 |
|
|
| |
Tipranavir/Ritonavir Outdoes Other Boosted PIs in Phase 3 Trial
|
| |
| |
Mark Mascolini
October 31, 2004
Twenty-four-week results from the first big efficacy trial of ritonavir-boosted tipranavir showed better responses to the new protease inhibitor than to other boosted PIs in people with multiple PI experience (1). An intention-to-treat analysis determined that 41.5% taking tipranavir/ritonavir versus 22.3% taking a different PI lowered their viral load at least 1 log (10-fold) by week 24. More people taking tipranavir/ritonavir also a reached viral load below 400 copies/mL or 50 copies/mL at week 24.
Researchers recruited people who had tried drugs from the three first antiretroviral classes, including at least two PIs. The median number of PIs taken measured four. All study participants had at least one primary PI mutation, but none had more than two of the critical mutations at protease sites 30, 82, 84, or 90. Thus the trial excluded people with the heaviest cross-resistance to PIs.
The median baseline viral load stood at 4.81 logs in the tipranavir group and 4.84 logs in the comparison groups. Both groups had a median CD4 count of 123 cells/µL before randomization. Researchers randomized 311 to start tipranavir/ritonavir and 309 to start another boosted PI (lopinavir in 61%, saquinavir in 21%, amprenavir in 14%, and indinavir in 4%).
Presenting the results at the October 10-November 2 ICAAC, Duke University's Charles Hicks did not specify how tipranavir/ritonavir compared with each of the other PIs taken, but he did present the comparison between tipranavir/ritonavir and the entire comparison arm. A week-24 noncompleter-equals-failure analysis ranked 41.5% taking tipranavir and 22.3% taking another PI as responders (more than a 10-fold drop in viral load) (P < 0.0001). More people taking tipranavir reached a viral load below 400 copies/mL (34.7% versus 16.5%, P < 0.001), and more reached a load under 50 copies/mL (P < 0.001). The tipranavir group also gained more CD4 cells than the comparison group (36 versus 6 cells/µL in a last-observation-carried forward analysis, P < 0.001).
Among people who added T-20 to tipranavir, 47.1% reached a viral load below 400 copies/mL and 32.8% went under 50 copies/mL. In contrast, among people adding T-20 to the other PIs, 21.9% got under 400 copies/mL and 14.3% under 50 copies/mL.
Although an expert panel looking at genotypic data proposed alternative PIs for people randomized to the control group, only about 30% of study clinicians used the recommended PI. Most clinicians—61%—picked lopinavir/ritonavir as the alternate PI, but that was probably the wrong choice for many people. A phenotypic analysis showed an average 77.8-fold change resistance to lopinavir at randomization. Nonetheless, fold-change resistance to the other PIs used was also high: 39-fold to indinavir, 27.2-fold to saquinavir, and 12.2-fold to amprenavir. The fold-change resistance to tipranavir averaged only 1.9-fold.
Rates of liver enzyme and lipid elevations proved higher with tipranavir/ritonavir than with the other PIs, although most were "transient and asymptomatic." Two people had to stop taking tipranavir/ritonavir because of grade 3 or 4 rises in alanine or aspartate aminotransferase (ALT or AST).
Reference
1. Charles Hicks. RESIST-1: a phase 3, randomized, controlled, open-label, multicenter trial comparing tipranavir/ritonavir to an optimized comparator protease inhibitor/r regimen in antiretroviral experienced patients: 24-week data. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). October 30-November 2, 2004. Washington, DC. Abstract H-1137a.
|
| |
|
|
|
|
|
