The fight against HIV remains a major public health challenge, primarily due to the persistence of viral reservoirs that require lifelong antiretroviral treatment. However, some individuals, known as "post-treatment controllers," manage to maintain an undetectable viral load even after stopping treatment.
Researchers from the Institut Pasteur, Inserm, and AP-HP, in a study funded by ANRS Emerging Infectious Diseases (ANRS MIE), have succeeded in identifying specific genetic and immune characteristics of a group of these individuals.
This research provides unprecedented insights into the immune mechanisms associated with controlling HIV without antiretroviral treatment and opens new perspectives for developing immunotherapies aimed at achieving remission or a cure for HIV infection. These findings were published in
Med on April 28, 2025.
Despite antiretroviral treatment, cells infected with HIV persist in the body, forming what are known as viral reservoirs. These reservoirs are responsible for a rapid viral rebound if treatment is interrupted.
However, some individuals maintain long-term control of the virus after stopping treatment. These are the "post-treatment controllers," described in the
VISCONTI study in 2013. These individuals are considered to be in long-term virological remission from HIV infection.
In some cases, the duration of control has already exceeded 25 years without treatment. Initiating early treatment, within the first days following infection during the acute phase, appears to promote such post-treatment control of HIV
1, but the immune mechanisms remained poorly understood until now.
This study, led by Asier Sáez-Cirión, head of the Viral Reservoirs and Immune Control Unit at the Institut Pasteur, identified that certain genetic characteristics associated with innate immune cells (Natural Killer or NK cells) are very frequently found in post-treatment controllers from the VISCONTI cohort.
In a retrospective analysis of the ANRS CO6 PRIMO cohort (where the genetic characteristics of over 1,600 participants followed since the beginning of their infection were analyzed), scientists confirmed that the presence of these genetic markers appears to favor long-term HIV remission in individuals who started treatment early and later discontinued it for various reasons.
The researchers show that the presence of these genetic markers is accompanied by specific populations of NK cells with an enhanced ability to control infection. "
These results support the role of NK cells in prolonged HIV remission and could guide the development of new immunotherapies," explains Asier Sáez-Cirión.
An ongoing clinical trial
To validate these findings, a clinical trial called ANRS 175
RHIVIERA01, sponsored by Inserm/ANRS MIE, was launched in March 2023. This trial aims to study the association between NK cell genetic markers and post-treatment interruption control.
As part of the trial, a closely monitored treatment interruption was proposed to 16 individuals carrying these genetic characteristics who had been treated since their primary infection. Analyses are ongoing.
In parallel, scientists are characterizing the precise influence of these remission-associated genetic markers on the programming and function of NK cells. This approach could lead to the development of immunotherapies to mobilize these specific cells in other people living with HIV.
"
This discovery represents a crucial step toward achieving long-term remission of HIV infection. In a context where access to antiretroviral programs is under serious threat, new therapies that allow people living with HIV to lead a normal life without lifelong treatment become even more necessary and urgent," concludes Asier Sáez-Cirión.