Pharmacologist predicts long road for AIDS research

Cheng
Photo by Yale.

Yung-Chi Cheng studies cancer and viral chemotherapy as Yale’s Henry Bronson Professor of Pharmacology. He spoke to the News on Monday about his research on anti-HIV drugs, as well as his perspective on the current state of HIV/AIDS research.

Q: Your lab made contributions to the development of several anti-HIV drugs. Could you elaborate on your lab’s research?

A: Our lab worked with festinavir five years ago, and emtricitabine and lamivudine way back. Emtricitabine and lamivudine were first-generation drugs discovered by other researchers, but they couldn’t move forward because they hadn’t demonstrated that they would not produce any side effects on mitochondria, which was a possibility of their mechanisms. Our lab conducted tests to show that they were nontoxic, allowing them to move forward and be developed by pharmaceutical companies. Festinavir is a different type of compound in the new generation that is now still in clinical trials.

Q: Are there many other labs researching anti-HIV therapies at Yale?

A: There are only two groups in pharmacology that are researching HIV therapy, but there are many investigators who are doing relevant research. Some are interested in vaccines, for example.

Q: What is Yale doing to support AIDS research?

A: Nothing. Yale itself is not using its resources to support AIDS research, at least to my knowledge. We get all our funding from the grants from the National Institutes of Health.

Q: Has this been a problem?

A: I think Yale should be using its own resources to support research in general, particularly at this period of time. The NIH money is not enough to sustain research.

Q: What are the challenges in discovering and improving upon anti-HIV drugs?

A: Just discovering a compound that’s very potent is not good enough. You also have to look at the toxicity. And you can’t just look at short-term toxicity. You need to take long-term toxicity into account, and that cannot be predicted by cell-culture studies in our lab. It takes long clinical studies to uncover those kinds of side effects, and few companies will be interested unless you can convince them that. For example, if it turns out festinavir has side effects, then we’ll have to keep looking.

Q: What improvements still need to be made to current anti-HIV drugs?

A: We have plenty of HIV drugs out there, and in combination they are doing a great job. But we are constantly trying to increase the therapeutic index, which measures potency versus toxicity. That is the major concern, and side effects are still a problem. You still need drugs with longer retention times. If a patient misses one dose, we don’t want any problems to arise. You also need a cocktail of drugs for the most effective therapy, and the best treatment procedure is still being worked out. Drugs always have room to be improved, but you have to know what to improve.

Q: What is the most important issue to address in the AIDS epidemic?

A: The number one issue is to prevent viral infection in the first place. The procedure to prevent infection is very simple. Lifetime treatment is a much more complicated protocol.

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