Mutations Resist New HIV Integrase Inhibitor

NEW YORK (Reuters Health) - Multiple mutations of HIV-1 can confer resistance against S-1360, the first integrase strand transfer inhibitor to have entered clinical development, according to Belgian researchers.

In the October 21st issue of AIDS, Dr. Myriam Witrouw and colleagues at the Catholic University of Louvain note that HIV integrase inhibition can prevent transfer of viral DNA into the host cell chromosome and thus disrupt replication.

To investigate possible resistance to this approach, the researchers passaged HIV-1 in cell culture in the presence of increasing concentrations of S-1360. This oral agent, which was initially developed in Japan, has already been tested in HIV-negative volunteers.

As the result of the selection process, nine mutations arose in the catalytic domain of integrase. Susceptibility to S-1360 fell by amounts ranging from two to more than 62-fold.

However, the researchers note that all mutants remained susceptible to the integrase DNA binding inhibitor V-165. This was also true of common anti-HIV drugs including zidovudine and nevirapine.

Given this, the researchers conclude that use of integrase strand transfer inhibitors along with integrase DNA binding inhibitors and current antiretroviral compounds, "is of potential interest when designing the next generation of anti-HIV drugs."

Source: AIDS 2004;18:2019-2028. [ Google search on this article ]

MeSH Headings: Biological Phenomena : Biological Phenomena, Cell Phenomena, and Immunity : Biological Sciences : Biology : Drug Resistance, Microbial : Enzyme Inhibitors : Enzymes, Coenzymes, and Enzyme Inhibitors : Genetics : Genetics, Microbial : Microbiologic Phenomena : Pharmacogenetics : Anti-HIV Agents : HIV Integrase Inhibitors : Integrase Inhibitors : Chemical Actions and Uses : Chemical Actions : Biological Sciences : Chemicals and Drugs