Could AIDS Drug Have Made a Difference?
WebMD News Archive
Dec. 21, 1999 (Atlanta) -- An experimental anti-HIV drug was moderately
effective and too toxic for at least half the people who took it, but was it
withdrawn from further development too soon? A study of the drug, published in
The Journal of the American Medical Association (JAMA), shows that the
drug might have been able to help HIV-infected people for whom other treatments
no longer worked.
Gilead Sciences Inc. discontinued U.S. development of the drug, adefovir
dipivoxil, after failing to win the approval of an FDA advisory committee. It
was the first time such a committee ever rejected an AIDS therapy. The drug is
still being considered as a possible treatment for hepatitis B.
The published study findings show that adefovir was effective when added to
existing treatments in patients whose HIV levels remained high. But 60% of
patients developed signs of kidney toxicity after taking the drug for 24 to 48
"This particular drug shows potent antiretroviral activity in patients
with HIV when given in combination with other agents," study co-author
Stephen W. Lagakos, PhD, tells WebMD. "It can add to the existing antiviral
effect of other drugs, that's very good. On the other hand, this drug has a
side effect that occurs in a high percentage of patients that is not
Based on these results, adefovir would not be an appropriate first-line
therapy. However, there currently are very few salvage options for patients
failing other agents. Lagakos believes that the trial results show adefovir
could be useful in such a setting.
"Patients who have failed on other antiretroviral drugs are in a
desperate situation," says Lagakos, a researcher at the Harvard School of
Public Health. "At some point people need help, and this drug has been
shown to be effective in patients who have failed other drugs. There is a real
risk of side effects, but they are reversible if you are aware of
There is evidence from other, smaller studies that a 60 mg dose of adefovir
might be less toxic and have a lower incidence of side effects than the 120 mg
dose used in the study. But this evidence, along with Lagakos' study, was too
thin for an FDA advisory committee, which last month voted 13 to 1 against
recommending adefovir for accelerated approval. Earlier this month, Gilead
withdrew adefovir from further U.S. development (an application for European
approval is still pending).
"It might be possible for [adefovir] to work at a lower dose level, but
it's not clear," Lagakos says. "It may be this was the wrong dosage of
this drug to test."
Lagakos believes that the committee gave too little consideration to the
findings of the large trial now published in JAMA.