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How do they Improve HIV Medicines?
Jun 27, 2005

You said that Combivir has been surpassed by Truvada (Viread and Emtriva combo pill) because this newer once daily agent has fewer overall side effects. Doesn't lamivudine remain the least toxic NRTI?

Have any researchers published information about how they go about making HIV medicines with less side effects or is it all just accidental? Until there is open research about what can be done to make medicines that are less toxic, progress will be slow.

The emphasis on antiviral drugs may be mistaken because all antiviral drugs attack processes in normal cells too.

Shouldn't clinicians who care demand more research focused on developing less toxic treatments instead of the blinkered focus on antivirals?

Response from Dr. Pierone

I do think that lamivudine remains the least toxic NRTI. Emtriva is very close in tolerability and its longer persistence in the body may shift the scales in its favor (by making resistance less likely to occur).

I am not an expert on drug development, but I think the general scheme is to identify agents that have activity against HIV in test tube models. These core compounds are then modified to enhance antiviral activity and limit test tube toxicity. Then the best candidates are taken forward to small animals, followed by human volunteers. So there is a method to the madness, but one can't underestimate accidental breakthroughs or setbacks.

I think that you are right - the current focus on antiretroviral drugs is blinkered. Many would argue though that new drug development involves a proven business model bring a better drug to market and sell it for a steep markup (preferably a drug that needs to be taken every day for years).

My personal view is that the future of antiretroviral therapy will involve immune-based therapies and possibly gene therapy. Once an effective HIV therapeutic vaccine is developed it will flip the world of HIV over on its head. How much of a stretch is it to imagine using a therapeutic vaccine as first-line therapy and reserving the drugs for vaccine failures? This may sound like pie in the sky, but the French recently published impressively positive data on a dendritic cell based therapeutic vaccine in Nature Medicine in December 2004. At Retrovirus in Feb 05 another French group presented positive results with ALVAC therapeutic vaccine. Many other research labs are in the chase for novel, less toxic, HIV therapies. Thanks for posting and stay tuned.

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