When scientists will win HIV October. Girl from South Africa managed to defeat HIV
Virus tanks in sleeping cells of the immune system - one of the reasons why there is no medicine from HIV By 2017, despite significant progress in the field of medicine and biomedical technologies, humanity has not yet invented the medicine from HIV . What are the difficulties? There are several difficult problems with the problems faced by scientists:
Virus tanks in sleeping cells of the immune system. Research recent years have shown that HIV may affect and stay not only in CD4. -Limphocytes, but also in other cells: macrophages, dendritic cells, astrocytes, as well as blood stem cells. The problem is that not all these cells are susceptible to used antiretroviral drugs, which means it is very difficult to achieve their complete destruction.
High mutating speed. Thus, the virus quickly adapts to drugs, producing stability to them. More about the features of the human immunodeficiency virus in a special article "HIV - a virus, about which is important to know."
Mechanisms helping to hide from the immune system. The immune system works on the principle of recognizing its own strangers. Therefore, to avoid destruction, the virus adapted to imitate the human cell proteins, which is invisible to human immunity. Moreover, HIV violates the normal connection between the cells of the immune system, which leads to failures in its work.
Official treatment of HIV infection today
Currently, the only method of treatment HIV -Infection is antiretroviral therapy. The principle of operation is to blocking various enzymes or virus receptors, with the help of HIV Exercises its livelihood. Officially, 28 drugs are approved in Russia. Depending on the fine mechanism of action, they are divided into several groups:
- Reverse transcriptase inhibitors;
- Protease inhibitors;
- Inhibitors integrase;
- Fusion inhibitors;
- CCR5 receptor antagonists.
Tablets are used one or various combinations daily throughout life. It would seem that, HIV The defeated, however, the problem of the stability of the virus to drugs is becoming more relevant and the question arises of the development of a fundamentally new approach to combat HIV.
Antiretroviral therapy allows you to block enzymes or virus receptors, with which it exercises life
New in the treatment of HIV
When the medicine appears from HIV ? Will a means that helps to avoid stage AIDS but? These questions are worried not one hundred people. As long as the scientific community is only small steps towards the answer. Activities of scientists in combating HIV affects several directions:
Development of new drugs against HIV.
Search for new forms of administration of antiretroviral drugs.
Use of auxiliary drugs.
Cell therapy.
New drugs against HIV
New in the treatment of HIV: Since 2010, 4 new molecules and 10 combinations of already created drugs have appeared. First medicine in the worldregistered to combat HIV , zidovudineappeared in 1987. Since then, almost every year it marks the opening of a new drug. For 2017 in the world for treatment HIV Officially resolved 42 drugs and their combinations. Since 2010, 4 new molecules and 10 combinations of already created preparations have appeared. Among them - Rilpiwarin, Doltegevir, Elviyegravir, Kobitsistat, and combinations - Tryumeks (Abacavir, Dolteghavir, Lamivudin), Evotez (Atazanavir, Kobitsistat), PRESKOBICS (Darunavir, Kobitsistat), Genvya (ElviTEGRAVIR, Cobitsistat, Emitcitabine, Tenofovir Alamifemid Fumarat), stribild (elvitegravir, kobitsistat, emtricitabine, tenofovir dizoproksida fumarate) odefsey (emtricitabine, rilpivirine, tenofovir alafenamida fumarate) komplera (emtricitabine, rilpivirine, tenofovir disoproxil fumarate) deskovay (emtricitabine, tenofovir alafenamida fumarate) Isentress, viramune.
However, all these drugs are variations of old molecules, the last time a new class of drugs was found decades ago..
The situation has changed the message that in 2017 the clinical trials of two groups of antiretroviral drugs with fundamentally different mechanisms of action are continued:
Inhibitors capsid. A drug - Ca1. located at the stage of research on animals violates the formation of the outer shell of the virusThereby preventing his reproduction. In 2018, it is planned to launch the first phase of the test drugs on a person.
Monoclonal antibodies. At the moment, two drugs are held by the last stages of tests on a person, so if we success, we can expect their appearance on the market in the next couple of years. Ibalizumab molecule binds to protein CD4. on the surface of human lymphocytes, thereby not giving the virus to penetrate the cells. This medicine showed its effectiveness for multiple drug resistance patients. HIV . Other molecule called Pro 140. Also causes a resistant suppression of the virus for a long time.
For 2017, 42 drugs and their combinations are officially resolved in the world for HIV treatment.
