Early treatment is a key to remission

People living with HIV must take antiretroviral treatment for life to prevent the virus from multiplying in their body. But some people, called “post-treatment controllers,” have been able to interrupt their treatment while maintaining an undetectable viral load for several years. Starting treatment early could promote long-term control of the virus if treatment is interrupted.

Scientists from the Pasteur Institute, CEA, Inserm, Paris Cité University and Paris-Saclay University, in collaboration with the Cochin Institute and with the support of MSD Avenir and ANRS Emerging Infectious Diseases, used an animal model to identify a window of opportunity for the introduction of treatment promoting remission of HIV infection. It appears that starting treatment four weeks after infection promotes long-term control of the virus after stopping treatment after two years of antiretroviral therapy.

These findings highlight how important it is for people with HIV to be diagnosed and start treatment as early as possible. The results were published in the journal Natural communications on January 11, 2024.

Research on the VISCONTI cohort, consisting of 30 post-treatment controllers, provided proof of concept of possible long-term remission for people living with HIV. These people received early treatment that lasted several years.

When they subsequently stopped their antiretroviral treatment, they were able to control their viremia for more than 20 years in some cases. At the time (in 2013), the team leading the VISCONTI study suggested that early treatment could help control the virus, but this remained to be proven.

In this new study, the scientists used a primate model of SIV infection which allowed them to control all the parameters (sex, age, genetics, viral strain, etc.) that could have an impact on the development of immune responses. and the progression of the disease. . They compared groups that received two years of treatment, starting either shortly after infection (in the acute phase), several months after infection (in the chronic phase), or no treatment.

The reproducible results show that starting treatment within four weeks of infection (as was the case for most participants in the VISCONTI study) strongly promotes viral control after stopping treatment. This protective effect disappears if treatment is started only five months later.

“We show the link between early treatment and control of infection after treatment interruption, and our study indicates that there is a window of opportunity to promote remission of HIV infection,” comments Asier Sáez-Cirión, head of the Viral Reservoirs and Immune System department at the Institut Pasteur. Control unit and co-last author of the study.

Scientists have also demonstrated that early treatment promotes the development of an effective immune response against the virus. Although the antiviral CD8⁺ The immune T cells developed in the first weeks after infection have a very limited antiviral potential, the early introduction of long-term treatment favors the development of memory CD8⁺ T lymphocytes, which have a stronger antiviral potential and are therefore able to effectively control the viral rebound that occurs after treatment interruption.

“We observed that early treatment maintained for two years optimizes the development of immune cells. They acquire an effective memory against the virus and can eliminate it naturally when a viral rebound occurs after stopping treatment,” explains Asier Sáez -Cirión.

These results confirm how important it is for people with HIV to be diagnosed and start treatment as early as possible. “Starting treatment six months after infection, a time frame that our study shows results in loss of effectiveness, is already considered a very short time frame compared to current clinical practice, with many HIV-positive people starting treatment years after infection because they received a diagnosis too late,” notes Roger Le Grand, director of IDMIT (Infectious Disease Models for Innovative Therapies) and co-last author of the study.

“Early treatment has a double effect: individually, because it prevents the diversification of the virus in the body and preserves and optimizes immune responses against the virus; and collectively, because it prevents the possibility of spreading the virus to other people “, adds Asier. Saez-Cirión.

These results should guide the development of new immunotherapies targeting immune cells involved in remission of HIV infection.