To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: HIV/AIDS MEETING: Sustiva Effective, More Cost Effective Than Protease Inhibitor URL: http://www.pslgroup.com/dg/FB74A.htm Doctor's Guide May 4, 1999
VICTORIA, BC -- May 4, 1999 -- The findings of four Canadian HIV/AIDS specialists together demonstrated that DuPont Pharmaceuticals Co.'s Sustiva(R) (efavirenz) in combination therapy is effective, flexible and more cost effective than a treatment containing a protease inhibitor. The studies were presented at the eighth annual Canadian Conference on HIV/AIDS Research in Victoria. Sustiva was approved for use in Canada in March 1999. Mr. Greg Williams, president of Williams Research.com Inc., presented a cost analysis demonstrating the health service utilisation savings of Sustiva therapy versus protease inhibitor therapy. The analysis determined that the average annual medical care cost per patient, excluding the cost of study medications, was significantly lower for Sustiva+ZDV+3TC than for indinavir+ZDV+3TC. According to Mr. Williams, the Sustiva health services utilisation-related costs savings of $358 CDN per year was primarily due to a higher incidence of moderate and severe adverse clinical events in the indinavir+ZDV+3TC study arm. The $358 figure does not include the cost of HIV medications themselves. Sustiva is priced 19 per cent less than protease inhibitors, thus a total cost savings would be approximately $1,500 CDN per year. The analysis was based on data from 450 patients and used a micro-economic costing model to estimate and project the annual costs of routine medical care (out-patient visits, laboratory tests, medical procedures and out-of-pocket expenses), hospitalisations, adverse clinical events, concomitant medications, treatment failure and clinical study dropouts. "Antiretroviral combinations that are viewed as being equivalent may incur different medical care costs," Mr. Williams explained. "This study is able to put an economic cost on adverse events related to therapy, which is something that has not been considered." Dr. Marianne Harris, Clinical Research Advisor of the Immune Deficiency Clinic of St. Paul's Hospital in Vancouver, is one of the first physicians in the world to document the effects of switching from a protease inhibitor-containing regimen to Sustiva. Her study followed 18 patients who received Sustiva as a replacement for a protease inhibitor in their combination regimen. The patients had a viral load (VL) less than 400 copies/ml for three to 28 months (median 13.5) prior to the switch. The main protease inhibitor-related adverse events leading to the change in regimen were lipodystrophy the redistribution of body fat; followed by gastrointestinal symptoms, nausea, diarrhea; elevated triglycerides; and severe paronychia, an inflammation of nail and separation of skin from the nail. In 17 of 17 patients with one or more viral load results available after the switch to Sustiva, the viral load remained below 400 copies/ml after two to seven months of treatment. Another important outcome was at least partial resolution of protease inhibitor adverse events in nine patients taking Sustiva. "Physicians have needed a potent treatment choice for patients who have not been able to tolerate protease inhibitor-related toxicity," Dr. Harris explained. "Results show that the strategy of replacing a protease inhibitor with Sustiva in a virologically-successful combination regimen can maintain the efficacy of protease inhibitors while reducing side effects which cause patients distress." Dr. Sharon Walmsley, Assistant Director of The Toronto Hospital Immunodeficiency Clinic, presented results of a study designed to characterise and identify predictors of antiretroviral (ARV) efficacy and toxicity observed with Sustiva use among HIV patients at the clinic. The study used a retrospective chart review of patients receiving Sustiva through the Expanded Access Program. Patients were included if they had at least one documented follow-up report. All 66 patients received prior antiretrovirals: 94 per cent had received a nucleoside reverse transcriptase inhibitor (NRTI), 85 per cent a protease inhibitor (PI), and 23 per cent a non-nucleoside reverse transcriptase inhibitor (NNRTI). Mean follow up was four months. Twenty-nine per cent of patients had viral suppression to less than 50 copies/ml, using the ultrasensitive assay. All these responders maintained undetectable viral loads through the follow-up period. An additional 12 patients achieved partial suppression (less than 1 log viral load reduction). Prior NNRTI experience predicted a poor response, while none of the following were significant predictors of efficacy; baseline viral load or CD4 count; number of antiretrovirals changed with Sustiva; or prior NRTI use with or without a protease inhibitor. Adverse effects, including rash and CNS effects, attributed to Sustiva occurred in 48 patients, which led to drug discontinuance in 11 patients, three due to rash and eight due to CNS effects. Dr. Stephen Shafran, director of the division of infectious diseases at the University of Alberta, presented a study on salvage therapy with Sustiva and abacavir after the failure of a protease inhibitor based regimen. As of April 15, 1999, 22 patients who had failed a protease inhibitor based regimen were treated with a salvage regimen, consisting of Sustiva and abacavir with or without other licensed antiretrovirals. The median duration of therapy was seven months and 18 (82 per cent) patients achieved a virologic response, defined as less than 0.5 log 10 viral load reduction, with 12 achieving a viral load below 400 copies/ml, using the Roche Amplicor assay. Of nine in whom an ultrasensitive assay (Roche), eight (89 per cent) had plasma viral loads below 50 copies/ml. Of three subjects with prior NNRTI experience, two failed to respond and one had only a partial response. Five patients discontinued therapy, one of which was due to an adverse event. Sustiva is approved for the treatment of HIV-1 infection, in combination with other antiretroviral agents. This is based on analyses of plasma HIV-RNA levels and CD4 cell counts in controlled studies of up to 24 weeks in duration. Sustiva is unique for its efficacy and simple dosing regimen. Three Sustiva capsules can be taken once a day compared to six to 18 pills per day for a protease inhibitor. Sustiva can be taken on an empty or full stomach; however, a high fat meal may increase the absorption of Sustiva and should be avoided. This flexibility around dosing with meals combined with its efficacy and potency may help patients maintain more normal lives while combating the HIV virus. Clinical trials with Sustiva have demonstrated that the majority of patients, including patients with baseline viral counts in excess of 100,000 units or copies per millilitre (copies/ml) had viral loads reduced to below quantifiable levels (less than 400 copies/ml). Sustiva is also active in the cerebrospinal fluid, a sanctuary for the virus that makes treatment more difficult. This potency, combined with its efficacy in first-line and salvage therapy, makes Sustiva an important addition to HIV therapy regimens, receiving expedited approval in both Canada and the United States. Sustiva has also proven to be generally well tolerated by patients. The most notable side effects associated with Sustiva therapy are nervous system symptoms and rash. Slightly greater than half of the patients, 52 per cent, have reported central nervous system symptoms that may include dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming, However, central nervous system effects were severe enough to cause treatment discontinuation in 2.6 per cent of patients. Rash is usually mild-to-moderate in severity and often resolves itself within one month of continued therapy with Sustiva. Among patients receiving Sustiva, 17 per cent discontinued therapy due to rash. --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. 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