AIDS TREATMENT NEWS Issue #264, February 7, 1997
The Community Program for Clinical Research on AIDS of the
U.S. National Institutes of Allergy and Infectious Diseases
is seeking over 2,000 volunteers for a phase III trial of GS
840 (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 to
100, 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 or
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 HIV
treatments, it is believed to be active against HIV in
macrophages 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 [GS
840] is safe to give to people infected with HIV who have a
low CD4+ cell count.
2. To find out if bis-POM PMEA helps to slow the growth of
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 5:00
p.m. Pacific time.