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Investigative Protease Inhibitor TMC114/R Overcomes Resistance in HIV Patients: Presented at ICAAC

By Ed Susman

WASHINGTON, DC -- December 22, 2005 -- Researchers said that the investigative protease inhibitor TMC114 boosted with ritonavir (TMC114/r) appears to overcome resistant HIV even among highly treatment-experienced patients.

Timothy Wilkin, MD, assistant professor of medicine, Weill Medical College of Cornell University, New York, New York, demonstrated that the ability of TMC114/r to allow patients to achieve undetectable viral loads was dose dependent.

In a presentation here at the 45^th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), he reported that about 39% of patients receiving the largest dose of TMC114 (600 mg) boosted by 100 mg of ritonavir were able to achieve an undetectable viral load using the 50-copy assay. In comparison, 7% of patients treated with the optimal protease inhibitor selected by the clinicians were able to reach an undetectable viral load. That difference was statistically significant at the P < .001 level, Dr. Wilkin said.

"In HIV patients with limited treatment options, TMC114/r provided significantly superior virologic response rates and CD4-positive cell increases versus control," Dr. Wilkin said on December 16^th.

"The recommended dose for further clinical development in treatment-experienced patients is 600 mg TMC114 and 100 mg ritonavir twice a day," he said.

Dr. Wilkin described the interim results of the Performance Of TMC114/r When Evaluated in triple-class-experienced patients with PI Resistance (POWER 2) trial, a 24-week, phase 2b study. In their substudy, his research team scrutinized what happened if patients were also on the fusion inhibitor enfuvertide, the only injectable antiretroviral drug available.

Among patients who received enfuvertide (Fuzeon) for the first time along with TMC114 at the highest dose twice daily, 64% achieved undetectable levels of HIV at 24 weeks. That compared with 30% of patients who received TMC114/r without the enfuvertide.

The use of ritonavir to boost the effectiveness of protease inhibitors has become a common therapeutic strategy. A small dose of ritonavir is given concurrently with a second protease inhibitor -- in this case TMC114.

The goal of boosting protease inhibitors is to pharmacologically enhance exposure to the second protease inhibitor through the inhibition of the enzyme cytochrome P450. Ritonavir boosting results in increased drug levels of the concomitantly administered protease inhibitor.

In addition to increased efficiency of the main drug, boosting with ritonavir also is associated with a decreased pill burden, added flexibility to the dosing schedule, and removal of fasting restrictions.

TMC114, being developed by Tibotec of Belgium, which sponsored the POWER 2 trial.


[Presentation title: TMC114/r Superior to Standard of Care in 3-Class-Experienced Patients: 24-Wks Primary Analysis of the Power 2 Study (C202). Abstract H-413]

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