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| |  Sustiva, In Combination Therapy, Achieves Viral Suppression, Preliminary Results Show TORONTO, ON -- February 2, 2000 -- Data presented at a major medical meeting in San Francisco demonstrate that a treatment regimen of DuPont Pharma's Sustiva(R) (efavirenz) with emtricitabine (FTC) and didanosine (ddI) appears to have a potent effect in suppressing HIV-RNA levels in HIV-infected patients. The data, from ANRS (Agence Nationale de Recherche sur les SIDA) trial 091, point to the potential efficacy of this once-daily antiretroviral regimen. Data from this open-label pilot study indicate that after 24 weeks of treatment, 39 of the 40 patients (98 percent) treated with Sustiva+FTC+ddI achieved viral suppression below 400 copies/mL and 37 patients (93 percent) achieved a plasma HIV-RNA below 50 copies/mL. The mean increase in CD4 cell count observed at week 24 was 151 cells/mm(3). "We are encouraged by these preliminary results as they highlight the efficacy and tolerability of this once-a-day HAART (Highly Active Antiretroviral Treatment) regimen," said Professor Jean-Michel Molina, MD, Clinique des Maladies Infectieuses, Hospital Saint-Louis, Paris, France. "The goal is to create treatment regimens that are powerful yet convenient for the patient to take. These data help us move closer to attaining this goal." ANRS 091 was a 24-week, open-label, pilot study of 40 antiretroviral-naive adults. Median plasma HIV-RNA at baseline was 4.8 log(10) copies/mL and the mean CD4 cell count was 396 cells/mm(3). All patients enrolled in the trial received 600 mg of Sustiva, 200 mg of FTC and either 400 mg of ddI if the patient's weight was greater than 60kg or 250 mg if their weight was less than 60 kg. In the study, patients took seven pills once-daily at bedtime. Safety data from this study indicate that 73 percent of patients (n equals 29) experienced transient nervous system events and 10 percent of patients (n equals 4) experienced rash. Mild diarrhea was also reported in 33 percent (n equals 13) of the patients studied. Additional data presented today indicate that Sustiva in combination with protease inhibitors demonstrates long-term viral suppression in HIV-infected patients, as well as CD4 cell recovery and maintenance. The findings, from DuPont Pharmaceuticals Study 003, highlight the potency and durability of combination treatment with Sustiva. The more traditional observed data analysis showed that after 132 weeks of treatment, 90.5 percent treated with Sustiva+indinavir (IDV) (38/42) achieved HIV-RNA suppression below quantifiable levels (i.e., less than 400 copies/mL). In the arm of the study that initially received indinavir monotherapy with the subsequent addition of Sustiva+stavudine (d4T), 70.8 percent of the patients (17/24) achieved HIV-RNA suppression below quantifiable levels. Using the more rigorous non-completer equals failure analysis(1), the study results indicate that 65.5 percent of patients treated with Sustiva+indinavir (IDV) (38/58) achieved HIV-RNA suppression below quantifiable levels, and 40.5 percent of the patients (17/42) receiving indinavir+Sustiva+stavudine achieved HIV-RNA suppression below quantifiable levels. Similar results were observed in a subgroup of patients with baseline viral loads greater than 100,000 copies/mL. The mean increase in CD4 cell count at 120 weeks was 374.8 ((+/-) 36.1) cells/mm(3) for patients treated with Sustiva+IDV. The mean increase in CD4 cell count at 120 weeks was 266.3 ((+/-) 36.1) cells/mm(3) for patients treated with Sustiva+IDV+stavudine (d4T). "These results confirm previous findings from Study 003 and reinforce the therapeutic role of combination treatment with Sustiva in providing patients with optimal virological outcomes for as long as two-and-a-half years," said Sharon Riddler, MD, Assistant Professor of Medicine, University of Pittsburgh School of Medicine. "Further, the strong, continued and sustained increase in CD4 cell counts indicate that Sustiva, in combination treatment, plays a role in immune recovery." Study 003 was a randomized, multicenter, double blind trial of 101 asymptomatic or mildly symptomatic patients. Initiated at a time when indinavir monotherapy was common, patients enrolled in Study 003 were randomized to receive Sustiva+IDV (n equals 59) or IDV alone (n equals 42). After the World AIDS Conference in Vancouver in 1996, the indinavir monotherapy arm was considered to be sub-optimal. Therefore, after 12 weeks of treatment, Sustiva and stavudine were added to the regimen of those patients randomized to receive IDV alone. At week 36, the dose of Sustiva was increased to 600 mg/day in both treatment arms. Mean HIV-1 RNA and CD4 cell counts of patients included in the trial were 5.06 ((+/-) 0.55) log(10)copies/mL and 283 +118 cells/mm(3) respectively. The most commonly reported treatment-related effects among all patients receiving Sustiva were diarrhea and nausea (n equals 93). In addition, data presented on Sunday, January 30th at this meeting in San Francisco may provide physicians with new options for managing methadone dosage changes in methadone-maintenance patients taking anti-HIV combination treatment with Sustiva. In this pharmacokinetic study, investigators noted that almost three-quarters of the 25 patients enrolled in the study experienced symptoms consistent with withdrawal eight to ten days after the initiation of treatment with Sustiva, which required a mean increase in methadone dose of 21.6 percent. The investigators concluded that an immediate increase in a patient's methadone dose may not be necessary and recommend frequent patient monitoring within the first two weeks of therapy to assist physicians in determining adequate methadone dosage increases. Since December 1998, the U.S. Department of Health & Human Services (DHHS) has recommended Sustiva as the only NNRTI to be included in preferred antiretroviral regimens intended for first-line treatment of HIV-infected individuals who are naive to therapy. Sustiva (efavirenz), developed by the DuPont Pharmaceuticals Company, 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 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 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, 1.7 per cent discontinued therapy due to rash. Women should not become pregnant while taking Sustiva because birth defects have been seen in primates 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. Related Links: Sustiva (efavirenz) and DuPont Pharmaceuticals Company.
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