What kind of disease: acquired immunodeficiency syndrome
We are starting a new series of texts: this time we will talk about complex diseases, many of which remain a mystery to scientists. In the first issue, acquired immunodeficiency syndrome and the human immunodeficiency virus that causes it.
This is a small virus that is transmitted through physiological fluids - blood, breast milk, semen and vaginal secretions. The virus cannot exist outside of a living organism; therefore, it is not transmitted through saliva, water, food, or ordinary household contacts. Unlike malaria and dengue fever, the virus is not transmitted by mosquitoes and other insects. In the saliva and gastric juice contains enzymes that destroy the virions (virus particles that exist outside a living organism). Therefore, the risk of being infected with the human immunodeficiency virus (HIV) through saliva is practically nil, except in cases of breastfeeding, when the infant has not yet formed such enzymatic protection.
HIV enters the human body, using CD4 receptors and the CCR5 co-receptor, attaches to T-lymphocytes, penetrates the membrane and infects T-cells, the main agents of immunity. From the point of view of the evolution of the virus, this is a very reasonable move - imagine that the head of the mafia clan is hiding from the police in the police station, where no one pays attention to it. In addition, there he regularly removes his identikit from the “Wanted” board and outweighs him on the board of honor. Gradually, he poach police officers to his side - and destroys law enforcement from the inside.
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Under the influence of the virus, the number of cells in the immune system decreases over time. When the number of T-helpers reaches a critical minimum (less than 200 / μL), the patient’s HIV status is replaced by the diagnosis of AIDS.
AIDS is an irreversible disease in which the patient becomes extremely vulnerable to pathogens. Now the body is almost completely lack of protection, and even a small bacterial infection, with which he had previously easily coped, can be the cause of death. It is not the virus itself, but opportunistic infections, which manifest themselves only against the background of other diseases, and cause the death of AIDS patients. These include tuberculosis, bacterial and fungal infections, Kaposi's sarcoma.
AIDS and related diseases take the lives of approximately 1.1 million people annually.
Human immunodeficiency virus refers to infections that have been carried from animals to humans (for example, H1N1 flu, malaria, West Nile fever). HIV is a mutated version of the monkey's immunodeficiency virus (Simian immunodeficiency virus) - a retrovirus that is safe for monkeys and appears to have been prevalent among the population for more than 32 thousand years. Transition of the virus occurred as a result of human contact with monkeys - primarily during the hunt for them of the African population.
There are two types of virus: HIV-1 and HIV-2. The first virus mutates much faster and is responsible for the majority of HIV infections. The second virus causes a similar disease, but decreases immunity more slowly and is worse transmitted. HIV-1 was transferred from chimpanzees and gorillas, HIV-2 from mangobey monkeys.
The virus was first diagnosed in 1981 in the United States, but a person has been infected before — and it appears to have happened several times.
Prior to that, it remained in small local settlements, but in the 20th century, thanks to globalization, it went beyond the African continent and spread throughout the world. In the Soviet Union, the first case of infection is dated 1987.
Radical treatment of HIV does not currently exist. HIV-positive patients are receiving antiretroviral therapy. It consists of several drugs that prevent the spread of the virus and the death of T cells and for decades inhibit the progress of the disease. In patients taking antiretroviral therapy, there is almost zero risk of transmitting the virus, and with certain precautions, they can even give birth to an HIV-negative child.
Typically, therapy consists of 3-4 drugs, each of which acts independently. One blocks the receptors and prevents the virus from infecting new cells (which does not affect those cells into which the virus has already penetrated). The second one prevents reverse transcription (when a double-stranded DNA molecule is restored along one strand of RNA) and thus prevents the virus from inserting its DNA into the human genome. Then this viral DNA must be delivered to the cell nucleus, so that it can be copied during each division - there are drugs that stop this process.
While complex therapy has shown its effectiveness, doctors and pharmacists continue to develop complexes that will be no less effective, but will consist of a smaller number of drugs.
Therapy significantly improved the quality and life expectancy of HIV-positive patients. By 2015, half of the patients had a lifespan of 50 years or more. But this leads to new problems: with age, chances are higher to meet with chronic diseases, which HIV-positive patients are obviously more difficult to resist. The main threat is a lung disease - chronic obstructive pulmonary disease (COPD), bacterial pneumonia, asthma. These diseases occur in 16-20% of HIV-infected patients. Their treatment also requires caution.
Antiretroviral therapy has several drawbacks. First, drugs that potentially affect DNA transcription have strong side effects: bone marrow suppression, liver cirrhosis, pancreatitis, and other diseases.
