PR Newswire; Thursday July 2, 8:00 am EST

``We are encouraged that these early results show Sustiva, in combination with other agents, suppresses HIV replication in the CSF. Since not all antiretrovirals cross the blood-brain barrier, the ability to control viral replication in the CSF will become increasingly critical when constructing durable combination treatment regimens,'' said Karen Tashima, M.D., assistant professor of Medicine, Brown University at The Miriam Hospital.

CSF and HIV-RNA drug levels were measured in eight patients who took Sustiva in combination with either Retrovir(R) (zidovudine, AZT) and Epivir(R) (lamivudine, 3TC),or Crixivan(R) (indinavir) alone, for a mean duration of 26.3 weeks. Both CSF and plasma levels of HIV-RNA were reduced to BQL at the time samples were collected, between 19 and 38 weeks of Sustiva treatment. Sustiva levels in the CSF achieved a mean concentration of 34.6 nM.

Pharmacokinetics of Sustiva and Norvir(R) (ritonavir):

Results from a study of Sustiva (600 mg, QD) coadministered with Norvir (500 mg, q12h) showed that Sustiva AUC and Cmax were increased by 21 percent and 14 percent, respectively, and ritonavir AUC and Cmax were increased by 18 percent and 24 percent, respectively. At the dose studied in uninfected volunteers, the combination of ritonavir and efavirenz was not well tolerated and was associated with a higher level of adverse clinical experiences and laboratory abnormalities (elevated liver enzymes).

Pharmacokinetics of Sustiva and Rifampin:

Data presented today show rifampin reduced the efavirenz AUC, area under the plasma concentration time curve, by 26 percent and Cmax, maximum plasma concentration, by 20 percent in 12 uninfected volunteers. Rifampin appeared to induce the metabolism of Sustiva in 10 of the 12 subjects; the metabolism of Sustiva in the other two participants appeared not to be induced. Adjustment of the dose of Sustiva is not recommended when coadministered with rifampin, however, the clinical significance of the reduced efavirenz levels is not known.

Virologic Resistance to Sustiva:

Results from a continued study to assess the virologic resistance profile of Sustiva also were presented today. As indicated in earlier scientific presentations, the study revealed that K103N was the predominant NNRTI- resistant viral genotype observed in Sustiva-treatment failures. These data were also presented last week at the Workshop on HIV Resistance and Treatment Strategies in Lake Maggiore, Italy.

Other Data Presented at the 12th World AIDS Conference:

Earlier this week, data were presented at the 12th World AIDS Conference showing:

* Sustiva given once daily in combination with AZT and 3TC in predominantly treatment-naive patients was shown to suppress HIV in a significantly greater proportion of patients than in patients taking Crixivan in combination with AZT and 3TC, a standard-of-care regimen, after 24 weeks of treatment in Study 006;

* After 72 weeks, Sustiva given once daily in combination with Crixivan suppresses HIV to below quantifiable levels (less than 400 copies/mL) in 85 percent of patients in Study 003;

* The combination of Sustiva with a standard-of-care three-drug regimen (Crixivan/AZT/3TC) suppresses HIV to below quantifiable levels in a significantly greater percentage of patients than does the three-drug regimen alone in nucleoside analog-experienced patients in Study 020;

* Sustiva used in combination with Viracept(R) (nelfinavir) significantly reduces HIV-RNA and elevates CD4 cell counts from baseline in both treatment-experienced and treatment-naive patients after 16 weeks in Study 024; and,

* All 11 treatment-naive patients randomized to Sustiva (600 mg)/AZT/3TC who reached the 36-week time point achieved HIV-RNA BQL, in Study 005.

DuPont Pharmaceuticals reports that Sustiva is generally well tolerated in clinical trials studying Sustiva in combination with protease inhibitors and/or nucleoside analogue reverse transcriptase inhibitors. Commonly reported side effects include rash, nausea, dizziness, diarrhea, headache and insomnia. Severe rashes were reported in less than one percent of patients receiving Sustiva. Pregnant women should not take this new medication unless the potential benefit to the mother outweighs the potential risk to the fetus.

DuPont Pharmaceuticals submitted a New Drug Application for Sustiva to the U.S. Food and Drug Administration on June 11, 1998 and intends to submit similar marketing applications with European and Canadian regulatory authorities. Meanwhile, the company has expanded access programs for Sustiva. For information, physicians and patients may call 800-998-6854 in the U.S. and Canada, or +44-0-1462-488263 in Europe.

DuPont Pharmaceuticals is a worldwide, research-based pharmaceutical company that markets its products under the DuPont Pharma name. DuPont announced on May 18, 1998 that it would acquire Merck's 50 percent interest in the company, which was formed in 1991.

DuPont Pharmaceuticals is focused 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. The company is also a leader in radiopharmaceuticals.

Norvir is a registered trademark of Abbott Laboratories.

Crixivan is a registered trademark of Merck & Co.

Retrovir and Epivir are registered trademarks of Glaxo Wellcome Inc.

Viracept is a registered trademark of Agouron.

SOURCE: DuPont Pharmaceuticals

980702
PR980704

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. .