Today, December 1, 2021, a new International AIDS Day is celebrated. It was in 1988 when the WHO proposed to decree this date. 33 years have passed and, until now, and despite the great efforts and resources invested, it has not been possible to find a vaccine to combat the disease.
On the contrary, in less than a year (and thanks to an unprecedented scientific, business and governmental mobilization), an immunogen has been obtained to deal with the dreaded SARS-CoV-2, the pathogen responsible for covid.
The HIV virus is much more complex than SARS-CoV-2 “
The question, in this sense, is obvious. What differentiates one virus from the other? Why does AIDS, after 40 years of its detection, still does not have a vaccine while the covid, months after it appeared, already had several immunogens on the market to combat it?
“They are completely different, the HIV virus is much more complex than SARS-CoV-2,” he explains to The vanguard Dr. Beatriz Mothe, Researcher at IrsiCaixa and the Foundation for the Fight against AIDS and Infectious Diseases at Germans Trias i Pujol Hospital.
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“In fact, the strategy that has been used for covid vaccines, which is to generate antibodies against the Spike protein, located on its surface, is what was done with the first candidate for an HIV vaccine, in the late 1980s. , but it failed ”, he adds.
With the covid, this researcher continues, everything has been “easier thanks to the prior knowledge of other coronaviruses, such as SARS or MERS”. Scientists knew that 90% of people who become infected with coronavirus resolve the infection spontaneously, generating antibodies against the Spike protein. “Therefore, developing a vaccine against this protein has been relatively easy,” says Mothe.
One of the main pitfalls of HIV is its great ability to mutate
However, with HIV the opposite is true. “99% of people who become infected do not control the virus spontaneously, and they generate antibodies that are useless. Therefore, we start from a totally different nature of the virus ”, points out this researcher.
One of the main pitfalls of HIV is its great variability. There is much talk about the variants that are appearing of SARS-CoV-2, but that ability to mutate is laughable compared to that of HIV.
It can be said that with HIV practically every infected individual has a different virus “
“This virus, in one person and in a single day, generates about 1,000 different mutations. We are practically talking about the fact that each infected individual has a different virus. That is why having a global vaccine is really very complex, the virus has a great facility to circumvent it ”.
There are more obstacles. SARS-CoV-2 attacks the cells of the respiratory system, causing pneumonia, while HIV infects the cells of the immune system, thereby weakening the patient. “It takes away our strength to fight him. What it does is exhaust us a lot in terms of immunity, ”says Mothe.
The problem with HIV is the viral reservoirs that it forms in the body, which remain latent “
“The problem with HIV is the viral reservoirs that it forms in the body, which remain latent,” says Ester Gea-Mallorquí, doctor in Virology and member of the Viral Immunology Unit at the University of Oxford. “We know that these reservoirs are created very quickly after infection, but we do not know how to eliminate them.”
When you want to find a vaccine – Gea-Mallorquí relates – what you try is to identify a target against a common area of the virus. The problem arises when it constantly mutates, something that greatly complicates the development of an effective immunogen.
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“It is very important to know in any disease what we call protection correlation, that is, what part of the immune system provides protection and helps to resolve the infection. But this is something we do not know about HIV ”, adds this virologist from the University of Oxford.
There are only 1% to 5% of people living with HIV who progress slowly to the disease (so-called Long-term non-progressors) and that they can maintain stable CD4 cell levels without the need for antiretroviral therapy, and between 0.35% and 0.8% of those infected who are able to control the infection and maintain a very low viral load (they are known What Elite Controllers).
In recent years, scientists have focused part of their attention on them in order to find a working vaccine. “We know a lot about these people who make up this group of controllers, but we still have many others to learn,” Gea-Mallorquí emphasizes.
Only about 1% of those infected with HIV are able to control the virus on their own
In 1983, HIV-1 (responsible for the global pandemic) was isolated for the first time, but three years later (1986) HIV-2 was isolated, a virus that also progresses to AIDS, although much more slowly. and that it is endemic, although it shares genetic structure and viral cycle with HIV-1.
