Surviving AIDS is no farfetched dream. For several years now, living with HIV —the virus that causes the infection— has meant neither impossible treatments nor a fatal horizon in the short term. Not only does antiretroviral therapy allow infected patients to enjoy a lifestyle similar to that of healthy individuals, but there are protocols in place that work well, should their condition worsen. The use of medication might be limited in some cases of HIV-positive patients. Now a study led by IrsiCaixa researchers has found some cases that are even more exceptional. A paper published in Scientific Reports describes the first three cases in the world of HIV-positive patients who have received no treatment after being diagnosed twenty-five years ago.
Javier Martínez Picado, an Icrea research professor with Catalonia’s IrsiCaixa AIDS Research Institute and the leading name behind the study, explains that the patients “likely became infected thirty years ago”. It is a known fact that it takes some HIV-positive individuals a long time before they become ill, but such a long period was unheard of. Martínez notes that, thanks to this survey, other isolated cases have cropped up across the world. They are known as “exceptional elite controllers” or EEC. The IrsiCaixa researchers, working with colleagues from other centres in Madrid and Seville, have studied these three patients —a man and two women— to ascertain how they have managed such a feat.
When the three patients became infected, their body began to produce antibodies against HIV but, for some reason, they succeeded in keeping the infection at bay naturally. This sort of natural control, which borders on what is known as a functional cure, meant that they did not need to take antiretroviral medication. As time went by —and given their unique conditions—, they were classed into the “elite controllers” subset. Such a long time span makes them exceptional, as does their immune system’s response to the characteristics of the virus. Both conditions are necessary. The researcher notes that “once the infection has ben detected, patients are usually given antiretroviral medication to prevent the immune system’s failure and ward off the opportunistic diseases that cause a patient’s health to deteriorate”. However, there is a smaller group of patients, the elite controllers, who exhibit a “natural control” of their viral load, which can extend for several years without any need for drugs. In very exceptional cases, as they have just found, this period can last decades.
The explanation lies in a combination of what might be termed as “defective viruses” and the patient’s immune response. The researcher explains that in such cases “the virus reproduces as in all HIV-positive patients”, but not quite in the same way. Under normal circumstances, the virus’ own proteins —which are essential for its reproduction— integrate into the patient’s cellular DNA to ensure its spread. The three patients who have been studied are no exception. But in their case the proteins integrate into areas of the genome that block the reproduction of the virus. In other words, they travel to the wrong place. It appears that they choose dark regions of the genome, also known as deserts. This is what once had erroneously been referred to as “junk DNA”.
The mechanism that has been identified means that the viral load detected in blood samples is up to ten times lower that in a patient who is taking antiretroviral medication. After analysing millions of samples, the researchers have failed to find a single virus that was capable of reproducing and spreading the infection. Furthermore, they have noticed that the levels of viral variability are extremely low —up to eight times lower—, which proves that their virus is rather inactive. In the three cases they have studied, the researchers have also spotted variations in the patients’ genome linked to the control of the HIV infection, hence their stronger immune response. The combination of all three factors paves the way for further research aimed at strengthening the immune system of patients and redirecting the virus to areas of the genome that make its replication unviable.