BUENOS AIRES, ARGENTINA -- July 9, 2001 -- Data presented today at the 1st International AIDS Society (IAS) Conference on human immunodeficiency virus (HIV) Pathogenesis and Treatment here showed that HIV treatment-naive patients taking a combination HIV treatment regimen containing anti-HIV drug Sustiva™ (efavirenz) experienced lower rates of treatment failure (viral load greater than 500 copies/mL) compared to a regimen including nevirapine (Viramune®) or a protease inhibitor.
In addition, the percentage of patients who changed regimens for reasons other than virologic failure was higher in the nevirapine and protease inhibitor arms which suggests that the regimens containing Sustiva may have been better tolerated.
"The data suggest that the regimens containing Sustiva performed better than the regimens including nevirapine or a protease inhibitor in treatment- naive patients when we looked at the response after six months," said Gail Matthews, M.D., Specialist Registrar in HIV Medicine, Chelsea & Westminster Hospital, London. "The initial response we saw in the patients taking Sustiva may reflect better tolerability with this regimen."
The data, using Kaplan-Meier estimates, showed that after six months of treatment, 92 percent of patients who received the non-nucleoside reverse transcriptase inhibitor (NNRTI) Sustiva as part of their regimen were still successfully responding to their initial treatment compared to 83 percent in the nevirapine arm and 79 percent in the protease inhibitor arm. The difference between the three treatment arms was statistically significant (p-value less than 0.0001.) The data was compiled from a retrospective analysis of 888 patients from two large observational databases collected from Chelsea & Westminster Hospital and the Royal Free Hospital (both in London).
Additional data presented indicate that, when using the intent-to-treat: non-completer=failure analysis, 11.4 percent (19/167) of the patients in the Sustiva arm failed after six months of treatment compared to 21.9 percent (52/237) taking the NNRTI nevirapine and 26.2 percent (127/484) taking a regimen including a protease inhibitor. The differences between the three treatment arms was statistically significant (p-value less than 0.001.)
These results are similar to data recently presented at the 8th Conference on Retroviruses and Opportunistic Infections in Chicago from the EuroSIDA database which showed that treatment-experienced HIV infected patients who were currently on a regimen containing nevirapine were at a 72 percent higher risk for developing virologic failure and at a 92 percent higher risk for
developing an AIDS defining event or death when compared to patients treated with a regimen containing Sustiva.
The objective of the study from London was to determine whether the choice between non-nucleoside reverse transcriptase inhibitors- (the class of antiretrovirals Sustiva and nevirapine are in) or protease inhibitor-containing regimens in antiretroviral-naive HIV positive patients is predictive of the likelihood of achieving an undetectable HIV-RNA level after six months of therapy. This study was not randomized and therefore the introduction of bias can not be completely excluded.
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 low frequency 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® (astemizole), Propulsid® (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.
SOURCE: DuPont Pharmaceuticals Company
Related Link: DuPont Pharmaceuticals Company.
