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; David
Powell CHC, Austin, TX; Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT. 09/08/06 Reference
W
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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