a SLACK Incorporated newspaper
January 1999
Abacavir is the first new nucleoside analogue reverse transcriptase inhibitor to be approved in more than three years.
Clinical trials have included treatment naive patients as well as patients taking multidrug regiments. The drug was also studied in children. Studies show that combinations containing abacavir have antiviral activity in treatment-naive patients. Patients who have had prolonged exposure to zidovudine (AZT, Retrovir, Glaxo) and lamivudine (3TC, Epivir, Glaxo) may have a minimal response to combinations containing abacavir. However, studies have shown some of these patients have experienced significant antiviral activity after switching to new combinations containing abacavir, the manufacturer said.
This approval is based on analyses of surrogate markers in controlled studies of up to 24 weeks. There are no results from trials evaluating long-term suppression of HIV-RNA or disease progression with abacavir. The approval of abacavir is based on results from three phase 3 studies. In an interim analysis at 16 weeks, the three drug combination of abacavir, lamivudine and AZT was superior to the combination of Epivir and AZT in reducing HIV viral load.
In this study, 75% of 87 patients on triple combination including abacavir were at less than 400 copies/mL compared with 35% of 86 patients on dual therapy. Through 16 weeks of therapy, the median CD4 changes from baseline were 47 cells/mm3 in the group receiving abacavir and 112 cells/mm3 in the placebo group. This difference was not statistically significant.
In a planned interim analysis at 24 weeks in children with extensive prior nucleoside treatment, the three drug combination of abacavir, lamivudine and AZT was shown to be superior to the combination of lamivudine and AZT in reducing viral load.
In this study, 13% of 102 patients on triple combination including abacavir were at less than 400 copies/mL compared to 2% of 103 patients on dual therapy. After 16 weeks of therapy, the median CD4 increases from baseline were 69 cells/mm3 in the group receiving abacavir and 9 cells/mm3 in the control group.
Preliminary findings from a second controlled study in therapy-naive adults were supportive of the efficacy of abacavir through 16 weeks of treatment. This study compares abacavir and Combivir (lamivudine-zidovudine, Glaxo Wellcome) with the combination of Crixivan (indinavir, Merck) and Combivir.
Abacavir will be dosed as one 300-mg tablet twice daily with no food or water restrictions or requirements. It is expected that abacavir will be available this month.
The most common adverse events were headache, nausea, vomiting, malaise and diarrhea when abacavir was taken, primarily with Epivir and Retrovir but also with all marketed and most investigational compounds. Lactic acidosis and severe hepatomegaly with steatosis have been reported with the use of nucleoside analogues. The most serious adverse event associated with abacavir is a hypersensitivity reaction that can be life threatening. The hypersensitivity reaction has been observed in approximately 3% to 5% of patients and is characterized by fever, skin rash, fatigue, and gastrointestinal symptoms, such as nausea, vomiting, diarrhea, or abdominal pain. The symptoms of this reaction get progressively worse if treatment continues.
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