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| |  HIV Treatment With Ziagen Plus Combivir Is Convenient And Effective SAN FRANCISCO, CA -- February 1, 2000 -- Preliminary 48-week data from an ongoing study of patients with undetectable levels of HIV who switched from a protease inhibitor-containing regimen to a regimen of Ziagen(R) (abacavir sulfate) + Combivir(R) (lamivudine/zidovudine) -- a regimen of just two pills taken twice a day -- were presented at a major scientific meeting in San Francisco. Ziagen, in combination with other antiretroviral agents, is currently approved for use in adults and children to treat HIV-1 infection. This indication is based on analyses of surrogate markers in controlled studies of up to 48 weeks in duration. Ziagen is dosed in adults as one 300-mg tablet twice daily with no food restrictions or liquid requirements. At present, there are no results from controlled trials evaluating long-term suppression of HIV-RNA or disease progression with Ziagen in the labeling. Patients with plasma HIV-1 RNA (viral load) <50 copies/mL (Roche Amplicor(R) Ultrasensitive assay) for at least six months on protease inhibitor-containing combination therapy and with no zidovudine-resistance mutation at codon 215 at baseline were randomized to either continue their current protease inhibitor-containing regimen or switch to Ziagen+Combivir. The mean duration of prior protease inhibitor therapy was 22.5 months for those on the continuation arm and 21 months for those on the Ziagen arm. The patients' viral loads were measured every four weeks during the first six months and then every three months. To date, 163 patients have been randomized and are evaluable, 79 in the continuation arm and 84 in the simplified arm. There have been five virologic failures in the continuation arm and seven virologic failures in the simplified arm. Among seven evaluable isolates from breakthrough patients in the simplified arm, 184 codon mutation (lamivudine) was present in five, 215 codon mutation (zidovudine) was present in six and 41 codon mutation (zidovudine) was present in five. Preliminary data from this study also evaluated serum cholesterol and lipid abnormalities experienced by the patients previously on protease inhibitor-containing combination therapy. At 48 weeks, median decreases in non-fasting cholesterol were -1.3 mmol/L for the simplified arm and -0.5 mmol/L for the protease inhibitor arm (P<0.001). Changes in non-fasting triglycerides were -1.0 mmol/L for the simplified arm and -0.1 mmol/L for the PI arm (P<0.05). In a pivotal study of Ziagen (CNA3003), triglyceride elevations (all grades) were more common on the abacavir arm (25 percent) than on the placebo arm (11 percent). "We are pleased with the interim results of this study which evaluates a convenient treatment regimen," said Lynn Smiley, M.D., vice president, HIV and Opportunistic Infections Clinical Development at Glaxo Wellcome. "We are firmly committed to developing medications and evaluating regimens that simplify the effective, yet often complex, regimens that HIV patients take." In clinical trials to date, the most commonly reported adverse events were headache, nausea, vomiting, malaise and diarrhea when Ziagen was taken, primarily with Epivir(R) (lamivudine) and Retrovir(R) (zidovudine) but also to a limited extent with all marketed and most investigational compounds. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including abacavir, zidovudine, lamivudine and other antiretrovirals. Zidovudine in Retrovir and Combivir has also been associated with anemia and neutropenia, especially in patients with advanced disease, and with symptomatic myopathy after prolonged use. The most serious adverse event associated with Ziagen is a hypersensitivity reaction that can be life threatening and has been fatal in some cases. In the thousands of patients who have taken Ziagen in clinical trials, hypersensitivity reaction has been observed in approximately 5 percent of patients. It is characterized by fever, skin rash, fatigue and gastrointestinal symptoms, such as nausea, vomiting, diarrhea or abdominal pain. Respiratory symptoms such as dyspnea, pharyngitis and cough may also occur. The diagnosis of hypersensitivity reaction should be carefully considered for patients presenting with symptoms of acute respiratory diseases, even if alternative respiratory diagnoses (pneumonia, bronchitis, flu-like illness) are possible. Therefore, patients should also watch for respiratory symptoms such as shortness of breath, sore throat or cough. Rechallenge is contraindicated after a diagnosis of hypersensitivity. Symptoms of this reaction usually occur within the first six weeks of treatment. The symptoms of this reaction get progressively worse during treatment, but generally resolve following permanent discontinuation of Ziagen. Patients experiencing these symptoms should stop taking Ziagen and contact a physician immediately. Patients experiencing this reaction must not take Ziagen again as restarting the drug after a hypersensitivity reaction has resulted in cases of life-threatening and fatal reactions. A medication guide for Ziagen is available to provide further information on optimizing care with this drug. Ziagen has a low likelihood of interactions with other antiretroviral drugs that are metabolized by the cytochrome P450 enzyme system. This is a favorable factor when trying to prescribe the multi-drug regimens required to treat HIV. Related Links: Epivir (lamivudine) and Retrovir(R) (zidovudine).
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