Researchers in the United States may have found a way to augment antiretroviral therapy's effectiveness against drug-resistant HIV strains. "Highly active antiretroviral therapy (HAART) is the standard treatment for infection with the human immunodeficiency virus (HIV)," explained Dr. Raymond F. Schinazi and colleagues working with Tucker, Georgia-based Pharmasset Inc., Emory University and the Veterans Affairs Medical Center in Atlanta, the University of Pittsburgh and the Veterans Affairs Medical Center in Pittsburgh, and the DuPont Pharmaceuticals Company in Wilmington, Del.

The cytidine nucleoside analog DPC 817 remains effective against viruses with resistance mutations countering reverse transcriptase inhibitors, a crucial element of HAART, according to Schinazi and coauthors.

Many HAART regimens utilize the nucleoside reverse transcriptase inhibitors (NRTIs) zidovudine and/or lamivudine, the researchers said. Viruses with mutations conferring protection from these agents remained vulnerable to DPC 817, which demonstrated powerful activity against wild-type viruses as well as resistant mutants.

DPC 817 had attractive qualities beyond its ability to target drug-resistant viral strains. The agent was quickly converted to its active metabolite, which remains in plasma for extended periods of time, study data showed. In fact, experiments with nonhuman primates suggested that the plasma half-life of DPC 817 was longer than that of several commonly used reverse transcriptase inhibitors ("DPC 817: A Cytidine Nucleoside Analog with Activity Against Zidovudine -- and Lamivudine-Resistant Viral Variants," Antimicrobial Agents and Chemotherapy, May 2002; 46(5):1394-1401).

"Together, these properties suggest that DPC 817 may be useful as a component of HAART regimens in individuals with resistance to older NRTI agents," Schinazi and colleagues concluded.

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