When will we finally defeat HIV?

When someone is wrong on the Internet

Corpus Publishing house has published a book by popular science journalist Asi Kazantseva "Someone is wrong on the Internet!".

The author continues to struggle with pseudoscientific myths and talks about whether vaccinations can cause autism, whether serious diseases are treated with homeopathy, whether GMOs are dangerous, and much more. Forbes publishes one of the chapters of the new book:
"When will we finally defeat HIV?"

It's not clear yet. Hardly in the next 10 years. But there is progress.

There are a lot of promising approaches. New antiretroviral therapy regimens focused on intensive treatment of the disease shortly after infection are being investigated – there is fragmentary evidence that, perhaps, in some cases, this allows suppressing the infection before it has invaded the body. A search is underway for drugs that could stimulate (!) the synthesis of new viral particles: when the DNA of the virus is embedded in the genome and is inactive, this reservoir of infection is almost impossible to detect, but the immune system fights with cells that intensively produce the virus. The first trials of gene therapy have already been conducted – several people were injected with their own CD4+ lymphocytes with an altered CCR5 coreceptor (the principle is the same as that of the Berlin patient, only without bone marrow transplantation), and the results were quite encouraging; at least, such cells normally survive in the bloodstream and are not susceptible to HIV infection. Another possible approach is to search for good, successful variants of antibodies against the virus with their subsequent administration to patients. And the most interesting story, although still far from clinical practice, is the application of a new method of gene editing, CRISPR/Cas9 (I'll talk about it in the chapter about GMOs), in order to just take and cut out viral DNA from the human genome. It has already been shown that this can actually be done in cell culture. It remains only to figure out how to do the same with a real patient.

The latest fashionable topic that is commonly talked about in connection with HIV is the prospects for creating a vaccine. Frankly, the prospects are vague. The universal principle of vaccination – "introduce a weakened pathogen or its fragments" – does not work well here. The pathogen cannot be injected at all, it is too dangerous. The body may develop antibodies to its fragments (and even then not all vaccines allow achieving such a result), but these will be antibodies only to the specific type of virus that was used to create the vaccine. As soon as a person encounters some other strain, he is vulnerable again. It's a similar story with the flu, against which we have to create a new vaccine every year. But HIV is even more diverse than the flu, and, fortunately, it does not occur so often that an attempt to develop (and inject every person!) vaccines against all existing strains turned out to be cost-effective.

We have to come up with more cunning approaches. For example, three vaccines are currently being developed in Russia. The Moscow Institute of Immunology has made a "Vichrepol" containing the most conservative, rarely changing HIV proteins (obtained by genetic engineering methods). The St. Petersburg Biomedical Center has a vaccine "DNA-4" – four HIV genes in one plasmid. Proteins are built according to genes in human cells, antibodies are formed to proteins, and an immune response is obtained. The vaccine created at the Novosibirsk State Center of Virology and Immunology "Vector" is called "Kombivichvak". It contains a complex and beautiful artificial protein TBI, which includes fragments of HIV antigens, spatially oriented in such a way that it is convenient for B-lymphocytes and T-lymphocytes to get acquainted with them. But none of these drugs has yet passed clinical trials of the second and third stages, which would allow evaluating the effectiveness. And it is at this moment that all hopes are usually destroyed. Sometimes it turns out that a new vaccine, the developers of which threatened to save humanity, not only does not reduce, but increases the risk of infection.

Testing the effectiveness of an HIV vaccine is a separate problem.

It is necessary to recruit a very large group of healthy people, half to introduce a vaccine, half to introduce a placebo, and then wait for several years to see which of them will become infected with HIV and who will not. People, in general, are rather frivolous creatures, they do not like to use condoms, and in any sufficiently large group that is monitored for a long time, there will definitely be infected. It remains only to compare how many infected people are in the group that received the vaccine, and how many are in the group that received the placebo.

The most successful HIV vaccine to date reduces the likelihood of infection by a third. This is better than nothing, but, alas, it is still not enough to launch mass vaccination. It is based on the repeated administration of two drugs. One of them is a viral vector that delivers three HIV genes to cells. The second is the viral glycoprotein gp120, created with the help of genetic engineering (a mushroom cap, if you still remember my attempts to describe the life cycle of the virus with the involvement of artistic images). 16,000 people took part in the tests. Half of them received injections of the real drug, half received a placebo. During three and a half years of observation, 56 people in the group who received the real vaccine and 76 people in the group who were administered a placebo became infected with HIV. There was no difference in the number of viral particles in the blood of those who were infected in the groups with the real vaccine and with placebo.

It is absolutely not necessary to conclude from this that the development of a vaccine against HIV is a hopeless matter. Researchers are actively working, the mechanisms of the immune response are becoming more and more clear, many parallel directions are developing, all of them contribute to the knowledge bank. Perhaps there will not be a sharp breakthrough in the development of an HIV vaccine in the coming years, but the effectiveness of drugs will become higher and sooner or later will reach a level at which vaccination already becomes meaningful. Just now, at the moment when I had already finished the chapter on HIV (on a rather pessimistic note) and was describing in the fourth chapter the impact of acupuncture on my work biography, scientific journalist Alexey Torgashev drew my attention (and the attention of the public) to three recent articles on how to vaccinate people in this way (more precisely, while animals), so that they produce broad-spectrum antibodies capable of neutralizing a large number of virus strains.

Here we need to remember again how antibodies are produced – I wrote about this in the chapter about vaccinations. At first, the B-lymphocyte binds to the antigen by accident, simply because its receptor has more or less come up. Then, after receiving a permissive signal from the T-lymphocyte, the B-lymphocyte begins to multiply and mutate at the same time, so that different variants of antibodies are obtained, among which it will be possible to choose the most suitable. And in order to get not just any antibodies to HIV at all, but antibodies of a certain structure directed at a specific fragment of the virus, many, many specific mutations must occur, and all in a certain, predetermined direction. That is, it is necessary to first introduce the first antigen in order, in principle, to provoke a series of mutations in the B-lymphocytes that recognized it. Then introduce a second antigen, so that among this new population of B-lymphocytes there is someone who binds to it - and also began to mutate in order to bind even better. Then introduce another antigen to select suitable B-lymphocytes for selection among these mutants of the third generation. And so on until exactly such antibodies appear that can effectively protect the patient from HIV.

With conventional vaccination, different people get different antibodies. Some catch the virus, conditionally, by the heel, others by the coat tails, and others by the ring finger.

And here it is necessary that the antibodies in all patients are formed in such a way as to catch the virus specifically for the third button of the shirt.

At the same time, if you enter only the buttons from the shirt at once, then the immune system is highly likely to ignore them, they do not look very much like a big dangerous criminal. It is necessary to introduce a shirt first, and then encourage those who contacted it with buttons, and then those who are with the third button. It sounds silly, but there is an illusion of understanding (at least for me). It is becoming clear that terribly complex and beautiful approaches are being used in the fight against HIV, so most likely we will wait for the final victory of humanity over the virus. In the meantime, it is necessary not to be afraid of HIV-infected people, not to think that they will die immediately or will not be able to work, to be friends with them calmly. When friendship comes to sex, use condoms. As, in fact, with any new partner.

Portal "Eternal youth" http://vechnayamolodost.ru 16.02.2015