In addition to the development of molecules with new mechanisms of action, studies of antiretroviral molecules continue Earlier famous classes:
New forms of administration of antiretroviral drugs
Intramuscular injections of extended action. The long period of decay of medication in the body is achieved by using nanoparticles. In the development of new forms of introducing drugs Rillapivin, Kabotehravir, as well as their combination, Doltegravir, Raltetegravir.
Clear. The advantage of rectal enema is the delivery of a large dose of the drug in directly into the rectum. Therefore, such a form of administration is considered as prevention. HIV -Infection.
Transdermal, or percutaneous administration in the form of gels and plasters. The use of such a form of delivery was studied on the preparations of Zidovudine, Zalvitabine, Didanosin, Lamivudine, and also IQP-0410 . The last molecule is considered the most promising. All drugs are tested so far only in test tubes, animal tests and people were not produced.
Auxiliary drugs
Crispr. /CAS9 , Zfn. , Talens. , meganucleazase.
The essence of all listed techniques is that certain proteins find a given plot in the thread DNA And there is a strictly defined number of nucleotides, stitching then the resulting ends together. The techniques have already been tested on humans and showed good results. The procedure in the simplified version is as follows: patients withdrawn some of their own CD4. Cells are processed using listed enzymes, and then again introduced to the patient.
Vaccine against HIV
Vaccines counter HIV We are divided into familiar to us preventive, not allowing diseases in healthy individuals, and therapeutic, helping already infected to fight the virus and prevent AIDS but. Attempts to create a vaccine are taken from the 80s of the 20th century. Since no vaccine has been registered. However, the last five years has become rich in clinical trials of new vaccines:
In 2016, a large-scale vaccine test was started in Africa HIV In humans. This is the first for 7 years a clinical study called HVTN. 702, which has come down to the last stages. The vaccine is based on the molecule, which showed its effectiveness, albeit modest, in the tests of 2009 in Thailand. Vaccine test results are expected by 2020.
At the same time, passed to the first phase of clinical trials on the people of vaccine VRC01. , which is antibodies, similar to those naturally produced in the body. The results are planned to receive in 2022.
Vaccine AD26 In 2017, the first successful tests in humans took place. In the same year, it is planned to move to a more large-scale phase of studies, which will take at least three years.
Cases of cure from HIV: what is known at the moment
To date four cases of cure from human immunodeficiency virus:
Timothy Ray Brown won a complete victory over HIV Berlin patient. For 2017 this year the only confirmed event of full cure from HIV . Timothy Ray Brown fell HIV -Infection in 1995. He took antiretroviral drugs for 11 years, and the disease was teaching unagusably, until he had found leukemia in 2006. For her treatment, a bone marrow transplant was needed. Then, who observed Timothy hematologist, came to choose the stem cell donor with mutation in protein CCR5 protecting cells from immunodeficiency virus. Transplantation was successful, and after a while scientists confirmed the absence of a virus in the patient's body.
Group Visconti. . This group is ranked 20 people who have ceased to take therapy, but at the same time have already had low blood virus levels for at least eight years and not demonstrating any symptoms of the disease. All patients began antiretroviral therapy a few weeks after infection. That's why an early start of reception of drugs is considered the basic principle of treatment HIV -Infection.
Child from Mississippey. This girl until 2014 was considered the second person who won the victory over HIV . The child was born in 2010 from HIV - Positive mother. 30 hours after birth, the baby conducted a course of intensive antiretroviral therapy, after which, over three years, the concentration of the virus was indefinable. However, in 2014, the virus in the blood of the girl was again found.
Boston patients. These two men as well as the Berlin patient, passed the transplantation of bone marrow cells due to lymphoma. However, after some time after the abolition of antiretroviral therapy, the virus returned.
By 2017, scientists did not find a remedy for HIV . However, all over the world is a promising development of new means of combating it. In the meantime, it is not necessary to wait when the medicine inv HIV . Modern antiretroviral therapy allows you to control the disease for long years.
American scientists have developed antibodies that kill up to 99% of HIV strains and are able to destroy an infection at an early stage. Clinical tests of the substance are scheduled to begin in 2018.
As noted by the Development Automs of the US National Institute of Health and the Pharmaceutical Company Sanofi. The international community to combat HIV called the development of scientists by the "interesting breakthrough". Clinical tests of the substance are scheduled to begin in 2018.
In the US, they learned to win 99% of HIV strains. The new development of scientists combines three types of antibodies to a powerful substance of a triple action.
