The National Center for Genomic Analysis (CNAG), based in the Barcelona Science Park, and IrsiCaixa have identified protective mechanisms in people with HIV resistant to disease progression. The scientific team has discovered, in this group of patients, the CCR5Δ32 genetic mutation, which protects against HIV, as well as an atypical immune response with lower activation and reduced levels of markers related to intestinal mucosal alterations. The study, published in the journal Med by Cell Press, opens new opportunities for the development of innovative therapies that could benefit people with HIV who, despite being on antiretroviral treatment, are unable to combat infections.

In the medical field, they are known as viremic non-progressors (VNPs). This phenotype is very rare among people living with HIV –representing only 0.1%– and, despite viral replication, they have the ability to maintain stable levels of immune cells. Until now, the scientific community has known very little about this subgroup, primarily that they maintain stable levels of CD4+ T lymphocytes, a type of immune cell that helps activate other cells to defend the body and is essential in fighting infections such as HIV. This distinctive feature allows them to resist progression to stages of immune deterioration typically caused by untreated HIV.

Now, IrsiCaixa, in collaboration with the National Center for Genomic Analysis (CNAG) and the Wistar Institute in Philadelphia, has characterized one of the most important cohorts of viremic non-progressors (VNPs). The study compared various viral, genetic, and metabolic factors of 16 VNPs with those of 29 people with HIV who exhibit standard progression of the viral infection.  Thanks to this multidisciplinary approach and the application of state-of-the-art genomic technologies, researchers have defined a unique immune profile in VNP patients, characterized by the presence of crucial immune protection mechanisms. Among these, the presence of the genetic mutation CCR5Δ32 stands out, located in one of the two copies of the gene in the human genome, which confers resistance to HIV, as well as a more regulated and balanced immune response. These findings represent a significant advancement in the design of new therapeutic interventions for other patients who do experience HIV disease progression.

This pioneering research has been made possible through the application of the most advanced technologies from CNAG, which have conducted single-cell analysis and characterization of the immune cells.

According to Dr. Holger Heyn, leader of the CNAG Single Cell Genomics team, and co-author of the study: “We are pleased that our high-resolution single-cell profiling has helped uncover the unique immune mechanisms of viremic non-progressors. By revealing distinct cellular compositions and protective immune traits, this study opens new possibilities for innovative therapies that could benefit broader patient populations resistant to standard treatments”.

» For further information: CNAG website [+]

» Reference article: Bayón-Gil et al., Host genetic and immune factors drive evasion of HIV-1 pathogenesis in viremic non-progressors, Med (2024), doi: 10.1016/j.medj.2024.09.007