Significant Success in Maintaining Viral Suppression Seen When Sustiva(TM) Is Substituted for Protease Inhibitors

Apr 02, 2001, 01:00 ET from DuPont Pharmaceuticals Company

    ISTANBUL, Turkey, April 2 /PRNewswire/ -- Data presented today indicate
 that DuPont Pharmaceuticals' anti-HIV drug Sustiva(TM) (efavirenz), when
 substituted for a protease inhibitor, successfully maintained viral load
 suppression (less than 50 copies/mL) in more patients than those who remained
 on their protease inhibitor-containing regimen.  The difference was
 statistically significant (p=0.002).
     The findings from DMP Study 266-027, presented at the 11th European
 Congress of Clinical Microbiology and Infectious Diseases (ECCMID) meeting
 here, demonstrate the potent antiviral activity of Sustiva, a non-nucleoside
 reverse transcriptase inhibitor (NNRTI), in a protease inhibitor-sparing
 regimen.
     In patients switched to Sustiva plus two nucleoside reverse transcriptase
 inhibitors (NRTIs) after an average of two years prior protease inhibitor
 therapy, 94 percent (65/69) maintained a viral load of less than 50 copies/mL
 through 48 weeks of treatment.  This compared to 74 percent (48/65) of
 patients who continued their initial regimen consisting of a protease
 inhibitor plus two NRTIs.  These data were statistically significant
 (p=0.002).  Mean CD4 cell count increases were comparable between the two
 arms, indicating a possible improvement in immunologic benefit.  The data were
 reported using the rigorous method called non-completer=failure analysis(1).
     "The data support the practice of switching patients who achieve viral
 suppression while on a protease inhibitor-containing regimen to one that
 includes Sustiva," said Professeur Jean-Louis Vilde, Chef du Service,
 "Maladies infectieuses et tropicales", Hopital Bichat, Paris.  "We've
 confirmed that Sustiva is as potent as a protease inhibitor through the
 successful maintenance of viral load suppression in protease inhibitor-
 experienced patients who switched to Sustiva and should be considered as part
 of a simple antiretroviral regimen that may enhance adherence for patients."
     DMP 266-027 is a 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.
 The mean duration of previous protease inhibitor use in the arm containing
 Sustiva was 23 months and 24 months in the arm continuing on protease
 inhibitors.  At baseline, the mean CD4 cell count in the Sustiva+NRTI arm was
 498 cells/mm3 (plus/minus 230) and 500 cells/mm3 (plus/minus 205) in the
 protease inhibitor+NRTI arm.
     Safety data from DMP 266-027 showed that two people discontinued from the
 arm containing Sustiva (one for virologic failure, one lost-to-follow-up) and
 13 discontinued from the protease inhibitor-containing arm (five for adverse
 experiences, one for virologic failure, five lost-to-follow-up, one for
 protocol violation and one for HIV-related disease.)  The most common adverse
 events reported among both treatment groups included nervous system events
 (abnormal dreams, dizziness, insomnia, impaired concentration), diarrhea,
 influenza-like symptoms and lipodystrophy.
     In February 2001, the U.S. Department of Health and Human Services (DHHS)
 continued, for the second year in a row, to list Sustiva as the only non-
 nucleoside reverse transcriptase inhibitor "strongly recommended" for use in
 first-line combination with NRTIs for the treatment of HIV-infected
 individuals.
     Sustiva is generally well tolerated.  The most common adverse events are
 nervous system symptoms (e.g., dizziness, insomnia, impaired concentration,
 somnolence, and abnormal dreaming) and mild to moderate rash.  These symptoms
 occur early in treatment and generally resolve within two to four weeks.  In a
 small number of patients, serious psychiatric adverse experiences have been
 reported.  In controlled trials, serious psychiatric symptoms observed were
 severe depression (0.9%), suicidal ideation or attempts (0.5%), aggressive
 behavior (0.3%), paranoid reactions (0.2%) and manic reactions (0.1%).  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 Sustiva.
 Patients should be cautioned not to operate hazardous machinery or drive if
 they experience nervous system symptoms.
     Sustiva is administered as three 200 mg capsules once-daily.  Sustiva
 should not be administered concurrently with Hismanal(R) (astemizole),
 Propulsid(R) (cisapride), Versed(R) (midazolam), Halcion(R) (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.
     DuPont Pharmaceuticals Company, a wholly owned subsidiary of DuPont, is a
 worldwide business focused on research, development and delivery of
 pharmaceuticals and imaging agents to treat unmet medical needs in the fights
 against HIV/AIDS, cardiovascular disease, inflammatory diseases, cancer and
 neurological diseases.
     DuPont (NYSE:   DD) is a science company, delivering science-based solutions
 that make a difference in people's lives in food and nutrition; health care;
 apparel; home and construction; electronics; and transportation.  Founded in
 1802, the company operates in 70 countries and has 93,000 employees.
     For full Sustiva prescribing information, please visit the company's
 Website at www.sustiva.com or call 1-800-4PHARMA (1-800-474-2762).
 
     Sustiva(TM) is a trademark of the DuPont Pharmaceuticals Company.
     The other brands listed are the registered trademarks of their respective
 owners and are not the trademarks of DuPont Pharmaceuticals.
 
     (1) Patients who remained in the study and maintained viral suppression
         (did not meet criteria for virologic failure) at the timepoint were
         considered successes.  Patients who had confirmed virologic rebound,
         discontinued the study or had missing data at the timepoint for any
         reason were considered failures.
 
