As a second patient is seemingly cured of HIV after receiving a stem-cell treatment for his (Hodgkin lymphoma) cancer, it begs the question of whether HIV is ‘incurable,’ as we have always assumed. This article will endeavour to explain how HIV and AIDS affect the human body, how Adam Castillejo was ‘cured’, and what all this means for the future of modern medicine.
HIV stands for the human immunodeficiency virus. It is a virus that attacks cells that would normally help the body fight infection (CD4 helper cells), making a person more vulnerable to other infections and diseases. CD4 helper cells are a subset of white blood cells that do not neutralise infections, but rather trigger the body’s response to infections.
There are 7 steps that HIV follows to multiply in the body. These are illustrated in the picture below. The process begins when HIV encounters a CD4 cell. The 7 steps in the HIV life cycle are
Not only does HIV attack CD4 cells, but it also uses the cells to make more of the virus. HIV destroys CD4 cells by using their replication machinery to create new copies of the virus. This ultimately causes the CD4 cells to swell and burst. Once the virus has destroyed a certain number of CD4 cells and the count drops below 200, a person will have progressed to AIDS.
You can get or transmit HIV through specific activities only. Most commonly, people get or transmit HIV through sexual behaviours and needle or syringe use. Only certain fluids- blood, semen, rectal fluids, vaginal fluids, and breast milk- from a person who has HIV can transmit HIV. It can also be transmitted from mother to baby during pregnancy via the placenta.
AIDS is the acquired immune deficiency syndrome. It is the name used to describe a number of potentially life-threatening infections and illnesses that happen when your immune system has been severely damaged by the HIV virus. Many people often confuse HIV and AIDS- HIV causes AIDS. HIV destroys CD4 T cells- white blood cells that play a significant role in helping your body fight disease. The fewer CD4 T cells you have, the weaker your immune system becomes. You can have an HIV infection, with few or no symptoms, for years before it turns into AIDS. AIDS is diagnosed when the CD4 T cell count falls below 200, or if you have an AIDS-defining complication, such as a serious infection or cancer. Thanks to better antiviral treatments, most people with HIV today don’t develop AIDS. Untreated, HIV typically turns into AIDS in about 8-10 years. AIDS only occurs once your immune system has been severely damaged and as mentioned before, is only diagnosed once the CD4 T cell count falls below 200, or if you have an AIDS-defining complication.
Antiretroviral medicines are normally used to treat HIV. They work by stopping the virus replicating in the body, allowing the immune system to repair itself and preventing further damage. These come in the form of tablets, which need to be taken every day. HIV is able to develop resistance to a single HIV medicine very easily, but taking a combination of different medicines makes this much less likely. On top of this, there are some people who are actually naturally resistant to HIV. CCR5 is the most commonly used receptor by HIV-1- the virus strain of HIV that dominates around the world- to enter cells. But a small number of people who are resistant to HIV have two mutated copies of the CCR5 receptor. This means the virus cannot penetrate cells in the body it normally infects. Researchers say it may be possible to use gene therapy to target the CCR5 receptor in people with HIV. Adam Castillejo was the second patient to be cured of HIV. He received a stem-cell treatment for a cancer (Hodgkin lymphoma) he had, and this rendered him virus-free. This is because the donor of the stem cells had the uncommon gene that gives them and now Mr Castillejo protection against HIV.
In order to understand how the phenomenon of Mr Castillejo becoming HIV free came about, it is important to look more closely at how stem cells work. Stem cells are special human cells that have the ability to develop (differentiate) into many different cell types, from muscle cells to brain cells. In some cases, they also have the ability to repair damaged tissues. Stem cells are divided into two main forms- embryonic stem cells and adult stem cells. The embryonic stem cells used in research today come from unused embryos resulting from an in vitro fertilisation procedure that are donated to science. These embryonic stem cells are pluripotent, meaning they can turn into more than one type of cell.
There are two types of adult stem cells. One type comes from fully developed tissues, like the brain, skin, and bone marrow. There are only small numbers of stem cells in these tissues, and they are more likely to generate only certain types of cells. For example, a stem cell derived from the kidney will only generate more kidney cells. The second type is induced pluripotent stem cells. These are adult stem cells that have been manipulated in a lab to take on the pluripotent characteristics of embryonic stem cells. Although induced pluripotent stem cells don’t appear to be clinically different from embryonic stem cells, scientists have not yet found one that can develop every kind of cell and tissue.
The only stem cell currently used to treat disease are hematopoietic stem cells- the blood cell-forming adult stem cells found in the bone marrow.
