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| |  Twice-Daily Viracept Demonstrates Anti-HIV Activity At 48 Weeks LA JOLLA, CA -- Sept. 25, 1998 -- Preliminary data from several clinical studies, presented at the 38th interscience conference on Antimicrobial Agents and Chemotherapy, indicate that twice-daily dosing of Agouron Pharmaceuticals, Inc.’s HIV protease inhibitor Viracept(R) (nelfinavir mesylate) in combination therapy produces anti-HIV effects at 48 weeks comparable to those resulting from standard three times daily dosing of the drug in combination therapy. In an ongoing European study conducted at 24 sites that will continue for 96 weeks, approximately 283 patients were initially randomised to receive either the standard three times daily (TID) dose of 750mg Viracept or one of three twice-daily (BID) Viracept doses (1,250mg, 1,000mg or 750mg) in combination with standard doses of Zerit(R) (d4T or stavudine) and Epivir(R) (3TC or lamivudine). The study protocol was subsequently amended to consolidate the comparison to the 1,250mg BID versus 750mg TID Viracept regimens in a total of 360 patients. Preliminary results from the BID dosing groups were compared with results from the TID dosing group. HIV in plasma fell below the limit of detection by the Roche Amplicor(TM) assay (less than 400 HIV RNA copies/mL) at 48 weeks in approximately 80 percent of patients in both the BID dosing groups (132/165) and the TID dosing group (48/59). Sixty-eight percent of patients (112/164) in the BID dosing groups and 64 percent of patients (38/59) in the TID dosing group achieved viral loads below the limit of detection when tested with an experimental ultrasensitive assay (less than 50 copies/mL) at 48 weeks. Mean CD4+ T-cell counts (infection-fighting cells of the immune system) at 48 weeks increased by 195 cells/mm3 and 174 cells/mm3 in the BID groups and the TID group, respectively. Prior to treatment, the mean viral load (the amount of HIV in plasma) of patients was approximately 5.0 log10 viral copies/mL of plasma. The mean baseline CD4+ T-cell counts were 273 and 254 cells/mm3 in the BID and TID groups, respectively. Patients enrolled in this study had less than six months of prior nucleoside antiretroviral therapy. The only side effect of moderate or greater intensity to occur in more than five percent of patients receiving Viracept was diarrhea, which occurred at a rate of 17 percent and 12 percent, respectively, in the BID and TID groups. New onset or exacerbation of diabetes mellitus and hyperglycemia, as well as increased bleeding in patients with hemophilia types A and B, have been reported with protease inhibitors. These European data were generally consistent with results presented from pilot studies conducted at three sites in the United States. Three 48-week studies were designed to assess BID regimens of Viracept in combination with two nucleoside analogs. At baseline, the mean viral load of the 34 patients enrolled in these studies was 4.8 log10 copies/mL, and their mean CD4+ T-cell count was 392 cells/mm3. Patients received 1,250mg Viracept BID + d4T + 3TC, 1,250mg Viracept BID + AZT + 3TC, or 1,000mg Viracept BID + AZT + 3TC. At 24 weeks, those patients who received the 1,000mg Viracept regimen were then increased to 1,250mg Viracept BID + AZT + 3TC for the remainder of the study. Of the 20 patients who were evaluated at week 48, 80 percent of patients (16/20) achieved viral loads below the limit of detection (less than 400 copies HIV RNA/mL); 79 percent of patients (15/19) tested with an experimental ultrasensitive assay (less than 50 copies/mL) at 48 weeks also achieved viral loads below the limit of detection. Patients' mean CD4+ T-cell increase from baseline was 104 cells/mm3. Viracept is indicated for the treatment of HIV infection when antiretroviral therapy is warranted. This indication is based on analyses of surrogate marker changes in patients who received Viracept in combination with nucleoside analogs or alone for up to 24 weeks. At present, there are no results from controlled trials evaluating the effect of therapy with Viracept on clinical progression of HIV infection, such as survival or the incidence of opportunistic infections. Related Links: Viracept, Agouron Pharmaceuticals, Inc.
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