New Class of AIDS Drugs on the Horizon
Jan. 27, 2000 (Atlanta) -- Discovery of the second member of a new class of
HIV drugs promises to greatly expand AIDS treatment options -- someday. Merck
researchers report in the journal Science that they have identified a
class of compounds that specifically attack integrase, an enzyme crucial for
HIV to reproduce in the body.
Current AIDS drugs also attack key HIV enzymes at various stages of viral
reproduction. Protease inhibitors attack the enzyme needed to break HIV
building blocks into correct sizes; reverse transcriptase inhibitors prevent
the virus from turning its RNA into the DNA needed to take over cells. Now
integrase inhibitors promise to prevent HIV from snipping open human DNA
and inserting its own genetic code. A combination of the three types of drugs
theoretically would increase the potency of AIDS drug cocktails.
HIV becomes resistant to any single drug. A combination of drugs, the
so-called AIDS cocktails, combats this problem. However, the virus eventually
becomes resistant to these as well. The hope is that by adding this new type of
drug, the cocktails will become vastly more effective.
The first integrase inhibitor was reported on at the 1996 international AIDS
conference by W. Edward Robinson, MD, PhD, of the University of California,
Irvine. These compounds were first isolated from plants of the Kallawaya people
"We are encouraged ... but it is in the very, very early stages of
development," Merck spokesperson Laurence Hirsch, MD, tells WebMD. "We
are a long way from having a new treatment for AIDS."
The findings, nevertheless, are stirring a great deal of interest. The
search has been stymied by the lack of a test that can identify true integrase
inhibitors. But now Merck researchers Daria J. Hazuda, PhD, and colleagues
report that they have developed just such a test -- and that screening of more
than 250,000 compounds led to the discovery of the new class of drugs.
"I think it sounds very promising," retroviral integrase expert
Samson Chow, PhD, tells WebMD in an interview to provide objective comment.
"These compounds are active specifically against integrase and can block
HIV replication. You have a whole new class of inhibitors now. Also, it is very
important that viruses with resistance mutations to protease and reverse
transcriptase inhibitors are sensitive to integrase. This opens up the
possibility of a whole new combination treatment regimen."
Robinson tells WebMD that the new paper confirms that integrase is an
exciting target for AIDS therapies because it offers a new type of drug to use
in combination with existing drugs. Indeed, studies in his laboratory show that
the effect with the other two types of AIDS drugs has "at least
additive" anti-HIV effect.
"Integrase is a viable target for drug therapy, and we are likely to see
integrase inhibitors in clinical trials in the next few years," Robinson