While in the latter, only approximately 1% of those affected are capable of controlling the virus themselves, in HIV-2 this percentage rises to 37%. That is why “studying HIV-2 can be of great interest to understand the control mechanisms and see if they can be applied to HIV-1,” explains Gea-Mallorquí.
Retroviral treatment can be given preventively to people with high-risk sexual behaviors
Until a vaccine arrives, retrovirals are the best tool to fight HIV. Thanks to them, a diagnosed person can have a life expectancy identical to that of a healthy individual. “At the tolerance level they are excellent. When you make a combination of two or three fourth drugs in such a way to the virus that it cannot generate resistance. They are doing very well, ”says Beatriz Mothe.
This retroviral treatment can be given preventively to people with high-risk sexual behaviors. “It has been very effective in preventing infection,” recalls Mothe. The person treated also does not transmit the virus. “You can have sex without a condom and it won’t be contagious. In the case of a woman, she can become pregnant without risk of transmitting the virus to the fetus. It is something very important to combat stigma, because the person treated can have a completely normal life ”, adds the IrsiCaixa researcher.
Diagnosing all those infected, one of the challenges
Beyond finding an effective immunogen, many challenges remain. Among these, diagnose all those infected. Up to ¼ of them are living with HIV without knowing it, “and they are people who are transmitting the virus,” recalls Mothe. “Another great challenge is late diagnosis. Between 30% and 40% of new diagnoses are still in the late phase, when the disease is more advanced. This makes them have a worse prognosis because they recover worse immunologically. This is where a small reduction in life expectancy is associated ”, adds this doctor.
There is also accessibility to treatment. In the first world it is not a problem, but in many poor countries there are still 20% of people who cannot access it.
Retrovirals versus vaccine
Although retrovirals work very well, they have nothing to do with a vaccine. A retroviral is a drug that does not kill the virus, but rather prevents it from replicating. “The vaccine, on the other hand, is intended to generate an immune response through antibodies and T cells, which (the antibodies) will do is prevent us from getting infected, and in the case of infecting us, the T cells would be able to eliminate the infected cells” , explains Mothe.
“Retroviral treatment is like insulin for a diabetic,” says this researcher. It does not cure the disease, what it does is keep the virus at bay. By the time the retroviral treatment is stopped, it is a matter of days before the virus reappears in the blood and begins to replicate again in a dizzying manner. “You can be in treatment for 10 years, with the virus under control, but a week without medication is enough for you to have the same amount of virus as 10 years ago. You don’t even weaken it, ”Mothe adds.
Retroviral treatment is like insulin for a diabetic “
The appearance of retrovirals was a complete revolution, making patients stop dying. With the emergence of HIV, patients perished from opportunistic diseases due to their very weakened immune systems. But with retrovirals this progression was cut off. “The former were very toxic, although they helped save many lives. However, in the late 1990s, a combination therapy with three drugs began to be administered to patients, and that is when mortality began to be drastically reduced, ”recalls Mothe.
Unlike SARS-CoV-2, HIV integrates into genetic material and becomes dormant in cells that are in a latent state and cannot be detected by the immune system because externally they are exactly the same as uninfected cells.
In the world
700,000 deaths a year still
For about five years, scientists have been working on strategies, which are called shock and kill, which aim to bring out these cells that go unnoticed. “We are trying to identify which cells are the reservoir of HIV so that they express the virus and thus the immune system is able to detect and kill them,” explains Ester Gea-Mallorquí.
“What we know now is that the earlier retroviral therapy is given, the more likely there is a period of virus control [sin tomar los fármacos]. But after a time without the medication, the virus resurfaces again ”, he adds.
The 700,000 people who still die a year in the world from AIDS are mostly untreated patients. “Usually they are people who have not had access to treatment or who have been diagnosed very late with an already very deteriorated immune system”, concludes Beatriz Mothe.
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