Category Archives: Immunology

Cancer Treatment Saves the Life of an HIV Patient – For the Second Time

I’m finally finding time to finish a blog post on the announcement Nature made earlier in March with a pretty big headline subject: for only the second time ever, an individual infected with HIV is “cured” – as much as it is humanly possible to be cured of HIV – via stem cell transplant.

University of Cambridge’s (UK) Ravindra Gupta, MD, led the study of this patient, whose name has not be released (I’ll use the term “2019 patient”). Researchers like Gupta actually warn against using the term “cured” to describe this person’s health status. So why are people (the media) saying that the 2019 patient is cured? Because the 2019 patient stopped taking antiretroviral drugs 18 months ago (16 months after receiving the stem cell transplant), and HIV has not returned.

Plus, the headline “person is cured of HIV” sounds a lot better than “person’s HIV’s levels have not returned after receiving stem cell transplant and halting antiretroviral treatment.” I won’t go on a tear about the issues with sensationalism in science journalism (right now, anyway).

The 2019 patient joins the ranks of Timothy Ray Brown, the ‘Berlin Patient,” who was “cured” in 2018 and still appears HIV free.

Berlin vs. London

Both Brown and the 2019 patient had a form of blood cancer that did not respond to chemotherapy, which prompted doctors to conduct a bone marrow transplant to replace diseased blood cells with healthy stem cells. These stem cells just so happened to also produce a very rare form of HIV-resistance. So these two patients came out of their procedure on their way to being both cancer-free and HIV-free.

In the case of the 2019 patient, doctors purposely chose a bone marrow donor who carried the HIV resistance trait – two copies of a mutation in a gene called CCR5. Experts estimate that just one percent of people of European descent carry the two-copy genetic mutation providing HIV resistance.

The CCR5 gene codes for a white blood cell receptor involved in the immune response to viral invaders like HIV. HIV binds the CCR5 receptor to attack white blood cells. So when CCR5 is not working normally due to a genetic mutation, HIV cannot attack white blood cells in the same way.

Before Brown received his stem cell transplant a decade ago, doctors tried aggressive chemotherapy and radiotherapy to treat his cancer. For the 2019 patient, doctors chose a less aggressive approach consisting of chemotherapy and drugs. Experts from the study acknowledge the difference in treatments as a sign that stem cell transplantation as a treatment for HIV infection does not require aggressive treatments to be effective.

Why only two?

So why not make stem cell transplant a standard procedure to treat HIV infection? The procedure is risky, more so than just continuing to suppress HIV with a daily drug regimen. The transplant could fail, or it could result in a lethal autoimmune attack. Other potential consequences include organ damage, respiratory distress, fluid overload, infection, and low platelets and red blood cells. Plus, HIV infection makes everything more dangerous.

Although stem cell transplants won’t quite work as a catch-all treatment for anyone infected with HIV, the basic concept behind the success of both patients “cured” of HIV yields promise. In laboratories all over the world, scientists are likely hard at work developing gene therapies targeting CCR5.

HIV/AIDS Basics

HIV (human immunodeficiency virus) is the virus – the “microbial agent” – that causes AIDS (acquired immunodeficiency syndrome) – the “disease – just like rhinovirus (“microbial agent”) causes the common cold (“disease”). HIV is a particularly devastating virus because it attacks the very cells employed by the human body to defend itself: CD4 immune cells.

Antiretroviral therapy (ART) does not lead to a cure, but it does improve quality of life and reduce the risk of an HIV-positive person passing the infection to someone else. ART accomplishes both tasks by preventing HIV from multiplying – minimizing the amount of virus in an infected person’s blood and preventing a person with an HIV infection from becoming a person with AIDS.

“It takes two to make a thing go right; It takes two to make it outta sight”
A commentary by Science Kara

Now that two people have been “cured” of HIV via the same means, I can’t image that it will be too long before researchers are publishing new studies on CCR5 gene therapy, conducting studies in vitro, in mice, and in chimpanzees. It will be a while until there are studies done with humans (per usual in science), but I don’t think it will be another 11 years before there is another major breakthrough in treatments for HIV more conclusive than ART.

In the midst of all the news reporting on the 2019 patient earlier this month, my favorite piece was from The Daily podcast and host Michael Barbaro from the New York Times. Barbaro goes beyond the science of the matter that I’ve discussed here and talks about the history of the HIV epidemic to truly represent how significant it is to declare the second “cure” of an individual infected with HIV.

References

Matthew Warren’s “Second patient free of HIV after stem-cell therapy.” published online as news for the journal Nature on March 5, 2019.

The National Institutes of Health website “AIDSinfo.”

Johns Hopkins Medicine

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Thinking About Immune Cells…

In a recent poll of my Twitter followers, I asked (on a whim while writing an article for work) what their favorite lymphocyte was.

Lymphocyte Poll

Cytotoxic T cells (Tc cells) were the clear winner (disclaimer – Twitter only allows four choices. There are of course many other lymphocytes to choose from). Tc cells are also known as Killer T cells, and rightfully so, due to the fact that they recognize certain patterns on the surfaces of cells either infected with an infectious microorganism or that are growing abnormally (tumor cells). Even their name suggests their nature: cyto – (cell) toxic (deadly). After recognizing the dangerous cells, Tc cells then act on their own to kill them, releasing enzymes like perforin, granzymes, and granulysin.

Perforin enzymes literally poke holes in the membrane of the suspicious cell, allowing granulysin and granzymes to enter. Granulysin attacks the surface of any viral particles, bacterial cells, or parasitic organisms that may have invaded. In some cases, granzymes enter the invader and cause it to self-destruct.

Or, in the words of University of South Florida medical school student Scott Nelson, “they can kill all by themselves.”

Lymphocyte Poll Response

Let’s take a minute and think about the underdogs of the poll results, the unsung heroes of immune protection: regulatory T cells. Although a meager nine percent of the responses to my poll indicated these lymphocytes were immune cells of choice, they certainly deserve a shout out.

While T helper cells are off stimulating cytokine production, activating B cells and running the block during a pathogenic invasion, the regulatory T cells stay primed for preventing any autoimmune activity that may occur by accident. The body’s immune system is prone to erring just like any other machine, and regulatory T cells exist to prevent and reverse any potentially deleterious actions of helper T cells if they were to accidentally target the body’s own cells, mistaking them as foreign antigens.

So while lymphocytes like T helper cells and Tc cells are out fighting pathogenic crime and protecting the body from infection (by all means a noble venture), regulatory T cells stay at home in case of dangerous mutiny or friendly fire.

Now you know a little bit more about what T cells do for our body, especially important to consider since we’re in the middle of flu season. On that note, I never even mentioned B cells, the other piece of the immunological puzzle, being the lymphocytes that are responsible for antibody production. Until next time…