Investigating the HIV-1 reservoir in the central nervous system

Upon interruption of antiretroviral therapy (ART) for HIV, the virus quickly starts replicating again from the persistent reservoir of latently HIV-1 infected cells. This makes lifelong adherence to ART crucial to keep the virus suppressed, but it also means that patients need regular monitoring and access to expensive treatments. Even with ART, people with HIV can still develop HIV-associated neurocognitive disorders (HAND), which affect brain function.

A lot is still unclear about the development and dynamics of the central nervous system (CNS) viral reservoir. The central nervous system (CNS) is a unique and immune-privileged microenvironment that restricts the entry of immune cells from the periphery. The scarcity of CD4 T cells in the CNS means that, for HIV-1 to replicate, it must adapt to a new host. Myeloid cells, such as microglia in the brain, express CD4 and HIV-1 co-receptors that allow for viral entry. However, these cells have fewer CD4 receptors than T cells, leading to the need for the virus to adapt and the development of HIV macrophage-tropic (M-tropic) variants. These lineages need a lower CD4 density for its binding and viral entry. It's still unclear how often and when these M-tropic variants emerge.

The brain may contain different HIV reservoirs made up of both CD4+ T cells and myeloid cells. These two types of reservoirs likely have different dynamics and contribute in unique ways to the progression of the disease and the rebound of the virus after ART stops. However, few studies have specifically examined myeloid reservoirs in the brain. Differences between T-tropic and M-tropic HIV strains, along with factors like the viral subtype and the person's sex, might influence how the virus establishes and behaves in the CNS.

Our study aims to explore both M-tropic and T-tropic HIV variants in the CNS, focusing on people, particularly women, from sub-Saharan Africa who are infected with subtype C. Understanding how these HIV variants behave in the CNS is crucial for future research into HAND and for developing potential cures for HIV.

Contact 
Nanouk Zuidmeer