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Research Leads to First Treatment for Drug-Resistant HIV

more easily absorbed and tolerated by the body, according to research results.

"In Phase 3 clinical trials of TMC-114, the majority of patients receiving the drug did very well with relatively few side effects," Mitsuya said. "Those patients showed a significant increase in their CD4 cell counts. Many of those patients have been treated for a year or more and have shown no signs of developing a significant resistance to the drug."

Ghosh is now expanding on his design, making alterations to the original molecule aimed at making even more effective treatments.

"The most recent protease inhibitors we created are exceedingly potent," he said.

Ghosh's work has opened the door to a new path for antiretroviral therapy.

"Earlier, researchers were unsure of how to deal with drug-resistant viruses," he said. "Problems that arose with treatments developed in the 1990s were disheartening. There was no concept on the horizon. We created a conceptually new class of protease inhibitors to combat drug resistance. That has renewed excitement in antiretroviral treatment and provided a direction for the future."

These new protease inhibitors are beneficial for reasons beyond their potency and enduring effectiveness, Ghosh said.

"Because they are synthetic, lab-created materials, they are amenable to cost-effective mass production. Keeping costs down greatly increases the accessibility of the drugs to Third World countries where the epidemic is worst."

The design, synthesis and evaluation of these new protease inhibitors will be detailed in a paper in the Aug. 24 issue of the Journal of Medicinal Chemistry and is currently available on the journal's Web site.

Irene Weber of Georgia State University, Eric Walters of Rosalind Franklin University of Medicine and Mitsuya co-authored the papers with Ghosh. Mitsuya characterized the molecules' effectiveness and Walters and Weber perfor
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