SAN FRANCISCO (Reuters Health) - New classes of antiretroviral drugs that prevent HIV from infecting cells are showing promise in early trials, researchers reported on Wednesday. The drugs also have the advantage of being able to be administered orally.
SCH-D is an antagonist of the CCR5 co-receptor, Dr. Mark Laughlin of Schering-Plough Research Institute in Kenilworth, New Jersey and colleagues reported Wednesday at the 11th Annual Retrovirus Conference. Preliminary results for SCH-C, an agent of the same class, have previously been reported (see Reuters Health reports June 18, 2003 and February 26, 2002.)
SCH-D showed it could reduce viral load in chronically infected patients who were treated for 14 days. The patients were assigned to one of three groups that evaluated SCH-D given b.i.d. at 10 mg, 25 mg, or 50 mg. In each group of 16 subjects, 12 received SCH-D and 4 received placebo.
The investigators observed a dose-related suppression of viral levels in the treated patients, with mean log10 reductions of 1.08, 1.56 and 1.62 for 10 mg, 25 mg, and 50 mg, respectively.
These are “fairly impressive reductions in viremia,” commented Dr. John Mellors of the University of Pittsburgh, who was not directly involved in the study.
Bristol-Myers Squibb researchers also reported preliminary data for BMS-488043, an oral small-molecule HIV-1 attachment inhibitor. BMS-488043 blocks viral entry by preventing the envelope protein gp120 from binding to cellular CD4 receptors.
Fifteen HIV-infected subjects received 800 mg BMS-488043 or placebo (three subjects) every 12 hours for 8 days. The drug was given orally with a high-fat meal.
During 2 weeks after starting the study drug, BMS-488043-treated subjects had a mean maximal decline in viral load of 1.0 log10 copies/mL, compared with 0.30 log10 copies/mL for placebo-treated patients, reported Dr. G. Hanna of Bristol-Myers Squibb in Princeton, New Jersey and colleagues.
The mean change from baseline in CD4 counts was 106 cells per microliter for BMS-488043-treated patients compared with 6 cells per microliter for placebo-treated patients.
The agent was “generally safe and well-tolerated.”
These findings provide “proof of concept” for BMS-488043, and further development of this drug and this class of antiretrovirals is warranted, the researchers conclude.
The HIV antiretroviral “pipeline is still promising,” Dr. Mellors added.
MeSH Headings:Immunologic and Biological Factors: Immunologic Factors: Membrane Proteins: Receptors, Cell Surface: Receptors, Immunologic: Receptors, Virus: Drugs, Investigational: Receptors, HIV: Receptors, Cytokine: Anti-HIV Agents: Receptors, Chemokine: Receptors, CCR5: Chemical Actions and Uses: Chemical Actions: Chemicals and DrugsCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
