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| |  ICAAC: Sustiva Combo May Provide Alternative Treatment For HIV/AIDS SAN DIEGO, CA -- Sept. 28, 1998 -- Clinical investigators presented data that confirm that people living with HIV and AIDS and their physicians now have a new choice for initial HIV therapy. Results from a 36-week study demonstrate that when used in combination with two nucleoside analogues DuPont Pharmaceuticals' new once-daily anti-HIV drug, Sustiva, continues to suppress HIV-RNA to low levels in patients with HIV infection. These results were obtained using the standard Amplicor(TM) assay, as well as the non-approved ultrasensitive assay, which is the new goal of therapy according to the IAS-USA guidelines. Efficacy data from this study in the Sustiva package insert are based on reduction in HIV-RNA at 24 weeks using the Amplicor(TM) assay. These and other Sustiva data were presented this weekend at the current 38th Interscience Conference on Antimicrobial Agents and Chemotherapy in San Diego. The FDA recently approved Sustiva, a non-nucleoside reverse transcriptase inhibitor (NNRTI) for treatment of HIV infection when used in combination with other antiretroviral agents. The 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, there are no results from clinical trials evaluating long-term suppression of HIV-RNA with Sustiva. The study, a large-scale, open-label Phase III clinical trial was designed to evaluate Sustiva (efavirenz) in combination with other commonly used antiretrovirals compared to the standard of care: After 36 weeks of treatment, the Sustiva/AZT/3TC combination suppressed viral load to below quantifiable levels (BQL, less than 400 copies/mL) in 73 percent (102/140) of patients as determined by the most rigorous method of reporting data (an analysis referred to as non-completer = failure). The proportion of patients achieving BQL in the Sustiva/indinavir arm and the indinavir/AZT/3TC arm by this analysis was 54 percent (74/136) and 51 percent (72/140), respectively. The disproportionate number of discontinuations in the control arm makes it difficult to assess the relative efficacy of the treatment regimens in this open-label study. Patients who entered the study with high viral load (greater than 100,000) copies/mL) also experienced HIV-RNA suppression to BQL. The results of this study are unlike previous studies where high baseline viral load increased the risk of treatment failure. The proportion of patients with high viral load achieving BQL at 36 weeks using the traditional observed data analysis was 97 percent (29/30), 64 percent (21/33) and 87 percent (20/23) for the Sustiva/AZT/3TC, Sustiva/indinavir, and indinavir/AZT/3TC combinations, respectively. For all patients in the study (450 patients), CD4 cell counts increased by more than 170 cells/mm3 from baseline. Efficacy data beyond 24 weeks and from patients with high viral load at study entry are not described in the Sustiva package insert. Safety data from the study at 36 weeks are similar to observations reported at 24 weeks. When Sustiva was combined with AZT/3TC, the most commonly reported treatment-related side effects (greater than or equal to) Grade 2 were nausea (11 percent), rash, maculopapular (10 percent), dizziness (nine percent), impaired concentration (eight percent), fatigue (seven percent) and headache (seven percent). Patients on regimens containing Sustiva experienced more nervous system symptoms (55 versus24 percent) and had more new-onset rashes (29 versus 16 percent) than patients on the indinavir/AZT/3TC arm. However, severe rashes were reported in less than one percent of patients receiving Sustiva in this study. Clinical investigators also presented results today from two DuPont Pharmaceuticals studies evaluating the use of Sustiva in a two-drug combination with a protease inhibitor. In both studies, results suggest that Sustiva, when used in combination with either Viracept or Crixivan, reduces HIV-RNA and elevates CD4 cell counts in HIV-1 infected patients. Results at 24 weeks from a an ongoing open-label Phase II clinical trial investigating the use of Sustiva in combination with Viracept, show reduction on HIV-RNA and increases in CD4 cell counts in both treatment- experienced and treatment-naive patients. Using the traditional observed data analysis, 77 percent (17/22) of treatment-naive patients achieved HIV-RNA BQL and 63 percent (15/24) of NRTI-experienced patients achieved HIV-RNA BQL. Patients experienced CD4 cell count increases of 49 cells/mm3 and 87 cells/mm3, respectively. Results from another study, which investigated the two-drug combination, Sustiva and Crixivan, showed 84 percent (37/44) of patients taking the combination maintained HIV-RNA BQL for 84 weeks using the observed data analysis. Patients experienced a CD4 cell count increase of 306 cells/mm3. Overall, safety data from clinical trials show Sustiva is generally well tolerated. The most significant adverse events associated with Sustiva therapy are nervous system symptoms, which are reported in 52 percent of patients (e.g., dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming). The discontinuation rate for nervous system symptoms was 2.6 percent. These symptoms occur early in treatment and generally resolve within a few weeks. Rarely, patients have more serious side effects that may affect mood or ability to think clearly. Skin rash, usually mild-to-moderate, was reported in 27 percent of patients. The incidence of severe rash was less than 1 percent and the discontinuation rate for any grade rash was 1.7 percent. The incidence of rash was higher in children (40 percent) than in adults and the incidence of severe rash was also higher in children (seven percent). Resistant virus emerges rapidly when NNRTIs are administered 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. Sustiva therapy should always be initiated in combination with at least one other antiretroviral agent to which the patient has not been previously exposed. Women should not become pregnant while taking Sustiva because birth defects have been seen in animals given Sustiva.
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