Secondly, medications must be taken regularly at a fixed time. Skips cannot be filled with a double dose of medication, and they significantly reduce the effectiveness of treatment. Now scientists are developing a formula for integrated ART, which could be used once a day.
Third, antiretroviral therapy is very expensive. In 2014, the cost of the annual course of treatment in Russia was 65–150 thousand rubles. The state assumes these costs, but there are often not enough medicines, and patients have to buy them themselves. Low-income patients cannot afford them. According to data for 2015, there are approximately 34–39 million people with HIV-positive status. Only half of them receive ART.
Although the virus binds to cells with CD4 receptors, the CCR5 co-receptor and the gene of the same name play an important role. CCR5 encodes a chemokine receptor protein, which plays an important role in the immune system. Gene deletion (absence of a DNA region) makes it impossible for HIV to attach to a T-cell. People with the CCR5 Δ32 gene variant cannot get HIV. In total, about 1-2% of the population has homozygotes with such a symptom, about 18-20% more heterozygotes, but this second option does not provide complete protection, but only reduces the risk of infection. The percentage of CCR5 Δ32 mutations in the European population is higher: presumably, it also reduced the risk of infection by bubonic plague, and therefore gave an evolutionary advantage to its carriers during the plague epidemic in Europe in 1347.
The antiretroviral properties of the CCR5 gene were discovered in 2003 and became a target for the development of drugs and vaccines against HIV. With the advent of the genome editing technology CRISPR-Cas9 , the first experiments were carried out to remove the virus from the infected organism. CRISPR-Cas9 is currently the most promising technology to fight HIV.
Until a vaccine against the virus has been developed, the only way to reduce the risk of infection is to use barrier methods of contraception, sterile needles and syringes if injections are necessary. “Loyalty to one partner”, which is mentioned in Russian social advertising, does not guarantee protection: according to statistics, about 40% of carriers of the virus are not aware of their positive status, and the spread of the virus has long gone beyond the criminal groups.
HIV prevention among drug addicts is familiar from the 90s free syringes or a more modern solution - special rooms for injections. Small rooms where drug addicts are given a sterile injection kit, and sometimes food and clean clothes, appeared in the Netherlands at the end of the 70s. In Russia, the project has not received distribution.
Male circumcision reduces the risk of contracting both HIV and other sexually transmitted diseases. Other means of prevention are being developed - vaccines, special condoms for protection during sexual intercourse, postcoital agents that will reduce the risk of infection after dangerous contact.
Ironically, prevention methods and social advertising, built on intimidation and shaming, can and does work effectively, but it creates another problem - the stigmatization of HIV-positive patients in society. Many still consider HIV / AIDS a disease of homosexuals, prostitutes, and heroin addicts, but these data are long outdated. And now the spread of the virus has reached such a level that anyone can become infected.
The virus is not transmitted through everyday contact, through airborne droplets, or even through saliva - and there is no practical sense in ostracizing HIV-positive patients. On the contrary, an adequate attitude towards HIV-positive patients helps to spread information about the need for regular examination and treatment.
The nature of the virus, the fact that it may not show itself for quite a long time, as well as costly therapy and the lack of hope for a complete cure, gave rise to the so-called HIV dissidence. “Positive” patients begin to doubt the real nature of the virus, consider it an invention of doctors for the sake of profit, refuse to accept therapy, spread such ideas among other patients.
HIV dissidents are an active carrier of infection: by refusing antiretroviral therapy, they keep the virus active and transmit it to partners. Often, HIV-positive children, who then remain without treatment, become victims of parents' dissidence.
At the end of this unfortunate text, we will tell you a good story about a man named Tim. In 1995, he was diagnosed with HIV-positive status. Tim was horrified by his new diagnosis: at that time there were far more examples of death with such a diagnosis than effective treatment, and antiretroviral therapy was only part of the clinical practice. Be that as it may, Tim began taking medications, and lived with his status for the next ten years.
In 2005, he was diagnosed with leukemia, which for an HIV-positive patient was almost equivalent to a death sentence. After two courses of chemotherapy, he went into remission, but the disease returned within a year. Needed bone marrow transplantation. Began the search for a donor.
Fortunately, Tim got a good doctor who read the scientific literature. In a medical journal, he came across the results of a study that certain variants of the CCR5 gene give carriers resistance to HIV. At that time, nothing was yet known about the CRISPR-Cas9 genome editing technology, and the doctor decided to simply find a donor with the CCR5 Δ32 mutation. And he found and performed a transplant, as a result of which Tim was cured of two diseases at once.
So Timothy Ray Brown, known as the “Berlin patient”, became the first person to be healed from HIV infection.
