Approved Research

HIV resistome

Lay summary

Exposed uninfected individuals remain seronegative for HIV-1 after multiple contacts with the virus, primarily through blood-derived products and high-risk sexual behavior. These individuals are essential for identifying biological factors that can modify the risk of infection. Most studies with exposed-uninfected cohorts have involved comparing the genetic background of virus-sensitive individuals against virus-resistant individuals. However, the results of these studies have been frustrating, and no new genes related to HIV susceptibility have been identified. Several hypotheses can explain these results, such as the heterogeneity in the populations and the selection criteria of the participating individuals. However, in recent years, we have carried out a genetic analysis of HIV acquisition in sexually exposed uninfected individuals from Spain, Italy, and the USA. This project has led to the identification of several genomic regions significantly associated with an increased risk of infection.

Aims: To replicate the results obtained in Spanish, Italian, and American populations in an independent population (UK), increasing the statistical significance of the results and confirming the role of these genes in the HIV resistance phenotype. Additionally, we propose to determine the heritability and shared genetic influence between the risk of HIV infection and other conditions such as autoimmune or psychiatric diseases.

Project duration: three years

Public health impact: Identification of new genetic factors influencing the risk of HIV infection will allow for a better understanding of the infection biology and may lead to the development of genetic counseling tools to assess individual risk. Additionally, the identification of new biological pathways associated with HIV resistance can be used for the development of novel drug targets as well as better immunization strategies. The results of this project are of genuine public health interest.