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IrsiCaixa investigates why some people living with HIV and receiving antiretroviral treatment have a lower viral reservoir than others in the same conditions. The Institute has found that a 47% of the reservoir of these individuals is found in short-lived cells, which could explain these lower levels
The main obstacle to achieving a cure for HIV is the ability of this virus to hide in a latent state within some of the cells it infects and, in this way, establish a viral reservoir unalterable against treatments and the immune system itself.
Now, a research team from the AIDS Research Institute
IrsiCaixa publishes an article in the Journal of Internal Medicine
in which a profile of people living with HIV has been characterized but, in their case, this viral reservoir is very small.
Comparing the characteristics of the reservoir of this profile of people with that of other people living with HIV, they have been able to confirm that their reservoir is minimal and that 47% of this latent virus resides in short-lived cells, which could explain its low amount.
This makes these people good candidates to receive future HIV cure strategies, since it would facilitate the elimination of this reservoir.
The course of HIV infection can be different for each person, and depends on factors such as the immune response against the virus, the characteristics of the infection or the moment in which the individual starts treatment, among others. Throughout more than 40 years of studying HIV, the scientific community has been able to detect the existence of profiles of people who manage to control the virus in an unusual way.
Two years ago, the group of Retrovirology and Clinical Studies (GREC) of IrsiCaixa described for the first time a profile of people who, despite needing antiretroviral treatment to keep the virus at bay, had a much smaller reservoir of HIV than average and, in addition, kept their immune system in good condition despite the ravages that the infection wreaks on immune cells.
“Studying this profile of response to infection is interesting not only to understand what factors help reduce the amount of viral reservoir and to be able to apply this knowledge to the design of an HIV cure, but also because these people are good candidates to apply.” healing strategies,” he explains. Javier Martinez-Picadoprincipal investigator of the GRSI group of IrsiCaixa and professor ICREA.
Two years after the identification of this profile of people, baptized with the name LoViReT (from English, Low Viral Reservoir Treated), a study has been launched that aims to better characterize these individuals.
The project has the participation of 22 LoViReT people –study group– and 22 people with a standard HIV reservoir –control group. Both the control group and the study group are people with HIV infection who receive antiretroviral treatment and who have had an undetectable viral load in their blood for at least 3 years.
By analyzing the total amount of HIV genome present in peripheral blood, the research team has been able to confirm that people in the LoViReT cohort have lower levels of viral reservoir compared to the control group.
In addition, they have seen that many of the viruses are defective and, in fact, 71% of the individuals in the LoViReT group have not been able to detect viruses capable of multiplying in the blood. “We know that the HIV reservoir quantity is five to ten times greater in lymphoid tissues, such as the rectum or lymph nodesin comparison with peripheral bloodwhich is why we thought it necessary to study, through biopsies, the amount of HIV in these tissues”, remarks Maria Salgado, a researcher associated with IrsiCaixa.
“The results conclude that people in the LoViReT cohort have a minimal amount of reservoir in these tissues, with values seven times lower than those indicated by literature data for people with a standard HIV reservoir,” he adds.
Finally, the distribution of the HIV reservoir in these people has also been analyzed and it has been shown that 47% of this virus was hidden in cells of the immune system that have a short life.
These results contrast with those of people with a standard viral reservoir, which is located predominantly in longer-lived cells of the immune system. “Short-lived cells are easier to eliminate with antiretroviral therapy and this could explain why the reservoir levels of people in the LoViReT group are lower,” explains Cristina Gálvez, an IrsiCaixa researcher.
Eliminating the reservoir is the first step in achieving a cure for HIV. That is why most healing strategies are initially aimed at controlling or eliminating the virus that remains dormant within the cells. It is interesting that there is a group of people who naturally already have a smaller reservoir. Their starting scenario favors the elimination of this viral reservoir, which makes them exceptional candidates to receive future HIV cure strategies”, comments Salgado.
One of these healing strategies focuses on reactivating the virus that is hidden in the cells that make up the reservoir so that the immune system and treatments can detect and eliminate it.
“For this profile of people, this strategy could be advantageous since they have less of a reservoir to destroy and, furthermore, a large part of this reservoir is located in cells that are easily eliminated with antiretroviral treatment,” concludes Martínez-Picado.
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