Sustained HIV Viral Suppression Restores Immune Potential: Victor Appay, PhD

For years, HIV has been synonymous not only with chronic infection but also with the specter of accelerated immune aging—an assumption that long-term damage to the immune system was inevitable, even in the era of effective treatment. But new data presented at the 2026 Conference on Retroviruses and Opportunistic Infections (CROI 2026) suggest a far more hopeful narrative: in people living with HIV (PWH) on decades of antiretroviral therapy (ART), the immune system may be more resilient—and even more adaptable—than previously believed.

At CROI 2026, Victor Appay, PhD, research director at INSERM and co-head of the “Vulnerability and Ageing of the Immune System” team at the ImmunoConcEpT unit at the University of Bordeaux, shared findings from a study titled “HIV-Specific T-Cell Responses in People With HIV on Long-Term ART.” The research examined how sustained viral suppression over 25 to 30 years reshapes HIV-specific CD8⁺ T-cell responses, offering fresh insight into immune reconstitution and the long-term prospects for HIV remission.

ART has transformed HIV into a manageable chronic condition by suppressing viral replication and preventing progression to AIDS. Yet the virus persists in latent reservoirs, posing a formidable barrier to a cure. CD8⁺ T cells, central to recognizing and eliminating infected cells, are critical to cure-oriented strategies. Historically, however, HIV-specific CD8⁺ T cells in individuals who began treatment during chronic infection have been described as exhausted and functionally impaired. Layered onto this is the well-documented phenomenon of accelerated immune aging in untreated HIV, raising concerns about whether older PWH retain the capacity to control the virus.

Using flow cytometry and single-cell RNA sequencing, the team characterized the phenotypic, functional, and transcriptomic features of HIV-specific CD8⁺ T cells in individuals with long-term ART exposure. The results were striking. Rather than exhibiting hallmarks of exhaustion or terminal differentiation, these cells showed features of early differentiation and “stemness,” with preserved proliferative and cytolytic potential—hallmarks of a rejuvenated immune profile.

In the accompanying interview, Appay reflects on how these findings build on years of research into immuno-aging. Although untreated HIV clearly accelerates immune decline, long-term ART appears to slow—and in some respects even reverse—these effects. Immune aging in treated individuals becomes more aligned with chronological aging rather than HIV-driven dysfunction. Sustained viral suppression, he emphasized, enables meaningful immune restoration.

The findings support a model of clonal succession in which older, exhausted CD8⁺ T-cell clones are gradually replaced by newly generated clones with improved functionality—cells that have been linked to posttreatment control. Despite thymic involution and age-related immune changes, the immune system in well-treated PWH demonstrates unexpected resilience.

As the population of older adults living with HIV grows, these results reshape conversations about healthy aging, vaccine responsiveness, and cure-directed strategies. In a context of restored immune competence, interventions designed to enhance HIV-specific CD8⁺ T-cell responses may be more viable than once assumed—bringing the field a step closer to the possibility of durable remission without lifelong therapy.