The Infectious Diseases group at the Vall d’Hebron Research Institute (VHIR) has led a study identifying several types of cells in which the human immunodeficiency virus (HIV) can remain hidden and resist the effects of standard antiretroviral therapies. These findings will help guide the development of new therapeutic approaches aimed at eliminating the virus from the body, something that is currently not possible. The study, published in Nature Communications, was carried out in collaboration with the Departments of Pathology, Otorhinolaryngology, and Obstetrics and Gynaecology at Vall d’Hebron University Hospital, IrsiCaixa, the Severo Ochoa Centre for Molecular Biology, and La Princesa University Hospital.

Today, antiretroviral treatments allow HIV to be controlled and prevent disease progression. However, it is not yet possible to completely eliminate the virus from the body, as part of it remains inactive within immune system cells. These cells form HIV reservoirs, which prevent the virus from being cleared by either the immune response or antiretroviral therapy. For this reason, they represent the main barrier to a definitive cure for people living with HIV.

Among the current strategies being explored to achieve an HIV cure is the reactivation of these cellular reservoirs using latency-reversing agents. These drugs are designed to reactivate the virus that lies dormant within cells, allowing it to be recognised and eliminated by the immune system.

To better understand the composition of these reservoirs, the study led by Vall d’Hebron established tissue models using samples from human tonsils, intestines, and cervixes obtained from surgical procedures and subsequently infected with the virus. Unlike previous studies, this approach reproduced the real conditions of tissues where HIV typically remains latent.

The results showed that HIV hides in a wide variety of cell types across different tissues. For instance, in the tonsils, the virus was mainly found in cells involved in the lymph node immune response, while in the intestine, the dominant reservoir consisted of tissue-resident memory cells. Moreover, depending on the tissue, the same type of cell may behave differently. “We found that there are many types of cells that keep HIV in a latent state, and these vary greatly between tissues and even within the same tissue”, explains Dr. Ana Gallego Cortés, postdoctoral researcher in the Infectious Diseases group at VHIR and first author of the study.

Finally, the team tested different latency-reversing agents and observed that their efficacy varied significantly across tissues and cell types. “These differences show that a combination of drugs is needed to reactivate all HIV reservoirs and eliminate the virus from all tissues. No single drug will be sufficient, so new therapeutic strategies will be required to achieve a cure”, concludes Dr. María José Buzón, co-head of the Infectious Diseases group at VHIR and leader of the study.

The project was made possible thanks to funding from the ”la Caixa” Foundation, the Spanish State Research Agency of the Ministry of Science and Innovation, the European Regional Development Fund (ERDF), the Ministry of Economy and Competitiveness, and the Instituto de Salud Carlos III.