Special Retrovirus Update
March 28, 2002
Two new classes of drugs in development look very encouraging. The newest class of drugs is the integrase inhibitors. Integrase is an enzyme used by HIV to insert its genetic message, or DNA, into cells. These compounds have been researched for years, but so far all of them have had too many side effects to move into human trials. A Japanese company, Shiongi, reported on a new integrase inhibitor called S-1360 that appears to be very potent and lacks significant side effects in animal testing. It will be moving into human trials this year.
The other class is the entry inhibitors, which block HIV from entering new cells. T-20 is furthest in development, but other compounds are also being developed which block other steps in the complex entry phase, including a compound called SCH C, made by Schering. HIV+ people not on any other anti-HIV drug were given SCH C for 10 days. (Unlike T-20, SCH C can be taken by mouth.) By day 3 there was a significant drop in viral load in the study participants.
A couple of presentations reviewed new data on second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs). These drugs would still be effective in people who have developed resistance to the current NNRTIs. The two drugs discussed were DPC 083 (from Bristol-Meyers Squibb) and TMC 125 (from Tibotec-Virco). DPC 083 has a modified Sustiva structure. The most common side effects were rash and some of the same central nervous system side effects as seen with Sustiva, but possibly at a lower rate. Both compounds were reported to produce up to a 1-log drop in viral load (i.e., viral loads dropped to one-tenth their previous rates) in people who had resistance to the other NNRTIs. Larger trials are planned for both compounds to confirm these encouraging preliminary results.
Merck presented some very encouraging early Phase I studies of a new vaccine that delivers HIV genes into cells using a harmless adenovirus. These studies showed that the vaccine generated strong immunologic responses in the majority of people who received the injections. The studies are ongoing to identify the best dose before beginning larger human trials.
The first results of a large study comparing three-drug versus four-drug combinations in people with low CD4 cells or high viral load (HIV RNA) were presented. The study was conducted by the AIDS Clinical Trials Group. The three regimens compared were a protease inhibitor (PI)-containing regimen, a two-PI regimen, and a PI plus a non-nucleoside drug (NNRTI). All people also received AZT and 3TC. The specific drugs used were Crixivan, Viracept and Sustiva. The group that received the PI plus the NNRTI had the best level of HIV suppression after 48 weeks.
This article was provided by Seattle Treatment Education Project. It is a part of the publication STEP Ezine.