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Elizabeth Boskey, Ph.D.

Approaching HIV Treatment from a New Direction

By February 18, 2013

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Developing new HIV treatments is a difficult process. Coming up with novel treatments, that are not simply improved versions of drugs we have now, is even harder. That was why I was so excited when I recently had the opportunity to talk to the scientists behind PRO 140, an HIV treatment that is currently under development.

PRO 140 is a monoclonal antibody that targets the primary HIV binding sites on CCR5. Like more "traditional" CCR5 blockers, the antibody prevents the entry of CCR5-tropic HIV into target cells. Unlike more traditional blockers, however, it seems to have fewer side effects and, in vitro at least, does not seem to lead to resistance. This may be because, unlike some earlier anti-CCR5 antibodies that were tested for treatment, PRO 140 blocks the two primary HIV binding sites simultaneously. That makes its protection much more difficult for HIV to evolve around than if it only blocked one such site.

Two preliminary studies have shown good treatment efficacy with PRO 140 in HIV positive individuals Because of this, the obvious question might seem to be, "if an antibody works as an HIV treatment, why can't we make a good treatment vaccine?" The answer has to do with a finicky bit of biology -- just immunizing people with the antigens you want to block does not mean they'll make antibodies that block them in the right way.

The fact that this antibody works so well, and blocks two separate domains of CCR5 simultaneously, is a reflection of its very specific structure. It's not an antibody that you can expect most people to make after vaccination, which is why the drug company working on the project is creating the precise antibody they need in the lab and delivering it directly. (That said, it might eventually be possible to teach individuals' bodies to make the antibody using gene therapy, but that's a long way down the pipeline.)

Finally, given that one of the current hot topics in HIV research is pre-exposure prophylaxis, I asked the CytoDyn scientists whether they thought that PRO 140 might eventually be useful as a prevention tool in addition to a therapeutic one. As it turns out, that's something they're testing in mice right now, and it will be very interesting to see the results. If PRO 140 does turn out to be relatively resistance-proof and non-toxic, it could address several of my worries about current PREP and PEP options, particularly if its effects last as long in the body as their current research suggests.

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