Boehringer Ingelheim GmbH
Ute E. Schmidt
For medical media, outside the US only
Ingelheim/Germany and Cape Town/South Africa, July 2009 – Results from the ARTEN* trial presented at the 5th International AIDS Society (IAS) conference in Cape Town, South Africa demonstrated non-inferiority regarding efficacy between Viramune® (nevirapine) and ritonavir boosted atazanavir (atazanavir/r) both combined with tenofovir and emtricitabine (Truvada ®). This head-to-head study also showed Viramune®´s more favourable effect on the lipid profile and now clearly confirms the combination’s place as an important first line therapy for patients with HIV.
“ARTEN puts to rest the concerns over a potential lack of efficacy of Viramune® in combination with Truvada®,” lead investigator of the ARTEN study, Dr Vicente Soriano, Assistant Director of the Department of Infectious Diseases, Hospital Carlos III, Madrid said. “The results confirm that the combination of Viramune® and Truvada® is a highly efficacious combination that significantly increases HDL-c, the so-called good cholesterol and does not increase the triglyceride levels.”
ARTEN is the first large-scale prospective study to compare two frequently prescribed lipid friendly, antiretrovirals(ARVs): atazanavir and Viramune®.1,2, ** Compared to values at baseline, Viramune® increased absolute HDL-c (the so called good cholesterol) to more than twofold the value achieved with atazanavir/r (9.7 mg/dL vs 3.9 mg/dL (P<0.0001). Mean increases in LDL cholesterol were 15 mg/dL in the nevirapine group and 10.5 mg/dL in the ATV/r group (p=0.011). However,the total cholesterol over HDL-c ratio was significantly in favour of Viramune®; (P<0.0001).3 Atazanavir/r increased mean triglyceride levels (28.1 mg/dL), on the other hand, in the Viramune® group mean triglyceride levels decreased from baseline 0.2 mg/dL (p <0.0001 for the difference).
The efficacy results confirmed that the combination of Viramune® with Truvada® is an effective treatment option for patients even with a high viral load. Of the patients who received nevirapine in the study (n=376), 67% achieved the study’s primary endpoint of viral load of <50 copies/mL versus 65% of ATV/r patients (n=193) at two consecutive visits prior to week 48 and without subsequent rebound or change of antiretroviral therapy prior to or at week 48.
In patients who began study treatment with viral loads below 100,000 copies/mL, 77% of nevirapine patients (n=146) and 85% of atazanavir/r patients (n=78) attained viral load of <50 copies/mL. In patients with a more advanced HIV infection who began study treatment with viral loads above 100,000 copies/mL, 60% of Viramune® patients (n=230) and 52 % (n=115) of atazanavir/r patients attained viral load of <50 copies/mL.
The overall rate of adverse events at 48 weeks was similar in all arms (SAEs Viramune® 9.6% vs. atazanavir 8.8%). The most common adverse event in the atazanavir/r arm was hyperbilirubin aemia with 54.4% of grade 3/4 bilirubin elevations. The most common adverse event in the Viramune® arms was rash (16.0%) compared to 12.4% rash with atazanavir/r. Liverenzyme elevations were reported as grade 3/4 AE in 4% of Viramune® and 1.5% of atazanavir/r patients. The discontinuation rate due to adverse events was 13.6% in the combined Viramune® and 3.6% in the atazanavir/r arm.
“ARTEN provides evidence that Viramune® is and continues to be, a potent choice in ARV therapy today, regardless of viral load. This is particularly important in late-presenting patients whose infection has already progressed. We see a considerable number of those in clinical practice.” said Dr Soriano.
At the end of 2007, approximately 33 million individuals were living with HIV.4 With successful antiretroviral therapy, the number of deaths per year has been declining5 and patients infected with HIV are now living longer. However, recent reports suggest that cardiovascular disease has become an important cause of morbidity and mortality in this population.6 Many are now also suffering increased rates of coronary heart disease.7
Dr. Manfred Haehl, MD, Senior Vice-President Medicine at Boehringer Ingelheim said “HIV patients are now increasingly looking for treatment strategies that have the most lipid friendly profile in order to consider broader aspects of their health. ARTEN clearly provides additional reassurance for physicians to treat with more confidence patients with a Viramune® and Truvada® combination.”
