Identification of a group of seropositive patients that can effectively control their infection without medication

• A study that involved the collaboration of IrsiCaixa researchers has identified a subgroup of patients among the so-called "elite controllers" who hold the key to the natural control of infection.
• The subgroup, which researchers call "the elite of the elite", has a blood level of HIV target cells, CD4 + lymphocytes, higher than the rest, without being subjected to medication. 
• Their genetic profile makes it possible to suspect that these subjects may not present complications associated with infection, such as cardiovascular risk, metabolic abnormalities, nerve and liver problems, kidney and bone conditions, the presence of which is associated with a decreased life expectancy of the people who are infected.

Researchers from the IrsiCaixa Institute for AIDS Research have participated in a study in which 30,000 genes of 35 people have been sequenced in order to analyze for the first time the genetic causes that give some people infected with HIV the ability to control the infection naturally, without medication, and thus prevent the development of AIDS. Among these patients, called elite controllers, the study identified a subgroup that presents some characteristics in their genetic profile that are very similar to those of uninfected individuals. This subgroup, which researchers call "the elite of the elite," presents a much less active immune system than that of the rest of controllers, showing that these people "do not need" to activate their immune system to control the infection, which makes it possible to think that they hold the key to the natural control of the infection.

The rest of people infected with HIV a chronically activated immune system, which is known to be associated with complications such as cardiovascular risk, metabolic abnormalities, nerve and liver problems, as well as kidney and bone disorders. The genetic characteristics of the subgroup of patients identified, which are very similar to those of uninfected people, lead us to think that these people will probably not present these complications. Therefore, this information may serve at short term to evaluate the predisposition of seropositive patients to develop these complications which shortens their life expectancy.

The study was presented at the last edition of the International Retrovirology Congress (CROI)  in Boston and published in the March issue of the Journal of Virology. The work was led by researchers at the Ragon Institute of Massachusetts General Hospital, Harvard, MIT, Boston. The IrsiCaixa researchers that participated in the study were Javier Martinez-Picado (ICREA) and Maria Jose Buzón.

The study analyzed messenger RNA samples- the form that the genetic material adopts to synthesize proteins- from three different groups. On the one hand, 12 elite controllers, for instance HIV-infected subjects but with a very low blood viral load, who are not receiving antiretroviral treatment. On the other hand, 9 HIV-infected subjects who are on antiretroviral treatment, and finally, 14 seronegative people, that is, people who are not infected.

The messenger RNA of the cells of the three study groups was subjected to transcriptomic analysis, a technique that allowed detecting the expression of 30,000 different genes of each person. Thanks to this analysis, it has been possible to determine that among the elite controllers there are two subgroups with differentiated genetic profiles: first, a subgroup that is very similar to that of patients under treatment, and secondly, another subgroup that is very similar genetically to seronegative people. The latter is the group that researchers have termed "the elite of the elite."

For some time, researchers working in this field were focusing their efforts on the mechanisms by which elite controllers are able to control the infection naturally and without medication. Determining each of the genes responsible for the ability to control infection is a first step to finding a therapy to eradicate HIV / AIDS infection.