Resistance Conference Reports
Each summer there is a closed research conference on HIV resistance. This year's meeting, the 3rd International Workshop on HIV Drug Resistance & Treatment Strategies, June 23-26 near San Diego, was particularly hard to get into, because attendance was limited to 200, and also because there is no international conference this year to provide an alternate venue. This writer did not try to attend the meeting. Fortunately several summaries and reports are available on the Web (see below, at the end of this article).The most definitive record of the conference is the published abstracts; these are not on the Web but were printed in advance of the meeting as a supplement to the journal Antiviral Therapy. Copies are available for $35 plus postage; for more information, send a request to janes@intmedpress.com. [Note: Antiviral Therapy, published by International Medical Press Ltd., should not be confused with Antiviral Research, published by Elsevier--another journal which also publishes an annual issue containing abstracts from a (different) conference on antiviral drug development.]
Since the abstracts had to be submitted well in advance, often they do not include the most important information from the meeting, either because it was not ready when the abstracts were written, or because it emerged in discussions at the meeting.
For example, RS-344 is a protease inhibitor developed at the U.S. National Cancer Institute. It is not in the abstracts or many of the summaries, but Jules Levin of the National AIDS Treatment Advocacy Project covered it, as follows:
John Erickson, a well-known researcher at the National Cancer Institute, has been in protease inhibitor research from early years and has been reporting for several years at AIDS conferences that he wanted to develop a protease inhibitor specifically designed to be active against viruses containing primary PI [protease inhibitor] resistance mutations. At the Resistance Workshop he discussed RS-344, a PI designed using structure-based approaches with a novel flexible core to target some of the active-site mutants. Erickson reported that RS-344 showed similar potency to currently available protease inhibitors in both enzymatic and cell culture assays. He showed a table of clinical isolates with high-level phenotypic resistance to multiple protease inhibitors. In every case these clinical isolates had either <4-fold or 4-10 fold resistance to RS-344. These clinical isolates had from 8 to 18 mutational changes. Erickson said he thought RS-344 looked good against these highly resistant viruses.
There is much interest in ABT-378 from Abbott, and in tipranavir from Pharmacia & Upjohn, mainly because of their potential usefulness in patients who have failed other protease inhibitors. Tipranavir seems to have a notably different resistance profile than approved protease inhibitors. And ABT-378 seemed to work well in patients who had failed a previous protease-inhibitor regimen--although some researchers saw this trial as a best-case test for second-line treatment, and want to see data on how well the drug will work in the more difficult treatment situations that many doctors and patients face. For more information, see the conference summaries, and the printed abstracts (Session I, "New Antiretrovirals").
Other drugs which may be particularly important include:
DAPD, a nucleoside analog which may be active against virus resistant to the approved drugs of that class;
AG1549, an NNRTI which may be active against HIV with the K103N mutation, which causes resistance to efavirenz and other drugs in that class;
T-1249, a fusion inhibitor like T-20;
And others reported in the summaries and the abstracts.
Resistance Conference Summaries
on the Web
ATP Doctor Fax, by the AIDS Treatment Project in UK, http://www.atp.org.uk/ (issue #71).
HIVandHepatitis.com, selected highlights of the conference by Harvey S. Bartnof, M.D., http://www.hivandhepatitis.com/int_conf_rpt.html
IAPAC (International Association of Physicians in AIDS Care): Brief Summary by Mark Mascolini, http://www.iapac.org/
International Medical Press, http://www.intmedpress.com (click on "Rapid Report").
National AIDS Treatment Advocacy Project, http://www.natap.org, has several reports by Jules Levin.
To Be Continued
( This article will be continued in a later issue. )
