Discussions and reflections on science and life

If only it were as simple as curing HIV.

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The following is old news, yet I am constantly surprised at how few people seem aware of it.

We have a cure for HIV. We have had one since 2007.

One thing that life is good at is living. The species would be in a pretty sorry state if we stood a chance of being wiped out by every passing epidemic. Certain immune individuals naturally arise  in any epidemic, and, as horrible as the HIV epidemic is, it is hardly our first rodeo. A long, long time ago, something (there is contention over whether it was bubonic plague, smallpox, or something else entirely) selected for a T-cell mutation in certain populations in Northern Europe. These populations proved more fit against whatever risk they were facing, and so were able to pass on their genes while their contemporaries passed away. These genes disseminated through the population and currently 5-15% of Europeans posses at least one allele coding for the mutation. As it so happens, possessing one copy of this allele slows the progression of HIV to AIDS by up to two years. Having two copies provides immunity.

This mutation is known as CCR5Δ32. Let’s parse that: C-C Chemokine Receptor 5 Deletion (which we use the Greek letter Delta as a shorthand for) of 32 bases. That deletion of 32 bases is so crippling that the CCR5Δ32 gene is incapable of making functional CCR5. This provides protection from HIV based on the manner in which the virus goes about infecting our cells.

Now, we are all familiar with the fact that HIV selectively infects so called ‘helper’ T-Cells. It does so through interactions between proteins on the surface of the virus and the CD4 molecule on the surface of the T-cell. What people often neglect to mention is that the presence of CD4 is necessary but not sufficient. HIV needs a secondary binding site in order to infect the cell. To this end, it uses CCR5 (and occasionally something else called CXCR4, but only in the late stage of infection). People who are heterozygous for the CCR5Δ32 mutation make less CCR5. People who are homozygous make none.

Beginning to see how this works? “But Caudoviral”, you say, “surely the presence of immunity isn’t in itself a cure!” And you would be right, if we were talking about anything but blood.

The advantage of blood is this: It all springs from a common well: the hematopoietic stem cell. So all we would have to do is take an HIV patient, use radiation to kill his immune system, and do a hematopoietic stem cell transplant from a donor who is homozygous for CCR5Δ32, and stand back and marvel as we have basically transplanted immunity to a disease. It’s absurdly simple. So simple it almost seems like it shouldn’t work. But it does.

In 2007, a 40-year-old, white male presented to a German hospital with a case of acute myeloid leukaemia. The patient had been diagnosed with HIV ten years earlier. Due to the leukaemia, a hematopoietic stem cell transplant was indicated. In addition to screening the donor bank for HLA matches, his doctors also screened for CCR5Δ32 homozygosity. They found a match. The procedure was carried out as planned and to this day the patient is HIV free. Cured.

But don’t take my word for it! The original article is available for free through the NEJM.

They are already looking for a second patient to replicate the results. So why aren’t we celebrating? Why isn’t the war over? Well, one of the great problems with any epidemic is that the medicine is only half the battle. Despite this being a dramatic and surprising result, despite this opening up a new door in the treatment of blood pathogens, the fact of the matter is that hematopoietic stem cell transplant is a complicated, dangerous, painful, and inherently unreliable procedure. Not to mention that it is expensive. We can’t use first world medicine to eradicate an epidemic in some of the poorest nations on the planet (if we could, so many more diseases would be a thing of the past, tb for example).

There is a bitter irony in having the power to cure a disease, but lacking the power to get that cure to everyone who needs it.

However, I can’t be entirely pessimistic. This has brought a great deal of attention to CCR5 as a potential target of therapy for HIV and several chemical CCR5 inhibitors are currently in testing. This might just be the breakthrough that leads to a better future, but I am not crossing my fingers.

Written by Caudoviral

01/10/2011 at 15:43

Posted in Biology, HIV/AIDS

One Response

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  1. […] comes in two flavors, CCR5 tropic and CXCR4 tropic. You might remember a post on CCR5 tropic HIV from a while back. It basically denotes which co-receptor is necessary for the virus to enter a cell (and yes, there […]

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