PRNewswire - Wednesday December 2, 1998

The panel recommended Sustiva as the first non-nucleoside reverse transcriptase inhibitor (NNRTI) for treatment of HIV-1 infected individuals to be included as a Preferred Agent in Table VI -- Recommended Antiviral Agents for Treatment of Established HIV Infection -- in Column A with the listed protease inhibitors. The Column A agents must be used in combination with two nucleoside reverse transcriptase inhibitors (NRTIs).

This marks the first time a compound other than a protease inhibitor has been included in Column A as a preferred agent. This is also the first time the panel has suggested a combination regimen containing an NNRTI as a preferred first-line treatment option.

"The data reviewed showed efavirenz, when combined with two nucleosides, demonstrated virologic results equivalent to those achieved with a protease inhibitor combined with two nucleosides," said John Bartlett, M.D., chairman of the DHHS panel. "Particularly important is the head-to-head comparison of the new efavirenz-containing regimen with a regimen included previously in the preferred category."

The 1998 guidelines can found on the HIV/AIDS Treatment Infomation Service website at http://www.hivatis.org.

Since it was approved on Sept. 18, 1998, more than 30,000 patients have initiated a regimen containing SustivaÖ (efavirenz), the first anti-HIV drug to be approved by the Food and Drug Administration (FDA) for once-daily dosing in combination with other anti-HIV drugs in both adult and pediatric patients.

"Recognition by an independent panel of experts such as the DHHS Guidelines Panel clearly illustrates the benefit of Sustiva as a first-line therapy, and expands the current standard of care to include a convenient protease inhibitor sparing regimen as an option," said Nicholas L. Teti, President, DuPont Pharmaceuticals Company. "Initial HIV therapy with Sustiva in a regimen that does not include a protease inhibitor allows patients to save protease inhibitors for later use. Moreover, the price of a regimen including Sustiva is about 28% less expensive than the current standard of care regimen which includes the most commonly dispensed protease inhibitor."*

Sustiva was approved by the U.S. FDA to be used in combination with other antiretroviral agents for the treatment of HIV-1 infection. This 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 controlled trials evaluating long-term suppression of HIV-RNA with Sustiva. The FDA approval of Sustiva, the first once-daily antiretroviral agent, on Sept. 18, 1998, based on results from clinical trials involving more than 2,000 patients. These results indicate that Sustiva reduces plasma viral RNA to below quantifiable levels (less than 400 copies/mL using the standard AmplicorÖ assay) in a majority of HIV-1-infected naive and treatment-experienced individuals in protease-inclusive two-, three-, and four-drug combinations.

Thirty six week data from one of the clinical trials examined by the panel show Sustiva, in combination with two nucleoside analogues -- lamivudine (3TC, Retrovir«) and zidovudine (AZT, Epivir«), suppressed HIV-RNA to below quantifiable levels in a greater proportion of patients than did the control arm consisting of a current standard of care regimen containing indinavir (Crixivan«), AZT and 3TC. More subjects from the indinavir, AZT, 3TC arm discontinued therapy because of adverse events, and this accounted for a substantial fraction of the difference between the treatment regimens. It is difficult to assess the relative efficacy of the treatment arms given the disproportional discontinuations in an open label study. The FDA has not evaluated long-term data on the use of Sustiva in a regimen without a protease inhibitor.

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.

Patients should be counseled that nervous system symptoms and rash occur early in treatment and generally resolve within two to four weeks with continued therapy with Sustiva. In controlled clinical trials, 52% of patients experienced nervous system symptoms and 2.6% discontinued therapy as a result. Bedtime dosing may reduce or alleviate the severity of nervous system symptoms. Patients should be cautioned not to operate hazardous machinery or drive automobiles if they experience nervous system symptoms. Additionally, 27% of patients experienced rash and 1.7% discontinued therapy as a result. Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash.

Women should not become pregnant while taking SustivaÖ (efavirenz) because birth defects have been seen in animals given Sustiva.

For questions about Sustiva, physicians and patients may call 1-800- 4PHARMA (1-800-474-2762), or visit the company's website at www.sustiva.com. DuPont Pharmaceuticals, a unit of DuPont's Life Sciences Enterprise, is a worldwide, research-based pharmaceutical company that markets its products under the DuPont Pharma name. The business focuses on research, development, and delivery of pharmaceuticals to treat unmet medical needs in the fight against HIV, cardiovascular disease, central nervous system disorders, cancer and arthritis-related disorders. DuPont Pharmaceuticals is also a leader in medical imaging.

Founded in 1802, DuPont is a global research and technology-based company committed to better things for better living. DuPont serves worldwide markets including food and nutrition; health care; agriculture; fashion and apparel; home and construction; electronics; and transportation. The company operates in about 70 countries and has 83,000 employees.

Data based on September 1998 Red Book.

Amplicor is a trademark of Roche Laboratories.

Crixivan is a registered trademark of Merck & Co.

Retrovir and Epivir are registered trademarks of Glaxo-Wellcome Inc.

SOURCE: DuPont Pharmaceuticals
981202
PR981204

Always watch for outdated information. This article first appeared in 1998. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1998. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .