The human immunodeficiency virus is almost defeated. But in virology, an incomplete victory is a defeat.
A four-year-old girl in Jackson, Mississippi, also known as the Mississippi baby, was believed to be one of only two people completely cured of HIV. In July 2014, after 27 months of remission, the virus reappeared in her blood.
Onset of HIV: monkeys, ulcers, syringes?
The sad history of the human immunodeficiency virus began around the middle of the 20th century in Central or West Africa. HIV is derived from the monkey immunodeficiency virus (SIV). The monkey virus itself can infect a person, but immunity usually easily copes with it: the virus can no longer be transmitted from person to person. At some point, VIO mutated, adapted to transmission between people and became incurable. How did VIO get to a person? Most likely, hunters of wild animals were the primary carriers of the simian virus. They become infected through wounds or bites from monkeys - there are still many carriers of SIV among African Bushmen.
But the emergence of HIV cannot be explained simply by the spontaneous mutation of SIV. Monkey hunting is not a new practice: African tribes have been practicing it for centuries. But it wasn't until the 20th century that the monkey virus became human. Moreover, this has happened several times over the past century. Scientists from the University of Alabama analyzed the history of the spread of HIV and compared it with molecular data on the genes of different strains of the virus. Researchers led by Beatrice H. Hahn concluded that the transformation of SIV into HIV was not an isolated event, but occurred at least several times.
How, then, is it to be explained that in the entire human history, HIV appeared only in the 20th century?
There are several versions. One by one, it's all about the urbanization of African countries. In the Congo and Cameroon, new cities arose by the hands of European colonists, but the standard of living in them was catastrophically low. The population became denser, but the first result of moving to cities was not the development of industry and trade, but unsanitary conditions and promiscuous sex. As a result, genital infections spread widely - including genital ulcers.
Normally, HIV has a fairly low infectiousness during heterosexual contact. But this figure rises sharply in the presence of concomitant infections and especially with genital ulcers. Perhaps this is what allowed HIV to get stronger and spread. According to another version, the HIV epidemic owes its origin not only to African unsanitary conditions, but also to European medicine. The twentieth century is called the "age of injections." The widespread use of intravenous drugs and vaccines, combined with poor hygiene, according to the American epidemiologist Ernest Drucker, could be the main reason for the large-scale transmission of the virus from person to person.
Plague of the XX century
Some of the HIV strains still exist only in Africa. But the most infectious of the virus variants managed to spread beyond the Black Continent and by the 1960s had reached the developed countries. In those days, nothing was known about the causes of the disease, later called AIDS. Only after 1983, when HIV itself was discovered, doctors and biologists began to try to reconstruct the sequence of events. In the twenty years leading up to this, a fatal disease affecting the immune system remained a mystery.
From a social point of view, the situation was complicated by the fact that the disease affected what seemed to be extremely marginal population groups at that time: first of all, homosexual men, drug addicts, in the USA - black immigrants from Haiti, from where the virus is believed to have got to America.For a long time in the public consciousness, the existence of AIDS allegedly legitimized all sorts of forms of homophobia, racism and class hatred. The censure and discrimination of AIDS patients, supported by religious groups, became extremely widespread - just like in medieval Europe, where Jews were regularly blamed for the plague - the Black Death.
But soon there was no time for religious debate. In the 1980s, the problem of HIV / AIDS arose for real, and talk about the "plague of the 20th century" began to gradually lose its metaphorical connotation.
AIDS - a global conspiracy? Over the decades, when scientific advances allowed AIDS patients to live almost normal lives on the condition of an ongoing medical diet, another group of accusations gained popularity. This time, pharmaceutical companies, "world governments" or other alleged beneficiaries of the AIDS epidemic were blamed for the disease. Some supporters of such conspiracy theories consider the link between HIV and AIDS to be fabricated. Despite the fact that this point of view is not consistent with the huge amount of independent data, it is nevertheless extremely common among the public far from science. More radical conspiracy theorists go further and deny the existence of HIV altogether - although scientifically, one can just as well deny the existence of amoebas. The systematic denial of AIDS at the state level in South Africa, according to experts, has cost the lives of hundreds of thousands of patients.
HIV infects immune cells. The virus attacks several types of cells, but the main focus of researchers is on CD4 + cells, also known as helper T cells. These cells help other cells in the immune system to recognize and eliminate infections. The virus enters the T-helpers and kills them both directly and indirectly - some of the diseased cells are recognized and killed by other immune cells. As a result, the content of CD4 + cells in the blood decreases to a critically low value, and the patient is diagnosed with AIDS. In the absence of medication, a patient with such a diagnosis is given 6 to 19 months of life.
AIDS is an infectious disease, which implies the theoretical possibility of developing a vaccine. In 1984, after the discovery of the virus, it was estimated that the HIV vaccine would be ready for testing within two years. But today, three decades later, scientists are still struggling to create it. There are reasons for cautious optimism, but no one wants to say unequivocally when an HIV vaccine will be available, and whether it will happen at all.
Fortunately, HIV in developed countries is not a death sentence today. A variety of drugs that slow down the multiplication of the virus or weaken its effect have been widely used since the late nineties. Thanks to them, HIV is no longer considered the main medical threat to humanity.
