tipranavir and 100mg ritonavir twice daily.3
The most common side-effects attributed to tipranavir were nausea and diarrhoea, and these largely occurred within the first 14 days of therapy. Later on in the trial, patients switched from a hard-filled gel capsule to a self-emulsifying drug delivery system, and this reduced the incidence of adverse events.
A major Phase IIb trial is being set up in nine countries, and Boehringer-Ingelheim plans to start a large-scale Phase III clinical trial programme with the drug later in the year.