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Nano Comes to HIV

April 2008

One of the most interesting reports from CROI 2008 described new types of drug delivery using "nano-technology." While scientists have been experimenting with such approaches for a number of years, presentations at CROI showed that this technology is much closer than previously believed.

Nano-technology offers the possibility of treatments taken only once every few weeks or even once every two months. This would usher in a whole new paradigm of HIV treatment, one that makes even today's "one pill once a day" regimens seem primitive and intrusive. Scientists revealed this approach using a number of different currently available drugs. Still, obstacles remain before anyone can expect to order an HIV nano-drug at the local pharmacy.

The term nano has become part of the language in many areas of science, including biology and drug development. It entered the public consciousness mostly through science fiction, associated with hordes of self-replicating tiny robots that either help or destroy human kind. In the real world, is simply refers to things that are very tiny. Nano is simply a term of measurement, very much like the "centi" in centimeter (one hundredth of a meter). In the simplest terms, nano means one-billionth of some measure. Scientists have shown the ability to make tiny but functional mechanisms and processes that operate on the nano scale, including drug delivery.

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Tibotec, who already brought two new HIV drugs to market in the last year, revealed an encouraging approach. They have a third drug, rilpivarine (TMC-278), moving toward FDA approval. It was with this drug that they showed their new nano-technology. Rilpivarine is a non-nucleoside reverse transcriptase inhibitors (NNRTI), in the same class as Sustiva (efavirenz) and Intelence (etravirine).

In experiments, they combined the drug with nano-crystals, creating a "nano-solution" which suspends the drug in the blood and particularly in lymph nodes. The HIV drug is released very slowly as the solution breaks down over many months, all the while maintaining adequate levels. So far, the drug in this solution has only been given to 48 HIV-negative volunteers, so its antiviral properties against HIV have yet to be measured. Studies are currently planned.

It is easy to imagine the potential benefits of such an approach. Instead of a daily diet of pills that are processed through the digestive system, a patient would simply get an injection, similar to a flu shot, once every few months, or as seldom as twice a year.

Although the Tibotec experiment used only one HIV drug, there's no reason that similar technology couldn't deliver several drugs at the same time. In fact, lab studies are already doing so. In another experiment, researchers at Creighton University in Omaha, NE combined Kaletra (lopinavir + ritonavir) with efavirenz into nano-particles and tested them in lab studies. Results showed that the nano-particles could provide sustained release of the three drugs for at least two weeks from a single dose. Longer release may well be possible.

Other experiments have been reported recently using nano-technology as a delivery mechanism for CCR5 entry inhibitors. There appears to be a great deal of interest in exploiting various forms of nano-technology for the next wave of simplifying therapy in HIV and other diseases.

One important concern with this approach is what might happen if a person has a serious allergic reaction to a drug that has been given this way. With most drugs, the harm of allergic reactions begins to lessen as soon as a person stops taking the drug. But when the drug has been given by nano-technology, it is in the bloodstream for weeks or months to come. This is not believed to be a major obstacle, however. It requires that the manufacturer develop some form of fast acting antidote or antibody that will destroy or block the activity of the nano-drug. Such an antidote is currently under development for rilpivarine, and it's safe to assume that any company using this technology will be required to do this.

It is amazing to see how far HIV drug technology has come in the last dozen or so years. When truly effective therapy first became available in 1996, it often required large numbers of pills that were difficult to swallow and had to be taken at least three times a day, often with great quantities of water and with or without food. By 2005 we had one-pill, once-a-day regimens. Now, just a few years later, we are on the can see the possibility of treatment that might be taken as little as a few times a year. Advances like nano-technology are exciting on their own. The speed at which this technology is advancing leads us to ask, can a true cure really be that far away?



  
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This article was provided by Project Inform. It is a part of the publication Project Inform Perspective. Visit Project Inform's website to find out more about their activities, publications and services.
 
See Also
CROI 2008 Study Abstract: "Long-Acting TMC278, a Parenteral Depot Formulation Delivering Therapeutic NNRTI Concentrations in Preclinical and Clinical Settings"
More Research on HIV/AIDS Treatment Strategies

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