Aptivus (tipranavir) Demonstrates Potent And Durable Treatment Response In HIV-positive Women

Main Category: HIV / AIDS
Also Included In: Clinical Trials / Drug Trials;  Women's Health / Gynecology
Article Date: 06 Aug 2007 - 0:00 PDT

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An analysis of the RESIST trials shows that Aptivus (tipranavir), used with ritonavir (Aptivus/r) as part of combination antiretroviral therapy, provides a potent and durable treatment response in highly treatment-experienced female patients through 48 weeks of treatment.1 These data were presented at the International AIDS Society congress in Sydney, Australia.

The findings from the RESIST trials reinforce that Aptivus provides therapeutic benefits for treatment-experienced HIV-positive women with limited treatment options. This analysis helps meet the need for more comparative data in HIV-positive women, as cohort studies and clinical trials have shown that the efficacy and safety of antiretroviral agents may vary across genders, said Sharon Walmsley, M.Sc., M.D., professor of medicine, University of Toronto, senior scientist, Toronto Hospital Research Institute, and director, Clinical Research, Immunodeficiency Clinic, Toronto Hospital.

Worldwide, there are more HIV-positive women than ever before, with nearly 18 million now living with the disease. Women of African and Latin American decent are disproportionately affected and account for a large number of infections in developed countries, including those in Europe.2

The combined RESIST trials enrolled 1,483 treatment-experienced HIV-positive patients, of those approximately 13 percent were women. One hundred and seventeen women were randomised to receive Aptivus/r. At week 48:

25.6 percent of women and 22.1 percent of men taking Aptivus/r achieved viral loads of less than 50 copies/mL.

After adjusting for protease inhibitor stratum, enfuvirtide use, and background reverse transcriptase inhibitor sensitivity, mean viral load change at last observation to week 48 from baseline was -1.46 log10 copies/mL in women and -1.30 log10 in men taking APTIVUS/r (p=0.1890).

The adjusted mean CD4 cell change from baseline at week 48 was 84.2 cells/mm3 in women and 52.4 cells/mm3 in men (p=0.0017).

Although a higher plasma concentration of tipranavir was observed in women, there were no increased subjective adverse events nor laboratory abnormalities versus male patients, added Dr. Walmsley. It is unclear whether this was the reason for the better CD4 cell count response among women participating in the study.

The overall safety profile was similar in men and women. Rates of adverse events leading to discontinuation were similar for both genders, and severe or serious adverse event rates were slightly higher for men.

Boehringer Ingelheim recently announced the initiation of the SPRING study, which will be one of the largest racially and gender diverse international studies of highly treatment-experienced HIV-1 infected patients. The trial will examine the safety, efficacy and pharmacokinetics of Aptivus/r in a racially diverse group of 200 female and 200 male treatment-experienced patients across eight countries in three continents.

About RESIST

The RESIST (Randomized Evaluation of Strategic Intervention in Multi-Drug ReSistant Patients with Tipranavir) trials are randomised, controlled, open-label, Phase III trials designed to study Aptivus 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 Aptivus/r.

About Aptivus

Aptivus 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.

Based on available clinical and in vitro data, Aptivus is active against most strains of HIV-1 that are resistant to commercially available protease inhibitors.

Currently, phase II and III studies in paediatric and other populations are fully enrolled and ongoing.

The most commonly reported side effects of at least moderate intensity in patients enrolled in the RESIST trials taking Aptivus are gastrointestinal, including diarrhoea, nausea, vomiting and abdominal pain. Fever, fatigue, headache, bronchitis, depression and rash also occurred. Gastrointestinal symptom disorders and elevated transaminase, cholesterol and triglycerides were more frequent in the Aptivus arm than in the comparator-ritonavir group but necessitated discontinuation of treatment in a minority of cases.

Aptivus boosted with low-dose ritonavir has been associated with reports of hepatic adverse events, which have included some fatalities. These have generally occurred in patients with advanced HIV disease taking multiple concomitant medications. Extra vigilance is warranted in patients with chronic hepatitis B or hepatitis C co-infection, as these patients have an increased risk of liver toxicity. The most common moderate to severe laboratory abnormalities were elevated liver enzymes and elevated lipid levels. Most laboratory abnormalities were asymptomatic and most patients were successfully treated without discontinuation.

Aptivus-containing HAART regimens have been associated with reports of both fatal and non-fatal intracranial hemorrhage (ICH) in some highly treatment-experienced patients. Caution should be used when prescribing Aptivus/r in patients who may be at risk of increased bleeding or who are receiving medications known to increase the risk of bleeding.

Aptivus does not cure HIV infection/AIDS or prevent the transmission of HIV to others. Patients may continue to develop opportunistic infections and other complications associated with HIV disease.

Apart from the EU, Aptivus has received U.S. marketing authorization by the FDA and was launched there in June 2005. Additional marketing authorizations from different countries have been received or are expected.

About Boehringer Ingelheim

Boehringer Ingelheim is committed to the research and development of novel antiretroviral agents. Apart from Aptivus (tipranavir), Viramune (nevirapine) is a product of original research done at Boehringer Ingelheim. Viramune was the first member of the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of anti-HIV drugs on the market. The company is involved in basic research in that area and is committed to improving HIV therapy by providing physicians and patients with innovative antiretroviral treatment options.

Boehringer Ingelheim is actively conducting clinical trial programs to further evaluate Aptivus and Viramune for the treatment of HIV-1 infection. The Aptivus clinical trial program is comprised of ongoing and planned studies in more than 1,400 treatment-experienced patients, including the SPRING study, which is examining the benefits of Aptivus in an ethnically and racially diverse highly treatment-experienced patient population and the POTENT study, which will compare the efficacy and safety of Aptivus versus darunavir. The Viramune clinical trial program includes the ArTEN trial, which aims to compare the efficacy and safety of Viramune dosed once-or twice-daily versus atazanavir boosted with ritonavir in HIV-positive antiretroviral-naive patients.

Please be advised

This release is from the Corporate Headquarters of Boehringer Ingelheim and is intended for all international markets. This being the case, please be aware that there may be some differences between countries regarding specific medical information including licensed uses. Please take account of this when referring to the material.

References:

1 Walmsley et al. Tipranavir/ritonavir (500/200 mg BID) demonstrated potent and durable virologic responses, and a favorable safety profile, in HIV-1 positive women participating in RESIST; 4th International AIDS Society (IAS) Conference on HIV Pathogenesis and Treatment; Sydney, Australia. Abstract #MOPDB04.

2 UNAIDS/WHO: 2006 Report on the global AIDS epidemic

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