Forty years of intense research can go a long way. In the case of AIDS-HIV, these last four decades have served to turn it into a chronic disease: today, one pill a day may be enough to control the virus and keep it undetectable and, therefore, untransmissible. But neither the successes in antiretroviral treatment, nor the comfort of its regimen, have caused the research to be relaxed.
Nowadays, new and groundbreaking lines of work are being opened , and all this coincides with a generational change: new researchers have arrived at the laboratory and the clinic who did not live the hardest years of the pandemic and who consider HIV as a fascinating challenge: “I was born around the year of the boom, but not I remember; I have received the vision of others ”, confesses Dr. Sara Morón-López, researcher at IrsiCaixa (Institute for AIDS Research, located at the Germans Trias y Pujol Hospital in Badalona, Barcelona). “In the eighties, doctors and nurses came across the disease abruptly; there were no treatments, everything was unknown and the stigma was total. We have already chosen to study this virus, which is perfect for its complexity, ”adds this doctor, whose work has been awarded the International Research Scholars Program in HIV, one of the only two that Gilead has awarded worldwide for research in this field.
Another doctor, Rocío Montejano, researcher in the Area of Infectious Diseases-Internal Medicine at IdiPaz (Research Institute of the Madrid hospital in La Paz), confirms this: “HIV is always a challenge, it never ceases to amaze us . We need the generational change because, in five or ten years, the great HIV experts will have to retire and, although we will always have their support, we will have to take the relief. There are always angles to study it from, and there will continue to be. ”
Is healing possible?
Inevitably, when we talk about HIV, we all think about a cure. As much as the treatment is comfortable, effective and safe, the dream is to definitively defeat the virus. Dr. Beatriz Mothe, associate researcher at IrsiCaixa, works in this line, who explains: “ There are a small percentage of people who you are living with HIV that does not need treatment; are able to control it spontaneously. We study them to see what characterizes them immunologically, with the idea of developing cure strategies and therapeutic vaccines in order to try to control the infection without medication. ”
The initial challenge is, how minimum, equate with them the results currently offered by antiretroviral treatment . “With these drugs, the patient is undetectable and, therefore, intransmissible. We must achieve the same and, so far, we have managed to lower viral load levels, but not to undetectable levels. ” The importance of this line of work, beyond ensuring that people with HIV do not have to be permanently with their guard up, is to be able to reach “that enormous percentage of people who, in other countries, do not have access to these treatments, and more considering that they need a lot of monitoring. That is why we are looking for a functional cure. ”
Bring the virus out of its hiding place
Sara Morón-López, who has been investigating the virus’s replication cycle for years, adds: “It has not been possible to cure HIV because the virus hides within cells . It stays there, latent, in any part of our body ”. And remember: “The virus enters the cell, infects it, integrates it and there is a point at which it needs to be expressed to produce new viruses. I have focused on trying to discover the cellular factors that regulate the HIV expression process. ”
With this, he seeks to achieve a specific treatment that can achieve, or regulate this step or reactivate the virus. “The idea is to activate the cells that are hiding the virus so that our immune system can recognize and eliminate them, or else silence them completely.” It would be equivalent to all those archaic, endogenous viruses that we have in our DNA and that stayed there, asleep forever.
“The virus has been hidden in areas of the genome. That makes it silenced ”, explains Dr. Morón-López
In this strategy, Morón-Lopez also studies people living with HIV without the need for treatment: “A discovery from this last year is that, in these patients, the virus has been hidden in areas of the genome where it is not expressed. And that makes it silenced ”, he points out.
The quality of life, always present
Beyond the lines of research that allow to defeat HIV, the day-to-day life of patients is not being neglected, and especially those known as Long Time Survivors (LTS). It is about that first generation that today has exceeded fifty and in which we are seeing how the virus, in many cases, causes accelerated aging. “They develop comorbidities ten years before, and in greater numbers,” explains Rocío Montejano from the Infectious Diseases Area of IdiPaz. “We see that it may be due to the treatments they took and, also, that there has been no secondary recovery of the immune system to the infection. This leads to immunosenescence [cambios que se producen en el sistema inmunitario a causa del envejecimiento y que afectan la inmunidad] that is associated with greater inflammation. ”
In his line of research, Montejano is comparing the chronological age (that of the DNI) with the biological age (the age of our body), to see the impact of the treatments. As the doctor explains, studying resistance “we try to detect archived mutations, see if they persist or not over time, determine the impact of those mutations that once were there and now are not, to look for other treatment options.”
An infection… of men?
Since its discovery until today, HIV has been considered an almost exclusively male infection and closely linked to men who have sex with men (MSM). “But this happens in the western world, and many times the perspective is lost that, globally and in numbers, it is a more feminine disease,” says Dr. Beatriz Mothe from IrsiCaixa de Badalona. “In the end, women are underrepresented and there is a gap of knowledge of how they respond to treatments, interactions with hormones …”.
To care for women living with HIV, we must add care directed at generational change in research, in which there is increasingly more women who, from the laboratory and the clinic, are assuming the challenge of defeating this disease and ensuring that patients have a better quality of life. Dr. Sara Morón-López points out in this regard: “It is important that there are men and women: we think differently and we have complementary points of view. It is much more enriching ”. Dr. Rocío Montejano adds: “In research, and even more so if you are treating complex patients, multidisciplinary management is important and taking everyone’s opinion into account. In my case, there may be greater involvement, greater dedication, but I don’t know if it has more to do with gender or person. ”