Nucleoside analogues — commonly called nukes — were among the earliest class of drugs developed for treating HIV/AIDS. These drugs work by interferring with a viral enzyme needed by HIV to help make new viruses. To a much lesser extent, nukes also interfere with at least one enzyme needed by cells, which is probably responsible for some of their side effects.

Conducting studies on nuke-related toxicity in people usually requires that small pieces of muscle or liver be collected for analysis. But this is not practical for regular care of PHAs. Doctors can also order tests to check for the amount of lactic acid (lactate) in the blood — high levels suggest mitochondrial (Mt) toxicity. However, higher-than-normal levels of lactate don't tell doctors exactly when their patients are going to experience symptoms of Mt toxicity.

Now researchers in Vancouver, British Columbia, may have a possible solution. Dr. Hélène Côté and other scientists have developed a novel test for measuring the amount of Mt DNA in blood samples. This is important because levels of Mt DNA decrease over time as mitochondria become damaged, such as when people are taking nukes. Dr. Côté's test relies on PCR technology — something that's commonly used in many tests, including the viral load test. If commercially developed, the new PCR-based test could be used for regular assessment of Mt toxicity in PHAs. In the following report, we describe recent research in this area done by Dr. Côté and colleagues.

REFERENCE

Côté HCF, Brumme ZL, Craib KJP et al. Changes in mitochondrial DNA as a marker of nucleoside toxicity in HIV-infected patients. New England Journal of Medicine 2002;346:811-820.

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