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| |  ROI CONFERENCE: Combo Therapy With Sustiva Instead Of Protease Inhibitor Maintains HIV Suppression CHICAGO, IL -- Feb. 4, 1999 -- Data presented today show that anti-HIV therapy including DuPont Pharmaceuticals' once-daily Sustiva(TM) (efavirenz) instead of the protease inhibitor, Crixivan(R) (indinavir), achieves viral suppression in a greater percentage of patients than combinations including a protease inhibitor and maintains suppression as well as combinations including the protease inhibitor. These results represent the first head-to-head comparison with a protease inhibitor-containing regimen after 48 weeks of therapy. Fewer patients in the arm containing Sustiva, AZT and 3TC (six percent) dropped out due to adverse events than in the Crixivan/AZT/3TC arm (19 percent). It is difficult to assess the relative efficacy of the treatment arms given the disproportionate discontinuations in an open-label study. Data were presented at the sixth conference on Retroviruses and Opportunistic Infections underway in Chicago. Data presented in the study indicates that Sustiva, when taken as a part of a combination without a protease inhibitor, maintains HIV suppression comparable to combination therapy that includes a protease inhibitor for up to 48 weeks. Researchers reported that significantly more antiretroviral-naive patients taking Sustiva in combination with AZT and 3TC exhibited suppressed levels of HIV to below quantifiable levels (less than 400 copies/ml) than people taking indinavir in combination with AZT and 3TC. This was evident at all time points from as early as the second week of treatment to the end of the 48-week analysis. New data demonstrates that the percentage of patients in both arms who achieved HIV-RNA levels BQL (less than 400 copies/mL) remained relatively constant from 24 to 48 weeks of treatment. When using the NC=F analysis, 71 percent of patients receiving Sustiva/AZT/3TC achieved HIV-RNA BQL (less than 400 copies/mL) at 48 weeks. When using the traditional observed data analysis, HIV-RNA reductions to BQL (less than 400 copies/mL) were recorded in 98 percent of patients taking the Sustiva/AZT/3TC combination. In comparison, 48 percent of patients receiving indinavir/AZT/3TC achieved BQL (less than 400 copies/mL) using NC=F and 86 percent achieved BQL (less than 400 copies/mL) using observed data analysis. These differences were statistically significant. At 24 weeks, no statistically significant differences were seen in observed data between the Sustiva/AZT/3TC and the indinavir/AZT/3TC arms. However, statistically significant differences are now seen between the two arms when analysed using NC=F and observed data. Similar results were achieved using the experimental ultrasensitive assay (BQL less than 50 copies/mL). However, the ultrasensitive assay has not yet been approved by the FDA for the quantification of viral load. In a retrospective analysis of the subgroup of patients with high viral load at baseline (greater than 100,000 copies/mL), the combination of Sustiva, AZT and 3TC also provided suppression of viral load through 48 weeks. Using NC=F, 70 percent of patients on the Sustiva triple combination experienced HIV-RNA levels BQL (less than 400 copies/mL) versus 42 percent in the indinavir/AZT/3TC arm of the study. Observed data show that 100 percent of such patients who received the Sustiva three-drug combination achieved BQL (less than 400 copies/mL), while 82 percent of patients taking indinavir/AZT/3TC achieved BQL (less than 400 copies/mL). Safety data from 48 weeks are similar to observations previously reported at 24 and 36 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 (12 percent), maculopapular rash (10 percent), dizziness (nine percent), impaired concentration (nine percent), fatigue (seven percent) and headache (seven percent). Patients on Sustiva experienced more nervous system symptoms (55 percent versus 24 percent) and had more new-onset rashes (29 percent 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. The U.S. Department of Health and Human Services' (DHHS) panel on clinical practices for treatment of HIV infection recently recommended that Sustiva be included as first-line therapy in the Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents. This marks the first time the panel has suggested a combination regimen containing an NNRTI as a preferred first-line treatment option. "These eagerly awaited 48 week data are consistent with the DHHS treatment guidelines recommending that Sustiva be included as first-line therapy," said lead author Karen Tashima, assistant professor of Medicine, Brown University at the Miriam Hospital in Providence, R.I. In another presentation on Sustiva at the conference, researchers analysed data from three DuPont Pharmaceuticals trials in which Sustiva was included as part of protease-inclusive or protease-sparing regimens for HIV-infected patients. The presented data include an analysis of one study, in which 59 protease-naive and NNRTI-naive patients were given Sustiva and indinavir for at least two years. Using NC=F, 66 percent of patients taking the Sustiva/indinavir combination maintained HIV-RNA BQL (less than 400 copies/mL) at 108 weeks. Eighty-eight percent of patients taking the two-drug combination maintained HIV-RNA BQL (less than 400 copies/mL) using observed data. Sustiva product labelling states that the most significant adverse events associated with Sustiva therapy are nervous system symptoms, which are reported in 52 percent of patients (for example, dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming). These symptoms occur early in treatment and generally resolve within two to four weeks. The discontinuation rate for nervous system symptoms was 2.6 percent. Rarely, patients experience more serious side effects that may affect mood or the ability to think clearly. Patients should be cautioned not to operate hazardous machinery or drive if they experience nervous system symptoms. Skin rash, usually mild-to-moderate, was reported in 27 percent of adults and 40 percent of children. Rash usually occurs in the first two weeks of therapy and resolves with continued treatment within one month. The incidence of severe rash was less than one percent in adults and seven percent in children. The discontinuation rate for any grade rash was 1.7 percent. Sustiva product labelling also states that 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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