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| |  ICAAC: Previous Use of Viramune or Rescriptor May Jeopardize Response To Sustiva SAN FRANCISCO, CA. -- September 29, 1999 -- Data from a virology sub-study of the DuPont Pharmaceuticals’ Sustiva™ (efavirenz) Expanded Access Program indicate that 78 percent of patients who initiate combination therapy with Viramune® (nevirapine) or Rescriptor® (delavirdine) were found to have HIV mutations that may jeopardize their ability to subsequently respond to combination therapy with Sustiva. According to the DHHS Guidelines, Sustiva is the only non-nucleoside reverse transcriptase inhibitor (NNRTI) listed among the preferred antiretroviral agents to be used in first-line combination treatment regimens for HIV-infected individuals who are naive to antiretroviral treatment. The findings were presented today at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy, in San Francisco, CA. Among 41 patients enrolled in a virology sub-study of the Sustiva Expanded Access Program, 76 percent reported prior use of nevirapine and 39 percent reported prior use of delavirdine. Among 27 patients with three month follow-up on combination therapy with Sustiva, 55 percent (n=15) were non-responders with viral loads greater than or equal to 400 copies/mL and 44 percent (n=12) were responders with viral loads less than or equal to 400 copies/mL. The genotyping at entry revealed 78 percent of patients had one or more mutations associated with NNRTI resistance. Most prevalent mutations were K103N (18 percent), Y181C+/-A98G (10 percent) and the double mutation K103N+Y181C (26 percent). When the therapeutic response to Sustiva was tracked against the genotypic information obtained, 7 of 8 patients with the K103N+Y181C double mutation were non-responders, as were 2 of 5 patients with the K103N mutation and 3 of 3 of the patients with the Y181C mutation at three months. These data suggest a decreased likelihood of response to combination therapy with Sustiva after failing another NNRTI. "We have to do what’s best for the patient," said Paul A. Friedman, M.D., President, DuPont Pharmaceuticals Research Laboratories. "By determining resistance patterns and their impact on subsequent therapy, we’re helping to provide patients and physicians with important information that will help shape the best course of treatment."
Additional Data on Sustiva Reinforce DHHS Guidelines The findings of a related study entitled "Baseline Prevalence of Mutations Linked to NNRTI Resistance in Naive Patients Enrolled in Clinical Studies of Efavirenz", presented Monday, suggest that the prevalence of mutant strains in NNRTI-naive patients does not affect patient response to combination therapy with the non-nucleoside reverse transcriptase inhibitor Sustiva. Data presented at the Sixth Conference on Retroviruses and Opportunistic Infections in February 1999 indicated that the prevalence of NNRTI-resistant mutations in treatment-naive patients varied between 15 and 25 percent.1 In the current analysis, investigators examined the prevalence of viral mutants in resistant NNRTI therapy-naive patients and their potential effects on the outcomes of combination regimens including Sustiva. In this analysis, investigators used a broadly inclusive list of variations in the HIV-1 RT gene that have been reported to confer reduced susceptibility to any NNRTI, as well as any associated compensatory mutations. The data demonstrated that despite a moderate prevalence of viral mutations associated with the development of resistance to any NNRTI (19 percent), the proportion of patients whose baseline viral genotype appeared to effect susceptibility to combination therapy including Sustiva was low (2.5 percent of patients; 4 out of 161). "These results provide hope to physicians who want to prescribe NNRTI regimens to their treatment-naive patients," said Lee Bacheler, Ph. D., Senior Investigator, Virology, DuPont Pharmaceuticals Research Laboratories.
Accelerated Approval and Product Labeling On September 17, 1998, the FDA granted accelerated approval for Sustiva, a non-nucleoside reverse transcriptase inhibitor (NNRTI), indicated for the treatment of HIV-1 infection in combination with other antiretroviral agents. This indication is based on analyses of plasma HIV-RNA levels and CD4 cell counts in controlled studies of up to 24 weeks in duration. At present, product labeling indicates there are no results evaluating long-term suppression of HIV-RNA with Sustiva. DuPont has submitted an application for traditional approval of Sustiva based on two studies showing long-term (48-week) durability. Sustiva has also received full approval in several countries in Europe, and received full approval in Canada on an accelerated basis.
Related Links: Viramune®; Rescriptor® and DuPont Pharmaceuticals.
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