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| |  Sustiva (Efavirenz) Instead Of Protease Inhibitor Maintains Antiretroviral Control TORONTO, ON -- July 17, 2000 -- Data recently presented indicate that DuPont Pharma's anti-HIV drug Sustiva® (efavirenz), when substituted for a protease inhibitor, successfully maintained viral load suppression (less than 50 copies/mL) in patients who had already achieved this level. The findings from DMP Study 266-027, a late-breaker poster at the XIIIth International AIDS Conference in Durban, South Africa, demonstrate the potent antiviral activity of Sustiva, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is an alternative regimen for patients who cannot tolerate protease inhibitor based regimens. Using the rigorous method of reporting data called non-completer equals failure analysis, the results indicate that through 24 weeks of treatment with Sustiva plus two nucleoside reverse transcriptase inhibitors (NRTIs), 97 percent (67/69) of patients maintained viral load less than 50 copies/mL. This is compared to 83 percent (54/65) of patients maintaining the initial treatment consisting of a protease inhibitor plus two NRTIs. These data were statistically significant (p equals 0.0076). Additionally, using a time-to-treatment failure analysis, 96 percent of patients were still below 50 copies/mL using Sustiva plus two NRTIs at 24 weeks compared to 85 percent using a protease inhibitor plus two NRTIs. Well- known and long used as a measurement of a drug's clinical efficacy in oncology, time-to-treatment failure measures the efficacy of a drug regimen as a function of the durability of its action over time. "The results support the use of Sustiva in alternative regimens due to the fact that it helped sustain more patients' low viral load than those who continued therapy with a protease inhibitor," said Professor Christine Katlama, Professeur des Universités, Médecin Des Hôpitaux, Paris, France. "The data help to confirm that Sustiva is as potent as a protease inhibitor and should be considered as part of a simple antiretroviral regimen that may enhance adherence for patients." DMP 266-027 is an ongoing, randomized, multicenter, open-label study of 165 antiretroviral-experienced, NNRTI-naive patients. Patients receiving a regimen containing protease inhibitor(s) plus NRTIs with plasma HIV-RNA levels less than or equal to 50 copies/mL were enrolled and then randomized to maintain the original NRTI regimen and substitute the protease inhibitor(s) with 600 mg of Sustiva once-daily or continue with their existing regimen. Enrolment into a third treatment arm was stopped at 31 patients due to poor enrolment and was not considered in the analysis. Safety data from DMP 266-027 show that one person discontinued from the arm containing Sustiva and seven discontinued from the protease inhibitor-containing arm. In January 2000, the U.S. Department of Health and Human Services (DHHS) named Sustiva as the only non-nucleoside reverse transcriptase inhibitor to be "strongly recommended" for use in first-line combination with NRTIs for the treatment of HIV-infected individuals. Sustiva (efavirenz), developed by the DuPont Pharmaceuticals Company, is approved, in capsule formulation, 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 4 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 HIV. 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 present in the cerebrospinal fluid, one of several sanctuaries for the virus that make treatment more difficult. The clinical significance of this presence is unknown. 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 adult patients. The most notable side effects associated with Sustiva therapy are nervous system symptoms and rash. In clinical trials 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, 1.7 per cent discontinued therapy due to rash. In controlled trials, serious psychiatric symptoms observed were severe depression (0.9 percent), suicidal ideation or attempts (0.5 percent), aggressive behavior (0.3 percent), paranoid reactions (0.2 percent) and manic reactions (0.1 percent). These problems were seen at a similar frequency in control groups and tended to occur more often in patients with a history of mental illness, where the frequency of each of these events was approximately one percent. A few suicides have been reported; however, a causal relationship to Sustiva has not been established. Patients with serious psychiatric experiences should contact their physician. Women should not become pregnant while taking Sustiva because birth defects have been seen in animals given efavirenz at levels similar to those given to humans. Patients should be cautioned not to operate hazardous machinery or drive if they experience nervous system symptoms. Sustiva should not be administered concurrently with Hismanal® (astemizole), Prepulsid® (cisapride), Versed® (midazolam), Halcion® (triazolam) or ergot derivatives. Current treatment guidelines recommend against the use of any antiretroviral agent as monotherapy. Therefore, Sustiva must not be used as a single agent to treat HIV or added on as a sole agent to a failing regimen. The choice of new antiretroviral agents to be used in combination with Sustiva should take into consideration the potential for viral cross-resistance. Sustiva therapy should always be initiated in combination with at least one other antiretroviral agent to which the patient has not been previously exposed. Related links: Sustiva, Hismanal, Prepulsid, Versed, Halcion and DuPont Pharma.
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