BUSINESS WIRE; Wednesday, July 1, 1998

In Study 408, once daily treatment with PREVEON as part of combination regimens was associated with a decline in HIV RNA of approximately 0.4 log10 at week 24 that was maintained through week 48. No change was observed in the placebo group at week 24 (p less than 0.0001). Changes in CD4 cell counts at week 24 included an increase of approximately 5 cells/mm3 in the PREVEON group and a decrease of approximately 5 cells/mm3 in the placebo group (p=0.11).

Study 408 Trial Design

Study 408 enrolled 442 patients who received treatment with either once daily PREVEON (120 mg) or placebo in addition to any approved anti-HIV treatment regimen the patient was receiving at the time of enrollment, provided that the patient had been on a stable regimen for at least eight weeks. The study was placebo controlled for 24 weeks, followed immediately by a 24 week open-label phase during which all continuing patients received PREVEON.

At baseline, patients had a median HIV RNA of 9,800 copies/mL and a median CD4 cell count of 326 cells/mm3. In addition, the patients had previously received treatment with an average of three nucleoside reverse transcriptase inhibitors and an average of three years of AZT treatment at the time of study enrollment; 39% of patients were receiving a protease inhibitor as part of their antiretroviral therapy.

The discontinuation rates, changes in background antiretroviral therapy and Grade 3 or 4 adverse events over the 24 week placebo-controlled portion of the study were similar in the PREVEON and placebo groups. Adverse events associated with PREVEON included changes in laboratory markers of renal function, gastrointestinal side effects, including nausea and vomiting, and weight loss. During the first 24 weeks, mild to moderate changes in laboratory markers of renal function were observed in 1% of patients assigned to PREVEON. By week 48, changes in markers of renal funciton were detected in 32% of patients treated with PREVEON. The laboratory changes were generally reversible upon dose reduction or dose interruption. Seven patients (3%) assigned to PREVEON had elevations in serum creatinine to greater than or equal to 2.0 mg/dL by 48 weeks.

Data Demonstrate Activity in Patients Infected with 3TC and AZT Resistant Virus

Gilead also presented data from a prospectively defined virology sub-study involving 142 patients enrolled in Study 408. These data demonstrate the anti- HIV activity of PREVEON in patients who have developed resistance mutations associated with the commonly used antiretroviral agents AZT (zidovudine) and 3TC (lamivudine). These data also demonstrate that once-daily treatment with PREVEON for 24 weeks was not associated with the emergence of the adefovir-associated resistance mutations (K65R or K70E) identified in vitro.

The mutation associated with the use of 3TC (M184V) was detected in 76% of patients at study entry. In the PREVEON treatment group, a mean HIV RNA change of -0.94 log10 was observed at 24 weeks in patients with the 3TC mutation alone; - 0.75 log10 in patients with the 3TC mutation and low-level AZT resistance; and - 0.51 log10 in patients with the 3TC mutation and high-level AZT resistance. These results compare to +0.09 log10, +0.07 log10 and -0.04 log10 respectively, in placebo patients with the same resistance patterns. Fourteen percent of patients had high-level AZT resistance mutations alone without the 3TC mutation at baseline; PREVEON was not associated with a decrease in HIV RNA levels in these patients.

Interim Analysis of Study 411 Shows Antiviral Activity in Treatment Naive Patients

Previously reported data summarizing a 20 week interim analysis of Study 411 was also presented at the symposium. These data suggest that once-daily treatment with PREVEON in combination with other anti-HIV agents reduces HIV RNA in treatment-naive patients in amounts similar to changes seen in a triple-drug control group. For example, approximately 80 percent of patients treated with one of four PREVEON containing combination regimens for 20 weeks achieved undetectable levels of HIV RNA (less than or equal to 400 copies/mL). The median HIV RNA decrease was 2.1 to 2.5 log10. These data are similar to results seen in the standard of care control group, in which 80 percent of patients had undetectable HIV RNA levels and a median HIV RNA decrease of 2.15 log10.

In this study, 85 patients were assigned to one of four regimens containing PREVEON (120 mg once per day), a protease inhibitor (indinavir) and one or two of the following reverse transcriptase inhibitors: zidovudine (AZT), lamivudine (3TC) or stavudine (d4T); the control group received AZT, 3TC and indinavir. The most frequently reported Grade 3 or 4 adverse events in this study included increases in liver transaminases observed in 5% of patients assigned to the placebo group and 8% of patients assigned to the PREVEON treatment groups.

Background Information

To date, more than 5,000 patients have received PREVEON through clinical trials, including more than 3,300 through an expanded access program in the United States for patients with limited treatment options. Side effects observed include changes in laboratory markers of renal function, dose-related gastrointestinal effects, including nausea and loss of appetite, and increases in liver transaminases. The renal abnormalities, including increases in serum creatinine, have primarily been observed in patients receiving PREVEON for 24 weeks or more. In all studies, PREVEON is co-administered with L-carnitine, a dietary supplement.

Gilead Sciences is an independent biopharmaceutical company that seeks to provide accelerated treatment solutions for patients and the people who care for them. The Company discovers, develops and commercializes proprietary therapeutics for important viral diseases, including a currently marketed product, VISTIDE(R) (cidofovir injection), for the treatment of CMV retinitis, a sight-threatening viral infection in patients with AIDS. In addition, the Company is developing products to treat diseases caused by HIV, hepatitis B virus and influenza virus. Gilead common stock is traded on The Nasdaq Stock Market under the symbol GILD.

Note to Editors: PREVEON is a trademark and VISTIDE is a registered trademark of Gilead Sciences, Inc. To receive more information, please visit the Gilead Web site at www.gilead.com or call Corporate Communications at 1-800-GILEAD-5 (1-800-445-3235).

--30--dl/sf* azs/sf

CONTACT: Gilead Sciences, Inc. Lana Lauher, 650/573-4858 (Investors) Laurie Hurley, 650/573-4894 (Media)

980701
BW980703

Copyright © 1998 - Business Wire. All rights reserved. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Business Wire, Permissions Desk, Business Wire, 1185 Avenue of the Americas, 3rd Floor, New York, NY 10036; Tel: (212) 575-8822; FAX: (212) 575-1854. http://www.businesswire.com.

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Broadway Cares/Equity Fights AIDS, Elton John AIDS Foundation, the National Library of Medicine, Pacific Life Foundation and donations from users like you.

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. .