HIV Resistance Sensor

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HIV Resistance Sensor

Chapter 57
HIV Resistance and genetics

Training video

Spoken text of the video

Section 1: Intro

Chapter 57, HIV resistance and genetics. This is a specific training for the HIV Resistance Sensor. This sensor has two different roles. For one, which is very interesting, some people are resistant to the common types of HIV, the AIDS virus. This in itself might be interesting but it is not particularly useful. The other part of this test is improved treatment for an HIV-infected person.

Section 2: The concept

Let me show you the concept. You will find this test here. It is really only useful for treatment. It might be interesting for some people who want to know whether they are resistant or not but again it does not have any practical use. It is more important for people who already suffer from HIV and want to improve their treatment. Now, let us have a look at a white blood cell. There are two copies of the CCRO5 gene. These produce a receptor. A receptor is a kind of structure that is on the surface of the cells. It is presented at the surface of these white blood cells. The HIV virus has developed a mode of hijacking this receptor and binds onto it and then uses it to get into the cell.

Then, it infects the cell with HIV. The cell would then produce more HIV viruses, release them and then they would then infect other cells. Really, the CCRO5 gene, which our body produces, is the mode of entry that the virus hijacked. If you have normal CCRO5 genes, you will be susceptible to HIV. However, there are genetic variations that modify the blueprint and the building instructions in these genes. If a person had two of these genetic variations, they will build a receptor, however, it would be built incorrectly. So, it would not work as it is supposed to. It would be different. What is interesting is that HIV cannot bind onto this receptor and cannot use it to get into the cells.

What happens is that this cell or this person is HIV-resistant. They can be exposed to the virus but they are not infected by it. So, you can have two normal genes. Then, you will have a normal risk of HIV. You can have two resistant genes, then you are resistant to HIV. Please, this is very important. If you counsel this person, this does not mean that you do not need to have safe sex because there are many other diseases and these are just equally as deadly as hepatitis and so on. So, it is not meant to be interpreted as “Great, I do not have to be careful!”. What this test is used for is if a person has one genetic variation and one normal gene. They will build a defective receptor, which the virus cannot bind to, but they will also produce a normal receptor but less of it and the virus will be able to enter the cells. However, the risk of infection is lower and the progression of the disease is slower. This is really the most important question for a person who has a contracted HIV: »Do I have the normal speed of progression or maybe do I have a slowed rate of infection?«

This is what you can have. You can have the normal risk, HIV resistance or a lower risk and a slower progression. These are the three different outcomes. There is a very interesting story on HIV and I want to tell it. This is a real story of Tim who is German and he has white blood cells like every one of us. He was infected with HIV. So, the white blood cells were infected and they were producing more HIV viruses and releasing them and then they were infecting more cells. What we know from what I have told you is that he produces the CCRO5 receptor because he has normal CCRO5 genes. So, as if that was not enough, he was also unlucky enough to develop leukemia. Leukemia is a cancer of white blood cells, which begin to continuously reproduce and divide uncontrollably. This in itself is cancer and a deadly disease just like HIV. For leukemia, the solution is chemotherapy. Chemotherapy does the following. It kills off all of the cells that grow rapidly. This kills off the whole immune system and the whole bone marrow, the system that produces blood cells and all of the white blood cells. All white blood cells are destroyed and died.

What people do after chemotherapy is they look for donor who has a matching tissue type so that the immune system does not recognize it as being foreign. So, there are these donor banks of bone marrow donors. The doctors did something very smart. They knew about his HIV infection. They also knew about the effect of this genetic variation. What happens is that they first killed off the immune system and all of the bone marrows started to produce new white blood cells. Then, they gave him a bone marrow transplant of a person who had the right genetics. So, they were HIV resistant. This bone marrow then multiplied and recolonized the bones and produced new white blood cells that were resistant to HIV. This then led the person to be cured. Not only from leukemia but also from HIV. This is a very interesting and smart way of using knowledge about genetics to perform almost a miracle.

Another question is: why do not we do that with every HIV patient? Because around 10 % of chemotherapy patients die because of it. So, actually doing the chemotherapy is more dangerous than living with HIV with proper treatment. So, it is not the cure for every one yet. It might be in the future something like this, but this is how this one person was cured.

Section 3: Treatment

Now, if we look at treatment for HIV, it has gone a long way. If we consider a healthy person, they have a mean lifespan of around 80 years. You take an HIV-infected person who contracts the virus at the age of 20, what you would see is 10 years of latency. So, no symptoms arise. He might have some cold symptoms, clearly likely to contract a cold at the beginning but then it is usually 10 years of no symptoms. This is also when he can infect other people. Then, the first symptoms arise and acquired immune deficiency happens and AIDS develops. The immune system breaks down. Then, bacteria infect the body and all sorts of viruses are unchecked and so on. This then leads to premature death at the mean age of 33 years. So, when infected at the age of 20, you have another 13 years to live if you do not have treatment.

As I said, treatment is very effective if it is done correctly. So, you live for 20 years, you get the infection and with correct treatment, antiviruses and antibiotics, if ever there is an infection, you can live around 52 more years in latency and you might still develop it in the end and have a slightly shorter lifespan but it is almost as long as a healthy person. Treatment is really very important for HIV-infected people because it can give them an almost normal lifespan. Of course, treatment needs to be effective. So, compliance with treatment is very crucial. There is the concept of pharmacogenetics. If you do not know what that means, please do watch the pharmacogenetics training, which is about how drugs work and how they are metabolized by the body. I will quickly explain it again in this example. Different drugs are metabolized and are converted by different enzymes and then they are removed from the body.

There might be a drug, like drug B, that goes through a certain gene. However, this gene in this case is mutated. So, the drug is not broken down. However, this person might take this drug once every day. Every time he or she takes the drug, the level increases and increases again until it reaches a toxic level. So, these genetic variations can influence which drugs might be broken down slower, which means they need to be taken at lower dosages. They might also activate some drugs and not activate some others, the so called pro-drugs. Some people might just not get a benefit from a drug and other people just need a different dosage, more or less.

This is what we do here. Drugs for infections, antibiotics, anti viruses and so on. You get a list like this in the report. It tells you the effect is normal, so most of these drugs would work normal. Breakdown is normal. All of these drugs are broken down at the normal speed. It is about 100 % and the dosage you should have is about 100 %. However, it could also be 0%. Your recommended daily dosage is also 0 % and an alternative is recommended. Then, you should really use a different drug if the drug is not cleared from the body at all or it might be cleared at 50 % of its speed then you need 50% of the dose. That way you make sure you get the right levels in the blood. You get perfect treatment and you avoid drugs that would cause side effects or that would not work at all. This improves HIV treatment success. As I have shown, this is a very critical part.

Section 4: Prevention

Alright. Prevention or the counseling part. Again, this is a sheet of paper in the report, which explains it in a very simple language. Do read through it. What you need to make sure of when you counsel a person is do not tell them this is a carte blanche for unprotected sex. There are many other diseases that might be infecting a person with unprotected sex. If the person is HIV resistant, this does not mean that they should not be careful.

If you are heterozygote, meaning one of the genes has the variation and the other one does not, it is a lower risk and it is slower progression of the disease. It is also no crate blanche for unprotected sex. It is just less likely to happen and it is going to be slower. If you are normal, you have the normal risk of being infected with HIV. Then, there is treatment. The most important part is find out which drugs are broken down and which to beat, choose the right drugs and the right dosages to make sure that the person gets the right benefit from the HIV drugs and gets the best possible treatment.

This is the end of chapter 57, HIV resistance and genetics, a specific training for the HIV Resistance Sensor.

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