GS 840 (Adefovir Dipivoxil): Broad-Spectrum Antiviral Trial, CD4 Count Under 100

The Community Program for Clinical Research on AIDS of theU.S. National Institutes of Allergy and Infectious Diseasesis seeking over 2,000 volunteers for a phase III trial of GS840 (also called adefovir dipivoxil, or bis-POM PMEA), a drug being developed by Gilead Sciences of Foster City, California. The trial, being run through the offices of hundreds of physicians and clinics in 16 U.S. cities, will test whether the drug, taken orally once a day, can increase survival of persons with advanced HIV, and also whether it can prevent the development of CMV disease. A similar trial will be run in Europe and Australia.

Volunteers need to have a CD4 count less than or equal to100, and be in reasonably good health ("not require considerable assistance and frequent medical care"). They can be using almost any medication, except for permanent or maintenance use of CMV treatments such as ganciclovir orfoscarnet.

GS 840 is an oral prodrug of PMEA, meaning that it is changed into PMEA in the body. PMEA itself has long been studied as an antiviral, but is less practical as a drug because it must be given by injection. In this study, participants will continue their regular antiviral treatments, and add GS 840(120 mg) or placebo once a day; the nutrient L-carnitine will also be given (to both the drug and placebo groups), at the request of the FDA, since GS 840 has been found to lower L-carnitine levels in the body.

GS 840 is known to be active against CMV, hepatitis B, HHV6(human herpes virus 6), and Epstein-Barr virus. It has shown modest activity against HIV, with about a 0.6 log decrease in viral load. Resistance seems to be slow to develop, and the drug is active against many viruses which have become resistant to other drugs. Unlike most available HIVtreatments, it is believed to be active against HIV inmacrophages as well as lymphocytes.

The informed consent for this trial lists its five purposes:

1. To find out if the investigational drug bis-POM PMEA [GS840] is safe to give to people infected with HIV who have alow CD4+ cell count.

2. To find out if bis-POM PMEA helps to slow the growth of HIV.

3. To find out if bis-POM PMEA helps people infected with HIV to live longer.

4. To find out if bis-POM PMEA helps to prevent people who are infected with CMV from developing CMV disease.

5. To find out if a special test that looks at how much CMV is in your blood helps to predict which people infected with CMV may develop CMV disease.

Bis-POM PMEA has been studied in more than 200 HIV-infected subjects who had a CD4+ cell count of 100 or more. Most of these subjects were not taking other drugs to treat HIV infection and were able to tolerate taking bis-POM PMEA."

Because much is unknown about how this drug will interact with treatments the volunteers are already using, the first 400 persons in this trial will be entered into a special safety-and-virology cohort and receive intensive followup. Also, the first 400 must be CMV positive by a blood test; later volunteers can be either CMV positive or negative.

For more information about this study, including participating physicians and clinics in your area, call the AIDS Clinical Trials Information Service, 800-TRIALS-A,between the hours of 9 a.m. to 7 p.m. Eastern time, Monday through Friday; ask for information about trials of GS 840 (or adefovir dipivoxil). Or call Gilead Sciences Medical Information, 800-GILEAD-5 (press 3), from 8:30 a.m. to 5:00p.m. Pacific time.