 

SOURCE DuPont Pharmaceuticals Company
    ISTANBUL, Turkey, April 2 /PRNewswire/ -- Data presented today indicate
 that DuPont Pharmaceuticals' anti-HIV drug Sustiva(TM) (efavirenz), when
 substituted for a protease inhibitor, successfully maintained viral load
 suppression (less than 50 copies/mL) in more patients than those who remained
 on their protease inhibitor-containing regimen.  The difference was
 statistically significant (p=0.002).
     The findings from DMP Study 266-027, presented at the 11th European
 Congress of Clinical Microbiology and Infectious Diseases (ECCMID) meeting
 here, demonstrate the potent antiviral activity of Sustiva, a non-nucleoside
 reverse transcriptase inhibitor (NNRTI), in a protease inhibitor-sparing
 regimen.
     In patients switched to Sustiva plus two nucleoside reverse transcriptase
 inhibitors (NRTIs) after an average of two years prior protease inhibitor
 therapy, 94 percent (65/69) maintained a viral load of less than 50 copies/mL
 through 48 weeks of treatment.  This compared to 74 percent (48/65) of
 patients who continued their initial regimen consisting of a protease
 inhibitor plus two NRTIs.  These data were statistically significant
 (p=0.002).  Mean CD4 cell count increases were comparable between the two
 arms, indicating a possible improvement in immunologic benefit.  The data were
 reported using the rigorous method called non-completer=failure analysis(1).
     "The data support the practice of switching patients who achieve viral
 suppression while on a protease inhibitor-containing regimen to one that
 includes Sustiva," said Professeur Jean-Louis Vilde, Chef du Service,
 "Maladies infectieuses et tropicales", Hopital Bichat, Paris.  "We've
 confirmed that Sustiva is as potent as a protease inhibitor through the
 successful maintenance of viral load suppression in protease inhibitor-
 experienced patients who switched to Sustiva and should be considered as part
 of a simple antiretroviral regimen that may enhance adherence for patients."
     DMP 266-027 is a 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.
 The mean duration of previous protease inhibitor use in the arm containing
 Sustiva was 23 months and 24 months in the arm continuing on protease
 inhibitors.  At baseline, the mean CD4 cell count in the Sustiva+NRTI arm was
 498 cells/mm3 (plus/minus 230) and 500 cells/mm3 (plus/minus 205) in the
 protease inhibitor+NRTI arm.
     Safety data from DMP 266-027 showed that two people discontinued from the
 arm containing Sustiva (one for virologic failure, one lost-to-follow-up) and
 13 discontinued from the protease inhibitor-containing arm (five for adverse
 experiences, one for virologic failure, five lost-to-follow-up, one for
 protocol violation and one for HIV-related disease.)  The most common adverse
 events reported among both treatment groups included nervous system events
 (abnormal dreams, dizziness, insomnia, impaired concentration), diarrhea,
 influenza-like symptoms and lipodystrophy.
     In February 2001, the U.S. Department of Health and Human Services (DHHS)
 continued, for the second year in a row, to list Sustiva as the only non-
 nucleoside reverse transcriptase inhibitor "strongly recommended" for use in
 first-line combination with NRTIs for the treatment of HIV-infected
 individuals.
     Sustiva is generally well tolerated.  The most common adverse events are
 nervous system symptoms (e.g., dizziness, insomnia, impaired concentration,
 somnolence, and abnormal dreaming) and mild to moderate rash.  These symptoms
 occur early in treatment and generally resolve within two to four weeks.  In a
 small number of patients, serious psychiatric adverse experiences have been
 reported.  In controlled trials, serious psychiatric symptoms observed were
 severe depression (0.9%), suicidal ideation or attempts (0.5%), aggressive
 behavior (0.3%), paranoid reactions (0.2%) and manic reactions (0.1%).  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 Sustiva.
 Patients should be cautioned not to operate hazardous machinery or drive if
 they experience nervous system symptoms.
     Sustiva is administered as three 200 mg capsules once-daily.  Sustiva
 should not be administered concurrently with Hismanal(R) (astemizole),
 Propulsid(R) (cisapride), Versed(R) (midazolam), Halcion(R) (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.
     DuPont Pharmaceuticals Company, a wholly owned subsidiary of DuPont, is a
 worldwide business focused on research, development and delivery of
 pharmaceuticals and imaging agents to treat unmet medical needs in the fights
 against HIV/AIDS, cardiovascular disease, inflammatory diseases, cancer and
 neurological diseases.
     DuPont (NYSE:   DD) is a science company, delivering science-based solutions
 that make a difference in people's lives in food and nutrition; health care;
 apparel; home and construction; electronics; and transportation.  Founded in
 1802, the company operates in 70 countries and has 93,000 employees.
     For full Sustiva prescribing information, please visit the company's
 Website at www.sustiva.com or call 1-800-4PHARMA (1-800-474-2762).
 
     Sustiva(TM) is a trademark of the DuPont Pharmaceuticals Company.
     The other brands listed are the registered trademarks of their respective
 owners and are not the trademarks of DuPont Pharmaceuticals.
 
     (1) Patients who remained in the study and maintained viral suppression
         (did not meet criteria for virologic failure) at the timepoint were
         considered successes.  Patients who had confirmed virologic rebound,
         discontinued the study or had missing data at the timepoint for any
         reason were considered failures.
 
 SOURCE  DuPont Pharmaceuticals Company