AIDS virus
This is a small virus that is transmitted through physiological fluids - blood, breast milk, semen and vaginal secretions. The virus cannot exist outside of a living organism; therefore, it is not transmitted through saliva, water, food, or ordinary household contacts. Unlike malaria and dengue fever, the virus is not transmitted by mosquitoes and other insects. In the saliva and gastric juice contains enzymes that destroy the virions (virus particles that exist outside a living organism). Therefore, the risk of being infected with the human immunodeficiency virus (HIV) through saliva is practically nil, except in cases of breastfeeding, when the infant has not yet formed such enzymatic protection.
HIV enters the human body, using CD4 receptors and the CCR5 co-receptor, attaches to T-lymphocytes, penetrates the membrane and infects T-cells, the main agents of immunity. From the point of view of the evolution of the virus, this is a very reasonable move - imagine that the head of the mafia clan is hiding from the police in the police station, where no one pays attention to it. In addition, there he regularly removes his identikit from the “Wanted” board and outweighs him on the board of honor. Gradually, he poach police officers to his side - and destroys law enforcement from the inside.
')
Under the influence of the virus, the number of cells in the immune system decreases over time. When the number of T-helpers reaches a critical minimum (less than 200 / μL), the patient’s HIV status is replaced by the diagnosis of AIDS.
Acquired Immunodeficiency Syndrome
AIDS is an irreversible disease in which the patient becomes extremely vulnerable to pathogens. Now the body is almost completely lack of protection, and even a small bacterial infection, with which he had previously easily coped, can be the cause of death. It is not the virus itself, but opportunistic infections, which manifest themselves only against the background of other diseases, and cause the death of AIDS patients. These include tuberculosis, bacterial and fungal infections, Kaposi's sarcoma.
AIDS and related diseases take the lives of approximately 1.1 million people annually.
Virus spread
Human immunodeficiency virus refers to infections that have been carried from animals to humans (for example, H1N1 flu, malaria, West Nile fever). HIV is a mutated version of the monkey's immunodeficiency virus (Simian immunodeficiency virus) - a retrovirus that is safe for monkeys and appears to have been prevalent among the population for more than 32 thousand years. Transition of the virus occurred as a result of human contact with monkeys - primarily during the hunt for them of the African population.
There are two types of virus: HIV-1 and HIV-2. The first virus mutates much faster and is responsible for the majority of HIV infections. The second virus causes a similar disease, but decreases immunity more slowly and is worse transmitted. HIV-1 was transferred from chimpanzees and gorillas, HIV-2 from mangobey monkeys.
The virus was first diagnosed in 1981 in the United States, but a person has been infected before — and it appears to have happened several times.
Prior to that, it remained in small local settlements, but in the 20th century, thanks to globalization, it went beyond the African continent and spread throughout the world. In the Soviet Union, the first case of infection is dated 1987.
Antiretroviral Therapy (ART)
Radical treatment of HIV does not currently exist. HIV-positive patients are receiving antiretroviral therapy. It consists of several drugs that prevent the spread of the virus and the death of T cells and for decades inhibit the progress of the disease. In patients taking antiretroviral therapy, there is almost zero risk of transmitting the virus, and with certain precautions, they can even give birth to an HIV-negative child.
Typically, therapy consists of 3-4 drugs, each of which acts independently. One blocks the receptors and prevents the virus from infecting new cells (which does not affect those cells into which the virus has already penetrated). The second one prevents reverse transcription (when a double-stranded DNA molecule is restored along one strand of RNA) and thus prevents the virus from inserting its DNA into the human genome. Then this viral DNA must be delivered to the cell nucleus, so that it can be copied during each division - there are drugs that stop this process.
While complex therapy has shown its effectiveness, doctors and pharmacists continue to develop complexes that will be no less effective, but will consist of a smaller number of drugs.
Therapy significantly improved the quality and life expectancy of HIV-positive patients. By 2015, half of the patients had a lifespan of 50 years or more. But this leads to new problems: with age, chances are higher to meet with chronic diseases, which HIV-positive patients are obviously more difficult to resist. The main threat is a lung disease - chronic obstructive pulmonary disease (COPD), bacterial pneumonia, asthma. These diseases occur in 16-20% of HIV-infected patients. Their treatment also requires caution.
Antiretroviral therapy has several drawbacks. First, drugs that potentially affect DNA transcription have strong side effects: bone marrow suppression, liver cirrhosis, pancreatitis, and other diseases.
Secondly, medications must be taken regularly at a fixed time. Skips cannot be filled with a double dose of medication, and they significantly reduce the effectiveness of treatment. Now scientists are developing a formula for integrated ART, which could be used once a day.