"They are more powerful and have a wider action than any separately taken natural antibody of those known today," said one of the authors of Research Gary Neubel.
As clarified, the most powerful natural antibodies are able to overcome up to 90% of HIV strains. "We have reached a coverage of 99%, and it is achieved at a very low concentration of the antibody," the nebel emphasized.
As a result of experiments on 24 monkeys, no animal has an infection after introducing HIV virus.
Recall that in the spring of the world community buzzed that scientists first managed to defeat HIV. In May, in the world media wrote that the new work relies on previous studies of the same team of scientists who were able to remove HIV from the genome of most tissues.
So, scientists from the medical school of the University of Temple and the University of Pittsburgh managed to fully cure animals from HIV using CRISPR generators.
As you know, HIV is very difficult to eradicate from the body because of its ability to hide in hidden reservoirs of the body, being "there" in sleeping condition. But now experts were able to completely remove HIV DNA from human cells implanted in the body of mice. It is noted that researchers for the first time in the world achieved complete elimination of HIV in animals, which makes the way to further clinical trials in humans.
New work relies on previous studies of the same team of scientists who were able to remove HIV from the genome of most tissues. A year later, experts were able to eliminate the virus from each tissue, confirming the results of previous tests and increasing the effectiveness of the gene editing strategy. Experts found that this strategy is effective in two cases - in the presence of acute infection and in the presence of chronic, or latent, infection. Just with the help of one use of the CRISPR / CAS9 genome editing technology, researchers managed to completely remove viral fragments from infected human cells embedded in tissues and mice organs.
The main advantage of the new drug is the absence of harmful influence on the human body. Today, patients with HIV can live dozens of years due to the reception of antiretroviral drugs - substances that suppress various stages of virus reproduction. However, due to strong side effects, patients have to periodically stop their reception for several weeks. This is the enemy and gets out of the trenches.
ON THIS TOPIC
Solve the problem was able to a group of molecular biologists from Yale. They carried out experiments not in real samples of cells and viruses, but on their virtual counterparts. Using computer models, scientists studied interaction with the virus known science of substances and drugs, swinging the most efficient. It was tested on mice.
"One dose of nanoparticles stoken by our" substance-1 "protected T-cells of mice from the mass death and kept the concentration of viral particles at a minimum level for three weeks." Substance-1 "is able to fight both conventional HIV clinical strains and With his "invulnerable" versions, "the researchers said to publish PNAS.
As the site wrote, Russia marked an increase in the number of ills of HIV by 43.4% (49.67 cases per 100 thousand population against mid-year-olds - 34.64). "In January-October 2017, in relation to the same period of 2016, the growth is insignificant - by 0.9% (49.67 per 100 thousand population versus 49.21)," said Rospotrebnadzor.
It is known that Russia ranks third in the world in the number of new cases of HIV infection. Ahead of our country in this indicator are South Africa and Nigeria. According to the executive director of UNAIDs Michel Sidibe, Russia needs an accelerated plan to combat this disease. He is confident that the country has everything to do this: scientific achievements, resources and a clear understanding of the nature of the epidemic.
Moscow, 14 Apr - RIA Novosti. Scientists have found in human DNA traces of a virus resembling HIV, with which our ancestors coped about 8 million years ago, the article published in the ELIFE magazine.
"Studying viral" fossils "can help us learn a lot about what happened in the distant past. For example, in this case we found out how viruses often give animals, which they infect, tools to fight them themselves, which often leads To extinct such viruses, "says Paul Bienias from Rockefeller University in New York (USA).
"Garbage" evolution
The human genome and actually all other animals and plants contain not only "their" genes and garbage DNA, but also fragments of various retroviruses, with whom our ancestors fought millions and tens of millions of years ago. Many of these viruses were so dangerous that they had time to destroy up to 99% of individuals before those managed to adapt to them and learn to neutralize pathogens.
Often the fragments of such viruses in the DNA of animals radically changed their appearance and evolution. For example, several years ago, scientists found out that retroviruses were "to blame" in the fact that mammals moved to the intrauterine tooling the cubs, and in the future they abandoned the bag and "invented" the placenta.
Traces of such viruses in the genome can be used to study the evolution of their carriers, since fragments of viral DNA gradually accumulate mutations, and their number gradually increases due to their ability to self-control. This is used by scientists, learning when our ancestors fought with some particular pathogen, have experienced sharp reductions in numbers or separated from related species.
