A second study has shown that tipranavir / ritonavir (Norvir) is more effective than other ritonavir-boosted protease inhibitor-based antiretroviral regimens for the treatment of highly experienced patients. Twenty-four week results from the RESIST-2 study were presented last week at the Seventh International Congress on Drug Therapy in HIV Infection in Glasgow.
The superiority of Boehringer Ingelheim’s new protease inhibitor tipranavir was demonstrated in 24-week data from the RESIST-1 study, presented last month at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington. The study showed that patients with multiple protease inhibitor resistance mutations had better virological and immunological outcomes than those on a comparator ritonavir-boosted protease inhibitor-based regimen.
The RESIST-2 study was almost identical in design to RESIST-1, but recruited patients from Europe and Latin America rather than North America.
Eight hundred and sixty-three patients were recruited for RESIST-2. They were required to have a viral load above 1000 copies/ml, with at least one primary protease inhibitor mutation from the group 30N, 46I/L, 48V, 50V, 82A/F/L/T, 84V, 90M and two or more mutations at codons 33, 82, 84 or 90 of the protease gene. Patients received an optimised background regimen, plus either tipranavir / ritonavir (500 / 200mg) or a ritonavir-boosted comparator protease inhibitor, consisting of lopinavir, indinavir (Crixivan), saquinavir (Invirase / Fortovase) or amprenavir (Agenerase).
After 24 weeks, an intent-to-treat (missing equals failure) analysis showed that 41% of the tipranavir arm had a drop in viral load of more than 1 log10 from a median baseline of 58,900 copies/ml. This compared to 15% in the comparator arm (p 10, p
More patients in the tipranavir arm had viral loads below 400 copies/ml (34 vs. 13%, p
CD4 cell counts rose more in the tipranavir arm than the comparator arm (31 vs. 1 cells/mm3, p = 0.022). Furthermore, fewer patients taking tipranavir discontinued treatment (17 vs. 29).
Twelve per cent of the patients were taking T-20 (enfuvirtide, Fuzeon) as part of their optimised background regimen. In contrast to the results from RESIST-1, the inclusion of T-20 did not cause a significant increase in the effectiveness of tipranavir: 38% of these patients had viral loads below 400 copies/ml, compared to 13% in the comparator arm, while 23 and 5% respectively had viral loads below 50 copies/ml.
Grade 3 or 4 adverse events were similar in the two arms (14 vs. 12%), with diarrhoea, nausea and vomiting being most common. However, the tipranavir arm had a higher incidence of laboratory abnormalities, particularly rises in cholesterol, triglycerides and the liver enzymes alanine aminotransferase (ALT; 5 vs. 2%, p
Boehringer Ingelheim filed licensing applications for tipranavir in the United States and the European Union last month, and hopes to receive a United States license by May 2005, with a European license to follow by late summer.
Cahn P et al. 24-week data from RESIST-2: phase 3 study of the efficacy and safety of either tipranavir/ritonavir (TPV/r) or an optimized ritonavir (RTV)-boosted standard-of-care (SOC) comparator PI (CPI) in a large randomized multicenter trial in treatment-experienced HIV+ patients. Seventh International Congress on Drug Therapy in HIV Infection, Glasgow, abstract PL14.3, 2004.