HIV and Innate Immunity: How Early Responses Shape the Evolution of Viral Reservoirs

HIV infection remains a significant challenge in the field of infectious diseases, particularly due to the persistence of viral reservoirs, even under antiretroviral therapy (ART). Reservoir cells, which harbor intact proviruses, are the main obstacle to eradicating the virus. Recently, the role of innate immunity in the selection and evolution of reservoir cells has garnered increasing interest, especially during the early initiation of ART. This study investigates these early mechanisms and their implications for HIV control.  

Understanding the Dynamics of Viral Reservoirs  

The study is based on data from a trial involving patients who started antiretroviral therapy during the acute phase of HIV infection. Using advanced tools such as genomic sequencing to identify intact proviruses and single-cell proteogenomic profiling to analyze phenotypic signatures, several key findings emerged:  

• Selection of Intact Proviruses: Rapid integration into repressive chromatin regions (heterochromatin), independent of adaptive immune responses.
• Unique Phenotypic Signatures: Increased expression of innate immunity markers such as HLA-C, HLA-G, and receptors for IL-10 and TGF-β, promoting deep latency and heightened resistance to clearance.
• Early Clonal Expansion: Significant proliferation of reservoir cells containing intact proviruses within the first six months of treatment, illustrating the early impact of ART on reservoir dynamics.

Innate Immunity: A New Lever in HIV Control  

These findings highlight the critical role of innate immunity in managing viral reservoirs. Leveraging these mechanisms could weaken reservoir cells and reduce their persistence. In addition to paving the way for new therapeutic strategies, these insights support the possibility of personalized treatments tailored to the immune specifics of each patient. Finally, identifying markers associated with latency offers an opportunity to design strategies aimed at reactivating or eliminating these reservoirs, with promising clinical studies on the horizon.