HIV continues to hide in cytotoxic T-cell clones

Antiretroviral treatment (ART) is very effective at controlling HIV, to a point where it can no longer be passed on, but the virus never disappears completely - it is hiding in about one in every million immune cells.

In particular, HIV hides in special cells known as cytotoxic CD4 T-cell clones. A study by researchers at the Yale School of Medicine, published in the journal Immunity, showed that cells infected with HIV are the best fighters of the immune system and are able to protect themselves from being destroyed by other immune cells. The team used multiomic sequencing to study these cells.

Cytotoxic CD4 T-cells, in which HIV hides, produce two specific proteins: Granzyme B to fight cancer, and Serpin B9 which protects against toxins. When HIV hides inside these well protected fighters the immune system is unable to destroy these infected cells.

The researchers also found that despite powerful HIV treatment, these powerful cells, in which HIV is hidden, can continue to clone themselves.

The main conclusions of the study were:

• Most T-cell clones infected with HIV are large and stable cytotoxic effectors.
• Some HIV infected cells express Serpin B9, which shields them against destruction by the immune system
• Early treatment cannot fully reduce chronic immune system activation.

People living with HIV have a higher level of inflammation, known as chronic antigenic stimulation, which increases the number of T-cells that are potentially concealing HIV.

"One of the immediate ways to eradicate hidden HIV is to control chronic antigenic stimulation in PLWH. When these dangerous pathogens disappear, the body will naturally reduce the number of cytotoxic T-cells, and therefore reduce the number of shelters for HIV," the team said.

Further research is needed to find answers to the following questions: A) Why is the number of cells, in which HIV hides, growing?, and B) How do we kill the virus without damaging key parts of the immune system?