This week we will talk about the second case of a patient with HIV cured, yes, you heard correctly, cured. As if the news was not relevant in itself, the secret of the cure was found in a cancer treatment. We are talking about Hodkin lymphoma and stem cell treatment.
https://infosida.nih.gov/understanding-hiv-aids/
As we explained in its day, the human immunodeficiency virus, or HIV, infects the cells of our immune system. Specifically, it has a predilection for CD4 + T lymphocytes (a type of white blood cell). These, in short, are what activate our immune system when a threat is detected and a good immune response must be orchestrated.
Why does this virus infect these cells specifically? Everything is determined by various proteins. One found on the surface of the virus, called GP120 and 3 found on the surface of the lymphocyte: CD4, CCR5, and CXCR4.
The lymphocyte CD4 protein acts as an anchor point for the virus, as a receptor. That is, the virus’s GP120 protein recognizes this CD4 from the lymphocyte and binds. At this point, the virus has already managed to identify the cells it is going to infect. What happen? That a second protein, a coreceptor is required: either CCR5 or CXCR4, for the virus to perform the next step: introduce its RNA into the cells.
What will depend on whether you use a coreceptor or another? Of the specific strain of HIV.
- Strain: According to the RAE, it is a group of related organisms, such as bacteria, fungi or viruses, whose common ancestry is known.
Come on, that a strain is the set of viruses that comes from a common HIV virus. If an HIV has a preference for a coreceptor this will be passed on to its “offspring” virus, creating a strain of HIV with a predilection for that coreceptor.
These coreceptors are therefore essential for the virus. Once the viral RNA has managed to enter the lymphocyte, it is converted to DNA. In the form of DNA, it will be integrated into the genome of this immune cell. Copying in each cell multiplication process. At some point, this viral DNA can transform into protein and assemble new viruses that will leave the lymphocyte and colonize new cells.
https://infosida.nih.gov/understanding-hiv-aids/
Now let’s go to Hodkin’s lymphoma. It is a cancer that affects lymphocytes (we already know that they are a type of white blood cell), usually in the lymph nodes. Therefore, it is a tumor type that compromises the capacity of the immune system to defend the body against a “threat”.
With both diseases understood, let us now turn to our patient: Adam. Adam was diagnosed in 2003 with HIV. As in all cases of HIV, the treatment is antiretrovirals: drugs that prevent the virus from proliferating. These drugs manage to control the infection and prevent the patient from progressing to AIDS (the most serious stage of HIV infection). However, these drugs fail to remove the HIV genes that are inserted into the genome of the patient’s lymphocytes.
Antiretrovirals what they do is chronify the disease. The disease is not eliminated from your body, but it does not kill you.
9 years later, in 2012, Adam received a second bad news: he had Hodkin’s Lymphoma. Consequently, Adam was forced to combine his antiretrovirals with the relevant cancer treatments. However, none of the lymphoma therapies turned out to be too effective for him. As a last alternative, it was decided to have Adam undergo a bone marrow transplant.
The bone marrow is a spongy tissue that is found inside the bones, and that contains the stem cells that make the blood cells of our body, including lymphocytes. More info about stem cells: https://www.mariairanzobiotec.com/celulas-madre-aplicaciones-mas-sorprendentes/
What happen? That for any transplant they need a donor and recipient to be compatible. Otherwise, immunological rejection of the transplanted organ or tissue appears. The recipient’s immune system recognizes the transplant as strange and orchestrates an immune response to neutralize it, which can end life itself. For this reason, searching for compatible donors is required.
In Adam’s case, the most compatible donor had a mutation (a change in the sequence of a gene). Do you know where In the CCR5 gene, the gene that produces the CCR5 protein, a protein that is found on the surface of lymphocytes and that HIV uses to infect them. That is, the donor’s bone marrow stem cells made CD4 + T cells without the CCR5 protein.
- It is estimated that 1% of the population of Northern Europe has this same mutation in its genome.
Thus, the new stem cells that Adam received began to produce these new lymphocytes, lymphocytes that were overtaking cancer patients (and that had the CCR5 protein). In other words, Adam started making lymphocytes immune to HIV infection. Because the HIV that was infecting him could not continue to proliferate in his new lymphocytes, it would eventually disappear from the body.
The result? After 16 months after the transplant, the doctors decided to stop his antiretroviral treatment. A year and a half later, without this HIV treatment, Adam’s tests were negative for the virus. In other words: Adam managed to heal from infection and cancer.
Let’s do a recap in case someone is lost.
HIV requires the CCR5 protein from our lymphocytes to infect them. Our patient was diagnosed with Hodkin lymphoma, a cancer that precisely affects lymphocytes and causes the immune system to lose its defense capacity.
After several treatments, the patient underwent a bone marrow transplant, in which all the cancer cells were replaced and replaced by new stem cells that produced healthy cells, healthy lymphocytes.
Coincidences of life, the stem cells inserted into the patient had a mutation in the CCR5 gene, and therefore it did not appear on the surface of the new lymphocytes, of the healthy ones. These new lymphocytes would not only cure Adam of cancer, but also HIV infection. The virus, unable to infect these new lymphocytes (could not find the gateway, CCR5) would eventually disappear permanently from the body of our patient, Adam.
Is this the first case of HIV cure? No! History repeated itself years before with another patient, Timothy. However, he was diagnosed with leukemia and not lymphoma. Something that does not change the course of events, since both received a bone marrow transplant that cured them of HIV.
(The case of the first patient had considerably more complications, precisely due to the immunological rejection derived from the bone marrow transplant and the total previous elimination of all the cells of his immune system).
What consequences has this magnificent scenario had? Open the door to using stem cell treatment to treat critically ill HIV patients. And why critics? Because bone marrow transplantation is still a high risk process due to the probability of immune rejection (between 40 and 50% mortality, so it is only worth it in critical cases).
Given this complication typical of transplants, another possibility arises: to extract stem cells from the patient with HIV and genetically modify it to eliminate this CCR5. In this way, they would be reimplanted as a bone marrow transplant and one would expect to see the same results without the potential danger of rejection as they are their own cells.
For the moment? Wait for investigations to progress. Science is a slow process, but the results end up coming and are often worth it.