BASINGSTOKE, ENGLAND -- July 11, 2001 -- New research findings were presented yesterday (July 10, 2001) regarding a Ziagen/Combivir regimen at the 1st International AIDS Society Conference on HIV Pathogenesis and Treatment.
The new findings show that a two-tablet twice daily regimen of Ziagen (abacavir) and Combivir (a fixed dose combination of zidovudine and lamivudine) provides superior efficacy as compared to the more complex indinavir plus Combivir regimen, and was associated with better tolerability and improved adherence during 48 weeks of therapy. The results highlight the benefits that a regimen, with significant improvements in tolerability and adherence, can have in the treatment of HIV-infected patients.
In the primary efficacy analysis at 48 weeks, (Intent to Treat, Missing/Switch=Failure, viral load <400 copies/mL) the Ziagen + Combivir arm was found to be statistically superior (p=0.002), with 66 percent of patients achieving an undetectable viral load, compared to 50 percent of patients taking the protease inhibitor (PI)-based regimen.
Conducting the same analysis by viral load strata demonstrated that Ziagen + Combivir was more effective than the PI-based regimen in patients who entered the study with a plasma viral load <100,000 copies HIV-1 RNA/mL. In patients who had higher plasma viral load at entry (>100,000 copies HIV-1 RNA/mL at baseline), the Ziagen + Combivir combination was at least equivalent to the PI-based regimen.
Commenting on the results, Dr. Asda Vibhagool, a lead investigator on the study and Assistant Professor, from Ramathibodi Hospital, Thailand, said; "For the long-term management of HIV-infected patients, the preferable treatment needs to provide a balance of three essential elements -- potency, adherence and tolerability -- to achieve clinical success. The triple nucleoside option in this study has demonstrated at least equivalent efficacy in patients with both low and high viral load at entry because it is more tolerable due to fewer adverse effects and because it is easy to adhere to due to the simplicity of the regimen."
A total of 72 percent of subjects in the Ziagen + Combivir group reported >95 percent adherence, compared with 45 percent of subjects in the indinavir + Combivir regimen (p<0.001). Fewer drug-related adverse events were reported in the Ziagen + Combivir group compared to the indinavir + Combivir combination - 65 percent and 87 percent respectively (p<0.001).
The 48 week data, comes from a randomized, open-label, multi-centre, equivalence trial, involving 342 therapy-naive adults. The study compared the durability of antiviral response, safety, tolerance and adherence to the triple nucleoside reverse transcriptase inhibitor (NRTI) regimen containing Ziagen + Combivir to the PI indinavir in combination with Combivir.
Patients in the Ziagen + Combivir group received four tablets per day; one tablet each of Combivir and Ziagen twice daily, with no food or water requirements. Patients in the indinavir + Combivir group received eight capsules/tablets per day; one Combivir tablet twice daily and two indinavir capsules three times daily, with food and water requirements.
These results demonstrate that the two-tablet, twice daily Ziagen + Combivir combination is at least as effective as PI-based triple therapy, with the added benefits of simplicity and enhanced patient adherence to therapy. The GlaxoSmithKline fixed-dose combination tablet, Trizivir, containing abacavir, lamivudine and zidovudine, administered as a single tablet twice daily, may
further enhance these benefits.
Treatment with Ziagen + Combivir is generally well tolerated. The most serious adverse event associated with Ziagen is a hypersensitivity reaction. Across clinical studies approximately 4 percent of subjects receiving Ziagen developed a hypersensitivity reaction, usually in the first six weeks of therapy. The presentation is variable but is characterized by the appearance of symptoms indicating multi-organ/body-system involvement. Almost all patients developing hypersensitivity reactions will have fever and/or rash as part of the syndrome, however reactions have occurred without rash or fever. Other symptoms may include but are not limited to nausea, vomiting, diarrhea, abdominal pain, dyspnea, cough, sore throat, malaise, lethargy, and myalgia. Patients who develop a hypersensitivity reaction must discontinue Ziagen and must never be re-challenged with Ziagen, or any other medicinal product containing abacavir (Trizivir).
SOURCE: Shire Pharmaceuticals Group plc
