AIDSWEEKLY Plus; Monday, November 15, 2004
Staff Medical Writers

"The specificity of nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) for the RT of human immunodeficiency virus type 1 (HIV-1) has prevented the use of simian immunodeficiency virus (SIV) in the study of NNRTIs and NNRTI-based highly active antiretroviral therapy.

"However, a SIV-HIV-1 chimera (RT-SHIV), in which the RT from SIV-mac239 was replaced with the RT-encoding region from HIV-1, is susceptible to NNRTIs and is infectious to rhesus macaques," scientists in the United States report.

"We have evaluated the antiviral activity of efavirenz against RT-SHIV and the emergence of efavirenz-resistant mutants in vitro and in vivo. RT-SHIV was susceptible to efavirenz with a mean effective concentration of 5.9±4.5 nM," wrote M.J. Hofman and coworkers, "and RT-SHIV variants selected with efavirenz in cell culture displayed 600-fold-reduced susceptibility."

"The efavirenz-resistant mutants of RT-SHIV had mutations in RT similar to those of HIV-1 variants that were selected under similar conditions. Efavirenz monotherapy of RT-SHIV-infected macaques produced a 1.82-log-unit decrease in plasma viral-RNA levels after 1 week.

"Thee virus load rebounded within 3 weeks in one treated animal," investigators said, "and more slowly in a second animal. Virus isolated from these two animals contained the K103N and Y188C or Y188L mutations."

"The RT-SHIV-rhesus macaque model may prove useful for studies of antiretroviral drug combinations that include efavirenz," Hofman suggested.

Hofman and colleagues published their study in Antimicrobial Agents and Chemotherapy (Efavirenz therapy in rhesus macaques infected with a chimera of simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2004 Sep;48(9):3483-90.

For more information, contact T.W. North, University California Davis, Center Comparative Medicine, School Vet. of Medicine, Davis, CA 95616, USA.

Publisher contact information for the journal Antimicrobial Agents and Chemotherapy is: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA.

The information in this article comes under the major subject areas of Biotechnology, Immunology, HIV/AIDS, Animal Model, Antiretroviral Therapy, and Chimera.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Hofman MJ, Higgins J, Matthews TB, et el., "Efavirenz therapy in rhesus macaques infected with a chimera of simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1", Antimicrob Agents Chemother. 2004 Sep;48(9):3483-90.

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