The Quick, The Beautiful, The Scientific Break Downb

By: Ilan Cerna-Turoff

HIV science is not sexy to most people.  But, translating medicine into simple language can be unbelievably interesting, powerful, and yes, sexy. There is something profound about understanding how drugs work in our bodies and how viruses evade our defenses and evolve. I am aware that my perspective is a bit quirky. Still, a point of advocacy exists in understanding this hard science: we cannot fully benefit from scientific advances as a community if we do not understand them. For this reason, I want to talk with you about treatment science and hopefully make something very complex, simple and clear.

Over the last couple years, the use of medicine for prevention, or biomedicine, has advanced tremendously. We now have multiple tools that can stop HIV transmission, and the forms are ever diversifying (gels, pills, and down the road, foams, rings, and maybe even insertable Listerine strips). “Treatment as prevention” has been the main focus of discussions.  In other words, if an HIV positive person takes his/her medication consistently, it will prevent him/her from passing on the virus to other people.  Less discussion has happened recently about the advances in finding a cure. Largely, we have not been talking about it because no big discovery has happened. Regardless, scientists are experimenting with novel approaches that may transform treatment for HIV positive people in the future.

In 2009, Timothy Ray Brown gained fame worldwide in 2009 as the first person to be cured of AIDS in Germany. He is a very unique case. Timothy, in essence, had a complete immune system transfer. After years of chemotherapy for a form of leukemia that affects the bone, he received a bone marrow transfer. The donor of the bone marrow was a Northern European who had a genetic mutation that he inherited from both his mother and father, which kept him from producing a receptor on his T-cells called CCR5-? 32. This mutation is only important because CCR5 is one of the sites that HIV binds with to enter the cell. This is not the only place HIV binds, but it seems that for most people, HIV first binds to the CCR5 site and later, in infection, switches to binding to the CXCR4 site. The mutation in CCR5 is also commonly known as the “Delta 32” mutation.  If you lack this binding site, you are immune to HIV (many Northern Europeans have this mutation and, therefore, is the only group who sometimes has immunity to HIV).  When they put this donor’s bone marrow into Timothy, he was cured of both his cancer and HIV.

There are some important things that we have learned out of this case. Already two HIV positive cancer patients have been treated with a similar regimen as Timothy, and we hope that they too will be cured. Although we may be able to replicate this procedure with people who have bone cancers, bone marrow transplants have a 30% mortality rate. If the cure kills 30% of patients, it is less effective than a lifetime on antiretroviral drugs. Instead, scientists are asking how they can produce a similar response in people who do not have bone cancers. One novel approach is genetic engineering of T-cells.

Scientists have been able to extract T-cells from patients’ bodies and genetically engineer them to have a similar response to HIV as Timothy Ray Brown. They basically use an enzyme –enzymes help chemical reactions to occur more quickly in the body– called a “zinc fingered protein,” which hits the spot on your DNA that causes your body to produce CCR5 receptors on your T-cells. The scientists then insert these genetically modified T-cells back into your body. The problem right now is that these T-cells die, and if you extract a few hundred, how are you going to get them to all of the places in your body where HIV hides? The future of this field hopes to genetically modify stem cells. These cells never die and for the extent of your life, create new body tissues as other cells die off. Eventually, a genetically engineered person could be cured.

Genetic engineering of people seems like some sci-fi, future world. We have mostly imagined this genetic engineering as a form of eugenics. Racist dystopias always make everyone blond or super-human like in the movie Gattaca. In the case of HIV, genetic engineering may offer a real possibility of a cure.

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