6th Conference on Retroviruses and Opportunistic Infections (CROI)
Second-Generation Drugs Fight Resistant Virus
There are now 13 FDA-approved drugs to treat HIV and 2 more drugs -- adefovir and amprenavir -- are in expanded access. Amprenavir is a protease inhibitor (PI) that may have some activity against HIV strains that are resistant to the four currently available PIs. Clinical trials of the protease inhibitor ABT-378 are ongoing in untreated ("naïve") people, but the hope for ABT-378 is that it will control HIV replication in people who are resistant to the other PIs. No data is yet available on the use of ABT-378 in people who have failed a PI, although a clinical trial is under way.
Agouron presented very preliminary information on two new drugs, AG 1776, which is a second-generation PI, and AG 1549, which is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI). These drugs are called second-generation because they appear to be active in vitro (in a test tube) against HIV that has become resistant to the current drugs in those classes. However, no data was presented on the pharmacologic properties of these drugs, for example, whether they are absorbed orally, how long they last in the system, and their potential toxicity. Before human trials can begin, much more animal research needs to be conducted on these two drugs. (Agouron did state that it expects to begin human trials of AG 1776 in 1999.)
DuPont presented pre-clinical data on two new NNRTI drugs that have good absorption and a long half-life in the body, DPC 961 and DPC 963, which may be effective against NNRTI-resistant viruses. However, the safety and effectiveness of these drugs has not been studied in human trials yet. Since most people who fail an NNRTI regimen will be resistant to the other 2 NNRTIs currently available, there is an urgent need for non-cross-resistant NNRTIs.
T-20: A New Class of Drugs
Trimeris Corp. has one of the more interesting new drugs to treat HIV, T-20, which interferes with the process of HIV binding to the CD4 (T-helper) cells. There are currently no other drugs that attack HIV at this point in its replication making this a whole new class of anti-HIV drugs called fusion inhibitors. In vitro studies showed that this drug had very potent effects on HIV. Now, a human study is showing similar good results.
HIV-positive people who had been heavily pre-treated received this drug was twice a day by injection under the skin. Although the study reported very significant reductions in HIV levels in the blood, this benefit lasted only a week or so. This could mean that resistance developed rapidly, or more likely, that the body developed antibodies that eliminated this small protein. Future studies will have to be conducted to examine the drugs ability to suppress HIV over longer periods of time and its toxicity and long-term tolerability. Nonetheless, this is an exciting trial because it proves that compounds that interfere with the process of HIV binding to CD4 cells can result in significant reductions in HIV levels in people who have been treated with most every antiretroviral drug available.
As the first drug in this new class T-20 is something to keep your eye on. The biggest problem is the shots required to administer the drug. Researchers are working on a small pager-sized pump that would administer the drug slowly and constantly. If this drug continues to show promise it could be a much needed new option for those failing other drug classes.
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This article was provided by Seattle Treatment Education Project.