Treatment may inhibit cells' "power centers" - AIDS - HIV-AIDS drug therapy side effects and mitochondria disease research

Companies that create HIV-AIDS drugs now have key information that could assist in making new medications with fewer side effects. Researchers Henry Weiner, a professor of biochemistry at Purdue University, West Lafayette, Ind., Steven Zollo of the National Institute of Standards and Technology, and Lauren Wood of the National Cancer Institute note the similarity between HIV-AIDS treatment side effects and diseases of the mitochondria, the "power centers" in cells, that affect the functioning of other parts of the cell. The researchers hypothesize that the drugs to combat HIV infection might inadvertently affect the functioning of the mitochondria.

"Finding that a drug affects a different target than the one it was designed for is not unusual," explains Weiner, an expert on protein processing in the mitochondria. The team speculates that current AIDS treatments using drugs that inhibit HIV proteins also could inhibit a key mitochondrial protein. This speculation fits the observation by doctors that side effects resembling mitochondrial dysfunction originated after new drugs became part of the standard drug "cocktail" used to treat AIDS patients. Highly active antiretroviral therapy has prolonged the lives of many, but has been associated with side effects such as diabetes, high cholesterol, and the development of fatty deposits as well.

To test the theory that the drugs were inhibiting the mitochondria, the researchers flooded them with large amounts of the medications and then measured the levels of processed protein in the mitochondria. They found that a number of HIV-AIDS drugs can inhibit mitochondrial processing.

Although these findings suggest a possible link between HIV-AIDS drugs and mitochondrial dysfunction, Weiner believes that investigating the mitochondria of patients in treatment, or using tissue culture grown in the lab, is the next step. "That is the only way to determine whether actual patients taking the medication are more than just slightly compromised by the effects of the HIV-AIDS medication on their mitochondria"

In the interim, he indicates that pharmaceutical manufacturers may find this information useful in efforts to develop medications with fewer side effects. "Drug companies making new AIDS protease inhibitors can take the enzyme we used and screen new potential drugs and select ones that can fight the virus, but not damage the mitochondria."

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