Antiretroviral therapy (ART) today, as a rule, consists of a cocktail of drugs that "hit" at different points in the life cycle of HIV and keep its blood levels at a barely noticeable level. While maintaining a medical regimen, ART allows patients to live relatively comfortably for decades. HIV has evolved from a deadly disease to an extremely unpleasant and costly, but sluggish infection.
The benefits of ART are twofold. First, they dramatically reduce the risk of developing AIDS in HIV-infected people, that is, a severe form of the disease, which sharply prolongs life and improves its quality. Secondly, a “suppressed” virus means low infectivity - as a result, ART works not only at the individual, but also at the social level.
The results of the widespread use of ART have been tangible in the last ten to fifteen years. The number of people living with HIV has stabilized globally.At the same time, the number of deaths and new infections has decreased.
This is especially noticeable, of course, in developed countries - in the United States, both indicators have more than halved since their peak in the mid-nineties. Most HIV-related deaths today occur in Africa. However, here, too, a gradual increase in the availability of ART leads to a steady decrease in the number of new infections and deaths from AIDS.
But with all its advantages, ART does not cure the disease, but only allows you to get along with it. Until July of this year, it was believed that only two HIV-positive patients managed to completely get rid of the virus. Now their number has been reduced to one.
One of the patients thought to be cured was a Mississippi girl who was born in 2010 to an HIV-positive mother. Usually, in such cases, doctors wait until the newborn is confirmed to have HIV before starting ART - what if the child was lucky and the virus was not transmitted from the mother? But in the case of the Mississippi baby, the decision was made to start intensive ART immediately after birth.
This decision was very successful. The girl was indeed HIV positive. But intensive therapy from the first hours of life did not allow the virus to settle in the still developing immune system of the newborn. After a few months, the virus was not detected in the girl's blood, despite the fact that she was no longer given antiviral drugs. Doctors continued to monitor the patient, and in 2013 announced that she was completely cured of HIV. But the joy was premature. A year later, the test results were again positive. The Mississippi Baby's remission lasted 27 months.
After the detection of HIV in the blood of a "Mississippi child", the only case of remission that continues to this day is the "Berlin patient", an American Timothy Ray Brown. In 2008, he received a blood stem cell transplant from an HIV-resistant donor. The existence of such naturally stable people has been known for a long time, but the exact mechanism of stability is unknown.
Why is HIV so difficult to eradicate? There are several reasons for this.
First, HIV, like other representatives of the group of retroviruses, does not just enter the cell, but is integrated into its genome. Once the genes of the virus are in the chromosomes of the host cell, it is very difficult, if not impossible, to "cut" them. In the genome, a virus can be dormant for years, but at the right time it can be activated and start reproducing.
Secondly, the cells themselves that become infected with HIV can remain in an inactive, almost "dormant" state for a long time. T-helpers are involved in the formation of immunological memory - the ability of the immune system to "remember" infections and respond quickly to them when re-infected (this ability of the immune system is the basis of vaccination). With "immunological memorization," a small group of cells that accurately recognize a particular parasite are retained in the body to multiply rapidly if the infection recurs. In 2009, a group of scientists from Montreal showed that it is in these memory cells that the bulk of the surviving viruses are hidden during active antiretroviral therapy.
Third, HIV is unusually volatile. Biologists of the late 20th century faced this problem on several fronts at once. Bacteria, for example, thanks to their variability, quickly became accustomed to most antibiotics discovered by scientists, and today again threaten to become one of the main medical problems of mankind. The situation with viruses is even worse: the set of their genes is so small that it is much easier for a virus to radically change its properties. This allows them to cheat immunity and develop resistance to drugs and vaccines.
All these properties of the virus lead to one disappointing conclusion: HIV is much easier to prevent than to cure.Indeed, the most effective means of fighting HIV / AIDS has become information about this disease - understanding the causes of its transmission and popularizing the simplest protection measures: condoms and disposable needles.
A New Look
Despite progress in the fight against HIV / AIDS, the virus remains a major global problem. After decades of unfulfilled hopes for a vaccine, the question arises: what if a vaccine never appears?
The respected medical journal Lancet recently published a review entitled "The End of AIDS: HIV as a Chronic Disease." It argues that while vaccine development remains a priority in HIV research, the medical community needs to think about the more “mundane” aspects of fighting the virus.
The reality, according to the authors of the study, is that scientists have managed to significantly reduce the number of new infections and deaths, and this decline continues today. This is good in itself. But there is also a downside to the coin: there are many more people living with latent HIV infection, which are constantly suppressed by ART. These are the ones that HIV researchers should first think about.
Thus, priorities should shift somewhat - for example, to the area of concomitant diseases. HIV-positive patients have a higher risk of cardiovascular disease, cancer and diabetes - these "first world problems" have already hit Africa. The solution of these problems directly concerns the HIV-infected as well.
Another important factor to which, according to the reviewers, attention should be paid, is the development of low-toxicity ART. In an environment where patients have to use drugs for several decades, even mildly toxic substances can make a significant contribution to HIV-related mortality. If the story of the "Mississippi baby" is considered successful (after all, the child has lived without HIV and without constant therapy for more than two years), then reducing the toxicity of ART for intensive care of infants should all the more become a priority.
Finally, it is worth looking at the opportunities and limitations of ART in perspective and reflecting on what the next phase of the fight against the virus should be. Existing therapies prevent HIV from multiplying and infecting more and more cells. But the complete elimination of all traces of the virus from the body, as the sad experience of the "baby from Mississippi" shows, is a much more difficult task.