Phase II clinical trial AELIX-003 confirms that the immune response to the HTI therapeutic vaccine helps improve HIV control without treatment

A Phase II clinical trial has confirmed that the combination of the HTI therapeutic vaccine—designed at IrsiCaixa, developed by AELIX Therapeutics and recently acquired by Gilead Sciences, Inc.—along with an immune system-modulating drug, is safe and capable of generating an immune response that improves virus control in the absence of antiretroviral treatment in some people. This study, published in Nature Communications, was led by researchers from the Fight Infections Foundation at Hospital Germans Trias i Pujol, IrsiCaixa, and Hospital La Paz, with collaboration from multiple hospitals across Spain.

Enhancing the immune system against HIV

Antiretroviral treatment suppresses the virus to undetectable levels, preventing the progression of infection and eliminating the risk of transmission—an established concept known as undetectable = untransmittable. However, finding a cure remains a top priority for the scientific community and for the 39 million people with HIV worldwide.

“The HTI therapeutic vaccine is designed to retrain the immune system of people with HIV to control the virus without treatment,” explains Beatriz Mothe, physician at Hospital Germans Trias i Pujol, researcher at IrsiCaixa and the Fundación Lucha contra las Infecciones, and one of the inventors of the vaccine alongside IrsiCaixa principal investigator Christian Brander. Brander adds: “With this study, we aimed to test the vaccine’s efficacy in a new format, reducing the number of vaccine doses and adding the compound Vesatolimod, which modulates the immune system.”

In this clinical trial, 50 people with HIV, who had received early treatment after acquiring the virus and had an undetectable viral load, were given the HTI vaccine in combination with the immune-modulating drug Vesatolimod. “The results demonstrate that the combination is safe and generates a robust immune response against HIV. Moreover, it confirms what we had observed in previous trials: that the immune response generated contributes to improving HIV control when antiretroviral treatment is temporarily interrupted,” states Lucía Bailón, first author of the study, physician at Hospital Germans Trias i Pujol, and researcher at the Fundación Lucha contra las Infecciones.

During the trial, after receiving the vaccine and Vesatolimod combination, participants underwent a supervised interruption of their antiretroviral treatment for up to 24 weeks. The results showed that, although all participants experienced a viral rebound, 33.3% of those who received the vaccine and immune-modulating drug were able to maintain better-controlled viral load levels throughout the treatment interruption period, compared to 23.5% in the group that did not receive the combination.

A simplified strategy

This trial involved multiple hospitals, reinforcing the validity of the results. Additionally, the study allowed for the evaluation of a simplified vaccination regimen compared to previous research, opening new possibilities for future combination designs. “The joint efforts of nine hospitals across Spain were key to evaluating this strategy and strengthening the reliability of the results,” highlights José Ramón Arribas, physician at Hospital La Paz and study coordinator.

Immune cells specifically targeting HIV

Analyses have shown that the HTI vaccine is capable of training the immune system so that its cells target specific regions of HIV. “This confirms that the vaccine is effectively impacting the immune system of people with HIV, and it is incredibly encouraging to know that we can achieve this,” says co-first author José Moltó, physician at Hospital Germans Trias i Pujol and researcher at the Fundación Lucha contra las Infecciones.

These findings represent a significant step forward in the development of therapeutic HIV strategies, paving the way for future clinical trials that combine this vaccine with other approaches in the search for a functional cure for the virus.

About the study

The study was conducted with the participation of Hospital Germans Trias i Pujol, Hospital La Paz, Hospital Universitario Vall d’Hebron, Hospital General Universitario Gregorio Marañón, Hospital Universitario de La Princesa, Hospital Clínic, Hospital Universitario de Bellvitge, Hospital Universitario Ramón y Cajal, and Hospital de la Santa Creu i Sant Pau.

The research team expresses its deepest gratitude to all the individuals who participated in this study. Without their commitment to advancing scientific research in the pursuit of an HIV cure, these promising results would not have been possible.