ARTEN is an international, open label, randomized, non-inferiority (12%margin) study comparing ATZ/r 300mg/100mg QD vs. NVP 200mg BID or 400mg QD, each combined with fixed-dose TDF 300mg/FTC 200mg QD. Treatment-naïve men and women with CD4 counts <400 and <250cells/mm3, respectively, were eligible. Primary end-point was treatment response (TR), defined as plasma HIV-RNA <50 copies/mL at two consecutive visits (i.e. weeks 24 and 36) and without subsequent rebound or change of ARVs prior to wk-48.
569 patients were randomised and treated. Baseline demographics and HIV-related characteristics were similar between groups. Mean HIV-RNA was 5.1 log10 copies/mL (64% >100,000 copies/mL); mean CD4 count was 183 cells/mm3.
Viramune® 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. Viramune® is indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection. This indication is based on one principal clinical trial that demonstrated prolonged suppression of HIV-RNA and several smaller supportive studies. Studies have also shown that patients switching to Viramune® from a PI-based regimen demonstrate an improved lipid profile while maintaining viral suppression. The most clinically important adverse events associated with Viramune® are rash and hepatic events, which have included fatal cases. Any patient can experience hepatic events; however, female gender and higher CD4+ cell counts at initiation of therapy place patients at greater risk. Women with CD4+ cell counts >250 cells/mm3 are at the greatest risk. Viramune® should not be initiated in adult females with CD4+ cell counts greater than 250 cells/mm3 or in adult males with CD4+ cell counts greater than 400 cells/mm3 unless the benefit outweighs the risk. The greatest risk of severe rash and hepatic events occurs in the first six weeks of therapy. It is essential that patients be monitored for these reactions at all times, and intensively during the first few months of therapy. Viramune® should be discontinued and not restarted following severe hepatic, skin or hypersensitivity reactions. The safety and efficacy of once-daily dosing have not been established.
About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 138 affiliates in 47 countries and 41,300 employees. Since it was founded in 1885, the independent, family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2008, Boehringer Ingelheim posted net sales of 11.6 billion euro while spending one fifth of net sales in its largest business segment Prescription Medicines on research and development.
*Atazanavir/Ritonavir on a background of Tenofovir and Emtricitabine (Truvada®a trademark of Gilead Science…) versus Nevirapine. The ARTEN study included one arm with patients treated with nevirapine in a once-daily dosing. Nevirapine is not indicated for once-daily dosing. The safety and efficacy of once-daily dosing have not been established.
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1 Martinez, E., et al., Substitution of nevirapine, efavirenz, or abacavir for protease inhibitors in patients with human immunodeficiency virus infection. N Engl J Med, 2003. 349(11): p. 1036-46.
2 Friis-Moller, N., et al., Cardiovascular disease risk factors in HIV patients – association with antiretroviral therapy. Results from the DAD study. Aids, 2003. 17(8): p. 1179-93.
3 Soriano, V et al., Prospective comparison of Nevirapine and Atazanavir/ritonavir both combined with Tenofovir DF/Emtricitabine in treatment-naïve HIV-1 infected patients: ARTEN Study week 48 results 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2009), July 19 -22, 2009, Poster LBPEB07
4 UNAIDS 2008 Report, http://www.unaids.org/en/KnowledgeCentre/HIVData/GlobalReport/2008/2008_Global_report.asp, Accessed 05 June 2009
5 Worldwide HIV & AIDS Statistics Commentary http://www.avert.org/worlstatinfo.htm, Accessed 05 June 2009
6 Lohse N, Hansen AB, Pedersen G, Kronborg G, Gerstoft J, Sørensen HT, Vaeth M, Obel N. Survival of persons with and without HIV infection in Denmark, 1995–2005. Ann Intern Med. 2007;146:87–95.
7 DAD Study Group, Friis-Møller N, Reiss P, et al., Class of antiretroviral drugs and the risk of myocardial infarction, N Engl J Med, 2007;356(17):1723–35.