Third, antiretroviral therapy is very expensive. In 2014, the cost of the annual course of treatment in Russia was 65–150 thousand rubles. The state assumes these costs, but there are often not enough medicines, and patients have to buy them themselves. Low-income patients cannot afford them. According to data for 2015, there are approximately 34–39 million people with HIV-positive status. Only half of them receive ART.
Genetic protection
Although the virus binds to cells with CD4 receptors, the CCR5 co-receptor and the gene of the same name play an important role. CCR5 encodes a chemokine receptor protein, which plays an important role in the immune system. Gene deletion (absence of a DNA region) makes it impossible for HIV to attach to a T-cell. People with the CCR5 Δ32 gene variant cannot get HIV. In total, about 1-2% of the population has homozygotes with such a symptom, about 18-20% more heterozygotes, but this second option does not provide complete protection, but only reduces the risk of infection. The percentage of CCR5 Δ32 mutations in the European population is higher: presumably, it also reduced the risk of infection by bubonic plague, and therefore gave an evolutionary advantage to its carriers during the plague epidemic in Europe in 1347.
The antiretroviral properties of the CCR5 gene were discovered in 2003 and became a target for the development of drugs and vaccines against HIV. With the advent of the genome editing technology CRISPR-Cas9 , the first experiments were carried out to remove the virus from the infected organism. CRISPR-Cas9 is currently the most promising technology to fight HIV.
Prevention
Until a vaccine against the virus has been developed, the only way to reduce the risk of infection is to use barrier methods of contraception, sterile needles and syringes if injections are necessary. “Loyalty to one partner”, which is mentioned in Russian social advertising, does not guarantee protection: according to statistics, about 40% of carriers of the virus are not aware of their positive status, and the spread of the virus has long gone beyond the criminal groups.
HIV prevention among drug addicts is familiar from the 90s free syringes or a more modern solution - special rooms for injections. Small rooms where drug addicts are given a sterile injection kit, and sometimes food and clean clothes, appeared in the Netherlands at the end of the 70s. In Russia, the project has not received distribution.
Male circumcision reduces the risk of contracting both HIV and other sexually transmitted diseases. Other means of prevention are being developed - vaccines, special condoms for protection during sexual intercourse, postcoital agents that will reduce the risk of infection after dangerous contact.
Stigmatization
Ironically, prevention methods and social advertising, built on intimidation and shaming, can and does work effectively, but it creates another problem - the stigmatization of HIV-positive patients in society. Many still consider HIV / AIDS a disease of homosexuals, prostitutes, and heroin addicts, but these data are long outdated. And now the spread of the virus has reached such a level that anyone can become infected.
The virus is not transmitted through everyday contact, through airborne droplets, or even through saliva - and there is no practical sense in ostracizing HIV-positive patients. On the contrary, an adequate attitude towards HIV-positive patients helps to spread information about the need for regular examination and treatment.
Hiv dissidence
The nature of the virus, the fact that it may not show itself for quite a long time, as well as costly therapy and the lack of hope for a complete cure, gave rise to the so-called HIV dissidence. “Positive” patients begin to doubt the real nature of the virus, consider it an invention of doctors for the sake of profit, refuse to accept therapy, spread such ideas among other patients.
HIV dissidents are an active carrier of infection: by refusing antiretroviral therapy, they keep the virus active and transmit it to partners. Often, HIV-positive children, who then remain without treatment, become victims of parents' dissidence.
At the end of this unfortunate text, we will tell you a good story about a man named Tim. In 1995, he was diagnosed with HIV-positive status. Tim was horrified by his new diagnosis: at that time there were far more examples of death with such a diagnosis than effective treatment, and antiretroviral therapy was only part of the clinical practice. Be that as it may, Tim began taking medications, and lived with his status for the next ten years.
In 2005, he was diagnosed with leukemia, which for an HIV-positive patient was almost equivalent to a death sentence. After two courses of chemotherapy, he went into remission, but the disease returned within a year. Needed bone marrow transplantation. Began the search for a donor.
Fortunately, Tim got a good doctor who read the scientific literature. In a medical journal, he came across the results of a study that certain variants of the CCR5 gene give carriers resistance to HIV. At that time, nothing was yet known about the CRISPR-Cas9 genome editing technology, and the doctor decided to simply find a donor with the CCR5 Δ32 mutation. And he found and performed a transplant, as a result of which Tim was cured of two diseases at once.
So Timothy Ray Brown, known as the “Berlin patient”, became the first person to be healed from HIV infection.
Source: https://habr.com/ru/post/399709/
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