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Scientists identify 6 key genes that will predict the course of the AIDS virus infection in each patient

  • IrsiCaixa researchers have analyzed the complete genome of more than 60 people infected with the AIDS virus and have identified 6 key genes that predict how the infection will progress in each patient.
  • At least 8% of new HIV infections occur in patients referred to as "rapidly progressing patients"; that is to say, patients who undergo a rapid deterioration- in some cases even fulminant deterioration- of  their immune system, which highlights the need to strengthen early diagnosis and prevention of the infection.
  • The discovery also opens a new avenue of research for the development of a vaccine against AIDS, given that the manipulation of these 6 genes involved in the activation of the immune system would stimulate a strong immune response against HIV.

The Journal of Clinical Investigation publishes in its last issue a study that has analysed the complete genome of more than 60  people infected by the human immunodeficiency virus (HIV). This has led to the identification of a group of genes involved in the rapid progression of the infection, making it possible to predict disease progression in each patient. The study reveals that at least 8 of every 100 people newly infected with HIV would respond to a rapid progression model. That is to say, an infection that develops very quickly in the body and in less than three years the patient´s immune system is severely impaired. The unexpectedly large number of patients with rapid progression emphasizes the need to strengthen early diagnosis to prevent fulminant cases of AIDS and to strengthen prevention.

This study opens a new avenue of research as part of the HIVACAT project for the development of the AIDS vaccine, undertaken  by an unprecedented public-private consortium which has become an international benchmark. Scientist point out that, given that these genes are involved in the activation of the immune system, the HIV vaccine could be developed in such a way that it was able to manipulate them to trigger an adequate immune response.

The study has been led by researchers from the IrsiCaixa Institute for AIDS research, driven by "la Caixa" Foundation and the Department of Health of the Generalitat of Catalunya; and has involved the participation of Hospital Clínico of Barcelona and the Blood and Tissue Bank, as well as other international institutions.  According to the IrsiCaixa researcher responsible for the study, Javier Martinez-Picado, who is also an ICREA research professor, "the identification of these 6 genes was possible because we have managed to recruit the first and largest follow up cohort of patients in whom the infection develops very quickly, and, in addition, we have also been able to identify the percentage of these types of patients, which is surprisingly high. Knowing these genes is essential to predict whether the patients' immune system will deteriorate rapidly and recommend treatments with greater guaranteed success."

So far, cases of rapid progression were anecdotal in the scientific literature, given the complexity for determining the date of infection and the short time available to identify these patients, including diagnosis and initiation of antiretroviral therapy.

The study has been conducted with a cohort developed in collaboration with the Lausanne University Hospital, in Switzerland, from the screening of thousands of patients, of whom more than 100 had developed a rapid progression of the infection. To be included in the cohort, patients needed to meet two basic conditions: that they had been tested for HIV prior to becoming infected, in order to determine the approximate date on which they became infected -that is, that it had been less than a year between the last HIV-negative test and the detection of infection-, and that in less than three years they presented a T4 cell lymphocyte blood level below 350 per cubic millimeter (which is the medical criterion to begin treating the disease).

In 66 of these patients, half of them from Barcelona and the other half from Switzerland, half a million positions of their DNA was analyzed as well as combinations of genes known as HLA, which in previous studies had already been associated with the rate of progression of HIV infection. The results confirmed this association in patients with rapid progression.

At the same time, the behavior of 25,000 genes in cells of the immune system of patients with rapid progression was studied and compared with the behavior of these same genes in cells of individuals who were also infected but with good immunity despite no antiretroviral therapy, the so-called “viremic non-progressor patients”.

In addition, and for the first time in the research of this diseases, these genetic results were compared against parallel models of infection by the simian immunodeficiency virus (SIV) in non-human primates. Specifically, HIV infection in rapid progressor and non-progressor viremic patients was compared with their SIV infection equivalents in macaques and mangabeys, respectively. This comparison allowed associating the behavior of six specific genes with the rate of disease progression.

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