Benyash and his colleagues opened another unusual example of how the viruses were "conducted" by the evolution of a person, comparing fragments of retroviruses discovered recently in human genomes, higher primates and various monkeys living in Africa.
Their attention was attracted by the Herv-T virus present in DNA of all monkeys and primates, which caused mass epidemics among our ancestors at least 25 million years ago. This pathogen, judging by the structure of its fragments, is completely "extinct" about 8-11 million years ago, the reason for which was a mystery for scientists.
Bay Virus His weapon
Comparing the structure of fragments of this virus in the genomes of people, monkeys and primates, Benjash and his colleagues were able to restore part of his genes and learn how he penetrated the body of the first dry monkeys, our common ancestors with modern primates of Africa.
As it turned out, he infected the cells, acting similarly to the immunodeficiency virus, clinging to a certain protein increase on their surface, MCT1, which the body uses for cleaning cells from lactic acid.
Analyzing the structure of the ENV gene, which is responsible for this function of the virus, scientists have come across an unexpected thing - this site has been preserved in the human genome almost in priority form, with extremely small changes. A similar picture was observed in all primates and monkeys, whose ancestors were dilated from the total tree of evolution with a person about 8 million years ago. March 23, 2016, 16:10
Biologists found a full-fledged ancient retrovirus in human DNAScientists believe that it can help find out what our ancestors were hurting, how could they defeat these viruses and how to use this knowledge to fight HIV and other modern retroviruses.After analyzing the differences in the structure of the original version of the ENV and its current "human" variation, scientists understood what happened to it. It turned out that the admiration body adapted the ENV to combat Herv-T using this gene to remove the MCT1 grows from the cell surface. Due to this, the virus simply cannot penetrate the cells, and they avoid infection.
"It seems that this gene got into the DNA of primates about 13-19 million years ago, and at about the same time its function was changed. The ancient monkeys were able to develop immunity to HERV-T, using its own genetic code," concludes Daniel Blanco-Melo (Daniel Blanco-Melo), Colleague Benyasha.
A girl from South Africa, born from HIV-infected mother, has been successfully successful for eight years without antiretroviral drugs. As LanCet magazine writes, such cases are extremely rare. Scientists carefully study them in order to detect the ways of complete disposal of infection.
Photo: Global Look Press / Caro / Eckelt
Over the past few years, doctors and virologists have encountered several cases when the patient's body suppressed HIV unusually or got rid of the virus forever or indefinitely long time. At the same time, viral particles still remained in the body of patients, but they were unable to multiply, or the virus sacked for several years. The case is known when a child from Mississippi lived for about five years before the emergence of repeated signs of infection.
Now a piggy bank of such rare cases has replenished a nine-year-old girl from South Africa, writes RIA "News". Scientists assume that its long-term resistance to the immunodeficiency virus was obtained by receiving the newest antiretroviral drugs in the juvenile age - the girl received drugs from the day of birth.
Avi Violary from Withersland University, speaking at the international AIDS community conference in Paris, stated that the reception of antiviral drugs at an early age helped the virus immunity to suppress the virus. Now you need to understand how this patient is different from the rest, the research has noted.
As Violary notes, the girl and her mother participated in a special program CHER, in which scientists have checked the popular idea of \u200b\u200bblocking HIV development. It is assumed that the reception of antiretroviral drugs at the first stages of the development of infection can give the body of the child time in order to adapt to HIV and begin to deal with it before the virus is exhausting the immune system.
As part of this program, children received large doses of antiretroviral drugs from the first month of life for 40 weeks. After that, the therapy was stopped and observed whether the infection will return. As time has shown, such an approach was quite successful, since early therapy slowed down the development of infection and presented with most children two years of life, when there was no need to take these drugs. In ten babies who participated in the experiment, the level of infection in the body remains extremely low to this day.
However, a nine-year-old girl who was able to completely get rid of the virus is the best proof of the effectiveness of antiretroviral therapy at an early age. According to scientists, the "early warning" strategy of infection works, in some cases it allows us to remove its development time for a very long time.
As Violary told, there are no full-fledged HIV particles in the blood of the girl, although the fragments of the virus are still present in the cells, but they do not multiply. Scientists hope that this virus is subsided forever and the girl do not have to return to reception of drugs, as mentioned above the child from Mississippi.
This case is advantageous to hope that in the future, doctors will be able or forever suppress HIV, or will make its development extremely slow.
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