A Summary of the Tipranavir US Expanded Access Program

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A Summary of the Tipranavir US Expanded Access Program

Tipranavir (Aptivus) is a novel non-peptidic protease inhibitor (PI) that received Food and Drug Administration approval in June 2005. It is administered with a low boosting dose of ritonavir (Norvir).

The U.S. Aptivus Expanded Access Program (EAP) opened in December 2004 to provide early access to tipranavir, and to further evaluate its safety in highly treatment-experienced patients using an open-label, non-randomized treatment protocol.

Data from the EAP were presented at the XVI International AIDS Conference in Toronto in August. Eligible patients received 500/200 mg tipranavir/ritonavir twice daily. Safety evaluations were performed at week 2, months 1, 2, and 3, and every 3 months thereafter. Viral loads and CD4 cell counts were recorded as per standard of care.

Eligible patients included those with triple antiretroviral class experience, prior use of more than 2 PI-based regimens, and a need for tipranavir in order to construct a viable regimen, as documented by the presence of PI resistance mutations. Patients were excluded if they had baseline liver enzyme levels of DAIDS Grade 3 or higher.

Results

• 915 patients enrolled in the EAP. • Patients had taken a median of 13 prior antiretroviral drugs: - 6 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs); - 1 non-nucleoside reverse transcriptase inhibitor (NNRTI); - 5 protease inhibitors;- 34% had taken enfuvirtide (Fuzeon, T-20) in the past.• The median baseline CD4 count was 90 cells/mm3 and the median baseline viral load was 63,800 copies/mL. • 14% had hepatitis co-infection. • Approximately 60% of EAP patients took enfuvirtide while using tipranavir.• The median time on tipranavir through the EAP was 113 days (range 1-236). • The mean reductions in viral load among evaluable patients were:- 1.14 log copies/mL at day 30 (n = 101);- 1.00 log copies/mL at day 60 (n = 157);- 1.17 log copies/mL at day 90 (n = 462);- 1.24 log copies/mL at day 180 (n = 206).• The mean CD4 count increase at 180 days was approximately 60 cells/mm3. • 7.5% of EAP participants discontinued tipranavir/ritonavir due to adverse events. • Only 3.3% developed Grade 3 or 4 aspartate or alanine aminotransferase (AST or ALT) levels.

Conclusion

In conclusion, the EAP investigators wrote, "In this highly treatment-experienced EAP population, Aptivus was generally well tolerated and no new adverse events were identified. Use of Aptivus/ritonavir in this population was associated with a significant reduction in viral load and an increase in CD4 cell count."

Kaiser Permanente, Los Angeles, CA; UT Southwestern Medical Center, Dallas, TX; CHC, Austin, TX; Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT.

09/08/06

ReferenceW Towner, E Race, K Brown, and others. Aptivus expanded access program (EAP) - a report on the U.S. experience with a novel ritonavir boosted protease inhibitor (PI/r). XVI International AIDS Conference. Toronto, August 13-18, 2006. Abstract CDB0392.

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