Researchers from the Pasteur Institute, in collaboration with Inserm and the Paris Hospital Network (AP-HP), have identified specific immunogenetic features in individuals capable of controlling HIV without continuous antiretroviral therapy (ART). These individuals, known as “post-treatment controllers,” maintain undetectable viral loads even after stopping treatment. The study, published on April 28, 2025, in the journal Med, opens new prospects for the development of immunotherapies aimed at achieving remission or even a complete cure for HIV infection.
It is known that HIV can persist in the body in the form of “viral reservoirs” even during ART, which leads to a rapid rebound of the virus after therapy is discontinued. However, some individuals—particularly those who began treatment at an early stage of infection—can achieve long-term remission without ongoing therapy. The 2013 VISCONTI study described such “post-treatment controllers,” some of whom have managed to control the virus for over 25 years without treatment.
Under the leadership of Asier Sáez-Cirión, head of the “Viral Reservoirs and Immune Control” unit at the Pasteur Institute, researchers found that certain genetic markers associated with natural killer (NK) cells are frequently found in post-treatment controllers. An analysis of more than 1,600 participants from the ANRS CO6 PRIMO cohort confirmed that the presence of these markers contributes to sustained remission in individuals who started treatment in the early stages of infection and later discontinued it. These genetic characteristics are accompanied by specific populations of NK cells capable of more effectively controlling the infection.
To validate these findings, a clinical trial, ANRS 175 RHIVIERA01, was launched in March 2023 under the coordination of Inserm/ANRS MIE. As part of the study, 16 individuals with the identified genetic markers, who began treatment immediately after infection, discontinued therapy under close medical supervision. The goal is to analyze the relationship between the genetic features of NK cells and the ability to control the virus after treatment is stopped.
This discovery marks an important step in understanding the mechanisms of immune control of HIV and may contribute to the development of new immunotherapies that enable sustained remission or even a complete cure for the infection.