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"The genetic variations that exist in the protease of these African strains are not sufficient to cause drug resistance by themselves," Freire said, "but they amplify the effects of drug-resistant mutations and therefore may lead to a faster long-term failure of the therapy."

According to Freire, the sparse clinical data available so far on the effectiveness of antiviral drugs in C and A subtype patients suggest initial responses to the drugs are similar to those achieved in North America and Europe. However, there are also indications that the long-term effectiveness of the drugs may be diminishing more rapidly in HIV-A and HIV-C patients.

"While several reasons have been advanced to explain these results, including lack of patient adherence to the demanding regimen of highly active antiretroviral therapy, the results we're presenting also suggest that a molecular basis for a poor long-term response might be present," Freire said.

Freire has been an outspoken advocate for changing drug design paradigms to better deal with existing and potential genetic variation in disease-causing pathogens. Genetic variation has been a key contributor to the spread of HIV, but drug development work has been focused almost exclusively on HIV-B, which is dominant in some regions but a minority in the worldwide epidemic. Approximately 70 percent of existing AIDS cases are HIV-A and HIV-C cases in Africa, and these subtypes can vary genetically from HIV-B by as much as 30 percent. Freire believes that these factors, together with his research results, make including HIV-A and HIV-C in AIDS drug development efforts a priority.

Earlier this year, in a commentary in "Nature: Biotechnology" and at the American Chemical Society national meeting, Freire asserted that drug designers should be able
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Contact: Michael Purdy
mcp@jhu.edu
410-516-7160
Johns Hopkins University
5-Jul-2002