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| |  ROI CONFERENCE: Triple Therapy With Ziagen Effective For Up To 48 Weeks CHICAGO, IL -- Feb. 1, 1999 -- Study results presented today indicate that Ziagen(TM) (abacavir sulfate), in combination with Epivir(R)(lamivudine, also known as 3TC(R)) and Retrovir(R) (zidovudine, AZT) lowers the amount of HIV in the blood to undetectable levels (less than 400 copies; Roche Amplicor Monitor(TM) assay) in 64 percent of patients (53 out of 83) for up to 48 weeks. The data from this study were reported today at the sixth conference on Retroviruses and Opportunistic Infections in Chicago. The study demonstrated that the probability that a patient receiving Ziagen+Epivir+Retrovir remains event free (event defined as plasma viral load greater than 400 copies/mL) for 48 weeks was 74 percent compared to 31 percent for patients receiving Epivir+Retrovir alone. Using an as-treated analysis, 92 percent of patients (48 of 52) who remained on the Ziagen+Epivir+Retrovir arm for the entire 48 weeks achieved undetectable levels of HIV. Upon study entry, patients had a median HIV RNA level of 35,000 copies/mL, a median CD4+ cell count of 450 cells/mm3, and no prior antiretroviral experience. Patients were randomised to one of two regimens, with 87 receiving Ziagen+Epivir+Retrovir, and 86 receiving Epivir+Retrovir. At week 16, patients were given the option to add open-label Ziagen to their regimens. Additionally, any patient whose viral load rose to above 400 copies/mL during the course of the study could add Ziagen and/or another FDA-approved antiretroviral agent(s). The percentage of patients on the Epivir+Retrovir arm who achieved undetectable levels (less than 400 copies/mL) at 48 weeks of therapy rose to 64 percent (32 of 50) after intensification of therapy with Ziagen. At week 48, the CD4+ cell change from baseline was comparable in both groups, with a median increase of 150 cells/mm3 in the group originally randomised to receive Ziagen+Epivir+Retrovir and 158 cells/mm3 in the dual therapy arm. "Ziagen is a potent addition to the HIV armamentarium," said the University of Miami's Margaret Fischl, M.D., the study's lead investigator who has extensive experience treating patients with Ziagen. Sixty-five patients (75 percent) on the dual therapy arm chose to add a new drug; 50 of them (59 percent) added Ziagen alone, while 15 (17 percent) added Ziagen and an additional agent(s). Only four patients (five percent) who began treatment with Ziagen+Epivir+Retrovir decided to add other antiretroviral(s), with eight patients (nine percent) deciding to remain on Epivir+Retrovir alone. Thirteen patients (15 percent) on the Epivir+Retrovir arm dropped out of the study, while 16 patients (18 percent) from the Ziagen+Epivir+Retrovir arm discontinued treatment. The results support 16-week data from this study, presented at the 12th World AIDS Conference in Geneva in June. These results showed that 75 percent of patients (65 of 87) on the triple drug combination therapy of Ziagen+Epivir+Retrovir had undetectable levels of HIV at 16 weeks, compared to 35 percent of patients (30 of 86) on dual therapy. The median CD4 increases from baseline were 47 cells/mm3 in the arm containing Ziagen and 112 cells/mm3 in the control group. Ziagen was granted accelerated approval by the FDA on December 17, 1998 for use in combination with other antiretroviral agents for the treatment of HIV-1 infection. This indication is based on analyses of surrogate markers in controlled studies of up to 24 weeks in duration. At present, there are no results from controlled trials evaluating long-term suppression of HIV RNA or disease progression with Ziagen. It is the 15th drug approved for HIV and the first new drug in its class (nucleoside analogue reverse transcriptase inhibitors) to be approved in more than three years. Ziagen is conveniently dosed as one 300-mg tablet twice daily with no food or water restrictions or requirements. Ziagen does not interact significantly with other drugs that are metabolised by the P450 enzyme system. This factor facilitates incorporation into multi-drug regimens of anti-HIV therapies. In clinical trials to date, the most common adverse events reported from patients receiving treatment regimens containing Ziagen were headache (16 percent), nausea alone (47 percent), nausea and vomiting (16 to 38 percent), fever (19 percent) and diarrhea (12 to 16 percent). 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 and other antiretrovirals. The most serious adverse event associated with Ziagen is a hypersensitivity reaction that can be life threatening and has been fatal in some cases. The hypersensitivity reaction has been observed in approximately five percent of patients receiving Ziagen in clinical trials and is characterised by fever, skin rash, fatigue and gastrointestinal symptoms, such as nausea, vomiting, diarrhea, or abdominal pain. The symptoms of this reaction get progressively worse during treatment. Patients experiencing these symptoms should stop taking Ziagen and contact a physician immediately. Symptoms of this reaction usually occur within the first six weeks of treatment and generally resolve following permanent discontinuation of Ziagen. Patients experiencing this reaction must not take Ziagen again as restarting the drug after a hypersensitivity reaction has resulted in cases of life-threatening hypotension and fatal reactions.
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