Stem cell transplants are used currently in the treatment of cancer. In a typical stem cell transplant for cancer very high doses of chemotherapy are used, sometimes along with radiation therapy, to try to kill all the cancer cells. This treatment also kills the stem cells in the bone marrow. Soon after treatment, stem cells are given to replace those that were destroyed. These stem cells are given into a vein, much like a blood transfusion. Over time, they settle in the bone marrow and begin to grow and make healthy blood cells. This process is called engraftment.
There are two main types of stem cell transplants.
Autologous stem cell transplants are when the stem cells come from the same person who will get the transplant. In this type of transplant, your own stem cells are removed, or harvested, from your blood before you get treatment that destroys them. Your stem cells are removed from either your bone marrow or your blood, and then frozen. After you get high doses of therapy, the stem cells are thawed and given back to you. One advantage of autologous stem cell transplant is that you’re getting your own cells back. You do not have to worry about the new stem cells (engrafted cells) attacking your body, or about getting a new infection from another person. But there can still be graft failure, which means the cells don’t go into the bone marrow and make blood cells like they should. A disadvantage of an autologous transplant is that cancer cells may be collected along with the stem cells, and later put back into your body. Another disadvantage is that your immune system is still the same as it was before the transplant. As the cancer cells were able to escape attack from your immune system before, they may be able to do so again. To help prevent this, some places treat the stem cells before giving them back to the patient to try to kill any remaining cancer cells- this is called purging. Again, this has problems because some normal stem cells can be lost during this process. This may cause your body to take longer to start making normal blood cells, and you might have very low and unsafe levels of white blood cells or platelets for a longer time, increasing risk of infections or bleeding problems.
Allogeneic stem cell transplants are when the stem cells come from a matched related or unrelated donor. In the most common type of allogeneic transplant, the stem cells come from a donor whose tissue type closely matches the patient’s. Blood taken from the placenta and umbilical cord of new-borns is a newer source of stem cells for allogeneic transplant. Called cord blood, this small volume of blood has a high number of stem cells that tend to multiply quickly. But the small volume normally does not contain enough stem cells for large adults, so is mostly used for children and smaller adults. A positive to this type of stem cell treatment is that the donor stem cells make their own immune cells, which could help kill any cancer cells that remain after high-dose treatment. This is called the graft-versus-cancer effect. Also, the donor can often be asked to donate more stem cells or even white blood cells if needed, and stem cells from healthy donors are cancer-free. Cons- the transplant might not take; the transplanted donor stem cells could die or be destroyed by the patient’s body before settling in the bone marrow. Also, the immune cells from the donor may not just attack the cancer cells- they could attack healthy cells in the patient’s body. This is called the graft-versus-host disease. There is also a very small risk of certain infections from the donor cells, but as donors are tested before they donate, this is rare. A higher risk comes from infections you had previously, and which your immune system has had under control. These infections may surface after allogeneic transplant because your immune system is suppressed by medicines called immunosuppressive drugs. Such infections could cause serious problems, if not death.
Of course, this all brings up the question of why can we not use stem cell transplants to cure all HIV patients? The answer is that it would not be possible to find enough genetically matched bone marrow donors with the naturally occurring genetic mutation to treat the 33 million people with HIV, even if that was desirable, safe and ethical. Also, most people with HIV already have very compromised immune systems, and so carrying out stem cell transplants would carry a significant risk, which may not be outweighed by the benefits.
A lot of research has gone into the potential of using gene therapy for treating and preventing diseases in general, and specifically for HIV. Gene therapy is an experimental technique that uses genes to treat or prevent disease. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patient’s cells instead of using drugs or surgery. There is research into several approaches to gene therapy, including:
- Replacing a mutated gene that causes disease with a healthy copy of the gene.
- Inactivating, or ‘knocking out’ a mutated gene that is functioning improperly and causing unwanted consequences.
- Introducing a new gene into the body to help fight a disease.
Gene therapy is a promising treatment option for a number of diseases, including inherited genetic disorders, some types of cancer, and certain viral infections. However, the technique is risky and is still under study to make sure that it will be safe and effective. Gene therapy is currently being tested only for diseases that have no other cures.
Gene therapy is promising in helping cure HIV because people who are naturally resistant to HIV have two copies of the CCR5 receptor due to a random mutation. Gene therapy could be used to give people the second mutated copy of this receptor if they target the CCR5 receptor, hence, curing people of HIV. However, gene therapy is still a controversial technique, and whilst many believe that it will become a staple of 21st century medicine, experts say society will be better served if medical researchers proceed slowly and prudently. Therefore, it is likely to be decades until gene therapy becomes normalised in modern medicine. And for specific treatments, such as this supposed HIV cure, many years of testing, clinical trials and waiting for approval would have to pass before the treatment becomes available.
Kiran Kuri, Year 13