For the first time in history, someone with HIV has been treated with cells edited in the lab. It was a bold attempt to try to replicate previous successes in “curing” HIV through bone marrow transplants, but the results were a mixed bag.

Your DNA is like a book, and each sentence is a gene. Imagine a word is misspelled. Sometimes, a misspelling won’t affect your ability to understand the sentence, but other times, it will be so bad that you’ll have trouble figuring out the intended meaning. Think of the difference between “I drive a car” and “I driv a car,” or “I like food” and “I like flod.” You might not be able to tell what that last sentence is even trying to say! Those misspellings are mutations, and sometimes mutations are relatively benign (“I driv a car”), while other times they can cause diseases (“I like flod”).

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A mutated version of the CCR5 gene confers near-immunity to HIV — but increases susceptibility to other viruses.

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CRISPR, pronounced crisper, is a powerful new technology that can edit genes. By cutting DNA at a specific location and replacing some of the letters in the genetic alphabet, CRISPR can edit genes like you can edit a document using “find and replace.” The hope is that, someday, CRISPR could be used to fight disease by tweaking faulty genes.

A Genetic Mutation that Thwarts HIV

Graphic: Gaius J. Augustus

HIV attacks by interlocking with receptors on the surface of certain immune cells. Most strains of HIV attach to a receptor called CCR5. Think of it like a doorknob, which the virus turns to enter the cell. But some people have a mutated, shriveled version of the CCR5 receptor. HIV can’t get its hand around the tiny knob to turn it — and is shut out of the cell.

About 1% of people of European descent have two copies of the mutated CCR5 gene — one from each parent. They are often said to be “immune” to HIV infection. In actuality, there are strains of HIV that have found another way to invade immune cells — so, at best, there is immunity to certain strains of HIV, but not all of them.

Using Bone Marrow Transplants to Give Patients “Immunity” to HIV

Earlier this year, scientists announced the second successful case of putting an HIV patient into long-term remission, seemingly clearing his body of the virus. The so-called Berlin Patient and London Patient both had HIV before coming down with blood cancers (leukemia and lymphoma, respectively). These cancers are often treated with bone marrow transplants — infusions of stem cells derived from the bone marrow of compatible donors.

If you want to get to the root of the problem, bone marrow is the place to start. These cells differentiate into every single blood cell, giving rise to the vast army of white blood cells deployed by the immune system to fight disease. In a patient with blood cancer, a bone marrow transplant allows the recipient to manufacture non-cancerous cells. And, if the donor had a double dose of the CCR5 mutation, the resulting immune cells would shut out any strain of HIV that needed the CCR5 receptor to invade it.

The Berlin and London patients received bone marrow transplants from donors with the double-CCR5 mutations, and once those new cells put down roots in the patients’ bodies, they started pumping out healthy blood cells — free of cancer, and impervious to HIV.

What About CRISPR?

Patients can’t receive bone marrow from just anyone — donors must be compatible. The pool of compatible donors is already small, so it’s especially difficult to find one whose immune cells carry the double-CCR5 mutation. So a lot of people have been excited about the potential of CRISPR: What if, instead of tracking down a compatible donor with the rare double mutation, we simply found compatible donors and then used CRISPR to edit their genes, removing the CCR5 receptors before infusing the bone marrow into the cancer patients? And, if we could, would it be safe?

Scientists in China have taken a small step toward answering those questions by treating a patient who had both leukemia and an HIV infection. They found a compatible bone marrow donor, but before transplanting it into the patient’s body, the used CRISPR to remove portions of the CCR5 gene, disabling it. The hope was that this edited bone marrow would put that patient’s cancer into remission and wipe out the HIV infection.

Nineteen months later (and counting), there is good news and bad news. The good news is the bone marrow transplant successfully put the patient’s leukemia in remission, and his edited bone marrow cells are still thriving. The bad news is most of these cells lacked the beneficial CCR5 mutation, which means HIV can continue to infect his cells. He is still on anti-HIV drugs to keep his infection in check.

The silver lining is the patient did not seem to experience any negative side effects from the gene editing. But for now, our optimism should remain cautious: The scientists’ report is not a “study” — it’s a description of one patient’s experience. It could be a fluke, but the authors claim it’s a proof of principle that the procedure could be safely performed on humans, with the aim to refine the process and eventually develop a cure.

What’s Needed

For CRISPR to be deployed in the fight against HIV, it needs to be a better editor. Only 2% of the patient’s T cells — the specific immune cell targeted by HIV — boasted the shriveled CCR5 receptor. Instead of correcting 1 out of 50 misspelled words, CRISPR needs to correct all of them.

But using CRISPR to edit cells prior to bone marrow transplantation wouldn’t be a magic bullet. Bone marrow transplants are risky procedures; it’s likely that no doctor would want to perform one solely to attempt to cure HIV. These transplants would only be performed to treat even more serious diseases like blood cancers; curing HIV would be icing on the cake.

Editing DNA is not something to be taken lightly, either. In the case of certain cancer patients, it could make a lot of sense. But we shouldn’t be so quick to assume that a double-CCR5 mutation is a good thing. While it does confer immunity to most types of HIV, it might make people more susceptible to influenza and West Nile virus. And there is plenty more about the CCR5 receptor we don’t yet know about. (A study published this summer found that people carrying the double-CCR5 mutation had shorter lifespans, but late last month the authors called for their paper to be retracted after finding a serious error in their analysis.)

Any Planned Parenthood health center can help you reduce risk of transmitting or acquiring HIV. We offer condoms, HIV screening, education, and preventive medication, and can connect you to treatment if you test positive for the virus.

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