GLASGOW, Scotland, November 15 /PRNewswire/ --
-- New Sub-analyses Provide Insight into Treatment Benefits
New data from the combined RESIST studies (RESIST-1 and RESIST-2) show that Aptivus(R) (tipranavir), used with ritonavir (tipranavir/r) as part of combination antiretroviral therapy, continued to provide a superior and durable treatment response in highly treatment-experienced patients versus a comparator group of protease inhibitors (p<0.001).(1) Further, a sub-analysis shows that tipranavir/r scored higher in quality of life measures compared to other protease inhibitors.(2) These data were presented at the 8th International Congress on Drug Therapy in HIV Infection in Glasgow, Scotland.
"The RESIST trial continues to provide insight into how to maximize treatment response with APTIVUS/r," said Professor Brian Gazzard, M.A., M.D., FRCP, consultant physician and research director, Department of HIV/GU Medicine, Chelsea Westminster Hospital, London, England. "Data show that APTIVUS provides a durable treatment option through nearly two years of therapy. This is important for this patient population who have limited treatment options."
Tipranavir and Long-Term Durability
At 96 weeks, tipranavir/r continues to outperform a group of ritonavir-boosted comparator protease inhibitors that include lopinavir/r (Kaletra(R)), amprenavir/r (Agenerase(R)), saquinavir/r (Invirase(R)) and indinavir/r (Crixivan(R)).(1) In the RESIST studies, treatment response was defined as a confirmed 1 log10 or greater decrease in viral load from baseline.(1)
When compared to these protease inhibitors:
- More than twice the percentage of patients in the tipranavir/r arm
responded to treatment: 26.9% vs. 10.9% achieved a viral load below 400
copies/mL; 20.4% vs. 9.1% achieved a viral load of less than 50
copies/mL, p<0.001.(1)
- The virologic benefits of a tipranavir-based regimen were enhanced by
co-administration of an antiretroviral agent from a new class, in this
case enfuvirtide: 34.7% vs. 14.4% of patients taking tipranavir/r
combined with first-time enfuvirtide use achieved an undetectable viral
load of less than 50 copies/mL, p=0.0002.(1)
- Patients taking tipranavir/r combined with first-time enfuvirtide use
achieved a greater mean change from baseline (-2.00 log10 copies/mL vs.
0.95 log10 copies/mL)(1) and a larger mean CD4+ cell count increase
(102 cells/mm^3 vs. 44 cells/mm^3) than comparator ritonavir-boosted
protease inhibitors.(1)
Tipranavir/r-Containing Therapy and Quality of Life
A 48-week sub-analysis within the RESIST patient population shows that patients treated with tipranavir/r experienced stable or greater improvements in health-related quality of life (HRQOL) in comparison to treatment with lopinavir/r, amprenavir/r, saquinavir/r or indinavir/r.(2) When compared to these protease inhibitors:
- Patients receiving tipranavir/r showed positive between group changes
for Mental Health Summary (MHS) (+1.47 points; p<0.05), Physician
Health Summary (PHS) (+0.99) and ten subscale scores: cognitive
Functioning (+1.04), energy/fatigue (+2.43; p<0.05), general health
perceptions (+3.53; p<0.05), health distress (+2.93; p<0.05), mental
health (+2.78; p<0.05), overall QOL (+2.72; p<0.05), pain (+2.19),
physical functioning (+1.89), role functioning (+2.83) and social
functioning scores (+1.68).(2)
- Patients receiving tipranavir/r reported these health-related quality
of life scores despite a higher frequency of treatment-related adverse
events (75.0 vs. 56.6 per 100 patient-exposure years).(2) Patients in
the tipranavir/r arm experienced a lower rate of non treatment-related
adverse events (514.4 vs. 562.8 per patient-exposure years).(2)
HRQOL was measured by the Medical Outcomes Study HIV (MOS-HIV) Health Survey, which consists of 35 questions which assess 10 dimensions of health-related quality of life.(3)
Susceptibility to Tipranavir/r-Containing Therapy Compared to Lopinavir/r
Another 48-week sub-analysis of isolates from patients in the RESIST studies found that a numerically higher percentage of patients who were genotypically lopinavir-sensitive, but had three or more lopinavir score mutations, taking a tipranavir/r-containing regimen achieved undetectable viral loads (less than 50 copies/mL) compared to patients who stayed on a lopinavir/r-containing regimen.(4) All patients had previously been treated with two or more PIs.(4) Results show:
- A higher percentage of patients receiving tipranavir/r experienced a
decrease in viral load to less than 50 copies/mL vs. patients receiving
lopinavir/r (44% vs. 27% in patients with 4-5 lopinavir mutations,
p=0.0739;(4) 26% vs. 13% in patients with 6-7 lopinavir mutations,
p=0.0603.(4)
These findings demonstrate that treatment regimens containing tipranavir/r as part of combination therapy may prevent persistent low-level viraemia (51-100 copies/mL) in genotypically lopinavir-sensitive patients with four or more lopinavir score mutations.(4) Persistent low-level viraemia has been associated with virological failure.(5)
"These analyses demonstrate again that an APTIVUS-based regimen can be used to address the critical therapeutic needs of the highly treatment-experienced HIV-positive patient population," said Dr. Andreas Barner, Vice-Chairman, Board of Managing Directors and Head of Corporate Board Division Pharma Research, Development and Medicine, Boehringer Ingelheim. "APTIVUS has already been studied in more than 6,800 patients, and Boehringer Ingelheim remains committed to defining the full clinical utility of APTIVUS in ongoing and planned clinical studies."
The tolerability profile of tipranavir/r was similar to that of other ritonavir-boosted protease inhibitors. Gastrointestinal symptom disorders and elevated transaminase, cholesterol and triglyceride levels were more frequent in the tipranavir/r arm than in the comparator-ritonavir arm but necessitated discontinuation of treatment in a minority of cases. Rates of leucopoenia and increased lipase concentrations were more frequent in the comparator ritonavir-boosted protease inhibitor arm.
Tipranavir Clinical Trial Programme
Boehringer Ingelheim is actively conducting a clinical trial programme to further evaluate tipranavir for the treatment of HIV-1 infection. The tipranavir clinical trial programme is comprised of ongoing and planned studies in more than 1,400 treatment-experienced patients, including paediatric, racially and gender diverse, or hepatitis co-infected patients.
About RESIST
The RESIST trials are randomised, controlled, open-label, Phase III trials designed to study tipranavir combined with ritonavir versus a group of ritonavir-boosted comparator protease inhibitors. The RESIST clinical trial programme is one of the largest study programs undertaken with an investigational antiretroviral agent in patients previously treated with three classes of antiretrovirals, with Phase II and III data from more than 1,400 patients taking the 500 mg/200 mg dose of tipranavir/r.
About Tipranavir
Tipranavir is a new non-peptidic protease inhibitor which works by inhibiting the viral protease, an enzyme needed to complete the HIV replication process. It is approved for combination antiretroviral treatment of HIV-1 infected adults that are highly pre-treated with virus resistant to multiple protease inhibitors.
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