Findings from the RESIST studies have shown that the new protease inhibitor tipranavir (Aptivus) continues to provide potent activity against HIV in patients with substantial treatment experience after 48 weeks of treatment. The data were presented in November at the Tenth European AIDS Conference / European AIDS Clinical Society in Dublin.
Tipranavir is the latest protease inhibitor to be approved in the United States and Europe, where it is licensed for use in patients who have experienced failure of previous protease inhibitor-based regimens. The approvals of the drug were based on 24-week data from the phase III RESIST-1 and RESIST-2 studies, showing that patients taking tipranavir had better outcomes than those in a comparator group.
The results of 48-week follow-up of the two studies, which were sponsored by tipranavir’s manufacturer, Boehringer Ingelheim, were presented at the Dublin conference. Since the two studies were very similar in their design, their results were combined.
“Tipranavir / ritonavir is a potent therapeutic option for treatment-experienced patients,” conclude the investigators. “It offers virological and immunological benefits to this patient group.”
The studies recruited 1483 patients, with experience of all three major classes of antiretroviral drugs. For inclusion in the study, the participants were required to have taken at least two protease inhibitor-based regimens and to have at least one primary protease inhibitor mutation. All of the patients were taking a failing protease inhibitor-based regimen, with a viral load above 1000 copies/ml.
The investigators randomised the patients to receive either tipranavir at a dose of 500mg twice daily, boosted with a twice-daily dose of 200mg ritonavir (Norvir), or a comparator protease inhibitor. This consisted of the best option, based on resistance testing, from a choice of ritonavir-boosted lopinavir (Kaletra), indinavir (Crixivan), saquinavir (Invirase / Fortovase) or amprenavir (Agenerase).
All of the patients also received an optimised background regimen that was chosen for each patient based on the results of genetic testing.
At the 48-week time point, 34% of the patients taking tipranavir had a viral load at least 1 log10 lower than at the start of the study. This compared to 15% in the comparator arm, a difference that was highly statistically significant (p
There was also a highly significant difference in the time to treatment failure between the two arms. While the median time to failure was 113 days in the tipranavir arm, more than half of the patients in the comparator arm did not respond to their drug combination, resulting in a median time to failure of 0 days (p
The superior outcome in the patients taking tipranavir was also reflected in the mean reduction in viral load (1.14 vs. 0.54 log10; p 3; p
As in the 24-week results, the potency of tipranavir was greater when it was combined with additional active antiretroviral drugs, particularly T-20 (enfuvirtide, Fuzeon). The side-effect profile was also similar in the 48-week analysis: while the incidence of severe side-effects was similar across the two arms, more patients taking tipranavir experienced elevations in liver enzymes and blood fats.
Cahn P et al. RESIST-1 (R-1) and RESIST-2 (R-2) 48 week meta-analyses demonstrate superiority of protease inhibitor (PI) tipranavir+ritonavir (TPV/r) over an optimized comparator PI (CPI/r) regimen in antiretroviral (ARV) experienced patients. Tenth European AIDS Conference / European AIDS Clinical Society, Dublin, abstract PS3/8, 2005.