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There’s still a lot of work to be done before HIV is cured, but this week scientists reported the second-ever case of full HIV remission in a patient.

Hosted by: Hank Green

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Sources:
https://www.nature.com/articles/s41586-019-1027-4
https://www.cdc.gov/hiv/basics/whatishiv.html
https://aidsinfo.nih.gov/understanding-hiv-aids/fact-sheets/19/45/hiv-aids--the-basics
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185609/
https://www.medicalnewstoday.com/articles/318091.php
http://www.leukemiabmtprogram.org/patients_and_family/treatment/blood_and_marrow_transplant/ric_transplant.html
https://www.researchgate.net/publication/265135041_Shift_of_HIV_Tropism_in_Stem-Cell_Transplantation_with_CCR5_Delta32_Mutation
http://www.aidsmap.com/Receptors-co-receptors-and-immunity-to-HIV/page/1391639/
https://www.nature.com/scitable/blog/viruses101/hiv_resistant_mutation
[INTRO ♪].

A little over a decade ago, doctors did something remarkable: they cured someone of HIV. Ever since that person—known as the Berlin patient—received a set of bone marrow transplants in 2007 and 2008, his HIV hasn’t come back.

Now, a new group of researchers seem to have done it again. In a study published this week in the journal Nature, European researchers report ‘the London patient’—the second-ever case of full HIV remission. And this time around, the protocol was a little gentler on the patient—so it may help us develop better strategies for HIV treatment or maybe, someday, a safe and effective cure.

HIV, or human immunodeficiency virus, is the virus that causes HIV infection and AIDS by attacking cells of the immune system. According to the US Centers for Disease Control, nearly 37 million people around the globe were living with HIV in 2017, and in that same year, around 940,000 people died from AIDS-related illnesses. These days, HIV is treatable with what’s called antiretroviral therapy.

The meds suppress the virus, but patients need to keep on them constantly to keep the virus in check, and that is inconvenient and costly. So, finding a way to send HIV into permanent remission—that is, to become so rare that it is no longer detectable in the bloodstream—is a high priority for medical scientists. The treatment in this new study isn’t a miracle drug; it’s a bone marrow transplant.

Specifically, a transplant from a person who is resistant to HIV. You see, in order to infect a cell, a virus floating around in the bloodstream needs to attach to the cell’s exterior. And in HIV’s case, it does that by anchoring to the CD4 receptor—a protein on the outside of certain white blood cells which is normally used to receive molecular messages from other cells.

The virus basically pretends to be one of those messages, but to fully latch on, it also has to bind one of CD4’s co-receptors—proteins that help the receptor do its job—and in most cases, it attaches to one called CCR5. But some people have a mutation which means they don’t properly produce this co-receptor, and that makes them resistant to HIV. In this study, the researchers transplanted bone marrow stem cells from a resistant donor into a patient infected with HIV.

Since bone marrow is what makes blood cells, the hope was that the patient would start producing blood cells without CCR5, making them resistant to the virus. And that is exactly what happened. When the researchers examined the patient’s white blood cells after the treatment, they found that their DNA contained the HIV-resistant mutation and they were no longer producing the CCR5 protein.

But most importantly, the cells weren’t being infected by HIV. This is essentially the same thing that researchers did a little over a decade ago with the Berlin patient, the first known person to experience the permanent remission of HIV. Except this time, the procedure was a little less harsh.

In both cases, the patient was’t actually just being treated for HIV, they were also being treated for cancer—acute myeloid leukemia in the Berlin case, and Hodgkin’s lymphoma in the London case. Both are cancers of blood cells, so to treat them, doctors generally kill off the cancerous cells and then perform a bone-marrow transplant to jump-start the patient’s immune system so they can recover. In the Berlin case, the patient received full body irradiation for the cancer, and then two separate transplants before achieving remission.

But in this new case, the patient received a less intensive and less risky reduced-intensity chemotherapy and only one transplant—and the procedure still succeeded. It is not a definite cure for everyone, though. In fact, similar transplants have been tried in other patients over the past decade, and they have not worked.

For example, a transplant was able to knock out CCR5 from one patient in a 2014 study, but that person also happened to be infected with the second variant of HIV which doesn’t use CCR5 to get into cells—instead, it attaches to the other co-receptor of CD4, CXCR4. So the virus started to go into remission, but within three weeks of the transplant, the other variant of the virus was on the rise. It might be possible to get rid of a person’s CXCR4 receptors in a similar way, since there are people with genetic mutations that break that protein, too, but so far, that has not been done.

In this new study, the researchers tested the patient’s blood after the transplant and found the cells were still susceptible to HIV that targets CXCR4, but that variant was not detected in the patient’s bloodstream. It’s been over 18 months since the patient stopped taking antiretrovirals, and the virus hasn’t come back. They’re careful to caution that it’s too early to say for sure that the patient is cured, but the results are really encouraging, because science is all about repeatability.

When you only have one example of a successful treatment, it’s hard to know if you’ve found something reliable, or if your so-called cure was just some kind of lucky fluke. But now we know the Berlin patient wasn’t an isolated case. But it’s still going to be some time before this knowledge could translate into affordable, effective cures for every person with HIV—and it might never.

After all, we’re still talking about a major procedure, and this is not something that can easily be given to people who live far from serious medical care. Even the reduced-intensity protocol undergone in the London case is an intensive chemotherapy program designed to suppress the immune system. And there are serious risks to it.

Afterwards, patients sometimes develop life-threatening complications or reject the transplanted marrow. Also, there is some evidence that people without CCR5 are more susceptible to other diseases, like West Nile virus or bacterial infections. So scientists need to figure out what the trade offs and the side effects are for any treatment which impairs or gets rid of CD4 co-receptors.

And all of this is assuming that we have enough donors to perform transplants in the first place. The mutations which knock out CCR5 or CXCR4 are not common, and donors have to match a patient in other ways, too, or the transplant will fail. Still, confirming the effectiveness of bone marrow transplants is a crucial first step.

There might be other ways to target these co-receptors that are cheaper and safer. And ultimately, the success of this case gives doctors renewed hope that, one day, HIV could become a thing of the past. Thanks for watching this episode of SciShow News!

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