The research results were presented at the 11th European AIDS Conference (EACS) in Madrid, Spain (October 24-27, 2007). Following are excerpts from a press announcement about the EACS presentation from Boehringer Ingelheim, the manufacturer of Aptivus:

At 156 weeks, Aptivus combined with ritonavir (Aptivus/r), continues to outperform a group of ritonavir-boosted comparator protease inhibitors that includes low dose ritonavir boosted lopinavir (Kaletra), amprenavir (Agenerase/r), saquinavir (Invirase/r), and indinavir (Crixivan/r). [Editor’s note: amprenavir has largely been replaced by its more potent pro-drug fosamprenavir (Lexiva).]

When compared to these protease inhibitors, through three years of therapy, treatment response rates* were almost three times higher in the Aptivus/r arm compared to the comparator arm (20.9% vs. 7.5%).

Moreover, patients taking Aptivus/r combined with first-time use of enfuvirtide [T-20; Fuzeon] achieved four-fold greater treatment response rates than patients with comparator protease inhibitors (37.9% vs. 8.2%). In this group, the proportion of patients who achieved a viral load of less than 50 copies/mL at week 156 was more than twice as high with Aptivus/r as with comparator protease inhibitors (21.8% vs. 9.3%).

“The new data show that for patients who achieve successful HIV suppression with tipranavir, the results are usually maintained over the long term. In a patient population for which treatment options are limited, this is an important achievement,” said lead author Charles Hicks, associate professor of medicine at Duke University, USA.

The adverse event profile for Aptivus/r was comparable with what has been reported in previous analysis. The patient exposure years (PEY)-adjusted adverse event profile was similar between Aptivus and the comparator protease inhibitors group.

About the RESIST Trials

The RESIST trials are randomised, controlled, open-label, Phase III trials designed to study Aptivus combined with ritonavir versus a group of ritonavir-boosted comparator protease inhibitors. The RESIST clinical trial programme is one of the largest study programs undertaken with an investigational antiretroviral agent in patients previously treated with three classes of antiretrovirals, with Phase II and III data from more than 1,400 patients taking the 500 mg/200 mg dose of Aptivus/r.

About Aptivus

Aptivus is a non-peptidic protease inhibitor which works by inhibiting the viral protease, an enzyme needed to complete the HIV replication process. It is approved for combination antiretroviral treatment of HIV-1 infected adults that are highly pre-treated with virus resistant to multiple protease inhibitors.

Based on available clinical and in vitro data, Aptivus is active against most strains of HIV-1 that are resistant to commercially available protease inhibitors.

Currently, Phase II and III studies in pediatric and other populations are fully enrolled and ongoing.

The most commonly reported side effects of at least moderate intensity in patients enrolled in the RESIST studies taking Aptivus are gastrointestinal, including diarrhea, nausea, vomiting, and abdominal pain. Fever, fatigue, headache, bronchitis, depression, and rash also occurred. Elevated transaminase, cholesterol, and triglycerides were more frequent in the Aptivus/r arm than in the ritonavir boosted comparator group but only in a minority of cases treatment discontinuation was necessary.

Aptivus boosted with low-dose ritonavir has been associated with reports of hepatic adverse events, which have included some fatalities. These have generally occurred in patients with advanced HIV disease taking multiple concomitant medications. Extra vigilance is warranted in patients with chronic hepatitis B or hepatitis C co-infection, as these patients have an increased risk of liver toxicity. The most common moderate to severe laboratory abnormalities were elevated liver enzymes and elevated lipid levels. Most laboratory abnormalities were asymptomatic and most patients were successfully treated without discontinuation.

Aptivus-containing HAART regimens have been associated with reports of both fatal and non-fatal intracranial hemorrhage (ICH) in some highly treatment-experienced patients. Caution should be used when prescribing Aptivus/r in patients who may be at risk of increased bleeding or who are receiving medications known to increase the risk of bleeding.

11/02/07

Source
Boehringer Ingelheim. New three-year data confirms Aptivus® (tipranavir) as effective and durable treatment option for treatment-experienced patients. Press Release. October 25, 2007.

Reference
C Hicks and others. Tipranavir/r (TPV/r) maintains long term virological suppression -- Three year follow-up of RESIST. 11th European AIDS Conference (EACS). Madrid, Spain. October 24-27, 2007. Abstract P4.3/70.